TY - JOUR T1 - Intraventricular concentration times time (C x T) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma. AN - 69576670; 10023723 AB - Intraventricular chemotherapy results in more uniform drug distribution within the subarachnoid space and allows for more flexible drug administration schedules. The authors report their experience with an intraventricular concentration times time (C x T) chemotherapy regimen for recurrent meningeal leukemia and lymphoma. Twenty-one patients (median age, 11.6 years) received C x T therapy for meningeal acute lymphoblastic leukemia (n = 18), Burkitt's lymphoma (n = 2), or undifferentiated leukemia (n = 1). Prior therapy included standard intrathecal (IT) methotrexate and cytarabine, cranial or craniospinal radiation (median, 24 Gy), and 0-5 experimental treatment modalities. C x T induction therapy consisted of 2 mg of intraventricular methotrexate administered daily for 3 days every 10 days, for 4 courses. Patients were then consolidated with 4 courses of alternating intraventricular cytarabine (15 mg/day) or methotrexate (2 mg/day) daily for 3 days every 2 weeks (2 courses of methotrexate and 2 courses of cytarabine). Maintenance therapy consisted of alternating monthly courses of C x T methotrexate or cytarabine. Ninety-three percent of patients (14 of 15) who were evaluable for response achieved a complete remission in a median of 10 days (range, 2-40 days). Median remission duration was 15 months. Fourteen patients died of recurrent disease or systemic treatment-related complications; 2 patients are alive, off treatment, and in continuous complete remission for 59+ and 89+ months; 1 patient experienced a meningeal relapse at 24 months on C x T therapy but was reinduced with the C x T regimen, received craniospinal radiation, and is in remission at 142+ months; and 3 are alive with disease at 32+, 72+, and 81+ months. One patient was lost to follow-up. This regimen appears to be an effective and well-tolerated palliative treatment for patients with recurrent meningeal leukemia and lymphoma. JF - Cancer AU - Moser, A M AU - Adamson, P C AU - Gillespie, A J AU - Poplack, D G AU - Balis, F M AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 511 EP - 516 VL - 85 IS - 2 SN - 0008-543X, 0008-543X KW - Antimetabolites, Antineoplastic KW - 0 KW - Cytarabine KW - 04079A1RDZ KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Antimetabolites, Antineoplastic -- adverse effects KW - Humans KW - Child KW - Cytarabine -- administration & dosage KW - Cytarabine -- adverse effects KW - Recurrence KW - Child, Preschool KW - Injections, Intraventricular KW - Methotrexate -- adverse effects KW - Adult KW - Treatment Outcome KW - Adolescent KW - Methotrexate -- administration & dosage KW - Female KW - Male KW - Remission Induction KW - Meningeal Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Burkitt Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69576670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Intraventricular+concentration+times+time+%28C+x+T%29+methotrexate+and+cytarabine+for+patients+with+recurrent+meningeal+leukemia+and+lymphoma.&rft.au=Moser%2C+A+M%3BAdamson%2C+P+C%3BGillespie%2C+A+J%3BPoplack%2C+D+G%3BBalis%2C+F+M&rft.aulast=Moser&rft.aufirst=A&rft.date=1999-01-15&rft.volume=85&rft.issue=2&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&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 - The pharmacokinetic characteristics of glycolated humanized anti-Tac Fabs are determined by their isoelectric points. AN - 69576272; 9927057 AB - To evaluate a method for preventing the nephrotoxicity caused by the high renal accumulation of radiolabeled or toxin-conjugated small immunoproteins used for cancer therapy, we conjugated humanized anti-Tac Fab fragments with various numbers of glycolate molecules [glycolated Fab fragments (glyco-Fabs)] and separated the conjugates by means of ion-exchange columns into three fractions, depending on their isoelectric points (pIs). We evaluated the biodistribution, pharmacokinetics, and catabolism in normal nude mice of nonglycolated Fab (pI > or = 9.3) and three different preparations of glyco-Fab, including strongly anionic glyco-Fab (sa-glyco-Fab: pI < or = 4.5), mildly anionic glyco-Fab (pI = 4.5-7), and mildly cationic glyco-Fab (pI = 7-9.3). In addition, the biodistributions of 125I-labeled sa-glyco-Fab and 131I-labeled nonglycolated Fab were evaluated in normal nude mice coinjected with 50 mg of L-lysine and/or 1 microg of furosemide and in a control group without coinjection. We then evaluated the serial biodistribution of 125I-labeled sa-glyco-Fab (4 microCi/1 microg) and 131I-labeled nonglycolated Fab (5 microCi/1 microg) in Tac antigen-positive (ATAC4) and -negative (A431) tumor-bearing nude mice with s.c. tumor xenografts derived from Tac antigen-positive ATAC4 cells and receptor-negative A431 cells. These animals were coinjected with 30 mg of lysine i.v. and 30 mg of lysine i.p. 15 min after the radiolabeled Fab injection. To evaluate the biodistribution data and study scintigraphic imaging, we performed serial scintigraphy on normal and tumor-bearing mice with all four 131I-labeled preparations. 125I-labeled mildly cationic glyco-Fab and 131I-labeled nonglycolated Fab had similar distributions, except in the kidney. However, both 125I-labeled anionic glyco-Fab preparations showed significantly different distributions from both cationic Fabs in the blood, liver, lung, and spleen. Renal accumulation of all four radiolabeled Fab preparations increased significantly as the pI increased (P < 0.01). In addition, the intact fraction of Fab excreted into urine increased as pI decreased. Therefore, the glomerular filtration depended on whether the charge on the Fab was positive or negative. The proportion of Fab reabsorbed by the proximal tubules increased as pI increased. 125I-labeled sa-glyco-Fab and 125I-labeled mildly anionic glyco-Fab showed a similar distribution in the blood and all organs except the kidney. Lysine led to an additional blocking effect on proximal tubular uptake of both sa-glyco-Fab and nonglycolated Fab. Addition of furosemide yielded only a small effect when used with lysine. With lysine, the sa-glyco-Fab:nonglycolated Fab estimated integral radioactivity ratios were 4.7 and 0.7 in the ATAC4 tumor and in the kidney, respectively. The use of anionic fragments, which may be used in conjunction with lysine, represents a promising approach that may help decrease the renal toxicity of other small fragments, the molecular weights of which range from Mr 40,000 to 70,000, and, thereby, allow higher doses of radiation to the tumor. JF - Cancer research AU - Kobayashi, H AU - Le, N AU - Kim, I S AU - Kim, M K AU - Pie, J E AU - Drumm, D AU - Paik, D S AU - Waldmann, T A AU - Paik, C H AU - Carrasquillo, J A AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Cancer Institute, NIH, Bethesda, Maryland 20892-1180, USA. Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 422 EP - 430 VL - 59 IS - 2 SN - 0008-5472, 0008-5472 KW - Immunoglobulin Fab Fragments KW - 0 KW - Iodine Radioisotopes KW - Receptors, Interleukin-2 KW - Furosemide KW - 7LXU5N7ZO5 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Lysine -- pharmacology KW - Animals KW - Isoelectric Point KW - Radioimmunodetection KW - Mice, Nude KW - Mice KW - Furosemide -- pharmacology KW - Tissue Distribution KW - Glycosylation KW - Female KW - Kidney -- metabolism KW - Immunoglobulin Fab Fragments -- metabolism KW - Receptors, Interleukin-2 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69576272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+pharmacokinetic+characteristics+of+glycolated+humanized+anti-Tac+Fabs+are+determined+by+their+isoelectric+points.&rft.au=Kobayashi%2C+H%3BLe%2C+N%3BKim%2C+I+S%3BKim%2C+M+K%3BPie%2C+J+E%3BDrumm%2C+D%3BPaik%2C+D+S%3BWaldmann%2C+T+A%3BPaik%2C+C+H%3BCarrasquillo%2C+J+A&rft.aulast=Kobayashi&rft.aufirst=H&rft.date=1999-01-15&rft.volume=59&rft.issue=2&rft.spage=422&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 - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonsubstrate recognition site residues are involved in testosterone hydroxylation by cytochrome P450 CYP 2C11. AN - 69552308; 9882461 AB - We have previously characterized an allelic variant of cytochrome P450 CYP 2C11 from the Gunn rat that differs at three positions (amino acids 4, 116, and 187) from the predominant allele from Wistar rats and that displays a dramatically reduced testosterone hydroxylation activity. To assess the relative contribution of these mutations to the decrease in the enzymatic activity we constructed single and double mutants and coexpressed them with reductase. Testosterone metabolism was determined with a baculovirus/insect cell expression system. None of the identified positions alone is critical for the activity since the reversion of one of these mutations is unable to restore fully the Wistar-type activity. The activity of CYP 2C11 containing either the Asn116Ser substitution or the Phe187Leu represents congruent with30% of the activity of the CYP 2C11 Wistar-type protein. In contrast, the activity of the Val4Ala mutated protein is only 10% that of the Wistar-type protein, close to that of the Gunn-type protein. This study reevaluates the contribution of amino acid 4 to the catalysis by cytochrome P450 2C11 and points out the role of extra SRS residues. Copyright 1999 Academic Press. JF - Archives of biochemistry and biophysics AU - Biagini, C P AU - Philpot, R M AU - Célier, C M AD - NIEHS-LST, MD F204, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 309 EP - 314 VL - 361 IS - 2 SN - 0003-9861, 0003-9861 KW - Testosterone KW - 3XMK78S47O 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 - Steroid 16-alpha-Hydroxylase KW - Index Medicus KW - Animals KW - Rats, Gunn KW - Gene Expression KW - Enzyme Activation -- genetics KW - Hydroxylation KW - Mutagenesis, Site-Directed KW - Rats KW - Baculoviridae -- genetics KW - Rats, Wistar KW - Substrate Specificity KW - Binding Sites -- genetics KW - Cell Line KW - Catalysis KW - Testosterone -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69552308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonsubstrate+recognition+site+residues+are+involved+in+testosterone+hydroxylation+by+cytochrome+P450+CYP+2C11.&rft.au=Biagini%2C+C+P%3BPhilpot%2C+R+M%3BC%C3%A9lier%2C+C+M&rft.aulast=Biagini&rft.aufirst=C&rft.date=1999-01-15&rft.volume=361&rft.issue=2&rft.spage=309&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 - 1999-02-11 N1 - Date created - 1999-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory effect of Bcl-2 on p53-mediated transactivation following genotoxic stress. AN - 69563373; 9927186 AB - In the cellular response to genotoxic stress, cell cycle checkpoint and apoptosis are considered to be two of the major biological events in maintaining genomic stability. The tumor suppressor p53 has been shown to play critical roles in these stress-induced cellular responses at least in part through the activation of its down-stream genes, such as p21CIP1/WAF1, GADD45 and BAX. In addition, p53 has been found to down-regulate the expression of BCL-2, which is able to block apoptosis induced by both p53-dependent and independent signaling events. In this report, we have found that increased expression of Bcl-2 protein in the human Burkitt's lymphoma WMN cell line suppressed apoptosis induced by different DNA-damaging agents. The induction of p53-regulated genes including GADD45, p21CIP1/WAF1 and BAX by genotoxic stress was substantially reduced in cells expressing high levels of Bcl-2 protein. Furthermore, Bcl-2 protein was shown to specifically suppress the p53-mediated transactivation of p21CIP1/WAF1 and PG13-CAT, which is a typical p53-binding-site reporter construct. Similarly, the inhibitory effect of Bcl-2 protein was seen in a GADD45 promoter reporter construct after treatment with methylmethane sulfonate or UV-radiation. These results indicate that in addition to its apoptosis-suppressing activity, Bcl-2 protein is able to inhibit transactivation of p53-regulated genes, which function in multiple important cellular responses to genotoxic stress, including the control of cell cycle checkpoints, cell growth suppression and DNA repair. JF - Oncogene AU - Zhan, Q AU - Kontny, U AU - Iglesias, M AU - Alamo, I AU - Yu, K AU - Hollander, M C AU - Woodworth, C D AU - Fornace, A J AD - Laboratory of Biological Chemistry, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/01/14/ PY - 1999 DA - 1999 Jan 14 SP - 297 EP - 304 VL - 18 IS - 2 SN - 0950-9232, 0950-9232 KW - Mutagens KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Tumor Suppressor Protein p53 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Apoptosis KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Gene Expression Regulation KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Mutagens -- pharmacology KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcriptional Activation KW - Methyl Methanesulfonate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitory+effect+of+Bcl-2+on+p53-mediated+transactivation+following+genotoxic+stress.&rft.au=Zhan%2C+Q%3BKontny%2C+U%3BIglesias%2C+M%3BAlamo%2C+I%3BYu%2C+K%3BHollander%2C+M+C%3BWoodworth%2C+C+D%3BFornace%2C+A+J&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1999-01-14&rft.volume=18&rft.issue=2&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers. AN - 69555180; 9888834 AB - Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies. JF - Journal of medicinal chemistry AU - Turpin, J A AU - Song, Y AU - Inman, J K AU - Huang, M AU - Wallqvist, A AU - Maynard, A AU - Covell, D G AU - Rice, W G AU - Appella, E AD - Laboratory of Antiviral Drug Mechanisms and Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, SAIC Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 1999/01/14/ PY - 1999 DA - 1999 Jan 14 SP - 67 EP - 86 VL - 42 IS - 1 SN - 0022-2623, 0022-2623 KW - Anti-HIV Agents KW - 0 KW - Capsid Proteins KW - Gene Products, gag KW - Ligands KW - NCP7 protein, Human immunodeficiency virus 1 KW - Pyridinium Compounds KW - Sulfonamides KW - Sulfones KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Virus Replication -- drug effects KW - Models, Molecular KW - Mice KW - Cell Line KW - Structure-Activity Relationship KW - Sulfones -- chemistry KW - Anti-HIV Agents -- chemistry KW - Pyridinium Compounds -- chemistry KW - Sulfonamides -- chemical synthesis KW - Pyridinium Compounds -- chemical synthesis KW - Anti-HIV Agents -- chemical synthesis KW - HIV-1 -- metabolism KW - Sulfonamides -- chemistry KW - Sulfones -- pharmacology KW - Sulfonamides -- pharmacology KW - Capsid -- antagonists & inhibitors KW - Anti-HIV Agents -- pharmacology KW - Pyridinium Compounds -- pharmacology KW - Zinc Fingers KW - Sulfones -- chemical synthesis KW - Gene Products, gag -- antagonists & inhibitors KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69555180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synthesis+and+biological+properties+of+novel+pyridinioalkanoyl+thiolesters+%28PATE%29+as+anti-HIV-1+agents+that+target+the+viral+nucleocapsid+protein+zinc+fingers.&rft.au=Turpin%2C+J+A%3BSong%2C+Y%3BInman%2C+J+K%3BHuang%2C+M%3BWallqvist%2C+A%3BMaynard%2C+A%3BCovell%2C+D+G%3BRice%2C+W+G%3BAppella%2C+E&rft.aulast=Turpin&rft.aufirst=J&rft.date=1999-01-14&rft.volume=42&rft.issue=1&rft.spage=67&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 - 1999-02-11 N1 - Date created - 1999-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stereospecific differences in repair by human cell extracts of synthesized oligonucleotides containing trans-opened 7,8,9, 10-tetrahydrobenzo[a]pyrene 7,8-diol 9,10-epoxide N2-dG adduct stereoisomers located within the human K-ras codon 12 sequence. AN - 69544506; 9888796 AB - The potent environmental carcinogen benzo[a]pyrene (BaP), following enzymatic activation to enantiomeric pairs of bay-region 7,8-diol 9, 10-epoxides (the benzylic 7-hydroxyl group and epoxide oxygen are cis for DE-1 diastereomers and trans for DE-2 diastereomers), reacts with DNA to form covalent adducts predominately at the exocyclic amino groups of purines. Specific adducts, corresponding to the trans opening of each of the four optically active BaP DE isomers at C-10 by the N 2-amino group of dG, were synthesized as appropriately blocked phosphoramidites and were incorporated at either the first or second G of codon 12 within the G-rich sequence of human K-ras codons 11-13: GCT G1G2T GGC. The adducted oligonucleotides were incorporated into plasmids by primer extension, followed by purification of the covalently closed circular constructs. Adducts derived from either (+)- or (-)-DE-2, placed at either G1 or G2, presented strong blocks to in vitro transcription elongation by bacteriophage T3 RNA polymerase, but only moderately blocked transcription elongation by human RNA polymerase II in nuclear extracts. Adducts derived from all four DEs, placed on either G1 or G2, were used as substrates in a DNA repair synthesis assay using human whole cell extracts. Adducts derived from three of the DE stereoisomers exhibited significant amounts of repair synthesis, but the (-)-DE-2 adduct experienced no repair synthesis above that of the control. Constructs containing a pre-existing nick at the sixth phosphodiester bond 3' to either (+)-DE-2 or (-)-DE-2 adducts exhibited increased repair synthesis. JF - Biochemistry AU - Custer, L AU - Zajc, B AU - Sayer, J M AU - Cullinane, C AU - Phillips, D R AU - Cheh, A M AU - Jerina, D M AU - Bohr, V A AU - Mazur, S J AD - Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224-6825, USA. Y1 - 1999/01/12/ PY - 1999 DA - 1999 Jan 12 SP - 569 EP - 581 VL - 38 IS - 2 SN - 0006-2960, 0006-2960 KW - Codon KW - 0 KW - DNA Adducts KW - Oligonucleotides KW - benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Stereoisomerism KW - Base Sequence KW - Transcription, Genetic -- drug effects KW - Humans KW - Molecular Sequence Data KW - Lymphocytes -- metabolism KW - Cell Nucleus -- drug effects KW - Bacteriophage T3 -- enzymology KW - Cell Line, Transformed KW - Cell Nucleus -- genetics KW - DNA-Directed RNA Polymerases -- genetics KW - Genes, ras KW - DNA Repair KW - Oligonucleotides -- chemistry KW - DNA Adducts -- chemistry KW - Oligonucleotides -- metabolism KW - Oligonucleotides -- chemical synthesis KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69544506?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stereospecific+differences+in+repair+by+human+cell+extracts+of+synthesized+oligonucleotides+containing+trans-opened+7%2C8%2C9%2C+10-tetrahydrobenzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide+N2-dG+adduct+stereoisomers+located+within+the+human+K-ras+codon+12+sequence.&rft.au=Custer%2C+L%3BZajc%2C+B%3BSayer%2C+J+M%3BCullinane%2C+C%3BPhillips%2C+D+R%3BCheh%2C+A+M%3BJerina%2C+D+M%3BBohr%2C+V+A%3BMazur%2C+S+J&rft.aulast=Custer&rft.aufirst=L&rft.date=1999-01-12&rft.volume=38&rft.issue=2&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn. AN - 69552301; 9878727 AB - Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 microg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX. Copyright 1999 Elsevier Science B.V. JF - Brain research AU - Szallasi, A AU - Farkas-Szallasi, T AU - Tucker, J B AU - Lundberg, J M AU - Hökfelt, T AU - Krause, J E AD - Department of Pharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden.szallasi@exchange.nih.gov Y1 - 1999/01/09/ PY - 1999 DA - 1999 Jan 09 SP - 177 EP - 184 VL - 815 IS - 2 SN - 0006-8993, 0006-8993 KW - Diterpenes KW - 0 KW - Neurokinin-1 Receptor Antagonists KW - Neurotoxins KW - Protein Precursors KW - RNA, Messenger KW - Receptors, Neurokinin-1 KW - Tachykinins KW - preprotachykinin KW - Substance P KW - 33507-63-0 KW - resiniferatoxin KW - A5O6P1UL4I KW - Ribonucleases KW - EC 3.1.- KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Pain Management KW - In Situ Hybridization KW - Tachykinins -- genetics KW - Protein Precursors -- genetics KW - Injections, Subcutaneous KW - Capsaicin -- administration & dosage KW - Ribonucleases -- metabolism KW - Male KW - Administration, Topical KW - Spinal Cord -- metabolism KW - RNA, Messenger -- metabolism KW - Diterpenes -- administration & dosage KW - Receptors, Neurokinin-1 -- genetics KW - Ganglia, Spinal -- metabolism KW - Spinal Cord -- drug effects KW - RNA, Messenger -- drug effects KW - Neurotoxins -- administration & dosage KW - Substance P -- antagonists & inhibitors KW - Receptors, Neurokinin-1 -- metabolism KW - Ganglia, Spinal -- drug effects KW - Substance P -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69552301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+systemic+resiniferatoxin+treatment+on+substance+P+mRNA+in+rat+dorsal+root+ganglia+and+substance+P+receptor+mRNA+in+the+spinal+dorsal+horn.&rft.au=Szallasi%2C+A%3BFarkas-Szallasi%2C+T%3BTucker%2C+J+B%3BLundberg%2C+J+M%3BH%C3%B6kfelt%2C+T%3BKrause%2C+J+E&rft.aulast=Szallasi&rft.aufirst=A&rft.date=1999-01-09&rft.volume=815&rft.issue=2&rft.spage=177&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 - 1999-02-26 N1 - Date created - 1999-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aminoglycoside neurotoxicity involves NMDA receptor activation. AN - 69539737; 9878779 AB - Previous studies have led to the hypothesis that the ototoxicity produced by aminoglycoside antibiotics involves the excitotoxic activation of cochlear NMDA receptors. If this hypothesis is correct, then these antibiotics should also injure neurons within the brain. Because aminoglycosides do not readily penetrate the blood brain barrier, we examined the effects of the aminoglycoside neomycin following intrastriatal injection. Neomycin (10-250 nmol) produced dose-dependent striatal damage manifested as an increased gliosis as measured by: (1) [3H]PK-11195 binding, (2) staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and (3) staining for OX-6, an MHC class II antigen expressed by microglia and macrophages. Co-injection of subthreshhold doses of NMDA potentiates the striatal damage produced by neomycin (10 nmol). Moreover, neomycin-induced striatal damage is attenuated by a combination of the NMDA antagonists ifenprodil and 5, 7-dichlorokynurenic acid. Intrastriatal administration of compounds structurally related to neomycin, but devoid of modulatory actions at NMDA receptors (paromamine and 2-deoxystreptamine), fail to produce neuronal damage. These data support the hypothesis that aminoglycoside-induced ototoxicity is, in part, an excitotoxic process involving the activation of NMDA receptors. Moreover, aminoglycosides may damage the central nervous system in individuals with compromised blood brain barriers. Copyright 1999 Published by Elsevier Science B.V. JF - Brain research AU - Segal, J A AU - Harris, B D AU - Kustova, Y AU - Basile, A AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute on Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. segalj@lilly.com Y1 - 1999/01/09/ PY - 1999 DA - 1999 Jan 09 SP - 270 EP - 277 VL - 815 IS - 2 SN - 0006-8993, 0006-8993 KW - Aminoglycosides KW - 0 KW - Glial Fibrillary Acidic Protein KW - Isoquinolines KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Neomycin KW - 1404-04-2 KW - N-Methylaspartate KW - 6384-92-5 KW - PK 11195 KW - YNF83VN1RL KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - N-Methylaspartate -- administration & dosage KW - Isoquinolines -- metabolism KW - Neomycin -- administration & dosage KW - Neomycin -- pharmacology KW - Injections, Intraventricular KW - Rats KW - Rats, Sprague-Dawley KW - Corpus Striatum -- chemistry KW - N-Methylaspartate -- pharmacology KW - Binding Sites -- drug effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Corpus Striatum -- drug effects KW - Glial Fibrillary Acidic Protein -- analysis KW - Corpus Striatum -- pathology KW - Drug Synergism KW - Immunohistochemistry KW - Male KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Aminoglycosides -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69539737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aminoglycoside+neurotoxicity+involves+NMDA+receptor+activation.&rft.au=Segal%2C+J+A%3BHarris%2C+B+D%3BKustova%2C+Y%3BBasile%2C+A%3BSkolnick%2C+P&rft.aulast=Segal&rft.aufirst=J&rft.date=1999-01-09&rft.volume=815&rft.issue=2&rft.spage=270&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 - 1999-02-26 N1 - Date created - 1999-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between p53 mutations and inducible nitric oxide synthase expression in human colorectal cancer. AN - 69545038; 9890175 JF - Journal of the National Cancer Institute AU - Ambs, S AU - Bennett, W P AU - Merriam, W G AU - Ogunfusika, M O AU - Oser, S M AU - Harrington, A M AU - Shields, P G AU - Felley-Bosco, E AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1999/01/06/ PY - 1999 DA - 1999 Jan 06 SP - 86 EP - 88 VL - 91 IS - 1 SN - 0027-8874, 0027-8874 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Nitric Oxide KW - 31C4KY9ESH KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - DNA Mutational Analysis KW - Humans KW - Colonic Polyps -- enzymology KW - Models, Biological KW - Mutagenesis KW - Adenoma -- enzymology KW - CpG Islands KW - Carcinoma -- enzymology KW - DNA, Neoplasm -- genetics KW - Adenoma -- genetics KW - Colonic Polyps -- genetics KW - Carcinoma -- genetics KW - Neoplasm Proteins -- biosynthesis KW - Genes, p53 KW - Nitric Oxide Synthase -- genetics KW - Neoplasm Proteins -- genetics KW - Nitric Oxide -- metabolism KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology KW - Nitric Oxide Synthase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69545038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+between+p53+mutations+and+inducible+nitric+oxide+synthase+expression+in+human+colorectal+cancer.&rft.au=Ambs%2C+S%3BBennett%2C+W+P%3BMerriam%2C+W+G%3BOgunfusika%2C+M+O%3BOser%2C+S+M%3BHarrington%2C+A+M%3BShields%2C+P+G%3BFelley-Bosco%2C+E%3BHussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1999-01-06&rft.volume=91&rft.issue=1&rft.spage=86&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1999 Sep 1;91(17):1509-11 [10469757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence and analysis of the genome of a baculovirus pathogenic for Lymantria dispar. AN - 69562714; 9887315 AB - The genome of the Lymantria dispar multinucleocapsid nucleopolyhedrovirus (LdMNPV) was sequenced and analyzed. It is composed of 161,046 bases with a G + C content of 57.5% and contains 163 putative open reading frames (ORFs) of >/=150 nucleotides. Homologs were found to 95 of the 155 genes predicted for the Autographa californica MNPV (AcMNPV) genome. More than 9% of the LdMNPV genome was occupied by 16 repeated genes related to AcMNPV ORF2. Readily identifiable homologs of several genes that have been reported to play important roles in the AcMNPV life cycle are not present; these include ie-2, a transcriptional transactivator, and gp64, a major envelope glycoprotein of the nonoccluded form of the virus. A number of genes lacking in AcMNPV but present in other baculoviruses were identified; these include two viral enhancing factor homologs, a second copy of a conotoxin-like gene, and a dutpase homolog. Although a single gene predicted to encode a large subunit of ribonucleotide reductase was found, two different copies of the small subunit gene were present. In addition, homologs of genes not previously reported for baculoviruses were identified, including a predicted protein with homology to DNA ligases and another that has motifs most closely related to a yeast mitochondrial helicase. Thirteen homologous regions (hrs) containing 54 repeated sequences that include 30-bp imperfect palindromes were identified. The imperfect palindromes are related to those from other baculoviruses. Copyright 1999 Academic Press. JF - Virology AU - Kuzio, J AU - Pearson, M N AU - Harwood, S H AU - Funk, C J AU - Evans, J T AU - Slavicek, J M AU - Rohrmann, G F AD - National Library of Medicine, National Institutes of Health, Bethesda, Maryland, 20894, USA. Y1 - 1999/01/05/ PY - 1999 DA - 1999 Jan 05 SP - 17 EP - 34 VL - 253 IS - 1 SN - 0042-6822, 0042-6822 KW - Inhibitor of Apoptosis Proteins KW - 0 KW - Mollusk Venoms KW - Viral Proteins KW - inhibitor of apoptosis, Nucleopolyhedrovirus KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Mollusk Venoms -- genetics KW - Sequence Homology, Nucleic Acid KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Open Reading Frames -- genetics KW - Nucleopolyhedrovirus -- genetics KW - Moths -- genetics KW - Genome, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69562714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sequence+and+analysis+of+the+genome+of+a+baculovirus+pathogenic+for+Lymantria+dispar.&rft.au=Kuzio%2C+J%3BPearson%2C+M+N%3BHarwood%2C+S+H%3BFunk%2C+C+J%3BEvans%2C+J+T%3BSlavicek%2C+J+M%3BRohrmann%2C+G+F&rft.aulast=Kuzio&rft.aufirst=J&rft.date=1999-01-05&rft.volume=253&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-17 N1 - Date created - 1999-02-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF081810; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalytic properties of selenophosphate synthetases: Comparison of the selenocysteine-containing enzyme from Haemophilus influenzae with the corresponding cysteine- containing enzyme from Escherichia coli AN - 17135266; 4438433 AB - The selD gene from Haemophilus influenzae has been overexpressed in Escherichia coli. The expressed protein was purified to homogeneity in a four-step procedure and then carboxymethylated by reaction with chloroacetate. N-terminal sequencing by Edman degradation identified residue 16 as carboxymethyl selenocysteine, which corresponded to the essential cysteine residue in the glycine-rich sequence of the E. coli selenophosphate synthetase. It would be expected that an ionized selenol of a selenocysteine in place of a catalytically essential cysteine residue would result in an enzyme with increased catalytic activity. To test this hypothesis we kinetically characterized the selenocysteine containing selenophosphate synthetase from H. influenzae and compared its catalytic activity to that of the cysteine containing selenophosphate synthetase from E. coli. Our characterization revealed the K sub(m) values for the two substrates, selenide and ATP, were similar for both enzymes. However, the selenocysteine- containing enzyme did not exhibit the expected higher catalytic activity. Based on these results we suggest a role of selenocysteine in H. influenzae that is not catalytic. JF - Proceedings of the National Academy of Sciences, USA AU - Lacourciere, G M AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD 20892, tcstadtman@nih.gov Y1 - 1999/01/05/ PY - 1999 DA - 1999 Jan 05 SP - 44 EP - 48 PB - National Academy of Sciences VL - 96 IS - 01 SN - 0027-8424, 0027-8424 KW - cysteine KW - selD gene KW - selenocysteine KW - selenophosphate synthase KW - Microbiology Abstracts B: Bacteriology KW - Haemophilus influenzae KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17135266?accountid=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=Catalytic+properties+of+selenophosphate+synthetases%3A+Comparison+of+the+selenocysteine-containing+enzyme+from+Haemophilus+influenzae+with+the+corresponding+cysteine-+containing+enzyme+from+Escherichia+coli&rft.au=Lacourciere%2C+G+M%3BStadtman%2C+T+C&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=1999-01-05&rft.volume=96&rft.issue=01&rft.spage=44&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; Haemophilus influenzae ER - TY - JOUR T1 - Analysis of correlated data in human biomonitoring studies. The case of high sister chromatid exchange frequency cells AN - 17128189; 4434849 AB - Sister chromatid exchange (SCE) analysis in peripheral blood lymphocytes is a well established technique that aims to evaluate human exposure to toxic agents. The individual mean value of SCE per cell had been the only recommended index to measure the extent of this cytogenetic damage until the early 1980's, when the concept of high frequency cells (HFC) was introduced to increase the sensitivity of the assay. All statistical analyses proposed thus far to handle these data are based on measures which refer to the individual mean values and not to the single cell. Although this approach allows the use of simple statistical methods, part of the information provided by the distribution of SCE per single cell within the individual is lost. Using the appropriate methods developed for the analysis of correlated data, it is possible to exploit all the available information. In particular, the use of random-effects models seems to be very promising for the analysis of clustered binary data such as HFC. Logistic normal random-effects models, which allow modelling of the correlation among cells within individuals, have been applied to data from a large study population to highlight the advantages of using this methodology in human biomonitoring studies. The inclusion of random-effects terms in a regression model could explain a significant amount of variability, and accordingly change point and /or interval estimates of the corresponding coefficients. Examples of coefficients that change across different regression models and their interpretation are discussed in detail. One model that seems particularly appropriate is the random intercepts and random slopes model. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Bonassi, S AU - Fontana, V AU - Ceppi, M AU - Barale, R AU - Biggeri, A AD - Department of Environmental Epidemiology and Biostatistics, National Cancer Institute, Largo Rosanna Benzi 10, 16132 Genoa, Italy Y1 - 1999/01/02/ PY - 1999 DA - 1999 Jan 02 SP - 13 EP - 21 PB - Elsevier Science B.V. VL - 438 IS - 1 SN - 1383-5718, 1383-5718 KW - lymphocytes KW - man KW - Genetics Abstracts; Toxicology Abstracts KW - Bioassays KW - Sister chromatid exchange KW - Genotoxicity testing KW - Lymphocytes KW - Toxicity testing KW - G 07220:General theory/testing systems KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17128189?accountid=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=Analysis+of+correlated+data+in+human+biomonitoring+studies.+The+case+of+high+sister+chromatid+exchange+frequency+cells&rft.au=Bonassi%2C+S%3BFontana%2C+V%3BCeppi%2C+M%3BBarale%2C+R%3BBiggeri%2C+A&rft.aulast=Bonassi&rft.aufirst=S&rft.date=1999-01-02&rft.volume=438&rft.issue=1&rft.spage=13&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 N1 - SubjectsTermNotLitGenreText - Sister chromatid exchange; Bioassays; Lymphocytes; Toxicity testing; Genotoxicity testing ER - TY - JOUR T1 - HIV RELATED ADMISSIONS IN A PSYCHIATRIC HOSPITAL A FIVE YEAR PROFILE AN - 872128839; 14606913 AB - Recent reports have indicated an increasing prevalence of HIV infection in the mentally ill. Reports have also emphasised the etiological role of HIV infection in psychiatric illness. The aim of this study was to assess the clinical and risk profile of psychiatric inpatients found seropositive for HIV infection. All psychiatric inpatients from a psychiatric hospital who tested positive for HI V infection over a five year period were assessed. The assessments included a detailed clinical history, psychiatric assessment and risk behaviour evaluation. Of the 2283 psychiatric patients tested, 51 were found to be seropositive. 43 patients were included in the study. 30 (69.7%) had a diagnosis of alcohol dependence, of which, 11 patients had comorbid psychiatnc diagnosis in the form of affective disorders (23%) and psychosis (14%). Personality disorders were seen in 9 patients. In 19% the clinical manifestation was considered to be etiologically related to HIV infection. The predominant risk behaviour was in the form of multiple partner heterosexual contacts. In several patients the risk behaviour had occurred during an episode of mental illness or under the influence of alcohol. The study demonstrates the importance of detecting and describing HIV infection and its manifestation among psychiatric patients. JF - Indian Journal of Psychiatry AU - Chandra, P S AU - Krishna, VAS AU - Ravi, V AU - Desai, A AU - Puttaram, S AD - CHANDRA, MD., Associate Professor, Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore-560029. Y1 - 1999 PY - 1999 DA - 1999 SP - 320 EP - 324 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 41 IS - 4 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - Risk assessment KW - Alcohol KW - Historical account KW - Affective disorders KW - Personality KW - personality KW - Infection KW - Drug dependence KW - Mental disorders KW - Human immunodeficiency virus KW - Psychosis KW - infection KW - mental disorders KW - Hospitals KW - Ethanol KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23110:Psychological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/872128839?accountid=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=Indian+Journal+of+Psychiatry&rft.atitle=HIV+RELATED+ADMISSIONS+IN+A+PSYCHIATRIC+HOSPITAL+A+FIVE+YEAR+PROFILE&rft.au=Chandra%2C+P+S%3BKrishna%2C+VAS%3BRavi%2C+V%3BDesai%2C+A%3BPuttaram%2C+S&rft.aulast=Chandra&rft.aufirst=P&rft.date=1999-01-01&rft.volume=41&rft.issue=4&rft.spage=320&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 revised - 2011-06-01 N1 - Last updated - 2013-09-09 N1 - SubjectsTermNotLitGenreText - Risk assessment; Drug dependence; Mental disorders; Psychosis; Affective disorders; Personality; Infection; Ethanol; Hospitals; Historical account; Alcohol; Human immunodeficiency virus; infection; personality; mental disorders ER - TY - JOUR T1 - MULTIPLE DRUG INTERACTION ACROSS MEDICAL SPECIALIZATIONS AN - 867737994; 14659325 AB - An epileptic patient on high dose carbamazepine monotherapy received erythromycin from a physician and ketoconazole from a dermatologist. Carbamazepine neurotoxicity developed as a result of a pharmacokinetic interaction between the three drugs. Precautions are suggested to minimize the risk of such drug interactions that span medical specializations. JF - Indian Journal of Psychiatry AU - Andrade, Chittaranjan AD - M.D., Additional Professor & Head, Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India Y1 - 1999 PY - 1999 DA - 1999 SP - 75 EP - 76 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 41 IS - 1 SN - 0019-5545, 0019-5545 KW - Risk Abstracts; CSA Neurosciences Abstracts KW - Drug interaction KW - Specialization KW - Erythromycin KW - Ketoconazole KW - Pharmacokinetics KW - risk reduction KW - Carbamazepine KW - Epilepsy KW - Neurotoxicity KW - Drugs KW - drug interaction KW - N3 11001:Behavioral and Cognitive Neuroscience KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/867737994?accountid=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=Indian+Journal+of+Psychiatry&rft.atitle=MULTIPLE+DRUG+INTERACTION+ACROSS+MEDICAL+SPECIALIZATIONS&rft.au=Andrade%2C+Chittaranjan&rft.aulast=Andrade&rft.aufirst=Chittaranjan&rft.date=1999-01-01&rft.volume=41&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-05-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Drug interaction; Carbamazepine; Epilepsy; Neurotoxicity; Specialization; Ketoconazole; Erythromycin; Drugs; Pharmacokinetics; risk reduction; drug interaction ER - TY - JOUR T1 - NALTREXONE IN PRIMARY HYPERPHAGIC OBESITY WITY HYPOCHONDRIACAL DISORDER - A CLINICAL STUDY AN - 867737968; 14659293 AB - Six well investigated patients of primary hyperphagic obesity with hypochondrical disorder were sequentially treated with psychoeducational methods alone and psychoeducational methods with naltrexone hydrochloride 50 mg daily orally for six weeks each. RMANOVA revealed no statically significant (p>0.05) decrease in body mass index suggesting that psychoeducational methods with naltrexone were as ineffective in reducing obesity as psychoeducational methods alone. The limitations of the study and implications for future research are discussed. JF - Indian Journal of Psychiatry AU - Pandey, Ravi S AU - Arya, S C AU - Subbakrishna, D K AD - S. PANDEY, M.D., Additional Professor of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore-560 029. Y1 - 1999 PY - 1999 DA - 1999 SP - 104 EP - 107 PB - Medknow Publications Pvt. Ltd., A-108/109 Kanara Business Center Mumbai 400075 India VL - 41 IS - 2 SN - 0019-5545, 0019-5545 KW - Physical Education Index; CSA Neurosciences Abstracts KW - Obesity KW - Body mass KW - Naltrexone KW - Patients KW - Body mass index KW - Psychiatry KW - Ethnic groups KW - N3 11001:Behavioral and Cognitive Neuroscience KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/867737968?accountid=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=Indian+Journal+of+Psychiatry&rft.atitle=NALTREXONE+IN+PRIMARY+HYPERPHAGIC+OBESITY+WITY+HYPOCHONDRIACAL+DISORDER+-+A+CLINICAL+STUDY&rft.au=Pandey%2C+Ravi+S%3BArya%2C+S+C%3BSubbakrishna%2C+D+K&rft.aulast=Pandey&rft.aufirst=Ravi&rft.date=1999-01-01&rft.volume=41&rft.issue=2&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Psychiatry&rft.issn=00195545&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2011-05-01 N1 - Last updated - 2013-08-23 N1 - SubjectsTermNotLitGenreText - Obesity; Body mass; Patients; Psychiatry; Ethnic groups; Naltrexone; Body mass index ER - TY - JOUR T1 - Nonstrategic Subjective Threshold Effects in Phonemic Masking AN - 85705416; 9907393 AB - Three backward-masking experiments (total N = 174) demonstrated that the magnitude of the phonemic mask reduction effect (MRE) is a function of subjective threshold & that the magnitude is also independent of stimulus-based response strategies. In these experiments, a target word (eg, bake) was backward masked by a graphemically similar nonword (eg, BAWK), a phonemically similar nonword (eg, BAIK), or an unrelated control (eg, CRUG). Experiments 1 & 2 had a low percentage (9%) of trials with phonemic masks & differed only in baseline identification rate. Experiment 3 controlled baseline identification rate at below & above subjective threshold levels, with 9% phonemic trials. The results were that identification rates were higher with phonemic masks than with graphemic masks, irrespective of the low percentage of phonemic trials. However, the magnitude of the phonemic MRE became large only when the baseline identification rate was below subjective threshold. The pattern of the phonemic MRE was interpreted as a result of rapid automatic phonological activation, independent of stimulus-based processing strategies. 2 Figures, 1 Appendix, 39 References. Adapted from the source document JF - Memory & Cognition AU - Xu, Benjamin AU - Perfetti, Charles A AD - National Instit Neurological Disorders & Stroke National Instits Health, 5N 250 Bldg 10 Center Dr MSC 140 Bethesda MD 20892 benxu@codon.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 26 EP - 36 VL - 27 IS - 1 SN - 0090-502X, 0090-502X KW - Orthography (61750) KW - Word Recognition (98200) KW - Phonemes (64600) KW - Masking (51450) KW - article KW - 4019: psycholinguistics; phonological processing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85705416?accountid=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=Memory+%26+Cognition&rft.atitle=Nonstrategic+Subjective+Threshold+Effects+in+Phonemic+Masking&rft.au=Xu%2C+Benjamin%3BPerfetti%2C+Charles+A&rft.aulast=Xu&rft.aufirst=Benjamin&rft.date=1999-01-01&rft.volume=27&rft.issue=1&rft.spage=26&rft.isbn=&rft.btitle=&rft.title=Memory+%26+Cognition&rft.issn=0090502X&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 - MYCGAO N1 - SubjectsTermNotLitGenreText - Masking (51450); Phonemes (64600); Word Recognition (98200); Orthography (61750) ER - TY - JOUR T1 - Neural Correlates of Semantic and Episodic Memory Retrieval AN - 85681146; 9910256 AB - To investigate the functional neuroanatomy associated with retrieving semantic & episodic memories, changes in regional cerebral blood flow (rCBF) were measured with positron emission tomography (PET) while subjects (Ss) generated single word responses to achromatic line drawings of objects. During separate scans, Ss either named each object, retrieved a commonly associated color of each object (semantic condition), or recalled a previously studied uncommon color of each object (episodic condition). Ss were also scanned while staring at visual noise patterns to provide a low-level perceptual baseline. Relative to the low-level baseline, all three conditions revealed bilateral activation of posterior regions of the temporal lobes, cerebellum, & left-lateralized activations in frontal regions. Retrieving semantic information, as compared to object naming, activated left inferior temporal, left superior parietal, & left frontal cortices. In addition, small regions of right frontal cortex were activated. Retrieving episodic information, as compared to object naming, activated bilateral medial parietal cortex, bilateral retrosplenial cortex, right frontal cortex, thalamus, & cerebellum. Direct comparison of the semantic & episodic conditions revealed bilateral activation in temporal & frontal lobes in the semantic task (left greater than right), & activation in medial parietal cortex, retrosplenial cortex, thalamus, & cerebellum (but not right frontal regions) in the episodic task. These results support the assertion that distinct neural structures mediate semantic & episodic memory retrieval. However, they also raise questions regarding the specific roles of left temporal & right frontal cortices during episodic memory retrieval, in particular. 3 Tables, 6 Figures, 83 References. Adapted from the source document JF - Neuropsychologia AU - Wiggs, Cheri L AU - Weisberg, Jill AU - Martin, Alex AD - Laboratory of Brain & Cognition, National Instit of Mental Health, Building 10, Rm 4C104, 10 Center Dr MSC 1366, Bethesda, MD 20892-1366 [tel/fax: 001-301-435-4928/402-6658; mailto:cheri@codon.nih.gov] Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 103 EP - 118 VL - 37 IS - 1 SN - 0028-3932, 0028-3932 KW - Cerebral Dominance (11500) KW - Color (13450) KW - Lexical Access (46630) KW - Semantic Memory (76750) KW - Aided Recall (01250) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85681146?accountid=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=Neuropsychologia&rft.atitle=Neural+Correlates+of+Semantic+and+Episodic+Memory+Retrieval&rft.au=Wiggs%2C+Cheri+L%3BWeisberg%2C+Jill%3BMartin%2C+Alex&rft.aulast=Wiggs&rft.aufirst=Cheri&rft.date=1999-01-01&rft.volume=37&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Neuropsychologia&rft.issn=00283932&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 - NUPSA6 N1 - SubjectsTermNotLitGenreText - Semantic Memory (76750); Aided Recall (01250); Color (13450); Cerebral Dominance (11500); Lexical Access (46630) ER - TY - JOUR T1 - Ideomotor apraxia in progressive supranuclear palsy: a case study. AN - 85316991; pmid-9918365 JF - Movement disorders : official journal of the Movement Disorder Society AU - Pharr, V AU - Litvan, I AU - Brat, D J AU - Troncoso, J AU - Reich, S G AU - Stark, M AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 162 EP - 166 VL - 14 IS - 1 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Neurofibrillary Tangles -- pathology KW - Diagnosis, Differential KW - Brain -- pathology KW - Humans KW - Atrophy KW - Middle Aged KW - Neuropsychological Tests KW - Male KW - Alzheimer Disease -- diagnosis KW - Alzheimer Disease -- pathology KW - Apraxias -- pathology KW - Supranuclear Palsy, Progressive -- pathology KW - Supranuclear Palsy, Progressive -- diagnosis KW - Apraxias -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85316991?accountid=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=Ideomotor+apraxia+in+progressive+supranuclear+palsy%3A+a+case+study.&rft.au=Pharr%2C+V%3BLitvan%2C+I%3BBrat%2C+D+J%3BTroncoso%2C+J%3BReich%2C+S+G%3BStark%2C+M&rft.aulast=Pharr&rft.aufirst=V&rft.date=1999-01-01&rft.volume=14&rft.issue=1&rft.spage=162&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 - AIDS-related plasmablastic lymphomas of the oral cavity and jaws: a diagnostic dilemma. AN - 85309044; pmid-9930548 AB - Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas are highly pleomorphic in their clinical, pathological, and biological features. Recent investigations have led to the identification of a particular type of AIDS-related non-Hodgkin's lymphomas presenting in the oral cavity and jaws. This novel category of AIDS-related non-Hodgkin's lymphomas derives from B-cells and has been defined as plasmablastic lymphoma on the basis of its morphological and immunophenotypic features. Clinically, AIDS-related plasmablastic lymphoma is generally limited to the oral cavity at the time of diagnosis, although extension to distant sites frequently occurs at a later stage. Histologically, AIDS-related plasmablastic lymphoma is composed of a monomorphic and cohesive pattern of plasmablasts with basophilic cytoplasm. Phenotypically, AIDS-related plasmablastic lymphoma fails to express the most common B-cell-associated surface antigens, whereas it consistently expresses high levels of plasma cell-associated markers, including VS38c and CD138/syndecan-1. For the purpose of differential diagnosis, the morphological and immunophenotypic peculiarities of AIDS-related plasmablastic lymphoma clearly distinguish these lymphomas from other categories of AIDS-related non-Hodgkin's lymphomas, as well as from undifferentiated large cell carcinomas. JF - The Annals of otology, rhinology, and laryngology AU - Carbone, A AU - Gaidano, G AU - Gloghini, A AU - Ferlito, A AU - Rinaldo, A AU - Stein, H AD - Division of Pathology, National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 95 EP - 99 VL - 108 IS - 1 SN - 0003-4894, 0003-4894 KW - Abridged Index Medicus; Index Medicus; AIDS/HIV KW - National Library of Medicine KW - Diagnosis, Differential KW - Humans KW - Antibodies, Neoplasm -- immunology KW - Antigens, CD -- immunology KW - Lymphoma, AIDS-Related -- pathology KW - Plasmacytoma -- pathology KW - Mandibular Neoplasms -- pathology KW - Oropharyngeal Neoplasms -- pathology KW - Maxillary Neoplasms -- pathology KW - Lymphoma, Non-Hodgkin -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85309044?accountid=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=AIDS-related+plasmablastic+lymphomas+of+the+oral+cavity+and+jaws%3A+a+diagnostic+dilemma.&rft.au=Carbone%2C+A%3BGaidano%2C+G%3BGloghini%2C+A%3BFerlito%2C+A%3BRinaldo%2C+A%3BStein%2C+H&rft.aulast=Carbone&rft.aufirst=A&rft.date=1999-01-01&rft.volume=108&rft.issue=1&rft.spage=95&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 - A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high-dose carboplatin as primary treatment of patients with small-volume residual ovarian cancer. AN - 85284379; pmid-9923815 AB - PURPOSE: Because intraperitoneal (i.p.) therapy may provide a therapeutic advantage and because hyperthermia enhances carboplatin (CBDCA) cytotoxicity, we evaluated the feasibility, toxicity, and pharmacokinetics of CBDCA given via continuous hyperthermic peritoneal perfusion (CHPP) in patients with small-volume residual ovarian cancer. Patients and METHODS: Six patients underwent optimal cytoreductive procedures (residual disease < or =5 mm) as initial treatment of stages II and III epithelial ovarian adenocarcinoma. All patients received a 90-min CHPP at a CBDCA dose of 800-1200 mg/m2, with the perfusate being recirculated rapidly from a reservoir through a heat exchanger, resulting in i.p. temperatures of 41-43 degrees C. Plasma, perfusate, and urine samples were collected and platinum was quantified by flameless atomic absorption spectrophotometry. RESULTS: At no time did any patient's core temperature exceed 40 degrees C. Peak perfusate platinum concentrations were 8- to 15-fold higher than peak ultrafilterable plasma concentrations. The permeability-area product was extremely high and variable (14-90 ml/min), resulting in a regional advantage of 1.9-5.3. The percentage of the dose absorbed ranged widely from 27% to 77%. Dose-limiting hematologic toxicity was observed at a dose of 1200 mg/m2 and this was associated with a CBDCA AUC in plasma of 11 mg min ml(-1). CONCLUSION: CHPP with CBDCA was safely given to three patients at a dose of 800 mg/m2, and dose-limiting hematologic toxicities observed at 1200 mg/m2, correlated with the plasma CBDCA exposure established when lower doses of CBDCA are given systemically. The pharmacokinetic data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area. Variable drug absorption and clearance make the prediction of systemic exposure highly uncertain. These findings may have important implications for novel therapies given i.p. JF - Cancer Chemotherapy and Pharmacology AU - Steller, M A AU - Egorin, M J AU - Trimble, E L AU - Bartlett, D L AU - Zuhowski, E G AU - Alexander, H R AU - Dedrick, R L AD - Section of Gynecologic Oncology, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1999 SP - 106 EP - 114 VL - 43 IS - 2 SN - 0344-5704, 0344-5704 KW - Ovarian Neoplasms KW - Area Under Curve KW - Antineoplastic Agents KW - Combined Modality Therapy KW - Human KW - Aged KW - Pilot Projects KW - Carboplatin KW - Infusions, Parenteral KW - Adult KW - Hyperthermia, Induced KW - Middle Age KW - Bone Marrow Diseases KW - Adenocarcinoma KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85284379?accountid=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=Cancer+Chemotherapy+and+Pharmacology&rft.atitle=A+pilot+phase+I+trial+of+continuous+hyperthermic+peritoneal+perfusion+with+high-dose+carboplatin+as+primary+treatment+of+patients+with+small-volume+residual+ovarian+cancer.&rft.au=Steller%2C+M+A%3BEgorin%2C+M+J%3BTrimble%2C+E+L%3BBartlett%2C+D+L%3BZuhowski%2C+E+G%3BAlexander%2C+H+R%3BDedrick%2C+R+L&rft.aulast=Steller&rft.aufirst=M&rft.date=1999-01-01&rft.volume=43&rft.issue=2&rft.spage=106&rft.isbn=&rft.btitle=&rft.title=Cancer+Chemotherapy+and+Pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Right parietal infarction with concomitant mutism. AN - 85239044; pmid-9925242 AB - Right brain damage results in a variety of cognitive and behavioural dysfunctions. Mutism however, has been described only with left or bihemispheric lesions involving the parietal lobe. We report an elderly man who had left faciobrachial monoparesis and concomitant mutism. His auditory-verbal comprehension was intact. MRI revealed a right parietal infarct involving the cortical and subcortical regions. Recovery from mutism during the course of treatment was abrupt and complete with no residual dysarthria. A possibility of diaschisis or impaired modulation of left hemispheric function due to right cerebral infarct, presenting as conversion reaction, is proposed for this rare association. JF - Acta Neurologica Scandinavica AU - Chaudhuri, J R AU - Anand, J AU - Shivshankar, N AU - Jaykumar, P N AU - Suvarna, A AU - Murali, T AU - Taly, A B AD - Department of Psychiatric & Neurological Rehabilitation, National Institute of Mental Health and Neuro Sciences, Bangalore, India. PY - 1999 SP - 77 EP - 79 VL - 99 IS - 1 SN - 0001-6314, 0001-6314 KW - Cerebral Infarction KW - Mutism KW - Human KW - Middle Age KW - Case Report KW - Laterality KW - Parietal Lobe KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239044?accountid=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=Acta+Neurologica+Scandinavica&rft.atitle=Right+parietal+infarction+with+concomitant+mutism.&rft.au=Chaudhuri%2C+J+R%3BAnand%2C+J%3BShivshankar%2C+N%3BJaykumar%2C+P+N%3BSuvarna%2C+A%3BMurali%2C+T%3BTaly%2C+A+B&rft.aulast=Chaudhuri&rft.aufirst=J&rft.date=1999-01-01&rft.volume=99&rft.issue=1&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Acta+Neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cytokines and apoptotic molecules in experimental melanin-protein induced uveitis (EMIU) and experimental autoimmune uveoretinitis (EAU). AN - 70829626; 10520900 AB - The cytokine profile and occurrence of apoptosis during experimental melanin-protein induced uveitis (EMIU) were investigated and compared with that of experimental autoimmune uveoretinitis (EAU). EMIU or EAU was induced in Lewis rats. Eyes were collected at different time points after immunization. Cytokine mRNA expression was identified in the inflammatory cells in the uvea of EMIU rats; IL-2, IFN-gamma and IL-12 increased at the peak of the inflammation, and then tapered off as inflammation subsided. IL-4 and IL-10 increased at the peak of ocular inflammation, and persisted with inflammation resolved. Fas and FasL were expressed consistently in ocular resident cells of EMIU, but were elevated in EAU. In EAU, Bcl-2 expression showed a sharp peak in inflammatory cells but not in the resident cells. In EMIU, high levels of Bcl-2 were present and persisted in both ocular resident and inflammatory cells. Expression of Bax was relatively stable in both EAU and EMIU. Cellular DNA fragmentation was detected in the retinal glial cells of EAU and some inflammatory cells of EMIU. In EMIU, the dynamics of Th1 cytokines were consistent with the ocular inflammation, whereas persistent expression of Th2 cytokines was consistent with their known regulatory role. The continuous high expression of Bcl-2 and the high ratio of Bcl-2 to Bax in the eyes of EMIU may possibly contribute to prevention of ocular tissue damage, and of inflammatory cells from undergoing apoptosis, thus resulting in chronic recurrent inflammation. JF - Autoimmunity AU - Li, Q AU - Sun, B AU - Matteson, D M AU - O'Brien, T P AU - Chan, C C AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 171 EP - 182 VL - 30 IS - 3 SN - 0891-6934, 0891-6934 KW - Cytokines KW - 0 KW - Melanins KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - In Situ Hybridization KW - Melanins -- pharmacology KW - Uvea -- immunology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Immunohistochemistry KW - Female KW - Autoimmune Diseases -- physiopathology KW - Autoimmune Diseases -- immunology KW - Apoptosis KW - Retinitis -- physiopathology KW - Retinitis -- immunology KW - Cytokines -- biosynthesis KW - Uveitis -- physiopathology KW - Uveitis -- immunology KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70829626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Autoimmunity&rft.atitle=Cytokines+and+apoptotic+molecules+in+experimental+melanin-protein+induced+uveitis+%28EMIU%29+and+experimental+autoimmune+uveoretinitis+%28EAU%29.&rft.au=Li%2C+Q%3BSun%2C+B%3BMatteson%2C+D+M%3BO%27Brien%2C+T+P%3BChan%2C+C+C&rft.aulast=Li&rft.aufirst=Q&rft.date=1999-01-01&rft.volume=30&rft.issue=3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&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 - Regulation of lactoferrin gene expression by estrogen and epidermal growth factor: molecular mechanism. AN - 70797921; 10505667 AB - Lactoferrin (LF) is a member of the transferrin gene family. Its expression in the mouse uterus is regulated by estrogen and epidermal growth factor (EGF). The author et al. cloned the LF gene promoter/enhancer region, and demonstrated that multihormone signaling pathways are involved in modulating LF gene activity. Three short but complex modules, within 400 bp from the transcription initiation site of the mouse LF gene, contain the response elements that are responsible for estrogen, retinoic acid, mitogen, and growth factor stimulation. These elements have been identified and characterized, using reporter constructs transiently transfected into human endometrial carcinoma RL95-2 cells. The author et al. used molecular approaches, such as deletion, insertion, and site-directed mutagenesis, to determine the relationship between the response elements, and to fine-map the crucial nucleotides within them. This article reviews the characterization of the estrogen and EGF response elements of the mouse LF gene promoter. JF - Cell biochemistry and biophysics 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. Teng@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 49 EP - 64 VL - 31 IS - 1 SN - 1085-9195, 1085-9195 KW - Estrogens KW - 0 KW - RNA, Messenger KW - Epidermal Growth Factor KW - 62229-50-9 KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Uterus -- metabolism KW - Animals KW - Promoter Regions, Genetic KW - Base Sequence KW - Models, Genetic KW - Humans KW - RNA, Messenger -- analysis KW - Molecular Sequence Data KW - Mice KW - Models, Biological KW - Female KW - Estrogens -- genetics KW - Lactoferrin -- genetics KW - Gene Expression Regulation KW - Epidermal Growth Factor -- pharmacology KW - Estrogens -- physiology KW - Epidermal Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70797921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caffeine-derived+N-nitroso+compounds.+V.+Carcinogenicity+of+mononitrosocaffeidine+and+dinitrosocaffeidine+in+bd-ix+rats&rft.au=Ivankovic%2C+S%3BSeibel%2C+J%3BKomitowski%2C+D%3BSpiegelhalder%2C+B%3BPreussmann%2C+R%3BSiddiqi%2C+M&rft.aulast=Ivankovic&rft.aufirst=S&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=933&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and properties of an EGF-like domain (residues 361-406) in the extreme N-terminal region of the mouse EGF precursor. AN - 70789897; 10495961 AB - Various proteins contain EGF-like domains that are not ligands for the EGF receptor. In the present study a cognate polypeptide for residues 361-406 of the mouse EGF precursor was synthesized by the solid-phase method. The product was renatured under oxidative conditions since it probably has an EGF-like array of three cystine disulfide bonds in its native state. HPLC analysis of the renaturation reaction revealed formation of a peak material with no apparent free-SH groups. Accordingly, the HPLC retention time of this product was readily increased by treatment (reduction of disulfides) with dithiothreitol. The renatured 46-mer (PEGF-1) did not displace 125I-EGF bound to rat liver membranes and 125I-PEGF-1 did not exhibit specific binding to membrane preparations from the mouse liver, mammary gland, or kidney, with or without Ca2+ in the binding medium. Although PEGF-1 contains a putative Ca2+ binding motif, specific binding of this cation by the polypeptide could not be demonstrated by electromobility shiff or incubation with 45Ca2+. Immunoassay of PEGF-1 and EGF in fractions obtained following gel filtration of mouse urine revealed multiple peaks of PEGF-1 immunoreactivity with the major peaks eluting at an Mr > 30 kDa. In contrast, virtually all the EGF immunoreactivity eluted at a volume similar to that of 125I-EGF. These data suggest that selective cleavage of the PEGF-1 domain from the precursor does not occur with the proclivity known for that of EGF. Instead, the PEGF-1 probably functions coordinately with other EGF-like domains while tethered to the precursor backbone. Finally, localization of PEGF-1 immunoreactivity occurred only in cell populations of the mouse previously demonstrated as sites for EGF/EGF precursor, which suggests that PEGF-1 is exclusively a domain of the EGF precursor. JF - Growth factors (Chur, Switzerland) AU - Diaugustine, R P AU - Henry, R AU - Sewall, C H AU - Suarez-Quian, C A AU - Walker, M P AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. diaugus2@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 37 EP - 48 VL - 17 IS - 1 SN - 0897-7194, 0897-7194 KW - Calcium Radioisotopes KW - 0 KW - Membrane Proteins KW - Peptide Fragments KW - Protein Precursors KW - epidermal growth factor precursor KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Membrane Proteins -- metabolism KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Peptide Fragments -- chemical synthesis KW - Rats KW - Peptide Fragments -- urine KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Protein Renaturation KW - Protein Precursors -- metabolism KW - Protein Precursors -- chemical synthesis KW - Epidermal Growth Factor -- chemical synthesis KW - Epidermal Growth Factor -- urine KW - Epidermal Growth Factor -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70789897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Growth+factors+%28Chur%2C+Switzerland%29&rft.atitle=Synthesis+and+properties+of+an+EGF-like+domain+%28residues+361-406%29+in+the+extreme+N-terminal+region+of+the+mouse+EGF+precursor.&rft.au=Diaugustine%2C+R+P%3BHenry%2C+R%3BSewall%2C+C+H%3BSuarez-Quian%2C+C+A%3BWalker%2C+M+P&rft.aulast=Diaugustine&rft.aufirst=R&rft.date=1999-01-01&rft.volume=17&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Growth+factors+%28Chur%2C+Switzerland%29&rft.issn=08977194&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 - Laboratory methods for the determination of genetic polymorphisms in humans. AN - 70060117; 10493255 AB - The determination of genetic polymorphisms for susceptibility to human disease has been rapidly increasing since the introduction of the polymerase chain reaction (PCR). In most laboratories the ability exists to conduct studies on more than 10,000 persons, and the prospect of even larger investigations is approaching. Many methods can be used for genotyping individuals but some are more common and less expensive than others. Newer methods will allow for automation. As the number of studies on genetic polymorphisms increases it is to be expected that more pitfalls will be encountered. While larger studies will reduce the importance of misclassification, quality control methods will have to be applied to the processing of large numbers of samples. JF - IARC scientific publications AU - Blömeke, B AU - Shields, P G AD - Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 133 EP - 147 IS - 148 SN - 0300-5038, 0300-5038 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Polymerase Chain Reaction KW - Humans KW - Quality Control KW - Genotype KW - DNA -- isolation & purification KW - Genetic Testing -- methods KW - Genetic Predisposition to Disease -- genetics KW - Polymorphism, Genetic -- genetics KW - DNA -- genetics KW - Genetic Predisposition to Disease -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70060117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Laboratory+methods+for+the+determination+of+genetic+polymorphisms+in+humans.&rft.au=Bl%C3%B6meke%2C+B%3BShields%2C+P+G&rft.aulast=Bl%C3%B6meke&rft.aufirst=B&rft.date=1999-01-01&rft.volume=&rft.issue=148&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Selection of candidate genes for population studies. AN - 70060082; 10493246 AB - A broad view of genetic susceptibility in humans suggests that high-penetrance hereditary genes cause a number of relatively uncommon tumours in the familial setting, while common cancers are Influenced by multiple susceptibility loci. Early investigations of the latter category focused on the role of genes In the metabolism of carcinogens (activation, detoxification) while current and planned studies extend to genes with diverse mechanisms involving DNA repair, cell cycle control, nutrient metabolism and other processes. The present report considers some methodological issues pertinent to the study of the common genes, focusing in particular on the selection of appropriate candidates for study. JF - IARC scientific publications AU - Caporaso, N AD - Pharmacogenetic Section, Genetic Epidemiology Branch, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 23 EP - 36 IS - 148 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Phenotype KW - Genotype KW - Animals KW - Polymorphism, Genetic KW - Humans KW - Male KW - Female KW - Carcinogens -- metabolism KW - Genetics, Population KW - Cytochrome P-450 Enzyme System -- genetics KW - Models, Genetic KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70060082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Selection+of+candidate+genes+for+population+studies.&rft.au=Caporaso%2C+N&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1999-01-01&rft.volume=&rft.issue=148&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Somatic alterations and metabolic polymorphisms. AN - 70057207; 10493247 AB - Cancer is a multistep process in which multiple genetic alterations occur, causing a cumulative adverse effect on the control of cell differentiation, cell division and growth control. Somatic alterations acquired at the level of the cell become fixed in the developing cancer as chromosomal translocations, deletions, inversions, amplifications or point mutations. Since the ultimate unit of susceptibility to carcinogens is at the level of the cell, somatic gene alterations play an important role in carcinogenesis, as all neoplastic tumours exhibit somatic alterations. The incorporation of somatic alterations, such as oncogenes and tumour-suppressor genes, into epidemiological research provides an opportunity to clarify the role of exposure, other genetic changes and prognosis in cancer pathogenesis. The manner in which environmental factors act to initiate, accelerate or retard neoplastic progression Is currently being investigated using somatic gene mutational spectra to identify specific etiological carcinogens. Exploring the relationships between germline and somatic alterations may help to identify the timing of genetic events, important etiological exposures and gene-gene epistatic phenomena. Examining somatic alterations within the context of carcinogen-metabolizing enzymes may elucidate specific carcinogenic mechanisms. The use of somatic alterations to predict prognoses for patients with various malignancies may also help to enhance our ability to define subgroups of patients with different disease courses and treatment responses. JF - IARC scientific publications AU - Freedman, A N AD - National Cancer Institute, Genetic Epidemiology Branch, Bethesda, MD 20892-7344, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 37 EP - 50 IS - 148 SN - 0300-5038, 0300-5038 KW - Index Medicus KW - Molecular Biology KW - Polymorphism, Genetic KW - Humans KW - Genes, p53 -- genetics KW - Cell Differentiation -- genetics KW - Cell Division -- genetics KW - Translocation, Genetic -- genetics KW - Genetic Predisposition to Disease KW - Neoplasms -- genetics KW - Hybrid Cells -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70057207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Somatic+alterations+and+metabolic+polymorphisms.&rft.au=Freedman%2C+A+N&rft.aulast=Freedman&rft.aufirst=A&rft.date=1999-01-01&rft.volume=&rft.issue=148&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - The impact of misclassification in case-control studies of gene-environment interactions. AN - 70048722; 10493251 AB - In this chapter we describe the impact of risk factor misclassification in case-control studies designed to estimate gene-environment interactions. We show that under certain scenarios even small amounts of exposure or genotype misclassification can substantially attenuate the interaction effect and, as a consequence, dramatically increase the sample size required to study these interactions. A consideration of how sample size is affected by exposure and genotype misclassification in the study design phase should help to identify situations where obtaining better risk factor information is crucial for the feasibility of studies. JF - IARC scientific publications AU - Rothman, N AU - Garcia-Closas, M AU - Stewart, W T AU - Lubin, J AD - NIH/NCI EPS, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 89 EP - 96 IS - 148 SN - 0300-5038, 0300-5038 KW - Index Medicus KW - Sensitivity and Specificity KW - Genotype KW - Probability KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Sample Size KW - Case-Control Studies KW - Genetic Predisposition to Disease -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70048722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gene+therapy&rft.atitle=Transfection+of+interleukin-12+cDNAs+into+tumor+cells+induces+cytotoxic+immune+responses+against+native+tumor%3A+implications+for+tumor+vaccination.&rft.au=Hoshino%2C+T%3BJiang%2C+Y+Z%3BDunn%2C+D%3BPaul%2C+D%3BQazilbash%2C+M%3BCowan%2C+K%3BWang%2C+J%3BBarrett%2C+J%3BLiu%2C+J&rft.aulast=Hoshino&rft.aufirst=T&rft.date=1998-05-01&rft.volume=5&rft.issue=3&rft.spage=150&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 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 - Differential effects of transforming growth factor-beta(s) and glial cell line-derived neurotrophic factor on gene expression of presenilin-1 in human post-mitotic neurons and astrocytes. AN - 70004340; 10473269 AB - Mutations in the presenilin-1 gene are linked to the majority of early-onset familial Alzheimer's disease cases. We have previously shown that the expression of transforming growth factor-beta is altered in Alzheimer's patients, compared to controls. Here we examine presenilin- expression in human post-mitotic neurons (hNT cells), normal human astrocytes, and human brain tumor cell lines following treatment with three isoforms of transforming growth factor-beta, or glial cell line-derived neurotrophic factor, a member of the transforming growth factor-beta superfamily. As the NT2/D1 teratocarcinoma cell line is treated with retinoic acid to induce differentiation to hNT cells, presenilin-1 messenger RNA expression is dramatically increased. Furthermore, there is a 2-3-fold increase in presenilin-1 messenger RNA expression following treatment of hNT cells with growth factors and similar results are found by Western blotting and with immunohistochemical staining for presenilin-1 protein. However, treatment of normal human astrocytes with cytokines results in minimal changes in presenilin-1 messenger RNA and protein. Interestingly, the expression of presenilin-1 in human U87 MG astrocytoma and human SK-N-SH neuroblastoma cells is only increased when cells are treated with glial cell line-derived neurotrophic factor or transforming growth factor-beta3. These findings suggest that endogenous presenilin-1 gene expression in human neurons can be induced by growth factors present in normal and diseased brain tissue. Cytokines may play a major role in regulating expression of presenilin-1 which may affect its biological actions in physiological and pathological conditions. JF - Neuroscience AU - Ren, R F AU - Lah, J J AU - Diehlmann, A AU - Kim, E S AU - Hawver, D B AU - Levey, A I AU - Beyreuther, K AU - Flanders, K C AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 1041 EP - 1049 VL - 93 IS - 3 SN - 0306-4522, 0306-4522 KW - GDNF protein, human KW - 0 KW - Glial Cell Line-Derived Neurotrophic Factor KW - Membrane Proteins KW - Neoplasm Proteins KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - PSEN1 protein, human KW - Presenilin-1 KW - Protein Isoforms KW - RNA, Messenger KW - RNA, Neoplasm KW - Transforming Growth Factor beta KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Neuroblastoma -- pathology KW - Tretinoin -- pharmacology KW - Brain Neoplasms -- pathology KW - Neoplasm Proteins -- biosynthesis KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Astrocytoma -- pathology KW - RNA, Neoplasm -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Teratocarcinoma -- pathology KW - RNA, Messenger -- biosynthesis KW - Blotting, Western KW - Glioblastoma -- pathology KW - Neoplasm Proteins -- genetics KW - Transforming Growth Factor beta -- pharmacology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Astrocytes -- drug effects KW - Membrane Proteins -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - Protein Isoforms -- pharmacology KW - Membrane Proteins -- genetics KW - Nerve Tissue Proteins -- pharmacology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70004340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Differential+effects+of+transforming+growth+factor-beta%28s%29+and+glial+cell+line-derived+neurotrophic+factor+on+gene+expression+of+presenilin-1+in+human+post-mitotic+neurons+and+astrocytes.&rft.au=Ren%2C+R+F%3BLah%2C+J+J%3BDiehlmann%2C+A%3BKim%2C+E+S%3BHawver%2C+D+B%3BLevey%2C+A+I%3BBeyreuther%2C+K%3BFlanders%2C+K+C&rft.aulast=Ren&rft.aufirst=R&rft.date=1999-01-01&rft.volume=93&rft.issue=3&rft.spage=1041&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Enhanced activity of estramustine, vinblastine, etoposide, and suramin in prostate carcinoma. AN - 70004138; 10466436 AB - Following hormonal therapy, few treatment regimens have activity in metastatic prostate cancer. Cytotoxic agents have minimal activity in this disease. However, combinations of cytotoxic agents may be beneficial. The activity of estramustine, vinblastine, etoposide, and suramin on cell growth was evaluated. Prostate specific antigen (PSA) is routinely used as a surrogate marker for disease progression. Many pharmacological agents alter PSA levels independently of their effect on tumor growth, the effect of these agents on PSA secretion was determined. Each agent was evaluated alone and in combination with the other drugs in two prostate cancer cell lines. In LNCaP cells, estramustine and suramin were cytostatic, while vinblastine and etoposide were cytotoxic. Estramustine down-regulated etoposide PSA secretion, while suramin had no effect. The effects of etoposide and vinblastine on PSA secretion were not evaluable. In PC-3 cells, only etoposide was cytotoxic. Tandem combinations were more cytotoxic than single agents in both cell lines. The addition of a third agent to the tandem combination produced less cytotoxicity. In our hands, the best combinations were estramustine/vinblastine, suramin/vinblastine, and suramin/etoposide. These combinations yielded 20-60% higher cytotoxicity than any of the drugs alone. JF - Neoplasma AU - Arah, I N AU - Dixon, S C AU - Horti, J AU - Figg, W D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 117 EP - 123 VL - 46 IS - 2 SN - 0028-2685, 0028-2685 KW - Estramustine KW - 35LT29625A KW - Vinblastine KW - 5V9KLZ54CY KW - Suramin KW - 6032D45BEM KW - Etoposide KW - 6PLQ3CP4P3 KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Prostate-Specific Antigen -- secretion KW - Tumor Cells, Cultured KW - Etoposide -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Estramustine -- administration & dosage KW - Vinblastine -- administration & dosage KW - Cell Division -- drug effects KW - Suramin -- administration & dosage KW - Drug Synergism KW - Male KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- secretion KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70004138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+cyclophosphamide-associated+bladder+cancer.&rft.au=Khan%2C+M+A%3BTravis%2C+L+B%3BLynch%2C+C+F%3BSoini%2C+Y%3BHruszkewycz%2C+A+M%3BDelgado%2C+R+M%3BHolowaty%2C+E+J%3Bvan+Leeuwen%2C+F+E%3BGlimelius%2C+B%3BStovall%2C+M%3BBoice%2C+J+D%3BTarone%2C+R+E%3BBennett%2C+W+P&rft.aulast=Khan&rft.aufirst=M&rft.date=1998-05-01&rft.volume=7&rft.issue=5&rft.spage=397&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 - 1999-09-16 N1 - Date created - 1999-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Possible mechanisms of induction of renal tubule cell neoplasms in rats associated with alpha 2u-globulin: role of protein accumulation versus ligand delivery to the kidney. AN - 69989373; 10457914 JF - IARC scientific publications AU - Melnick, R L AU - Kohn, M C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 119 EP - 137 IS - 147 SN - 0300-5038, 0300-5038 KW - Alpha-Globulins KW - 0 KW - Carcinogens KW - Ligands KW - Index Medicus KW - Rats KW - Animals KW - Sex Factors KW - Environmental Exposure KW - Disease Models, Animal KW - Kidney Diseases -- etiology KW - Species Specificity KW - Protein Binding KW - Male KW - Kidney Diseases -- chemically induced KW - Carcinogens -- adverse effects KW - Kidney Tubules -- pathology KW - Kidney Tubules -- drug effects KW - Kidney Neoplasms -- chemically induced KW - Alpha-Globulins -- urine KW - Alpha-Globulins -- drug effects KW - Kidney Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69989373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Possible+mechanisms+of+induction+of+renal+tubule+cell+neoplasms+in+rats+associated+with+alpha+2u-globulin%3A+role+of+protein+accumulation+versus+ligand+delivery+to+the+kidney.&rft.au=Melnick%2C+R+L%3BKohn%2C+M+C&rft.aulast=Melnick&rft.aufirst=R&rft.date=1999-01-01&rft.volume=&rft.issue=147&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741. AN - 69987553; 10458219 AB - To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Abrams, J AU - Aisner, J AU - Cirrincione, C AU - Berry, D A AU - Muss, H B AU - Cooper, M R AU - Henderson, I C AU - Panasci, L AU - Kirshner, J AU - Ellerton, J AU - Norton, L AD - University of Maryland Cancer Center, Baltimore, MD, USA. AbramsJ@CTEP.nci.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 64 EP - 73 VL - 17 IS - 1 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Megestrol Acetate KW - TJ2M0FR8ES KW - Index Medicus KW - Prospective Studies KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Disease Progression KW - Aged KW - Middle Aged KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Megestrol Acetate -- administration & dosage KW - Megestrol Acetate -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69987553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-response+trial+of+megestrol+acetate+in+advanced+breast+cancer%3A+cancer+and+leukemia+group+B+phase+III+study+8741.&rft.au=Abrams%2C+J%3BAisner%2C+J%3BCirrincione%2C+C%3BBerry%2C+D+A%3BMuss%2C+H+B%3BCooper%2C+M+R%3BHenderson%2C+I+C%3BPanasci%2C+L%3BKirshner%2C+J%3BEllerton%2C+J%3BNorton%2C+L&rft.aulast=Abrams&rft.aufirst=J&rft.date=1999-01-01&rft.volume=17&rft.issue=1&rft.spage=64&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 - 1999-09-03 N1 - Date created - 1999-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemicals associated with tumours of the kidney, urinary bladder and thyroid gland in laboratory rodents from 2000 US National Toxicology Program/National Cancer Institute bioassays for carcinogenicity. AN - 69983406; 10457919 JF - IARC scientific publications AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 211 EP - 225 IS - 147 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Index Medicus KW - United States KW - Rats KW - Animals KW - Sex Factors KW - National Institutes of Health (U.S.) KW - Mice KW - Species Specificity KW - Toxicology KW - Male KW - Female KW - Thyroid Neoplasms -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Urinary Bladder Neoplasms -- chemically induced KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69983406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Chemicals+associated+with+tumours+of+the+kidney%2C+urinary+bladder+and+thyroid+gland+in+laboratory+rodents+from+2000+US+National+Toxicology+Program%2FNational+Cancer+Institute+bioassays+for+carcinogenicity.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1999-01-01&rft.volume=&rft.issue=147&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of the Bog gene (RBBP9) to syntenic regions of mouse chromosome 2G1-H1 and human chromosome 20p11.2 by fluorescence in situ hybridization. AN - 69970032; 10449909 JF - Cytogenetics and cell genetics AU - Woitach, J T AU - Hong, R AU - Keck, C L AU - Zimonjic, D B AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 252 EP - 253 VL - 85 IS - 3-4 SN - 0301-0171, 0301-0171 KW - Carrier Proteins KW - 0 KW - Cell Cycle Proteins KW - Intracellular Signaling Peptides and Proteins KW - Neoplasm Proteins KW - RBBP9 protein, human KW - Rbbp9 protein, mouse KW - Rbbp9 protein, rat KW - Retinoblastoma Protein KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Retinoblastoma Protein -- metabolism KW - In Situ Hybridization, Fluorescence KW - Chromosome Mapping KW - Carrier Proteins -- metabolism KW - Chromosomes, Human, Pair 20 -- genetics KW - Carrier Proteins -- genetics KW - Mice -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69970032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Assignment+of+the+Bog+gene+%28RBBP9%29+to+syntenic+regions+of+mouse+chromosome+2G1-H1+and+human+chromosome+20p11.2+by+fluorescence+in+situ+hybridization.&rft.au=Woitach%2C+J+T%3BHong%2C+R%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Woitach&rft.aufirst=J&rft.date=1999-01-01&rft.volume=85&rft.issue=3-4&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&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 - Gene-specific and mitochondrial repair of oxidative DNA damage. AN - 69952024; 10443426 JF - Methods in molecular biology (Clifton, N.J.) AU - Anson, R M AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institutes on Aging, National Institutes of Health, Baltimore, MD, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 257 EP - 279 VL - 113 SN - 1064-3745, 1064-3745 KW - DNA, Mitochondrial KW - 0 KW - Mutagens KW - Reactive Oxygen Species KW - DNA KW - 9007-49-2 KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - Animals KW - X-Rays KW - Methylene Blue -- pharmacology KW - Cell Survival -- drug effects KW - Blotting, Southern -- methods KW - Humans KW - Cell Culture Techniques -- methods KW - Centrifugation, Density Gradient -- methods KW - Mutagens -- pharmacology KW - Cell Line KW - DNA, Mitochondrial -- radiation effects KW - DNA -- isolation & purification KW - DNA, Mitochondrial -- drug effects KW - DNA Repair KW - DNA Damage KW - Mitochondria -- metabolism KW - DNA, Mitochondrial -- isolation & purification KW - DNA -- radiation effects KW - Mitochondria -- genetics KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69952024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Gene-specific+and+mitochondrial+repair+of+oxidative+DNA+damage.&rft.au=Anson%2C+R+M%3BBohr%2C+V+A&rft.aulast=Anson&rft.aufirst=R&rft.date=1999-01-01&rft.volume=113&rft.issue=&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&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 - [An empirical study on the increase of mild alcoholics in Japan]. AN - 69935092; 10434759 JF - Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica AU - Shimizu, S AU - Fujiwara, M AU - Shirasaka, T AU - Sakamoto, T AU - Kato, M AU - Yamana, J AU - Imamichi, H AU - Maeoka, K AU - Ito, T AU - Takemoto, T AD - National Institute of Mental Health, National Center of Neurology and Psychiatry. Y1 - 1999 PY - 1999 DA - 1999 SP - 411 EP - 426 VL - 101 IS - 5 SN - 0033-2658, 0033-2658 KW - Index Medicus KW - Nursing KW - Japan -- epidemiology KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69935092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seishin+shinkeigaku+zasshi+%3D+Psychiatria+et+neurologia+Japonica&rft.atitle=%5BAn+empirical+study+on+the+increase+of+mild+alcoholics+in+Japan%5D.&rft.au=Shimizu%2C+S%3BFujiwara%2C+M%3BShirasaka%2C+T%3BSakamoto%2C+T%3BKato%2C+M%3BYamana%2C+J%3BImamichi%2C+H%3BMaeoka%2C+K%3BIto%2C+T%3BTakemoto%2C+T&rft.aulast=Shimizu&rft.aufirst=S&rft.date=1999-01-01&rft.volume=101&rft.issue=5&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Seishin+shinkeigaku+zasshi+%3D+Psychiatria+et+neurologia+Japonica&rft.issn=00332658&rft_id=info:doi/ LA - Japanese 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 - Reversible nephrotoxicity of onconase and effect of lysine pH on renal onconase uptake. AN - 69902321; 10412952 AB - To examine the histopathology of the kidney in mice following repeated injections of the antitumor drug onconase, and to determine whether lysine, which reportedly blocks kidney uptake of other basic proteins, blocks the high renal uptake of onconase. Mice received repeated intraperitoneal onconase injections over 3 weeks. Kidneys were examined by light microscopy after 1 week, 3 weeks, and 5 weeks (2 weeks after cessation of injections) and compared to kidneys from animals receiving a similar schedule of PBS injections. Renal uptake of radioiodinated onconase was measured in animals receiving intraperitoneal injections of lysine solutions of acidic and neutral pH given at -30, 0 and + 5 min relative to intravenous onconase injection. Renal onconase uptake was also measured in animals made metabolically acidotic by ingestion of ammonium chloride, arginine chloride or lysine dihydrochloride from the drinking water. Onconase caused acute moderate multifocal proximal renal tubular necrosis, and this toxicity was reversed by 2 weeks after drug withdrawal. Intraperitoneal injections of lysine dihydrochloride in PBS (pH 1.5) reduced renal onconase uptake at 15 min from 67.9+/-13.4% to 17.0+/-3.8% of the injected dose without affecting the plasma concentration and also reduced the fraction of degraded onconase in the urine. However, neutral solutions of lysine dihydrochloride at pH 7.4 or lysine acetate at pH 7.1 were ineffective at blocking renal onconase uptake. Furthermore, renal onconase uptake was minimally or not affected by a state of metabolic acidosis. Proximal tubular toxicity of onconase was reversible. Renal onconase uptake was blocked by lysine at pH 1.5 but not at neutral pH. JF - Cancer chemotherapy and pharmacology AU - Vasandani, V M AU - Burris, J A AU - Sung, C AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 164 EP - 169 VL - 44 IS - 2 SN - 0344-5704, 0344-5704 KW - Antineoplastic Agents KW - 0 KW - Egg Proteins KW - Ribonucleases KW - EC 3.1.- KW - Lysine KW - K3Z4F929H6 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Animals KW - Hydrogen-Ion Concentration KW - Acidosis -- metabolism KW - Mice KW - Mice, Inbred BALB C KW - Female KW - Lysine -- pharmacology KW - Kidney -- metabolism KW - Egg Proteins -- pharmacokinetics KW - Kidney -- pathology KW - Ribonucleases -- toxicity KW - Kidney -- drug effects KW - Antineoplastic Agents -- toxicity KW - Egg Proteins -- toxicity KW - Ribonucleases -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69902321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemotherapy+and+pharmacology&rft.atitle=Reversible+nephrotoxicity+of+onconase+and+effect+of+lysine+pH+on+renal+onconase+uptake.&rft.au=Vasandani%2C+V+M%3BBurris%2C+J+A%3BSung%2C+C&rft.aulast=Vasandani&rft.aufirst=V&rft.date=1999-01-01&rft.volume=44&rft.issue=2&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&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 - Inhibition of pristane-induced peritoneal plasmacytoma formation. AN - 69871316; 10396075 AB - While the mechanism of how Indo inhibits PCTGEN is not established, Several hypothetical explanations provide new potential experimental approaches. Indo may block production of cytokines such as Il-6 in accessory cells that are critical for B-cell growth, viability and maturation, or it may directly target B cells via PPAR-gamma receptors. The latter mode of action is described in other cell types but not yet defined in B cells. JF - Current topics in microbiology and immunology AU - Potter, M AU - Kutkat, L AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 351 EP - 61; discussion 361-2 VL - 246 SN - 0070-217X, 0070-217X KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carcinogens KW - Interleukin-6 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Terpenes -- toxicity KW - Specific Pathogen-Free Organisms KW - B-Lymphocytes -- drug effects KW - Animals KW - Mice, Mutant Strains KW - Carcinogens -- toxicity KW - Mice KW - Interleukin-6 -- pharmacology KW - B-Lymphocytes -- immunology KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Plasmacytoma -- prevention & control KW - Peritoneal Neoplasms -- chemically induced KW - Peritoneal Neoplasms -- prevention & control KW - Plasmacytoma -- chemically induced KW - Peritoneal Neoplasms -- immunology KW - Plasmacytoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69871316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Inhibition+of+pristane-induced+peritoneal+plasmacytoma+formation.&rft.au=Potter%2C+M%3BKutkat%2C+L&rft.aulast=Potter&rft.aufirst=M&rft.date=1999-01-01&rft.volume=246&rft.issue=&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-20 N1 - Date created - 1999-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic shuttle vector assays for assessing oxidative B-cell mutagenesis in vivo. AN - 69870631; 10396077 AB - The recent development of transgenic mutagenicity assays provides new opportunities for evaluating mutagenic processes in vivo. To asses mutant frequencies in tissue B cells, we decided to take advantage of two such assays that utilize the transgenic shuttle vectors, lambda LIZ and pUR288. Our main interest in this research is to test two basic premises of inflammation-induced plasmacytoma development in genetically susceptible BALB/c mice; i.e., the possibility that plasmacytoma precursor cells may become targets of phagocyte-mediated oxidative mutagenesis in situ and the prospect that plasmacytoma susceptibility/resistance genes may contribute to these phenotypes by enhancing/reducing oxidative mutagenesis in B cells. Based on our preliminary experience with the lambda LIZ and pUR288 transgenic in vivo mutagenicity tests, we propose to employ these assays as broadly applicable tools for assessing overall mutagenesis during normal and aberrant (malignant) B-cell development. Furthermore, transgenic shuttle vector assays appear to lend themselves as ideal methods to associate general B-cell mutagenesis with the peculiar, B cell-typical somatic hypermutation processes that target the V(D)J gene segment, the proto-oncogene bcl-6 and perhaps other, still unknown loci. JF - Current topics in microbiology and immunology AU - Felix, K AU - Kelliher, K AU - Bornkamm, G W AU - Janz, S AD - Laboratory of Genetics, NCI, NIH, Bethesda, MD, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 369 EP - 75; discussion 376-7 VL - 246 SN - 0070-217X, 0070-217X KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Plasmacytoma -- genetics KW - Plasmacytoma -- metabolism KW - Plasmids -- genetics KW - Bacteriophage lambda -- genetics KW - Phagocytes -- metabolism KW - Mice KW - Genetic Vectors KW - B-Lymphocytes -- metabolism KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69870631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+topics+in+microbiology+and+immunology&rft.atitle=Transgenic+shuttle+vector+assays+for+assessing+oxidative+B-cell+mutagenesis+in+vivo.&rft.au=Felix%2C+K%3BKelliher%2C+K%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1999-01-01&rft.volume=246&rft.issue=&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+microbiology+and+immunology&rft.issn=0070217X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-20 N1 - Date created - 1999-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine agonist-mediated rotation in rats with unilateral nigrostriatal lesions is not dependent on net inhibitions of rate in basal ganglia output nuclei. AN - 69866685; 10391472 AB - Current models of basal ganglia function predict that dopamine agonist-induced motor activation is mediated by decreases in basal ganglia output. This study examines the relationship between dopamine agonist effects on firing rate in basal ganglia output nuclei and rotational behavior in rats with nigrostriatal lesions. Extracellular single-unit activity ipsilateral to the lesion was recorded in awake, locally-anesthetized rats. Separate rats were used for behavioral experiments. Low i.v. doses of D1 agonists (SKF 38393, SKF 81297, SKF 82958) were effective in producing rotation, yet did not change average firing rate in the substantia nigra pars reticulata or entopeduncular nucleus. At these doses, firing rate effects differed from neuron to neuron, and included increases, decreases, and no change. Higher i.v. doses of D1 agonists were effective in causing both rotation and a net decrease in rate of substantia nigra pars reticulata neurons. A low s.c. dose of the D1/D2 agonist apomorphine (0.05 mg/kg) produced both rotation and a robust average decrease in firing rate in the substantia nigra pars reticulata, yet the onset of the net firing rate decrease (at 13-16 min) was greatly delayed compared to the onset of rotation (at 3 min). Immunostaining for the immediate-early gene Fos indicated that a low i.v. dose of SKF 38393 (that produced rotation but not a net decrease in firing rate in basal ganglia output nuclei) induced Fos-like immunoreactivity in the striatum and subthalamic nucleus, suggesting an activation of both inhibitory and excitatory afferents to the substantia nigra and entopeduncular nucleus. In addition, D1 agonist-induced Fos expression in the striatum and subthalamic nucleus was equivalent in freely-moving and awake, locally-anesthetized rats. The results show that decreases in firing rate in basal ganglia output nuclei are not necessary for dopamine agonist-induced motor activation. Motor-activating actions of dopamine agonists may be mediated by firing rate decreases in a small subpopulation of output nucleus neurons, or may be mediated by other features of firing activity besides rate in these nuclei such as oscillatory firing pattern or interneuronal firing synchrony. Also, the results suggest that dopamine receptors in both the striatum and at extrastriatal sites (especially the subthalamic nucleus) are likely to be involved in dopamine agonist influences on firing rates in the substantia nigra pars reticulata and entopeduncular nucleus. JF - Neuroscience AU - Ruskin, D N AU - Bergstrom, D A AU - Mastropietro, C W AU - Twery, M J AU - Walters, J R AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 935 EP - 946 VL - 91 IS - 3 SN - 0306-4522, 0306-4522 KW - Dopamine Agonists KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Oxidopamine KW - 8HW4YBZ748 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Hypothalamus -- physiology KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Thalamic Nuclei -- metabolism KW - Apomorphine -- pharmacology KW - Behavior, Animal -- physiology KW - Electrophysiology KW - Rotation KW - Male KW - Corpus Striatum -- physiology KW - Dopamine Agonists -- pharmacology KW - Corpus Striatum -- metabolism KW - Substantia Nigra -- drug effects KW - Stereotypic Movement Disorder -- physiopathology KW - Corpus Striatum -- drug effects KW - Basal Ganglia -- physiology KW - Substantia Nigra -- physiology KW - Neural Inhibition -- physiology KW - Stereotypic Movement Disorder -- chemically induced KW - Oxidopamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69866685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Dopamine+agonist-mediated+rotation+in+rats+with+unilateral+nigrostriatal+lesions+is+not+dependent+on+net+inhibitions+of+rate+in+basal+ganglia+output+nuclei.&rft.au=Ruskin%2C+D+N%3BBergstrom%2C+D+A%3BMastropietro%2C+C+W%3BTwery%2C+M+J%3BWalters%2C+J+R&rft.aulast=Ruskin&rft.aufirst=D&rft.date=1999-01-01&rft.volume=91&rft.issue=3&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Liposomal nystatin against experimental pulmonary aspergillosis in persistently neutropenic rabbits: efficacy, safety and non-compartmental pharmacokinetics. AN - 69851941; 10381106 AB - The activity of liposomal nystatin against invasive pulmonary aspergillosis was investigated in persistently neutropenic rabbits. Treatment groups included liposomal nystatin at dosages of 1, 2 and 4 mg/kg/day intravenously, or amphotericin B deoxycholate 1 mg/kg/day administered intravenously after normal saline loading. As compared with untreated controls, liposomal nystatin administered at 2 and 4 mg/kg/day prolonged survival and reduced fungus-mediated tissue injury and excess lung weight at post-mortem in a similar manner to amphotericin B. Although amphotericin B was superior in clearing infected lung tissue, treatment with all regimens of liposomal nystatin led to a significant reduction in pulmonary fungal tissue burden. During treatment, ultrafast CT-scan demonstrated ongoing resolution of pulmonary lesions at 2 and 4 mg/kg/day, but not at 1 mg/kg/day. With the exception of mild increases in blood urea nitrogen (BUN) and serum creatinine values during treatment at 2 and 4 mg/kg/day, which were similar to those found in amphotericin B-treated rabbits, liposomal nystatin was well tolerated. Preliminary pharmacokinetic studies in non-infected animals established linear drug disposition of liposomal nystatin in plasma over the investigated dosage range and peak plasma levels above the MIC for the test strain after multiple daily dosing for 7 days. Liposomal nystatin increased survival and provided reduced tissue injury, effective microbiological clearance and tolerable side effects in experimental pulmonary aspergillosis in persistently neutropenic rabbits, thus providing a rational basis for further investigations in clinical trials. JF - The Journal of antimicrobial chemotherapy AU - Groll, A H AU - Gonzalez, C E AU - Giri, N AU - Kligys, K AU - Love, W AU - Peter, J AU - Feuerstein, E 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, MD 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 95 EP - 103 VL - 43 IS - 1 SN - 0305-7453, 0305-7453 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Nystatin KW - 1400-61-9 KW - Amphotericin B KW - 7XU7A7DROE KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Animals KW - Area Under Curve KW - Lung -- diagnostic imaging KW - Rabbits KW - Blood Urea Nitrogen KW - Lung -- pathology KW - Creatinine -- blood KW - Survival Rate KW - Half-Life KW - Radiography KW - Amphotericin B -- pharmacology KW - Female KW - Organ Size -- drug effects KW - Lung -- microbiology KW - Aspergillosis -- microbiology KW - Antifungal Agents -- toxicity KW - Lung Diseases, Fungal -- drug therapy KW - Aspergillosis -- mortality KW - Lung Diseases, Fungal -- mortality KW - Aspergillosis -- drug therapy KW - Neutropenia -- complications KW - Nystatin -- pharmacology KW - Antifungal Agents -- blood KW - Nystatin -- toxicity KW - Lung Diseases, Fungal -- microbiology KW - Antifungal Agents -- pharmacology KW - Nystatin -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69851941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+antimicrobial+chemotherapy&rft.atitle=Liposomal+nystatin+against+experimental+pulmonary+aspergillosis+in+persistently+neutropenic+rabbits%3A+efficacy%2C+safety+and+non-compartmental+pharmacokinetics.&rft.au=Groll%2C+A+H%3BGonzalez%2C+C+E%3BGiri%2C+N%3BKligys%2C+K%3BLove%2C+W%3BPeter%2C+J%3BFeuerstein%2C+E%3BBacher%2C+J%3BPiscitelli%2C+S+C%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=1999-01-01&rft.volume=43&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+antimicrobial+chemotherapy&rft.issn=03057453&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 - Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. AN - 69841723; 10378870 AB - Although it is generally accepted that pro-inflammatory cytokines produced by cells of the central nervous system play important roles in the communication between the central nervous system and the immune system during sepsis, it is not clear whether these cytokines are produced in the brain under subseptic conditions. In this study, we used in situ hybridization to examine the mRNA expression of the pro-inflammatory cytokines IL-1beta and TNFalpha in the brains of rats 2 and 12 h after they were challenged by peripheral injections of lipopolysaccharide (LPS) ranging from 0.01 to 1000 microg/kg. Unlike septic doses of LPS (> 500 microg/kg), which induce global expression of pro-inflammatory cytokines in the brain, subseptic doses of LPS (0.01-10 microg/kg) induced IL-1beta and TNFalpha mRNA expression only in the choroid plexus, the circumventricular organs, and meninges. The expression of the cytokine-responsive immediate early gene I kappaB alpha was induced in the brain after doses of LPS as low as 0.1 microg/kg. I kappaB alpha mRNA expression was confined to sites where IL-1beta and TNFalpha were expressed. These results indicate that the induction and action of pro-inflammatory cytokines during subseptic infection occur at the blood-brain barrier and at circumventricular organs, which may be sites for elaboration of signal molecules that communicate peripheral immune status to the brain. JF - Journal of neuroimmunology AU - Quan, N AU - Stern, E L AU - Whiteside, M B AU - Herkenham, M AD - Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892-4070, USA. Y1 - 1999/01/01/ PY - 1999 DA - 1999 Jan 01 SP - 72 EP - 80 VL - 93 IS - 1-2 SN - 0165-5728, 0165-5728 KW - Interleukin-1 KW - 0 KW - Lipopolysaccharides KW - Proto-Oncogene Proteins c-fos KW - RNA, Messenger KW - Receptors, Interleukin-1 KW - Tumor Necrosis Factor-alpha KW - Caspase 1 KW - EC 3.4.22.36 KW - Index Medicus KW - Solitary Nucleus -- immunology KW - Animals KW - Caspase 1 -- metabolism KW - Injections, Intravenous KW - Proto-Oncogene Proteins c-fos -- immunology KW - Solitary Nucleus -- chemistry KW - Receptors, Interleukin-1 -- antagonists & inhibitors KW - Gene Expression Regulation, Enzymologic -- immunology KW - Paraventricular Hypothalamic Nucleus -- chemistry KW - Paraventricular Hypothalamic Nucleus -- immunology KW - Autoradiography KW - Subfornical Organ -- immunology KW - Rats KW - Receptors, Interleukin-1 -- immunology KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Paraventricular Hypothalamic Nucleus -- enzymology KW - Proto-Oncogene Proteins c-fos -- genetics KW - Solitary Nucleus -- enzymology KW - Subfornical Organ -- chemistry KW - Caspase 1 -- immunology KW - Subfornical Organ -- enzymology KW - Male KW - Brain -- enzymology KW - Interleukin-1 -- immunology KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- immunology KW - Encephalitis -- immunology KW - Interleukin-1 -- genetics KW - Encephalitis -- chemically induced KW - Brain -- immunology KW - Encephalitis -- metabolism KW - Tumor Necrosis Factor-alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69841723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+pro-inflammatory+cytokine+mRNAs+in+the+brain+after+peripheral+injection+of+subseptic+doses+of+lipopolysaccharide+in+the+rat.&rft.au=Quan%2C+N%3BStern%2C+E+L%3BWhiteside%2C+M+B%3BHerkenham%2C+M&rft.aulast=Quan&rft.aufirst=N&rft.date=1999-01-01&rft.volume=93&rft.issue=1-2&rft.spage=72&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 - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of lipopolysaccharide-induced neurotoxicity in mixed cortical neuron/glia cultures by femtomolar concentrations of pituitary adenylate cyclase-activating polypeptide. AN - 69816735; 10366006 AB - Stimulation of murine primary mixed cortical neuron/glia cultures with lipopolysaccharide, an endotoxin, was used as a model for inflammatory disorders of the central nervous system. Lipopolysaccharide (20 microg/ml) increased the secretion of lactate dehydrogenase, a marker for cell injury, and nitric oxide into the culture medium. The lipopolysaccharide-induced release of lactate dehydrogenase into the culture medium was reduced by pituitary adenylate cyclase-activating polypeptide (PACAP) at 10(-14)-10(-12) M. The 27- and 38-amino-acid forms of PACAP were equipotent and their dose-response curves were U-shaped. PACAP6-38, a specific type I PACAP receptor antagonist, blocked the reduction by PACAP38 of the lipopolysaccharide-induced release of lactate dehydrogenase. The lipopolysaccharide-induced secretion of nitric oxide into the culture medium was reduced by PACAP at 10(-14)-10(-12) M and 10(-8)-10(-6) M. The 27- and 38-amino-acid forms of PACAP were equipotent. PACAP6-38 blocked the reduction of the lipopolysaccharide-induced secretion of nitric oxide by PACAP38 at 10(-12) M, but not at 10(-8) M. Vasoactive intestinal polypeptide reduced the lipopolysaccharide-induced release of lactate dehydrogenase into the culture medium at 10(-14)-10(-12) M, but these concentrations of vasoactive intestinal polypeptide had no effect on the lipopolysaccharide-induced secretion of nitric oxide. PACAP6-38 did not effect the reduction of the lipopolysaccharide-induced release of lactate dehydrogenase into the culture medium by 10(-12) M vasoactive intestinal polypeptide. These results indicate that stimulation of type I PACAP receptors by femtomolar concentrations of PACAP can prevent neuron death in a model for inflammatory disorders of the CNS. These results suggest that PACAP is also an extraordinarily potent inhibitor of some microglial functions. JF - Neuroscience AU - Kong, L Y AU - Maderdrut, J L AU - Jeohn, G H AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 493 EP - 500 VL - 91 IS - 2 SN - 0306-4522, 0306-4522 KW - Adcyap1 protein, mouse KW - 0 KW - Lipopolysaccharides KW - Neuropeptides KW - Neuroprotective Agents KW - Neurotoxins KW - Nitrites KW - Peptide Fragments KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Tumor Necrosis Factor-alpha KW - pituitary adenylate-cyclase-activating-peptide (6-38) KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Coculture Techniques KW - Animals, Newborn KW - Animals KW - Nitrites -- metabolism KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Peptide Fragments -- pharmacology KW - Mice KW - Tumor Necrosis Factor-alpha -- metabolism KW - Neuroglia -- cytology KW - Cerebral Cortex -- cytology KW - Neuropeptides -- pharmacology KW - Cerebral Cortex -- physiology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Lipopolysaccharides -- toxicity KW - Neuroglia -- drug effects KW - Neuroglia -- physiology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69816735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Reduction+of+lipopolysaccharide-induced+neurotoxicity+in+mixed+cortical+neuron%2Fglia+cultures+by+femtomolar+concentrations+of+pituitary+adenylate+cyclase-activating+polypeptide.&rft.au=Kong%2C+L+Y%3BMaderdrut%2C+J+L%3BJeohn%2C+G+H%3BHong%2C+J+S&rft.aulast=Kong&rft.aufirst=L&rft.date=1999-01-01&rft.volume=91&rft.issue=2&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Mutations and altered expression of the human cancer genes: what they tell us about causes. AN - 69793246; 10353382 AB - To understand the causes of cancer, it is necessary to elucidate the molecular basis and environmental factors that influence the carcinogenesis process. Cancers are progressive diseases characterized by the accumulation of defects in many different genes. The patterns of mutation of some genes identified in tumours suggest a direct action of chemicals binding to and altering DNA. Other cancer-associated genes may be altered as a consequence of endogenous mutagens, germ-line mutations, spontaneous mutations that occur during cell replication or increased genetic instability in precancerous cells. Recent advances in molecular biology and genetics have provided new tools and concepts for studying the causes of cancer. We know that cancers are caused by a combination of environmental and genetic factors, and the discovery of the molecular alterations that occur at various stages in different tumours is increasing our understanding of these causes. Thus, we are now beginning to discover which genes are involved, how they function normally and in tumour tissues and why cancers develop after a series of genetic and epigenetic changes in certain cells. As data from studies on cancer-associated genes have accrued, the categories of genes and molecular pathways that have been found to play a role in carcinogenesis have also increased. Genes involved in development and other normal cellular processes have been implicated in cancer. These include genes involved in signal transduction, cell cycle control, DNA repair, cell growth and differentiation (growth factors and growth factor receptors), transcriptional regulation, senescence and apoptosis. Genes involved in angiogenesis, immune regulation, cellular responses to stress, motility, adhesion and invasion are also involved, but less is known about their relationship to carcinogenesis, and these processes are not discussed in this review. The diverse nature of these categories of cancer-related genes indicates the variety of processes that must be disrupted in order for tumours to develop. Many of the genes have several functional domains, and the functions of some have only recently been proposed. In this review, we describe some of the major classes of genes implicated in human cancers and some of the major findings on genetic alterations and dysfunction in human tumours. Comparisons are made with certain rodent models. JF - IARC scientific publications AU - Devereux, T R AU - Risinger, J I AU - Barrett, J C AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 19 EP - 42 IS - 146 SN - 0300-5038, 0300-5038 KW - Index Medicus KW - DNA Repair -- genetics KW - Animals KW - Mutagenicity Tests KW - Molecular Biology KW - Humans KW - Signal Transduction -- genetics KW - Environmental Exposure KW - Germ-Line Mutation KW - Proto-Oncogenes -- genetics KW - Neoplasms -- chemically induced KW - Neoplasms -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69793246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Mutations+and+altered+expression+of+the+human+cancer+genes%3A+what+they+tell+us+about+causes.&rft.au=Devereux%2C+T+R%3BRisinger%2C+J+I%3BBarrett%2C+J+C&rft.aulast=Devereux&rft.aufirst=T&rft.date=1999-01-01&rft.volume=&rft.issue=146&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Mutation patterns in non-ras oncogenes and tumour suppressor genes in experimentally induced tumours. AN - 69791393; 10353385 JF - IARC scientific publications AU - Perantoni, A O AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research & Development Center, Maryland 21702-1201, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 87 EP - 122 IS - 146 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Transforming Growth Factors KW - 76057-06-2 KW - Index Medicus KW - Genotype KW - Animals KW - Transforming Growth Factors -- drug effects KW - Humans KW - Mutation, Missense KW - Transforming Growth Factors -- genetics KW - Mutagenesis -- drug effects KW - Oncogenes -- genetics KW - Neoplasms, Experimental -- classification KW - Genes, Tumor Suppressor -- drug effects KW - Oncogenes -- drug effects KW - Neoplasms, Experimental -- chemically induced KW - Genes, Tumor Suppressor -- genetics KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Mutagenesis -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69791393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Mutation+patterns+in+non-ras+oncogenes+and+tumour+suppressor+genes+in+experimentally+induced+tumours.&rft.au=Perantoni%2C+A+O%3BRice%2C+J+M&rft.aulast=Perantoni&rft.aufirst=A&rft.date=1999-01-01&rft.volume=&rft.issue=146&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Genetically altered mouse models for identifying carcinogens. AN - 69790783; 10353386 JF - IARC scientific publications AU - Tennant, R W AU - Stasiewicz, S AU - Mennear, J AU - French, J E AU - Spalding, J W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 123 EP - 150 IS - 146 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Index Medicus KW - Genes, ras KW - Animals KW - Genes, p53 KW - Biological Assay KW - Mice KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Disease Models, Animal KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69790783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Genetically+altered+mouse+models+for+identifying+carcinogens.&rft.au=Tennant%2C+R+W%3BStasiewicz%2C+S%3BMennear%2C+J%3BFrench%2C+J+E%3BSpalding%2C+J+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1999-01-01&rft.volume=&rft.issue=146&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Mutations in ras genes in experimental tumours of rodents. AN - 69788510; 10353384 AB - Studies of carcinogenesis in rodents are valuable for examining mutagenesis in vivo. An advantage of evaluating the frequency and spectra of ras mutations in chemically induced neoplasms is that the additional data at the molecular level indicate whether the carcinogenic effect is due to the chemical and is not a spontaneous event, as illustrated by the numerous examples in Appendices 1 and 2. In addition, data on the frequency and spectra of ras mutations in spontaneous and chemically induced neoplasms clearly expand the toxicological database by providing information helpful for understanding the pathogenesis of carcinogenesis. For example: (1) ozone-induced lung neoplasms had two unique mutations, one (codon 61 K-ras CTA mutation) consistent with a direct genotoxic event and a second (codon 12 K-ras G --> T transversion) consistent with an indirect genotoxic effect; (2) isoprene-induced Harderian gland neoplasms had a unique K-ras A --> T transversion at codon 61 which provided evidence that formation of an epoxide intermediate was involved; (3) 1,3-butadiene-induced neoplasms had a characteristic K-ras G --> C transversion mutation at codon 13 which was also consistent with a chemical-specific effect; (4) methylene chloride-induced liver neoplasms had an H-ras mutation profile at codon 61 similar to that of spontaneous tumours, suggesting that methylene chloride promotes cells with 'spontaneously initiated' ras mutations and (5) oxazepam-induced liver neoplasms had a low frequency of ras mutations, suggesting a nonmutagenic pathway of carcinogenesis. By extending the evaluation of rodent tumours to include molecular studies on ras mutation spectra and abnormalities in other cancer genes with human homologues, a number of hypotheses can be tested, allowing the most complete understanding of carcinogenesis in rodents and in potential extrapolation to the human risk situation. JF - IARC scientific publications AU - Sills, R C AU - Boorman, G A AU - Neal, J E AU - Hong, H L AU - Devereux, T R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 55 EP - 86 IS - 146 SN - 0300-5038, 0300-5038 KW - Carcinogens KW - 0 KW - Codon KW - Index Medicus KW - Animals KW - Humans KW - Rodentia KW - Codon -- drug effects KW - Genes, ras -- genetics KW - Codon -- genetics KW - Genes, ras -- drug effects KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Carcinogens -- toxicity KW - Germ-Line Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69788510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IARC+scientific+publications&rft.atitle=Mutations+in+ras+genes+in+experimental+tumours+of+rodents.&rft.au=Sills%2C+R+C%3BBoorman%2C+G+A%3BNeal%2C+J+E%3BHong%2C+H+L%3BDevereux%2C+T+R&rft.aulast=Sills&rft.aufirst=R&rft.date=1999-01-01&rft.volume=&rft.issue=146&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=IARC+scientific+publications&rft.issn=03005038&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 - Adenoviral vectors capable of replication improve the efficacy of HSVtk/GCV suicide gene therapy of cancer. AN - 69784518; 10341876 AB - A major obstacle to the success of gene therapy strategies that directly target cancer cells is the poor vector distribution within solid tumors. To address this problem, we developed an E1b 55 kDa attenuated, replication-competent adenovirus (Ad.TKRC) which expresses the herpes simplex-1 thymidine kinase (HSVtk) gene to sensitize tumors to ganciclovir (GCV). Efficacy of this combined strategy was tested in nude mice with subcutaneous human A375 melanoma and ME180 cervical carcinomas. Intratumoral injection of a replication-defective adenoviral vector expressing HSVtk (Ad.TK) followed by GCV treatment resulted in doubling of the survival time of mice bearing A375 tumors and 20% long-term survival of mice with ME180 tumors. Treatment of tumors with Ad.TKRC without GCV resulted in a similar antitumor effect, confirming that the replicating vector has an oncolytic effect. When GCV was initiated 3 days after Ad.TKRC injection, survival of mice with each tumor type was greatly prolonged, with 60% of animals with ME180 tumors surviving for over 160 days. These results confirm that both the oncolysis caused by a replicating virus and suicide/prodrug gene therapy with HSVtk/GCV have potent antitumor effects. When combined, these two approaches are complementary resulting in a significantly improved treatment outcome. JF - Gene therapy AU - Wildner, O AU - Morris, J C AU - Vahanian, N N AU - Ford, H AU - Ramsey, W J AU - Blaese, R M AD - Clinical Gene Therapy Branch/National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1851, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 57 EP - 62 VL - 6 IS - 1 SN - 0969-7128, 0969-7128 KW - Antimetabolites KW - 0 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Virus Replication KW - Animals KW - Uterine Cervical Neoplasms -- therapy KW - Ganciclovir -- therapeutic use KW - Molecular Sequence Data KW - Mice, Nude KW - Mice KW - Antimetabolites -- therapeutic use KW - Melanoma -- therapy KW - Female KW - Neoplasms, Experimental -- therapy KW - Genetic Therapy -- methods KW - Simplexvirus -- enzymology KW - Adenoviridae -- physiology KW - Genetic Vectors -- genetics KW - Thymidine Kinase -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69784518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy&rft.atitle=Adenoviral+vectors+capable+of+replication+improve+the+efficacy+of+HSVtk%2FGCV+suicide+gene+therapy+of+cancer.&rft.au=Wildner%2C+O%3BMorris%2C+J+C%3BVahanian%2C+N+N%3BFord%2C+H%3BRamsey%2C+W+J%3BBlaese%2C+R+M&rft.aulast=Wildner&rft.aufirst=O&rft.date=1999-01-01&rft.volume=6&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Gene+therapy&rft.issn=09697128&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 - Genetic sequence - M73260; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rhabdomyosarcoma: an overview. AN - 69778281; 10337369 AB - Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal muscle lineage. With approximately 250 cases diagnosed yearly in the United States, it is the third most common extracranial solid tumor of childhood after Wilms' tumor and neuroblastoma. Important epidemiologic, biologic, and therapeutic differences have been elucidated within the RMS family. Common sites of primary disease include the head and neck region, genitourinary tract, and extremities. A site-based tumor-nodes-metastasis staging system is being incorporated into use for assessing prognosis and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system. The development of intensive multimodality treatment protocols tested in large-scale international trials has resulted in significant improvements in outcome, especially for patients with local or locally extensive disease for whom a 60%-70% disease-free survival can be expected. Despite aggressive approaches incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy, the outcome for patients with metastatic disease remains poor. Future challenges include the development of less toxic therapy for patients with localized disease and new approaches for patients with metastatic disease. JF - The oncologist AU - Dagher, R AU - Helman, L AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 34 EP - 44 VL - 4 IS - 1 SN - 1083-7159, 1083-7159 KW - Index Medicus KW - Disease-Free Survival KW - Neoplasm Staging KW - Humans KW - Child KW - Urogenital Neoplasms -- pathology KW - Head and Neck Neoplasms -- therapy KW - Rhabdomyosarcoma -- pathology KW - Urogenital Neoplasms -- therapy KW - Head and Neck Neoplasms -- pathology KW - Rhabdomyosarcoma -- therapy KW - Rhabdomyosarcoma -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69778281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncologist&rft.atitle=Rhabdomyosarcoma%3A+an+overview.&rft.au=Dagher%2C+R%3BHelman%2C+L&rft.aulast=Dagher&rft.aufirst=R&rft.date=1999-01-01&rft.volume=4&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=The+oncologist&rft.issn=10837159&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 - Cyclosporine A-induced hyperactivity in rats: is it mediated by immunosuppression, neurotrophism, or both? AN - 69769168; 10338283 AB - Cyclosporine A (CsA) immunosuppressive treatment has become an adjunctive therapy in neural transplantation of dopamine-secreting cells for treatment of Parkinson's disease (PD). Recently, CsA and its analogues have been shown to promote trophic effects against neurodegenerative disorders, and therefore CsA may have direct beneficial effects on dopaminergic neurons and dopamine-mediated behaviors. The present study examined the interaction between the reported CsA-induced hyperactivity and the possible alterations in nigral tyrosine hydroxylase (TH)-immunoreactive neurons in rats with damaged blood-brain barrier. CsA was administered at a therapeutic dose (10 mg/kg/day, IP, for 9 days) used in neural transplantation protocol for PD animal models. CsA-treated animals displayed significantly higher general spontaneous locomotor activity than control animals at drug injection days 7 and 9. Histological assays at day 9 revealed that there was a significant increase in TH-immunoreactive neurons in the nigra of CsA-treated rats compared to that of the vehicle-treated rats. The nigral TH elevation was accompanied by suppressed calcium-phosphotase calcineurin activity, indicating an inhibition of host immune response. This is the first report of CsA exerting simultaneous immunosuppressive and neurotrophic effects, as well as increasing general spontaneous locomotor behavior. These results support the utility of CsA as a therapeutic agent for PD and other movement disorders. JF - Cell transplantation AU - Borlongan, C V AU - Stahl, C E AU - Fujisaki, T AU - Sanberg, P R AU - Watanabe, S AD - National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurobiology, Baltimore, MD 21224, USA. cborlong@intra.nida.nih.gov PY - 1999 SP - 153 EP - 159 VL - 8 IS - 1 SN - 0963-6897, 0963-6897 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Calcineurin KW - EC 3.1.3.16 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Dopamine -- secretion KW - Animals KW - Calcineurin -- isolation & purification KW - Substantia Nigra -- growth & development KW - Substantia Nigra -- enzymology KW - Rats KW - Tyrosine 3-Monooxygenase -- analysis KW - Motor Activity KW - Rats, Wistar KW - Models, Neurological KW - Female KW - Blood-Brain Barrier KW - Immunosuppression KW - Cyclosporine -- adverse effects KW - Hyperkinesis -- chemically induced KW - Hyperkinesis -- etiology KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69769168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+transplantation&rft.atitle=Cyclosporine+A-induced+hyperactivity+in+rats%3A+is+it+mediated+by+immunosuppression%2C+neurotrophism%2C+or+both%3F&rft.au=Borlongan%2C+C+V%3BStahl%2C+C+E%3BFujisaki%2C+T%3BSanberg%2C+P+R%3BWatanabe%2C+S&rft.aulast=Borlongan&rft.aufirst=C&rft.date=1999-01-01&rft.volume=8&rft.issue=1&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Cell+transplantation&rft.issn=09636897&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 - Reanalysis of the Mayo Lung Project data: the impact of confounding and effect modification. AN - 69743211; 10321372 AB - To examine whether age at entry, history of cigarette smoking, exposure to non-tobacco lung carcinogens, or previous pulmonary illnesses were confounders or effect modifiers of the relation between screening and lung cancer mortality in the Mayo Lung Project. The Mayo Lung Project was a randomised, controlled, clinical trial conducted between 1971 and 1986 in 9211 male smokers over the age of 45 in Minnesota (USA). The group screened received chest x ray examination and sputum cytology every four months for six years. The unscreened group were recommended to obtain usual care (annual chest x ray examination and sputum cytology). After follow up, lung cancer mortality was similar in both groups. Proportional hazard models were used to analyse data. A variable was considered a confounder if its inclusion in a model changed the rate ratio for screening by more than 15%; a variable was considered an effect modifier if its stratum-specific rate ratio for screening differed by a factor of two. None of the four aforementioned variables changed the rate ratio associated with screening (1.07) by more than 2%. The effect of screening may have differed by years smoked (rate ratio for smoking fewer than 30 years 2.4; rate ratio for smoking 30 or more years 1.0), though we suspect that this result occurred by chance. Adjustment for or stratification by four established lung cancer risk factors did not alter the original findings of the Mayo Lung Project. JF - Journal of medical screening AU - Marcus, P M AU - Prorok, P C AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 47 EP - 49 VL - 6 IS - 1 SN - 0969-1413, 0969-1413 KW - Index Medicus KW - Minnesota KW - Age Factors KW - Risk Factors KW - Humans KW - Life Expectancy KW - Environmental Exposure KW - Lung Diseases -- epidemiology KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Male KW - Proportional Hazards Models KW - Smoking KW - Mass Screening KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- diagnosis KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69743211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Changes+in+expression+of+15-lipoxygenase+and+prostaglandin-H+synthase+during+differentiation+of+human+tracheobronchial+epithelial+cells.&rft.au=Hill%2C+E+M%3BEling%2C+T%3BNettesheim%2C+P&rft.aulast=Hill&rft.aufirst=E&rft.date=1998-05-01&rft.volume=18&rft.issue=5&rft.spage=662&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 - 1999-06-28 N1 - Date created - 1999-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of long-term oral administration of DDT on nonhuman primates. AN - 69738139; 10235477 AB - Because of reports on tumorigenic activity in different animal species exposed to DDT a decision was made in 1969 to evaluate the long-term effects of DDT on 24 cynomolgus and rhesus monkeys. DDT (20 mg/kg) was given in the diet for 130 months, followed by an observation period that ended in 1994. The two cases of malignant tumor detected in the DDT group included a metastatic hepatocellular carcinoma in a 233-month-old male and a well-differentiated adenocarcinoma of the prostate in a 212-month-old monkey. Benign tumors detected in the DDT group included three cases of leiomyoma, two of which were uterine and one, esophageal. No tumor was detected in the control group of 17 monkeys. Fatty changes in the liver were observed in 52.9% of the DDT group and 29.4% of the control group. More specific signs of hepatotoxicity were documented microscopically in seven DDT monkeys. Severe tremors and histological evidence of CNS and spinal cord abnormalities were observed in six DDT monkeys. The present findings show clear evidence of hepatic and CNS toxicity following long-term DDT administration to cynomolgus and rhesus monkeys. However, the two cases involving malignant tumors of different types are inconclusive with respect to a carcinogenic effect of DDT in nonhuman primates. JF - Journal of cancer research and clinical oncology AU - Takayama, S AU - Sieber, S M AU - Dalgard, D W AU - Thorgeirsson, U P AU - Adamson, R H AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 219 EP - 225 VL - 125 IS - 3-4 SN - 0171-5216, 0171-5216 KW - Carcinogens KW - 0 KW - Insecticides KW - DDT KW - CIW5S16655 KW - Index Medicus KW - Administration, Oral KW - Animals KW - Macaca fascicularis KW - Mammary Glands, Animal -- drug effects KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Ovary -- drug effects KW - Prostatic Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Uterus -- drug effects KW - Liver -- drug effects KW - Leiomyoma -- chemically induced KW - Macaca mulatta KW - Time Factors KW - Female KW - Male KW - Insecticides -- toxicity KW - Neoplasms, Experimental -- chemically induced KW - DDT -- blood KW - DDT -- toxicity KW - Carcinogens -- toxicity KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69738139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+long-term+oral+administration+of+DDT+on+nonhuman+primates.&rft.au=Takayama%2C+S%3BSieber%2C+S+M%3BDalgard%2C+D+W%3BThorgeirsson%2C+U+P%3BAdamson%2C+R+H&rft.aulast=Takayama&rft.aufirst=S&rft.date=1999-01-01&rft.volume=125&rft.issue=3-4&rft.spage=219&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 - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Cancer Res Clin Oncol. 2000 Apr;126(4):246 [10782899] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage. AN - 69735963; 10226938 AB - In vivo microdialysis was used to study the effects of restraint stress (30 min) and amphetamine (AMPH) (5 mg/kg, i.p.) in awake adult male rats with neonatal ventral hippocampal (VH) damage. Extracellular levels of dopamine (DA), dihydrophenylacetate (DOPAC), homovanillate (HVA) and 5-hydroxyindolacetate (5-HIAA) were measured in the nucleus accumbens (NA). There were no differences in the baseline levels of DA, DOPAC, HVA or 5-HIAA in the lesioned as compared to the sham rats. Release from restraint resulted in increased extracellular levels of DA in the sham but not in the lesioned animals. AMPH increased DA release in both sham operated and lesioned animals, but this increase was significantly attenuated in the lesioned rats. Our data suggest that this developmental lesion alters function of the dopaminergic system in response to environmental and pharmacological challenge. JF - Journal of neural transmission (Vienna, Austria : 1996) AU - Lillrank, S M AU - Lipska, B K AU - Kolachana, B S AU - Weinberger, D R AD - Clinical Brain Disorders Branch, IRP, NIMH, Neuroscience Center, Washington, D.C., USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 183 EP - 196 VL - 106 IS - 2 SN - 0300-9564, 0300-9564 KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Ibotenic Acid KW - 2552-55-8 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Amphetamine KW - CK833KGX7E KW - Dopamine KW - VTD58H1Z2X KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Space life sciences KW - Rats KW - Animals, Newborn KW - Animals KW - Restraint, Physical KW - Rats, Sprague-Dawley KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Hydroxyindoleacetic Acid -- metabolism KW - Homovanillic Acid -- metabolism KW - Ibotenic Acid -- toxicity KW - Time Factors KW - Male KW - Stress, Physiological -- metabolism KW - Hippocampus -- physiology KW - Nucleus Accumbens -- drug effects KW - Nucleus Accumbens -- metabolism KW - Dopamine -- metabolism KW - Amphetamine -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69735963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neural+transmission+%28Vienna%2C+Austria+%3A+1996%29&rft.atitle=Attenuated+extracellular+dopamine+levels+after+stress+and+amphetamine+in+the+nucleus+accumbens+of+rats+with+neonatal+ventral+hippocampal+damage.&rft.au=Lillrank%2C+S+M%3BLipska%2C+B+K%3BKolachana%2C+B+S%3BWeinberger%2C+D+R&rft.aulast=Lillrank&rft.aufirst=S&rft.date=1999-01-01&rft.volume=106&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Journal+of+neural+transmission+%28Vienna%2C+Austria+%3A+1996%29&rft.issn=03009564&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 - Infectious disease emergencies in primary care. AN - 69708326; 10214210 AB - Infectious disease emergencies can be described as infectious processes that, if not recognized and treated immediately, can lead to significant morbidity or mortality. These emergencies can present as common or benign infections, fooling the primary care provider into using more conservative treatment strategies than are required. This review discusses the pathophysiology, history and physical findings, diagnostic criteria, and treatment strategies for the following infectious disease emergencies: acute bacterial meningitis, ehrlichiosis, Rocky Mountain spotted fever, meningococcemia, necrotizing soft tissue infections, toxic shock syndrome, food-borne illnesses, and infective endocarditis. Because most of the discussed infectious disease emergencies require hospital care, the primary care clinician must be able to judge when a referral to a specialist or a higher-level care facility is indicated. JF - Lippincott's primary care practice AU - Kwitkowski, V E AU - Demko, S G AD - National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. PY - 1999 SP - 108 EP - 125 VL - 3 IS - 1 SN - 1088-5471, 1088-5471 KW - Nursing KW - Fasciitis, Necrotizing -- diagnosis KW - Humans KW - Endocarditis, Bacterial -- therapy KW - Child KW - Rocky Mountain Spotted Fever -- therapy KW - Endocarditis, Bacterial -- diagnosis KW - Shock, Septic -- therapy KW - Rocky Mountain Spotted Fever -- diagnosis KW - Meningitis, Bacterial -- diagnosis KW - Adult KW - Meningitis, Bacterial -- therapy KW - Nurse Practitioners KW - Shock, Septic -- diagnosis KW - Middle Aged KW - Fasciitis, Necrotizing -- therapy KW - Female KW - Male KW - Communicable Diseases -- therapy KW - Emergency Medical Services -- methods KW - Communicable Diseases -- diagnosis KW - Primary Health Care -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69708326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Infectious+disease+emergencies+in+primary+care.&rft.au=Kwitkowski%2C+V+E%3BDemko%2C+S+G&rft.aulast=Kwitkowski&rft.aufirst=V&rft.date=1999-01-01&rft.volume=3&rft.issue=1&rft.spage=108&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 - 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 - Antibiotics in primary care: focus on fluoroquinolones and other new and investigational antimicrobial agents. AN - 69708274; 10214201 JF - Lippincott's primary care practice AU - Pau, A K AU - Slone, R B AD - National Institutes of Health, Warren G. Magnuson Clinical Center, Bethesda, MD 20892-1196, USA. PY - 1999 SP - 39 EP - 54 VL - 3 IS - 1 SN - 1088-5471, 1088-5471 KW - Anti-Bacterial Agents KW - 0 KW - Anti-Infective Agents KW - Fluoroquinolones KW - Nursing KW - Drug Interactions KW - Humans KW - Patient Selection KW - Anti-Infective Agents -- therapeutic use KW - Anti-Bacterial Agents -- therapeutic use KW - Bacterial Infections -- microbiology KW - Primary Health Care -- trends KW - Anti-Bacterial Agents -- pharmacology KW - Anti-Infective Agents -- pharmacology KW - Primary Health Care -- methods KW - Bacterial Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69708274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antibiotics+in+primary+care%3A+focus+on+fluoroquinolones+and+other+new+and+investigational+antimicrobial+agents.&rft.au=Pau%2C+A+K%3BSlone%2C+R+B&rft.aulast=Pau&rft.aufirst=A&rft.date=1999-01-01&rft.volume=3&rft.issue=1&rft.spage=39&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 - 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 - Treatment of pulmonary tuberculosis. AN - 69707962; 10214202 JF - Lippincott's primary care practice AU - LeMasters, C Z AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1999 SP - 55 EP - 58 VL - 3 IS - 1 SN - 1088-5471, 1088-5471 KW - Antitubercular Agents KW - 0 KW - Nursing KW - Drug Interactions KW - Diagnosis, Differential KW - Humans KW - Drug Monitoring KW - Adult KW - Child KW - Tuberculosis, Pulmonary -- etiology KW - Tuberculosis, Pulmonary -- diagnosis KW - Antitubercular Agents -- therapeutic use KW - Tuberculosis, Pulmonary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69707962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+pulmonary+tuberculosis.&rft.au=LeMasters%2C+C+Z&rft.aulast=LeMasters&rft.aufirst=C&rft.date=1999-01-01&rft.volume=3&rft.issue=1&rft.spage=55&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 - 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 - Curative and population medicine: bridging the great divide. AN - 69693684; 10202265 AB - There are gaps in understanding between practicing physicians (curative medicine) and those trained in public health and epidemiology (population medicine). In the last century, these groups were closer, as physicians played a role in public health, sanitation and in the prevention of the spreading of infection. However, with the recent extraordinary successes of the biomedical model in explaining disease, and the ensuing explosion of remarkable - and expensive - medical procedures and treatments, public health, preventive medicine and the population approach in general have been overshadowed. In this essay, I try to explain how the training of physicians and the daily care of patients may hinder their appreciation of the population model. For instance, for many of the myriad decisions involved in patient care in daily practice, there is little evidence, population derived or otherwise. What little evidence there is may be dominated by personal experiences, opinions and values. Additionally, the statistical and epidemiologic approach necessary for the maintenance of health and prevention of illness may not be valued by practitioners whose training and focus is on treating sick people one by one. To illustrate these disparities in understanding, examples are given from the NIH Consensus Conference on mammography screening for women aged 40-49, and from the use of science in the courtroom in adjudicating toxic tort cases. Understanding population medicine requires an appreciation of the concepts of chance, probability and statistics and of epidemiologic principles, difficult areas for many - including the general public. These topics play a small to nonexistent role in the formal training of most physicians. Some closing of the gap in understanding may be occurring. It is hoped this essay will help. JF - Neuroepidemiology AU - Ferguson, J H AD - Office of Medical Applications of Research, National Institutes of Health, Bethesda, MD 20892, USA. jferg@helix.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 111 EP - 119 VL - 18 IS - 3 SN - 0251-5350, 0251-5350 KW - Index Medicus KW - United States KW - Public Health KW - Mammography KW - Breast Neoplasms -- diagnosis KW - Humans KW - Adult KW - Population KW - Jurisprudence KW - Middle Aged KW - Male KW - Female KW - Clinical Medicine KW - Community Health Planning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69693684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroepidemiology&rft.atitle=Curative+and+population+medicine%3A+bridging+the+great+divide.&rft.au=Ferguson%2C+J+H&rft.aulast=Ferguson&rft.aufirst=J&rft.date=1999-01-01&rft.volume=18&rft.issue=3&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Neuroepidemiology&rft.issn=02515350&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 - Descending modulation of opioid-containing nociceptive neurons in rats with peripheral inflammation and hyperalgesia. AN - 69680593; 10197770 AB - Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger RNA and peptide levels in nociceptive neurons of the spinal dorsal horn. Descending axons modulate nociceptive transmission at the spinal level during inflammatory pain, and may play a role in the development of persistent pain. The role of descending bulbospinal pathways in opioid-containing nociceptive neurons was examined. Removal of descending inputs to the spinal cord was performed by complete spinal transection at the midthoracic level. Seven days after spinal transection, rats received a unilateral hindpaw injection of complete Freund's adjuvant, a noxious stimulus that produces inflammation and hyperalgesia. Tissues from the L4 and L5 segments of the spinal cord were removed and analysed by northern blotting and immunocytochemistry. Spinal transection resulted in a further increase in both dynorphin and enkephalin messenger RNA content following complete Freund's adjuvant injection. There was a similar distribution and number of dynorphin-immunoreactive cells in transected rats compared to rats which received sham surgery. These data suggest that increased dynorphin messenger RNA ipsilateral to inflammation, in rats without descending axons, was due to increased expression within the same cells and not to recruitment of additional dynorphin-expressing cells. This reflects a greater dynamic response of nociceptive neurons to noxious stimuli in the absence of descending modulation. Therefore, the net effect of descending afferents on spinal nociceptive circuits may be to reduce the response of opioid-containing neurons to noxious stimulation from the periphery. JF - Neuroscience AU - MacArthur, L AU - Ren, K AU - Pfaffenroth, E AU - Franklin, E AU - Ruda, M A AD - Cellular and Molecular Mechanisms Section, Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 499 EP - 506 VL - 88 IS - 2 SN - 0306-4522, 0306-4522 KW - Enkephalins KW - 0 KW - Protein Precursors KW - RNA, Messenger KW - Tachykinins KW - preprotachykinin KW - Dynorphins KW - 74913-18-1 KW - Calcitonin Gene-Related Peptide KW - 83652-28-2 KW - Freund's Adjuvant KW - 9007-81-2 KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Animals KW - Calcitonin Gene-Related Peptide -- genetics KW - Inflammation -- physiopathology KW - Blotting, Northern KW - Inflammation -- chemically induced KW - Protein Precursors -- genetics KW - Denervation KW - Rats KW - Ganglia, Spinal -- cytology KW - Rats, Sprague-Dawley KW - Tachykinins -- genetics KW - RNA, Messenger -- metabolism KW - Spinal Cord -- chemistry KW - Spinal Cord -- physiology KW - Gene Expression -- physiology KW - Male KW - Spinal Cord -- cytology KW - Enkephalins -- genetics KW - Hyperalgesia -- physiopathology KW - Nociceptors -- physiology KW - Dynorphins -- genetics KW - Neurons, Afferent -- physiology KW - Hyperalgesia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69680593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Descending+modulation+of+opioid-containing+nociceptive+neurons+in+rats+with+peripheral+inflammation+and+hyperalgesia.&rft.au=MacArthur%2C+L%3BRen%2C+K%3BPfaffenroth%2C+E%3BFranklin%2C+E%3BRuda%2C+M+A&rft.aulast=MacArthur&rft.aufirst=L&rft.date=1999-01-01&rft.volume=88&rft.issue=2&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer. AN - 69629113; 10079371 AB - The purpose of this review is to illustrate some of the technical and biological hurdles that need to be addressed when developing new gene therapy based clinical trials. Gene transfer approaches can be used to "mark" cells to monitor their persistence in vivo in patients, to protect cells from toxic chemotherapeutic agents, correct a genetic defect within the target cell, or to confer a novel function on the target cell. Selection of the most suitable vector for gene transfer depends upon a number of factors such as the target cell itself and whether gene expression needs to be sustained or transient. The TCR gene transfer approach described here represents one innovative strategy being pursued as a potential therapy for metastatic melanoma. Tumor reactive T cells can be isolated from the tumor infiltrating lymphocytes (TIL) of melanoma patients. A retroviral vector has been constructed containing the T cell receptor (TCR) alpha and beta chain genes from a MART-1-specific T cell clone (TIL 5). Jurkat cells transduced with this virus specifically release cytokine in response to MART-1 peptide pulsed T2 cells, showing that the virus can mediate expression of a functional TCR. HLA-A2 transgenic mice are being used to examine whether transduced bone marrow progenitor cells will differentiate in vivo into mature CD8+ T cells expressing the MART-1-specific TCR. Expression of the human TCR alpha and beta chain genes has been detected by RT-PCR in the peripheral blood of HLA-A2 transgenic mice reconstituted with transduced mouse bone marrow. Expression of the TIL 5 TCR genes in the peripheral blood of these mice was maintained for greater than 40 weeks after bone marrow reconstitution. TIL 5 TCR gene expression was also maintained following transfer of bone marrow from mice previously reconstituted with transduced bone marrow to secondary mouse recipients, suggesting that a pluripotent progenitor or lymphocyte progenitor cell has been transduced. JF - Pathology oncology research : POR AU - Clay, T M AU - Custer, M C AU - Spiess, P J AU - Nishimura, M I AD - National Cancer Institute, National Institutes of Health, Surgery Branch, Bethesda, MD 20892, USA. Tim_Clay@nih.gov.usa Y1 - 1999 PY - 1999 DA - 1999 SP - 3 EP - 15 VL - 5 IS - 1 SN - 1219-4956, 1219-4956 KW - Epitopes KW - 0 KW - HLA-A2 Antigen KW - Lymphokines KW - MART-1-Melan-A(27-35) epitope KW - Neoplasm Proteins KW - Receptors, Antigen, T-Cell, alpha-beta KW - Index Medicus KW - Animals KW - COS Cells KW - Humans KW - Gene Expression KW - HLA-A2 Antigen -- genetics KW - Cell Differentiation KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Jurkat Cells -- secretion KW - Transfection KW - Graft Survival KW - Neoplasm Metastasis KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Genetic Vectors -- genetics KW - Retroviridae -- genetics KW - Lymphokines -- secretion KW - Radiation Chimera KW - Melanoma -- pathology KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Neoplasm Proteins -- immunology KW - Receptors, Antigen, T-Cell, alpha-beta -- immunology KW - Hematopoietic Stem Cell Transplantation KW - T-Lymphocytes, Cytotoxic -- immunology KW - Genetic Therapy KW - Melanoma -- therapy KW - Melanoma -- immunology KW - Hematopoietic Stem Cells -- metabolism KW - Epitopes -- immunology KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69629113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pathology+oncology+research+%3A+POR&rft.atitle=Potential+use+of+T+cell+receptor+genes+to+modify+hematopoietic+stem+cells+for+the+gene+therapy+of+cancer.&rft.au=Clay%2C+T+M%3BCuster%2C+M+C%3BSpiess%2C+P+J%3BNishimura%2C+M+I&rft.aulast=Clay&rft.aufirst=T&rft.date=1999-01-01&rft.volume=5&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Pathology+oncology+research+%3A+POR&rft.issn=12194956&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 - Do antipsychotic medications decrease the risk of suicide in patients with schizophrenia? AN - 69616925; 10073396 AB - The lifetime risk of suicide in persons with schizophrenia is much greater than that in the general population. The role of antipsychotic medications in decreasing suicide risk in schizophrenia has been little studied, and results often appear inconclusive and even confusing when issues such as dose-response effect are examined. Yet, evidence exists that both the traditional and newer antipsychotic medications reduce the risk of suicide and suicide attempts in schizophrenia. Because side effects are potentially significant risk factors in suicide, considerable incentive exists to examine whether newer antipsychotic agents that have a lower incidence of extrapyramidal side effects offer greater safety for this population. JF - The Journal of clinical psychiatry AU - Palmer, D D AU - Henter, I D AU - Wyatt, R J AD - Neuropsychiatry Branch, Department of Health and Human Services, NIH-NIMH, Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 100 EP - 3; discussion 111-6 VL - 60 Suppl 2 SN - 0160-6689, 0160-6689 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Suicide, Attempted -- statistics & numerical data KW - Suicide, Attempted -- psychology KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Schizophrenic Psychology KW - Suicide, Attempted -- prevention & control KW - Antipsychotic Agents -- administration & dosage KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Suicide -- statistics & numerical data KW - Suicide -- psychology KW - Suicide -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69616925?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatry&rft.atitle=Do+antipsychotic+medications+decrease+the+risk+of+suicide+in+patients+with+schizophrenia%3F&rft.au=Palmer%2C+D+D%3BHenter%2C+I+D%3BWyatt%2C+R+J&rft.aulast=Palmer&rft.aufirst=D&rft.date=1999-01-01&rft.volume=60+Suppl+2&rft.issue=&rft.spage=100&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&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 - Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland development and neoplasia. AN - 69610278; 10070255 AB - Growth and morphogenesis in the mammary gland depend on locally derived growth factors such as those in the epidermal growth factor (EGF) superfamily. Cripto-1 (CR-1, human; Cr-1, mouse)--also known as teratocarcinoma-derived growth factor-1--is a novel EGF-related protein that induces branching morphogenesis in mammary epithelial cells both in vitro and in vivo and inhibits the expression of various milk proteins. In the mouse, Cr-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and expression increases during pregnancy and lactation. Cr-1/CR-1 is overexpressed in mouse and human mammary tumors and inappropriate overexpression of Cr-1 in mouse mammary epithelial cells can lead to the clonal expansion of ductal hyperplasias. Taken together, this evidence suggests that Cr-1/CR-1 performs a role in normal mammary gland development and that it might contribute to the early stages of mouse mammary tumorigenesis and the pathobiology of human breast cancer. JF - BioEssays : news and reviews in molecular, cellular and developmental biology AU - Salomon, D S AU - Bianco, C AU - De Santis, M AD - Tumor Factor Growth Section, LTIB, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 61 EP - 70 VL - 21 IS - 1 SN - 0265-9247, 0265-9247 KW - Biomarkers, Tumor KW - 0 KW - GPI-Linked Proteins KW - Intercellular Signaling Peptides and Proteins KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - TDGF1 protein, human KW - Tdgf1 protein, mouse KW - Epidermal Growth Factor KW - 62229-50-9 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Gene Expression Regulation, Developmental KW - Female KW - Pregnancy KW - Mammary Neoplasms, Animal -- physiopathology KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- physiopathology KW - Mammary Glands, Animal -- physiology KW - Mammary Neoplasms, Animal -- genetics KW - Breast Neoplasms -- metabolism KW - Mammary Glands, Animal -- embryology KW - Breast -- embryology KW - Neoplasm Proteins -- physiology KW - Mammary Glands, Animal -- pathology KW - Breast -- pathology KW - Breast -- physiology KW - Mammary Neoplasms, Animal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69610278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.atitle=Cripto%3A+a+novel+epidermal+growth+factor+%28EGF%29-related+peptide+in+mammary+gland+development+and+neoplasia.&rft.au=Salomon%2C+D+S%3BBianco%2C+C%3BDe+Santis%2C+M&rft.aulast=Salomon&rft.aufirst=D&rft.date=1999-01-01&rft.volume=21&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=BioEssays+%3A+news+and+reviews+in+molecular%2C+cellular+and+developmental+biology&rft.issn=02659247&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 - Structure-function analysis of muscarinic receptors and their associated G proteins. AN - 69610219; 10069496 AB - Each member of the muscarinic receptor family (M1-M5) can interact only with a limited subset of the many structurally closely related heterotrimeric G proteins expressed within a cell. To understand how this selectivity is achieved at a molecular level, we have used the G(i/0)-coupled M2 and the Gq/11-coupled M3 muscarinic receptors as model systems. We developed a genetic strategy involving the coexpression of wild type or mutant muscarinic receptors with hybrid or mutant G protein alpha subunits to identify specific, functionally relevant receptor/G protein contact sites. This approach led to the identification of N- and C-terminal amino acids on alpha(q) and alpha(i) that are critical for maintaining proper receptor/G protein coupling. Moreover, several receptor sites were identified that are likely to be contacted by these functionally critical G alpha residues. To gain deeper insight into muscarinic receptor structure, we recently developed a cysteine disulfide cross-linking strategy, using the M3 muscarinic receptor as a model system. Among other structural modifications, this approach involves the removal of most native cysteine residues by site-directed mutagenesis, the insertion of three factor Xa cleavage sites into the third intracellular loop, and systematic 'reintroduction' of pairs of cysteine residues. Following treatment of receptor-containing membrane preparations with factor Xa and oxidizing agents, disulfide cross-linked products can be identified by immunoprecipitation and immunoblotting studies. This approach should greatly advance our knowledge of the molecular architecture of muscarinic and other G protein-coupled receptors. JF - Life sciences AU - Kostenis, E AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 355 EP - 362 VL - 64 IS - 6-7 SN - 0024-3205, 0024-3205 KW - Disulfides KW - 0 KW - Oxidants KW - Receptor, Muscarinic M2 KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Recombinant Fusion Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - EC 3.6.5.1 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - GTP-Binding Protein alpha Subunits, Gi-Go -- metabolism KW - Cysteine -- metabolism KW - Oxidants -- pharmacology KW - COS Cells KW - Cysteine -- genetics KW - Amino Acid Sequence KW - Protein Binding KW - Disulfides -- metabolism KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Base Sequence KW - Transfection KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Mutation KW - Amino Acid Substitution KW - Receptors, Muscarinic -- genetics KW - GTP-Binding Proteins -- metabolism KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69610219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Structure-function+analysis+of+muscarinic+receptors+and+their+associated+G+proteins.&rft.au=Kostenis%2C+E%3BZeng%2C+F+Y%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1999-01-01&rft.volume=64&rft.issue=6-7&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&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 - Relative rates of AIDS among racial/ethnic groups by exposure categories. AN - 69609072; 10063784 AB - The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated among racial/ethnic populations using Centers for Disease Control and Prevention HIV (human immunodeficiency virus)/Surveillance reports assuming that racial/ethnic distributions reflect that of the US Census Data from 1990. For comparison, a rate of 1 was assigned to whites in each calculation. The overall relative rates were whites--1, African Americans--4.7, Hispanics--3, Asian/Pacific Islanders--0.4, and Native Americans--0.5. Acquired immunodeficiency syndrome surveillance data show higher rates of AIDS for African Americans and Hispanics compared with whites, Asians/Pacific Islanders, and Native Americans. The relative rates for African Americans and Hispanics compared with whites were highest for injecting drug users, heterosexual contact, and pediatric patients. These results led us to explore possible explanations for increased AIDS reporting in African Americans and Hispanics. We then explored available national datasets regarding those variables. The analyses indicate that variables such as access and receptivity to HIV prevention and treatment efforts, race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic status, and substance abuse interact in a complex fashion to influence HIV transmission and progression to AIDS in affected communities. JF - Journal of the National Medical Association AU - Haverkos, H W AU - Turner, J F AU - Moolchan, E T AU - Cadet, J L AD - National Institute of Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 17 EP - 24 VL - 91 IS - 1 SN - 1943-4693, 1943-4693 KW - Index Medicus KW - AIDS/HIV KW - Socioeconomic Factors KW - Sexually Transmitted Diseases -- ethnology KW - Humans KW - Adult KW - Child KW - Substance-Related Disorders -- ethnology KW - Adolescent KW - United States -- epidemiology KW - Population Surveillance KW - Acquired Immunodeficiency Syndrome -- ethnology KW - Continental Population Groups UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69609072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medical+Association&rft.atitle=Relative+rates+of+AIDS+among+racial%2Fethnic+groups+by+exposure+categories.&rft.au=Haverkos%2C+H+W%3BTurner%2C+J+F%3BMoolchan%2C+E+T%3BCadet%2C+J+L&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1999-01-01&rft.volume=91&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Medical+Association&rft.issn=19434693&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: MMWR Morb Mortal Wkly Rep. 1982 Jul 9;31(26):353-4, 360-1 [6811853] Am J Med. 1984 Mar;76(3):493-500 [6322585] JAMA. 1988 Oct 7;260(13):1922-9 [3047449] Public Health Rep. 1989 Sep-Oct;104(5):411-5 [2508169] J Consult Clin Psychol. 1990 Feb;58(1):57-69 [2181006] Am J Public Health. 1993 Dec;83(12):1759-61 [8259813] J Natl Med Assoc. 1994 Oct;86(10):745-59 [7807559] N Engl J Med. 1994 Nov 24;331(21):1422-7 [7969281] AIDS Educ Prev. 1994 Feb;6(1):12-26 [8024940] MMWR Morb Mortal Wkly Rep. 1994 Mar 11;43(9):155-60 [8164640] Fam Plann Perspect. 1993 Nov-Dec;25(6):257-62 [8313950] AIDS Educ Prev. 1992 Spring;4(1):52-60 [1543644] Science. 1995 Nov 24;270(5240):1372-5 [7481828] Acta Paediatr Suppl. 1997 Jun;421:15-6 [9240851] N Engl J Med. 1997 Sep 18;337(12):847-9 [9295243] N Engl J Med. 1997 Oct 2;337(14):1003-5 [9309109] Am J Public Health. 1991 Nov;81(11):1498-505 [1951814] Erratum In: J Natl Med Assoc 1999 Apr;91(4):192 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amelioration of TCDD-induced teratogenesis in aryl hydrocarbon receptor (AhR)-null mice. AN - 69597596; 10048156 AB - The aryl hydrocarbon receptor (AhR) mediates many of the biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and transcriptional activation of genes encoding a number of xenobiotic metabolizing enzymes. Prenatal exposure of mice to TCDD causes severe alterations in embryo and fetal development, including hydronephrosis and cleft palate. However, the mechanisms underlying these effects are unclear. In this work, the teratogenicity of TCDD in AhR-null mice was evaluated to determine if this effect is mediated by the AhR. Homozygous wild-type (+/+) or AhR-null (-/-) female mice were mated with males of the same genotype overnight. On gestation day (GD)-10, mice were intubated orally with either corn oil (vehicle control) or 25 micrograms/kg TCDD. Fetuses were examined on GD18 for visceral and skeletal alterations. For non-TCDD-exposed litters, all developmental endpoints were comparable between genotypes, with the exception of a lower incidence of large interfrontal bones in (-/-) mice. For TCDD-exposed litters, (+/+) fetuses had a significantly greater incidence of cleft palate, hydronephrosis, small kidneys, tortuous ureters and greater dilation of the renal pelves and ureters compared to (-/-) fetuses. Interestingly, an increased resorption rate was observed in (-/-) fetuses exposed to TCDD. Results from this work demonstrate that fetal development per se is generally unaffected by the absence of the AhR or that other genes may have compensated for the loss of the AhR. More importantly, these data indicate that the AhR mediates TCDD-induced teratogenicity. Further, since a higher percentage of resorptions was observed in (-/-) litters from TCDD-treated dams, it is possible that AhR-independent mechanisms contribute to TCDD-induced developmental toxicity. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Peters, J M AU - Narotsky, M G AU - Elizondo, G AU - Fernandez-Salguero, P M AU - Gonzalez, F J AU - Abbott, B D AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 86 EP - 92 VL - 47 IS - 1 SN - 1096-6080, 1096-6080 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Teratogens KW - Index Medicus KW - Maternal-Fetal Exchange KW - Animals KW - Homozygote KW - Mice KW - Female KW - Pregnancy KW - Receptors, Aryl Hydrocarbon -- physiology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Teratogens -- toxicity KW - Receptors, Aryl Hydrocarbon -- genetics KW - Abnormalities, Multiple -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69597596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amelioration+of+TCDD-induced+teratogenesis+in+aryl+hydrocarbon+receptor+%28AhR%29-null+mice.&rft.au=Peters%2C+J+M%3BNarotsky%2C+M+G%3BElizondo%2C+G%3BFernandez-Salguero%2C+P+M%3BGonzalez%2C+F+J%3BAbbott%2C+B+D&rft.aulast=Peters&rft.aufirst=J&rft.date=1999-01-01&rft.volume=47&rft.issue=1&rft.spage=86&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 - 1999-04-27 N1 - Date created - 1999-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of p21 by p53 and Rb in cellular response to oxidative stress. AN - 69591197; 10029406 AB - Oxidative stress to mammalian cells causes cellular damage and triggers inducible cellular responses leading to cell death by apoptosis. In this paper, we report that p53 was required for programmed cell death induced by oxidative stress in both mouse and human cells and that p53 transactivation was involved in induction of oxidative cell death. Furthermore, we show that p21 was highly responsive to oxidative stress in a p53-dependent manner and that ectopic expression of p21 could increase cellular susceptibility to oxidative stress in the absence of p53. However, p21 was not required for p53-directed oxidative cell death because mouse embryo fibroblasts MEFs lacking p21(p21-/- MEFs) were still susceptible to oxidative cell death. Interestingly, bax, a cell-death mediator regulated by p53, was overexpressed in p21-/- MEFs that underwent cell death by oxidative stress, suggesting a compensation for loss of p21 that may be responsible for the existence of cell-death responses in p21-knockout mouse fibroblasts. Finally, we provide evidence that the retinoblastoma gene product (Rb) is a negative regulator of p21 and a repressor of the cellular apoptotic process. Because p21 is regulated by p53 positively and by Rb negatively, p21 may be a link between p53 and Rb in determining cell fate after oxidative damage. JF - Molecular carcinogenesis AU - Yin, Y AU - Solomon, G AU - Deng, C AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 15 EP - 24 VL - 24 IS - 1 SN - 0899-1987, 0899-1987 KW - BAX protein, human KW - 0 KW - Bax protein, mouse KW - CDKN1A protein, human KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - Retinoblastoma Protein KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Estradiol KW - 4TI98Z838E KW - Cycloheximide KW - 98600C0908 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Fibroblasts -- drug effects KW - Apoptosis KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Estradiol -- pharmacology KW - Mice KW - Fibroblasts -- cytology KW - Transcriptional Activation KW - Mice, Knockout KW - Fibroblasts -- physiology KW - Gene Expression Regulation, Neoplastic KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Tumor Cells, Cultured KW - Transfection KW - Lung Neoplasms KW - Cycloheximide -- pharmacology KW - Enzyme Inhibitors -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Carcinoma, Non-Small-Cell Lung KW - Cell Line KW - Cyclins -- deficiency KW - Retinoblastoma Protein -- metabolism KW - Oxidative Stress -- drug effects KW - Cyclins -- metabolism KW - Gene Expression Regulation -- drug effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69591197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+regulation+of+p21+by+p53+and+Rb+in+cellular+response+to+oxidative+stress.&rft.au=Yin%2C+Y%3BSolomon%2C+G%3BDeng%2C+C%3BBarrett%2C+J+C&rft.aulast=Yin&rft.aufirst=Y&rft.date=1999-01-01&rft.volume=24&rft.issue=1&rft.spage=15&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 - 1999-03-10 N1 - Date created - 1999-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of carbohydrate deficient transferrin to gamma glutamyl transpeptidase in evaluating progress of patients in treatment for alcoholism. AN - 69591071; 10029211 AB - Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity. Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT. Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders. JF - Alcoholism, clinical and experimental research AU - Allen, J P AU - Sillamaukee, P AU - Anton, R AD - U. S. National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 115 EP - 120 VL - 23 IS - 1 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Narcotic Antagonists KW - Transferrin KW - carbohydrate-deficient transferrin KW - Naltrexone KW - 5S6W795CQM KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Index Medicus KW - Sensitivity and Specificity KW - Narcotic Antagonists -- therapeutic use KW - Humans KW - Biomarkers -- analysis KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Biomarkers -- blood KW - Male KW - Female KW - Naltrexone -- therapeutic use KW - Transferrin -- analogs & derivatives KW - Clinical Enzyme Tests KW - Alcoholism -- diagnosis KW - gamma-Glutamyltransferase -- blood KW - Transferrin -- analysis KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69591071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+P2Y1+receptor%3A+molecular+modeling+and+site-directed+mutagenesis+as+tools+to+identify+agonist+and+antagonist+recognition+sites.&rft.au=Moro%2C+S%3BGuo%2C+D%3BCamaioni%2C+E%3BBoyer%2C+J+L%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Moro&rft.aufirst=S&rft.date=1998-04-23&rft.volume=41&rft.issue=9&rft.spage=1456&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 - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of p53-induced cell-cycle arrest. AN - 69587973; 10029405 AB - Activation of the tumor suppressor protein p53 can lead to arrest in both G1 and G2 stages of the cell cycle and, in some cells, to apoptotic cell death. In this study, we showed that the p53 response to a chemotherapeutic drug, actinomycin D, was reversible in both normal and tumor cells, even when a substantial proportion of tumor cells were undergoing apoptosis. Despite the clear reversibility of the p53-induced cell-cycle arrest after removal of actinomycin D, a substantial proportion of the cells arrested in G2 failed to resume normal cell-cycle progression and underwent another round of DNA synthesis. This endoreduplication probably reflects a function of the cyclin-dependent kinase inhibitor p21Waf1Cip1, which is expressed in response to p53. Our observation that this abnormal re-replication of DNA occurred in both transformed and untransformed cells after reversal of a p53 response may have implications for the eventual outcome of tumor therapies in which p53 is transiently expressed in a substantial number of normal as well as tumor cells. JF - Molecular carcinogenesis AU - Bates, S AU - Hickman, E S AU - Vousden, K H AD - ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 7 EP - 14 VL - 24 IS - 1 SN - 0899-1987, 0899-1987 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA, Neoplasm KW - Enzyme Inhibitors KW - Tumor Suppressor Protein p53 KW - Dactinomycin KW - 1CC1JFE158 KW - Index Medicus KW - Apoptosis KW - Humans KW - Mutagenesis KW - Gene Expression Regulation, Neoplastic KW - Tumor Cells, Cultured KW - Kinetics KW - Cyclins -- metabolism KW - Enzyme Inhibitors -- metabolism KW - G1 Phase KW - G2 Phase KW - Time Factors KW - DNA, Neoplasm -- biosynthesis KW - Cyclins -- genetics KW - DNA Replication KW - Dactinomycin -- pharmacology KW - Genes, p53 KW - Cell Cycle -- physiology KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69587973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reversal+of+p53-induced+cell-cycle+arrest.&rft.au=Bates%2C+S%3BHickman%2C+E+S%3BVousden%2C+K+H&rft.aulast=Bates&rft.aufirst=S&rft.date=1999-01-01&rft.volume=24&rft.issue=1&rft.spage=7&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 - 1999-03-10 N1 - Date created - 1999-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. AN - 69585791; 10027577 AB - Glucagon-like peptide-1 is the main hormonal mediator of the enteroinsular axis. Recently, it has additionally received considerable attention as a possible new treatment for Type II (non-insulin-dependent) diabetes mellitus. Its major disadvantage is that its duration of action is too short to achieve good 24-h metabolic control. Exendin-4, which is produced in the salivary glands of Gila monster lizards, is structurally similar to glucagon-like peptide-1 and shares several useful biological properties with glucagon-like peptide-1. It binds the glucagon-like peptide-1 receptor, stimulates insulin release and increases the cAMP production in beta cells. We report that exendin-4 is a more potent insulinotropic agent when given intravenously to rats than is glucagon-like peptide-1 (ED50 0.19 nmol/kg for glucagon-like peptide-1 vs 0.0143 nmol/kg for exendin-4) and causes a greater elevation in cAMP concentrations in isolated islets. Of even greater interest we found that when given intraperitoneally only once daily to diabetic mice it had a prolonged effect of lowering blood glucose. After 1 week of treatment blood glucoses were 5.0+/-2.6 mmol/l compared to diabetic concentrations of 13.2+/-2.8 mmol/l. After 13 weeks of daily treatment HbA1c was 8.8+/-0.4% in non-treated diabetic animals compared with 4.7+/-0.25% in treated diabetic animals. Blood glucoses also were lower (p < 0.005) and insulin concentrations higher (p < 0.02) in the treated animals. Exendin-4 could therefore be preferable to glucagon-like peptide-1 as a long-term treatment of Type II diabetes. JF - Diabetologia AU - Greig, N H AU - Holloway, H W AU - De Ore, K A AU - Jani, D AU - Wang, Y AU - Zhou, J AU - Garant, M J AU - Egan, J M AD - Drug Design and Development Section, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 45 EP - 50 VL - 42 IS - 1 SN - 0012-186X, 0012-186X KW - Blood Glucose KW - 0 KW - Carrier Proteins KW - Hemoglobin A, Glycosylated KW - Insulin KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Receptors, Cell Surface KW - Receptors, Leptin KW - Venoms KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Lizards KW - Carrier Proteins -- genetics KW - Insulin -- blood KW - Islets of Langerhans -- drug effects KW - Mice KW - Energy Intake -- drug effects KW - Rats KW - Hemoglobin A, Glycosylated -- metabolism KW - Body Weight -- drug effects KW - Venoms -- administration & dosage KW - Rats, Wistar KW - Mice, Inbred C57BL KW - Cyclic AMP -- metabolism KW - Crosses, Genetic KW - Islets of Langerhans -- metabolism KW - Venoms -- pharmacology KW - Protein Precursors -- pharmacology KW - Diabetes Mellitus, Type 2 -- drug therapy KW - Blood Glucose -- metabolism KW - Peptides -- administration & dosage KW - Blood Glucose -- drug effects KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Diabetes Mellitus, Type 2 -- physiopathology KW - Diabetes Mellitus, Type 2 -- blood KW - Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69585791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetologia&rft.atitle=Once+daily+injection+of+exendin-4+to+diabetic+mice+achieves+long-term+beneficial+effects+on+blood+glucose+concentrations.&rft.au=Romanova%2C+L+Y%3BAlexandrov%2C+I+A%3BNordan%2C+R+P%3BBlagosklonny%2C+M+V%3BMushinski%2C+J+F&rft.aulast=Romanova&rft.aufirst=L&rft.date=1998-04-21&rft.volume=37&rft.issue=16&rft.spage=5558&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-26 N1 - Date created - 1999-04-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of human immunodeficiency virus type 1 by Tat/Rev-regulated expression of cytosine deaminase, interferon alpha2, or diphtheria toxin compared with inhibition by transdominant Rev. AN - 69581027; 10022535 AB - A retroviral vector was designed to express toxic proteins only in the presence of the HIV-1 Rev and/or Tat protein(s). The design of this vector incorporates an HIV-specific expression cassette that consists of three elements: the U3R region of the HIV-1 IIIB LTR provides the promoter and Tat-responsive element, a modified intron derived from the human c-src gene facilitates the splicing of inserted genes, and the HIV-1 RRE region enhances the transport of unspliced mRNAs. To further limit potential readthrough transcription, the expression cassette was inserted in the reverse transcriptional orientation relative to the retroviral vector LTR. Three different genes, interferon alpha2, diphtheria toxin (DT-A), and cytosine deaminase, were inserted into this vector. Tat and Rev inducibility was demonstrated directly by a >300-fold induction of interferon production and functionally by a decrease in colony-forming units when a Tat and Rev expression vector was titered on HeLa cells harboring the inducible DT-A cassette. The Tat-inducible cytosine deaminase gene was tested in the Sup-T1 T cell line and shown to inhibit HIV-1 production only when engineered cells were grown in the presence of 5-fluorocytosine. To test the ability of this system to inhibit HIV-1 infection in bulk PBL cultures, a series of transduction and challenge experiments was initiated with both the interferon and DT-A vectors. Protection against infection was documented against three HIV strains in PBLs. Last, the interferon and DT-A vectors were compared with a vector encoding a transdominant Rev protein and were shown to mediate equal or greater inhibition of HIV-1. JF - Human gene therapy AU - Ragheb, J A AU - Couture, L AU - Mullen, C AU - Ridgway, A AU - Morgan, R A AD - National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01/01/ PY - 1999 DA - 1999 Jan 01 SP - 103 EP - 112 VL - 10 IS - 1 SN - 1043-0342, 1043-0342 KW - Diphtheria Toxin KW - 0 KW - Gene Products, rev KW - Gene Products, tat KW - HIV Core Protein p24 KW - Interferon-alpha KW - rev Gene Products, Human Immunodeficiency Virus KW - tat Gene Products, Human Immunodeficiency Virus KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Index Medicus KW - AIDS/HIV KW - Blotting, Northern KW - Humans KW - Transduction, Genetic KW - Genetic Therapy KW - Plasmids KW - Genetic Vectors KW - HIV Core Protein p24 -- chemistry KW - Retroviridae -- genetics KW - Immunohistochemistry KW - Time Factors KW - Cell Line KW - Nucleoside Deaminases -- biosynthesis KW - HIV-1 -- genetics KW - Gene Products, rev -- metabolism KW - Interferon-alpha -- biosynthesis KW - Diphtheria Toxin -- biosynthesis KW - HIV-1 -- physiology KW - Gene Products, tat -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69581027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+human+immunodeficiency+virus+type+1+by+Tat%2FRev-regulated+expression+of+cytosine+deaminase%2C+interferon+alpha2%2C+or+diphtheria+toxin+compared+with+inhibition+by+transdominant+Rev.&rft.au=Ragheb%2C+J+A%3BCouture%2C+L%3BMullen%2C+C%3BRidgway%2C+A%3BMorgan%2C+R+A&rft.aulast=Ragheb&rft.aufirst=J&rft.date=1999-01-01&rft.volume=10&rft.issue=1&rft.spage=103&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 - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The neuroleptic malignant syndrome: an Indian experience. AN - 69572529; 9924872 AB - A study was performed to investigate the clinical presentation and outcome of the neuroleptic malignant syndrome (NMS) in a large teaching psychiatric hospital in India. Thirteen cases were identified after a thorough search of intensive care unit (ICU) records during the 4-year period between 1990 and 1993. Information collected from these cases was then compared against data from a representative control group of 252 inpatients who received neuroleptics, drawn randomly from each of the 4 years of the study. Statistical comparisons were made using Student's t test, the chi-square test, and Fisher's exact test. The incidence of NMS was 1.41 per 1,000 cases treated with neuroleptics (95% confidence interval, 0.71 to 2.14 per 1,000) and the mortality from NMS was 38%. Patients who developed NMS had a significantly higher incidence of coexisting physical or neurological illness and received a higher mean neuroleptic dose. Neuroleptic loading rates were not different in the NMS and control samples. Fluphenazine decanoate was implicated as a causative factor of NMS in a significantly higher proportion of these patients. The group with a fatal outcome was significantly older and received a higher neuroleptic dose than the control group, but not compared with the group that recovered. JF - Comprehensive psychiatry AU - Chopra, M P AU - Prakash, S S AU - Raguram, R AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. PY - 1999 SP - 19 EP - 23 VL - 40 IS - 1 SN - 0010-440X, 0010-440X KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Causality KW - India -- epidemiology KW - Disease Susceptibility KW - Chi-Square Distribution KW - Humans KW - Retrospective Studies KW - Adult KW - Confidence Intervals KW - Incidence KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Psychotic Disorders -- drug therapy KW - Neuroleptic Malignant Syndrome -- physiopathology KW - Antipsychotic Agents -- administration & dosage KW - Antipsychotic Agents -- adverse effects KW - Neuroleptic Malignant Syndrome -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69572529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comprehensive+psychiatry&rft.atitle=The+neuroleptic+malignant+syndrome%3A+an+Indian+experience.&rft.au=Chopra%2C+M+P%3BPrakash%2C+S+S%3BRaguram%2C+R&rft.aulast=Chopra&rft.aufirst=M&rft.date=1999-01-01&rft.volume=40&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Comprehensive+psychiatry&rft.issn=0010440X&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 effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats. AN - 69571121; 9973233 AB - Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis. JF - Neurochemical research AU - Kawamura, M AU - Schwartz, J P AU - Nomura, T AU - Kopin, I J AU - Goldstein, D S AU - Huynh, T T AU - Hooper, D R AU - Harvey-White, J AU - Eisenhofer, G AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 25 EP - 32 VL - 24 IS - 1 SN - 0364-3190, 0364-3190 KW - RNA, Messenger KW - 0 KW - Dihydroxyphenylalanine KW - 63-84-3 KW - Oxidopamine KW - 8HW4YBZ748 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Neurons -- metabolism KW - Chromaffin Cells -- metabolism KW - Organ Specificity KW - RNA, Messenger -- genetics KW - Male KW - Tyrosine 3-Monooxygenase -- metabolism KW - Gene Expression Regulation, Enzymologic KW - Tyrosine 3-Monooxygenase -- genetics KW - Sympathetic Nervous System -- physiology KW - Norepinephrine -- metabolism KW - Sympathectomy, Chemical KW - Dihydroxyphenylalanine -- metabolism KW - Dopamine -- metabolism KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69571121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+research&rft.atitle=Differential+effects+of+chemical+sympathectomy+on+expression+and+activity+of+tyrosine+hydroxylase+and+levels+of+catecholamines+and+DOPA+in+peripheral+tissues+of+rats.&rft.au=Kawamura%2C+M%3BSchwartz%2C+J+P%3BNomura%2C+T%3BKopin%2C+I+J%3BGoldstein%2C+D+S%3BHuynh%2C+T+T%3BHooper%2C+D+R%3BHarvey-White%2C+J%3BEisenhofer%2C+G&rft.aulast=Kawamura&rft.aufirst=M&rft.date=1999-01-01&rft.volume=24&rft.issue=1&rft.spage=25&rft.isbn=&rft.btitle=&rft.title=Neurochemical+research&rft.issn=03643190&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-03 N1 - Date created - 1999-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by inducing hypertrophy and inhibiting apoptosis. AN - 69567169; 9934848 AB - Phenobarbital (PB) is a non-genotoxic liver tumor promoter used extensively in initiation-promotion protocols. To determine the mode of PB action, double transgenic mice overexpressing both the c-myc and transforming growth factor (TGF)-alpha genes were treated with PB in the food for 10 weeks, from 3 weeks of age. After 3-4 weeks on PB a peak in liver mass was noted, which subsequently leveled off at a value approximately 30% above untreated animals. The mitotic index in mice given PB peaked at 1 week of treatment and was significantly elevated compared with untreated animals. No significant difference between treated and untreated animals was seen thereafter, although a trend of PB-associated mitotic suppression was noticeable. The apoptotic index also showed a trend of suppression compared with untreated animals, significant after prolonged PB administration. Dysplastic hepatocytes were more prominent in PB-treated mice than untreated animals, particularly pericentrally. Removal of PB from the diet at 4 weeks of treatment led to a dramatic increase in apoptosis. This accompanied a drop in the liver mass to the level of untreated controls by 10 days. Throughout the study, PB-treated animals showed markedly lower levels of TGF-beta1 ligand, coincident with an elevated level of the anti-apoptotic protein Bcl-2. On withdrawal of PB, the levels of all these proteins rapidly changed to mirror those seen in untreated mice. In all treatment groups, no change in the levels of epidermal growth factor receptor, TGF-beta receptors I and II or Bcl-xS/L were seen. We conclude from our data that PB stimulates liver growth in double transgenic c-myc/TGF-alpha mice by induction of liver hypertrophy and inhibition of apoptosis, brought about by both a decrease in signaling through the TGF-beta pathway and an increase in Bcl-2. The data support the hypothesis that PB promotes neoplastic development through a reduction in the incidence of cell death. JF - Carcinogenesis AU - Sanders, S AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 41 EP - 49 VL - 20 IS - 1 SN - 0143-3334, 0143-3334 KW - Bcl2l1 protein, mouse KW - 0 KW - Carcinogens KW - Proto-Oncogene Proteins c-bcl-2 KW - Receptors, Growth Factor KW - Transforming Growth Factor alpha KW - Transforming Growth Factor beta KW - bcl-X Protein KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Transforming Growth Factor beta -- biosynthesis KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Animals KW - Receptors, Growth Factor -- biosynthesis KW - Cell Division -- drug effects KW - Mice KW - Mice, Transgenic KW - Genes, bcl-2 KW - Receptors, Growth Factor -- genetics KW - Hypertrophy KW - Mice, Inbred CBA KW - Mice, Inbred C57BL KW - Diet KW - Transforming Growth Factor beta -- genetics KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Organ Size -- drug effects KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Transforming Growth Factor alpha -- genetics KW - Liver -- drug effects KW - Genes, myc KW - Apoptosis -- drug effects KW - Carcinogens -- toxicity KW - Gene Expression Regulation -- drug effects KW - Phenobarbital -- toxicity KW - Phenobarbital -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69567169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phenobarbital+promotes+liver+growth+in+c-myc%2FTGF-alpha+transgenic+mice+by+inducing+hypertrophy+and+inhibiting+apoptosis.&rft.au=Sanders%2C+S%3BThorgeirsson%2C+S+S&rft.aulast=Sanders&rft.aufirst=S&rft.date=1999-01-01&rft.volume=20&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. AN - 69566648; 9934851 AB - Our previous studies indicate that cadmium in mice can inhibit the formation of chemically induced and spontaneously occurring tumors in the liver and lung. Cadmium is an effective anti-tumor agent when given at non-toxic doses and even when given well after tumor formation, implying a unique sensitivity in certain tumor cells. The present studies tested the ability of cadmium to inhibit growth and progression of transplanted human pulmonary tumor xenografts. Male athymic nude mice were inoculated with either H460 cells, originally derived from a non-small cell pulmonary carcinoma, or DMS 114 cells, originally derived from a small cell lung carcinoma, under the left renal capsule. Starting 1 week later mice received 0, 125 or 250 p.p.m. cadmium in the drinking water, levels without effect on host animal growth or survival, and were observed over the next 4 weeks (H460 cells) or 100 days (DMS 114 cells). An additional experiment gave cadmium as an i.v. loading dose (20 micromol/kg) 4 days after renal inoculation with H460 cells and 200 p.p.m. cadmium in the drinking water from 7 days onward, with an observation period of 28 days. Cadmium caused dose-related reductions in the growth of tumors resulting from the inoculation of either H460 or DMS 114 cells of up to 83%. Additionally, cadmium reduced the rate of tumor metastasis to the lung by up to 58%. Cadmium treatment had no effects on either Bcl-2 or Bax protein expression in tumor xenografts, indicating that apoptotic pathways probably do not contribute to this anti-neoplastic effect. These studies show cadmium can effectively reduce growth and progression of human lung carcinoma xenografts in a fashion that is probably independent of apoptosis. JF - Carcinogenesis AU - Waalkes, M P 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, NC 27709, USA. waalkes@niehs.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 65 EP - 70 VL - 20 IS - 1 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Neoplasm Transplantation KW - Administration, Oral KW - Animals KW - Injections, Intravenous KW - Subrenal Capsule Assay KW - Humans KW - Transplantation, Heterologous KW - Tumor Cells, Cultured -- transplantation KW - Mice, Nude KW - Mice KW - Male KW - Carcinoma, Small Cell -- pathology KW - Carcinoma, Non-Small-Cell Lung -- prevention & control KW - Cadmium Chloride -- administration & dosage KW - Lung Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- therapeutic use KW - Lung Neoplasms -- secondary KW - Carcinoma, Small Cell -- secondary KW - Apoptosis -- drug effects KW - Carcinoma, Non-Small-Cell Lung -- secondary KW - Carcinoma, Small Cell -- prevention & control KW - Cadmium Chloride -- therapeutic use KW - Anticarcinogenic Agents -- administration & dosage KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69566648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cadmium-induced+inhibition+of+the+growth+and+metastasis+of+human+lung+carcinoma+xenografts%3A+role+of+apoptosis.&rft.au=Waalkes%2C+M+P%3BDiwan%2C+B+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1999-01-01&rft.volume=20&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence analysis of the rat Brca1 homolog and its promoter region. AN - 69561598; 9892727 AB - Since the identification of the human breast and ovarian cancer gene, BRCA1, a large spectrum of germline mutations has been characterized that predispose women to developing these diseases. We have determined the complete coding sequence for the rat BRCA1 homolog and compared it with those of the mouse, dog, and human to help identify the important functional domains of the BRCA1 protein. The overall rat Brcal amino acid identity compared with the predicted mouse, dog, and human gene products is 81%, 69%, and 58%, respectively. In spite of this low overall homology, the amino terminal RING finger domain and one of two nuclear localization signals are highly conserved among these species. In addition, two BRCT domains at the carboxy terminus and a highly acidic region are relatively well conserved. We have also identified several putative regulatory elements through comparison of the bidirectional BRCA1 promoter regions among the rat, mouse, and human genes. These include motifs for CCAAT and G/C boxes, as well as potential SP1, CREB, and NFkB transcription factor binding sites. Finally, analysis of splice variants from rat mammary gland, ovary, testis, spleen, and liver tissues revealed that, while alternative transcripts are detectable, full-length transcripts are the predominant steady-state form. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Bennett, L M AU - Brownlee, H A AU - Hagavik, S AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. Bennett@nichs.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 19 EP - 25 VL - 10 IS - 1 SN - 0938-8990, 0938-8990 KW - BRCA1 Protein KW - 0 KW - NBR1 protein, human KW - Nbr1 protein, mouse KW - Nbr1 protein, rat KW - Proteins KW - Index Medicus KW - Animals KW - Genetic Variation KW - Blotting, Northern KW - Humans KW - Transcription, Genetic KW - Amino Acid Sequence KW - Mice KW - Tissue Distribution KW - Proteins -- genetics KW - Rats KW - Rats, Sprague-Dawley KW - Promoter Regions, Genetic KW - Conserved Sequence KW - Sequence Analysis KW - Dogs KW - Molecular Sequence Data KW - Species Specificity KW - Female KW - BRCA1 Protein -- genetics KW - Sequence Homology, Amino Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69561598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.atitle=Sequence+analysis+of+the+rat+Brca1+homolog+and+its+promoter+region.&rft.au=Bennett%2C+L+M%3BBrownlee%2C+H+A%3BHagavik%2C+S%3BWiseman%2C+R+W&rft.aulast=Bennett&rft.aufirst=L&rft.date=1999-01-01&rft.volume=10&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Mammalian+genome+%3A+official+journal+of+the+International+Mammalian+Genome+Society&rft.issn=09388990&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 - Genetic sequence - AF080589; GENBANK; AF036760; AF080590 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-alpha is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII). AN - 69560596; 9892208 AB - Tumor necrosis factor (TNF)-alpha is a potent anticancer agent that seems to selectively target tumor-associated vasculature resulting in hemorrhagic necrosis of tumors without injury to surrounding tissues. The major limitation in the clinical use of TNF has been severe dose-limiting toxicity when administered systemically. However, when administered in isolated organ perfusion it results in regression of advanced bulky tumors. A better understanding of the mechanisms of TNF-induced antitumor effects may provide valuable information into how its clinical use in cancer treatment may be expanded. We describe here that the release of a novel tumor-derived cytokine endothelial-monocyte-activating polypeptide II (EMAPII) renders the tumor-associated vasculature sensitive to TNF. EMAPII has the unique ability to induce tissue factor production by tumor vascular endothelial cells that initiates thrombogenic cascades, which may play a role in determining tumor sensitivity to TNF. We demonstrate here that constitutive overexpression of EMAPII in a TNF-resistant human melanoma line by retroviral-mediated transfer of EMAPII cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro. This interaction between tumors and their associated neovasculature provides an explanation for the focal effects of TNF on tumors and possibly for the variable sensitivity of tumors to bioactive agents. JF - Cancer research AU - Wu, P C AU - Alexander, H R AU - Huang, J AU - Hwu, P AU - Gnant, M AU - Berger, A C AU - Turner, E AU - Wilson, O AU - Libutti, S K AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/01/01/ PY - 1999 DA - 1999 Jan 01 SP - 205 EP - 212 VL - 59 IS - 1 SN - 0008-5472, 0008-5472 KW - Cytokines KW - 0 KW - Neoplasm Proteins KW - RNA-Binding Proteins KW - Tumor Necrosis Factor-alpha KW - small inducible cytokine subfamily E, member 1 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Neovascularization, Pathologic -- drug therapy KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Retroviridae KW - Mice, Nude KW - Mice KW - Female KW - Neoplasm Proteins -- biosynthesis KW - RNA-Binding Proteins -- biosynthesis KW - RNA-Binding Proteins -- genetics KW - Melanoma -- genetics KW - Drug Resistance, Neoplasm -- genetics KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Neoplasm Proteins -- genetics KW - Melanoma -- drug therapy KW - Melanoma, Experimental -- drug therapy KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Melanoma, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69560596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+sensitivity+of+human+melanoma+to+tumor+necrosis+factor+%28TNF%29-alpha+is+determined+by+tumor+production+of+the+novel+cytokine+endothelial-monocyte+activating+polypeptide+II+%28EMAPII%29.&rft.au=Wu%2C+P+C%3BAlexander%2C+H+R%3BHuang%2C+J%3BHwu%2C+P%3BGnant%2C+M%3BBerger%2C+A+C%3BTurner%2C+E%3BWilson%2C+O%3BLibutti%2C+S+K&rft.aulast=Wu&rft.aufirst=P&rft.date=1999-01-01&rft.volume=59&rft.issue=1&rft.spage=205&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 - 1999-02-04 N1 - Date created - 1999-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of effect of cytoplasmic tail truncations on human immunodeficiency virus type 2 ROD env particle release activity. AN - 69560492; 9847387 AB - In addition to its role in receptor binding, the envelope glycoprotein of certain human immunodeficiency virus type 2 (HIV-2) isolates, including ROD10, exhibits a biological activity that enhances the release of HIV-2, HIV-1, and simian immunodeficiency virus particles from infected cells. The present study aims at better defining the functional domains involved in this biological activity. To this end, we have characterized the envelope protein of the ROD14 isolate of HIV-2, which, despite 95% homology with the ROD10 envelope at the amino acid level, is unable to enhance viral particle release. Site-directed mutagenesis showed that the presence of a truncation in the cytoplasmic tail of the ROD14 envelope was not responsible for the lack of activity, as previously reported for the HIV-2 ST isolate (G. D. Ritter, Jr., G. Yamshchikov, S. J. Cohen, and M. J. Mulligan, J. Virol. 70:2669-2673, 1996). Similarly, several modifications of the length of the ROD10 envelope cytoplasmic tail did not impair its ability to enhance particle release, suggesting that, in the case of the HIV-2 ROD isolate, particle release activity is not regulated by the length of the cytoplasmic tail. JF - Journal of virology AU - Bour, S P AU - Aberham, C AU - Perrin, C AU - Strebel, K AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA. sbour@nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 778 EP - 782 VL - 73 IS - 1 SN - 0022-538X, 0022-538X KW - Gene Products, env KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Cytoplasm KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Gene Products, env -- chemistry KW - Gene Products, env -- physiology KW - Virion -- physiology KW - Herpesvirus 2, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69560492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+G+protein-coupled+receptors+block+insulin+and+ras-induced+adipocytic+differentiation+in+3T3-L1+cells%3A+evidence+for+a+PKC+and+MAP+kinase+independent+pathway.&rft.au=Crespo%2C+P%3BFont+de+Mora%2C+J%3BAaronson%2C+D+S%3BSantos%2C+E%3BGutkind%2C+J+S&rft.aulast=Crespo&rft.aufirst=P&rft.date=1998-04-17&rft.volume=245&rft.issue=2&rft.spage=554&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: AIDS. 1988 Oct;2(5):383-8 [3146268] J Virol. 1988 Dec;62(12):4691-6 [2846880] J Virol. 1989 Sep;63(9):3784-91 [2788224] J Virol. 1990 Feb;64(2):890-901 [2296086] J Virol. 1992 Jun;66(6):3971-5 [1583738] J Virol. 1993 Feb;67(2):1006-14 [8419635] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7381-5 [8346259] Virology. 1995 Oct 20;213(1):158-68 [7483259] J Virol. 1996 Feb;70(2):809-19 [8551619] J Virol. 1996 Feb;70(2):820-9 [8551620] J Virol. 1996 Apr;70(4):2669-73 [8642705] Virology. 1996 Jul 1;221(1):22-33 [8661411] J Virol. 1996 Dec;70(12):8285-300 [8970948] EMBO J. 1998 Aug 10;17(5):1289-96 [9482726] Science. 1986 Jul 18;233(4761):343-6 [2425430] Nature. 1986 Dec 18-31;324(6098):691-5 [3025743] Nature. 1987 Apr 16-22;326(6114):662-9 [3031510] J Virol. 1988 Jan;62(1):139-47 [3257102] Science. 1988 Jun 10;240(4858):1525-9 [3375832] Nature. 1988 Aug 11;334(6182):532-4 [3043230] Science. 1988 Sep 2;241(4870):1221-3 [3261888] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163-7 [2472639] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. AN - 69559667; 9892191 AB - Treatment of estrogen receptor (ER)-positive MCF-7 human breast cancer cells with retinoic acid (RA) inhibited cell growth and increased cell adhesion to fibronectin. In contrast, ER- MDA-MB-231 cells failed to respond. Western blot analysis showed that tyrosine phosphorylation of two major bands at Mr 125,000 and Mr 68,000 was induced by RA in ER+ MCF-7 human breast carcinoma cells. However, this induction was a late phenomenon detectable at 12 and 24 h, but not within 3 h. A similar increase of tyrosine phosphorylation by RA was observed in ER+ human breast cancer cell lines T-47D and ZR-75-1, but not in the ER- cell lines MDA-MB-231, MDA-MB-453, and MDA-MB-468. Focal adhesion kinase and paxillin, which localize in focal adhesion plaques and may play important roles in the integrin signaling pathway, were identified as the major proteins showing RA-induced tyrosine phosphorylation. The retinoid X receptor-selective compound SR11237 failed to induce tyrosine phosphorylation, indicating that retinoid X receptor activation is not involved in this phenomenon. In contrast, stable overexpression of a truncated RA receptor (RAR) alpha cDNA, RARalpha403, with strong RAR dominant negative activity prevented the increase in tyrosine phosphate, suggesting that RAR signaling is involved in RA-induced tyrosine phosphorylation. Tyrosine phosphorylation was induced the most by the RAR-alpha (193836), followed by RAR-gamma (194433), but was not significantly induced by RAR-gamma (193174)-selective retinoids. This study demonstrates a coordinated albeit relatively late effect of RA on cell adhesion and tyrosine phosphorylation in ER+ human breast cancer cells and suggests RAR-alpha as the major responsible retinoid receptor. JF - Cancer research AU - Zhu, W Y AU - Jones, C S AU - Amin, S AU - Matsukuma, K AU - Haque, M AU - Vuligonda, V AU - Chandraratna, R A AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/01/01/ PY - 1999 DA - 1999 Jan 01 SP - 85 EP - 90 VL - 59 IS - 1 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Cell Adhesion Molecules KW - Cytoskeletal Proteins KW - PXN protein, human KW - Paxillin KW - Phosphoproteins KW - Receptors, Retinoic Acid KW - Tyrosine KW - 42HK56048U KW - Tretinoin KW - 5688UTC01R 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 - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Tumor Cells, Cultured KW - Humans KW - Signal Transduction -- drug effects KW - Tyrosine -- metabolism KW - Female KW - Phosphorylation -- drug effects KW - Breast Neoplasms -- drug therapy KW - Tretinoin -- pharmacology KW - Cell Adhesion Molecules -- metabolism KW - Breast Neoplasms -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Tretinoin -- therapeutic use KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69559667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoic+acid+increases+tyrosine+phosphorylation+of+focal+adhesion+kinase+and+paxillin+in+MCF-7+human+breast+cancer+cells.&rft.au=Zhu%2C+W+Y%3BJones%2C+C+S%3BAmin%2C+S%3BMatsukuma%2C+K%3BHaque%2C+M%3BVuligonda%2C+V%3BChandraratna%2C+R+A%3BDe+Luca%2C+L+M&rft.aulast=Zhu&rft.aufirst=W&rft.date=1999-01-01&rft.volume=59&rft.issue=1&rft.spage=85&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 - 1999-02-04 N1 - Date created - 1999-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Natural history and treatment of lupus nephritis. AN - 69558792; 9952276 AB - Renal involvement occurs in the majority of patients with systemic lupus erythematosus. Contemporary therapeutic regimens for immunosuppression and for the treatment of hypertension, hyperlipidemia, infections, and seizures have likely contributed to improvements in the prognosis of these patients over the last four decades. Corticosteroids usually ameliorate the manifestations of lupus nephritis but achieve less complete and sustained remissions than do cytotoxic drugs. Among the cytotoxic drugs, pulse cyclophosphamide has one of the best profiles of efficacy and toxicity. Because each episode of exacerbation of lupus nephritis results in cumulative scarring, atrophy and fibrosis, we recommend continued maintenance treatment for 1 year beyond the point of complete remission of proliferative lupus nephritis. Studies are in progress to determine whether innovative treatment strategies will enhance efficacy and minimize toxicity associated with cytotoxic drug therapies. Lupus membranous nephropathy poses a lower risk of renal failure, but persistent nephrotic syndrome confers risks of cardiovascular events; this form of lupus nephritis is usually treated with less intensive regimens of corticosteroids, cytotoxic drugs, or cyclosporine. The prognosis and overall success of treatment for lupus nephritis seem to vary widely among geographically and racially diverse populations. The causes for the apparently worse prognosis and poorer responses to treatment of lupus nephritis in Black patients are currently unexplained and require further study. Until such data are available, caution is clearly warranted in extrapolating evidence, particularly about prognosis and effects of treatment, among different populations of patients with lupus nephritis. JF - Seminars in nephrology AU - Austin, H A AU - Balow, J E AD - Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 2 EP - 11 VL - 19 IS - 1 SN - 0270-9295, 0270-9295 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - Survival Rate KW - Risk Factors KW - Humans KW - Prognosis KW - Disease Progression KW - Incidence KW - Recurrence KW - Male KW - Female KW - Kidney Failure, Chronic -- diagnosis KW - Lupus Nephritis -- physiopathology KW - Lupus Nephritis -- drug therapy KW - Lupus Nephritis -- epidemiology KW - Kidney Failure, Chronic -- therapy KW - Lupus Nephritis -- diagnosis KW - Kidney Failure, Chronic -- epidemiology KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69558792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nephrology&rft.atitle=Natural+history+and+treatment+of+lupus+nephritis.&rft.au=Austin%2C+H+A%3BBalow%2C+J+E&rft.aulast=Austin&rft.aufirst=H&rft.date=1999-01-01&rft.volume=19&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Seminars+in+nephrology&rft.issn=02709295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-16 N1 - Date created - 1999-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlations among polychlorinated biphenyls, dioxins, and furans in humans. AN - 69558292; 9884741 AB - Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration. JF - American journal of industrial medicine AU - Gladen, B C AU - Longnecker, M P AU - Schecter, A J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. gladen@niehs.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 15 EP - 20 VL - 35 IS - 1 SN - 0271-3586, 0271-3586 KW - Benzofurans KW - 0 KW - Dibenzofurans, Polychlorinated KW - Dioxins KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Benzofurans -- blood KW - Dioxins -- blood KW - Polychlorinated Biphenyls -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69558292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correlations+among+polychlorinated+biphenyls%2C+dioxins%2C+and+furans+in+humans.&rft.au=Gladen%2C+B+C%3BLongnecker%2C+M+P%3BSchecter%2C+A+J&rft.aulast=Gladen&rft.aufirst=B&rft.date=1999-01-01&rft.volume=35&rft.issue=1&rft.spage=15&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 - 1999-03-10 N1 - Date created - 1999-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. AN - 69558093; 9920079 AB - Short term treatment with spironolactone, testolactone, and, after the onset of central puberty, deslorelin can normalize the rate of growth and bone maturation in boys with familial male-limited precocious puberty. To test the hypothesis that this treatment can achieve long term normalization of the growth and development of these children, we examined the growth rate, bone maturation rate (change in bone age/change in chronological age), and predicted adult height of 10 boys who were treated with spironolactone (5.7 mg/kg x day) and testolactone (40 mg/kg x day) for at least 6 yr. Deslorelin (4 microg/kg x day) treatment was initiated 2.6 +/- 1.3 yr after beginning spironolactone and testolactone treatment. The growth rate normalized within 1 yr of starting treatment and remained normal during the next 5 yr of treatment (P < 0.001). The rate of bone maturation normalized during the second year of treatment and remained normal thereafter (P < 0.001). Predicted height increased from 160.7 +/- 14.7 centimeters at baseline to 173.6 +/- 10.1 centimeters after 6 yr of treatment (P < 0.05 during the fourth through the sixth year of treatment compared to baseline). We conclude that long term treatment with spironolactone, testolactone, and, after central puberty, deslorelin normalizes the growth rate and bone maturation and improves the predicted height in boys with familial male-limited precocious puberty. The ultimate effect of this approach on adult height will require further study. JF - The Journal of clinical endocrinology and metabolism AU - Leschek, E W AU - Jones, J AU - Barnes, K M AU - Hill, S C AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA. ellen_leschek@nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 175 EP - 178 VL - 84 IS - 1 SN - 0021-972X, 0021-972X KW - Spironolactone KW - 27O7W4T232 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Testosterone KW - 3XMK78S47O KW - Triptorelin Pamoate KW - 57773-63-4 KW - Testolactone KW - 6J9BLA949Q KW - deslorelin KW - TKG3I66TVE KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Testosterone -- blood KW - Bone Development -- drug effects KW - Child KW - Adolescent KW - Triptorelin Pamoate -- analogs & derivatives KW - Male KW - Growth -- drug effects KW - Child, Preschool KW - Testolactone -- adverse effects KW - Spironolactone -- adverse effects KW - Testolactone -- administration & dosage KW - Spironolactone -- administration & dosage KW - Puberty, Precocious -- drug therapy KW - Gonadotropin-Releasing Hormone -- administration & dosage KW - Puberty, Precocious -- genetics KW - Gonadotropin-Releasing Hormone -- analogs & derivatives KW - Puberty, Precocious -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69558093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Six-year+results+of+spironolactone+and+testolactone+treatment+of+familial+male-limited+precocious+puberty+with+addition+of+deslorelin+after+central+puberty+onset.&rft.au=Leschek%2C+E+W%3BJones%2C+J%3BBarnes%2C+K+M%3BHill%2C+S+C%3BCutler%2C+G+B&rft.aulast=Leschek&rft.aufirst=E&rft.date=1999-01-01&rft.volume=84&rft.issue=1&rft.spage=175&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 - 1999-02-03 N1 - Date created - 1999-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited. AN - 69557575; 9886075 AB - The transport of glucose across the blood-brain barrier (BBB) is mediated by the high molecular mass (55-kDa) isoform of the GLUT1 glucose transporter protein. In this study we have utilized the tritiated, impermeant photolabel 2-N-[4-(1 -azi-2,2,2-trifluoroethyl)[2-3H]propyl]-1,3-bis(D-mannose-4-ylo xy)-2-propylamine to develop a technique to specifically measure the concentration of GLUT1 glucose transporters on the luminal surface of the endothelial cells of the BBB. We have combined this methodology with measurements of BBB glucose transport and immunoblot analysis of isolated brain microvessels for labeled luminal GLUT1 and total GLUT1 to reevaluate the effects of chronic hypoglycemia and diabetic hyperglycemia on transendothelial glucose transport in the rat. Hypoglycemia was induced with continuous-release insulin pellets (6 U/day) for a 12- to 14-day duration; diabetes was induced by streptozotocin (65 mg/kg i.p.) for a 14- to 21-day duration. Hypoglycemia resulted in 25-45% increases in regional BBB permeability-surface area (PA) values for D-[14C]glucose uptake, when measured at identical glucose concentration using the in situ brain perfusion technique. Similarly, there was a 23+/-4% increase in total GLUT1/mg of microvessel protein and a 52+/-13% increase in luminal GLUT1 in hypoglycemic animals, suggesting that both increased GLUT1 synthesis and a redistribution to favor luminal transporters account for the enhanced uptake. A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by in situ hybridization. In contrast, no significant changes were observed in regional brain glucose uptake PA, total microvessel 55-kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30-40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface. JF - Journal of neurochemistry AU - Simpson, I A AU - Appel, N M AU - Hokari, M AU - Oki, J AU - Holman, G D AU - Maher, F AU - Koehler-Stec, E M AU - Vannucci, S J AU - Smith, Q R AD - Experimental Diabetes, Metabolism, and Nutrition Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 238 EP - 247 VL - 72 IS - 1 SN - 0022-3042, 0022-3042 KW - Affinity Labels KW - 0 KW - Azides KW - Disaccharides KW - Glucose Transporter Type 1 KW - Glycosides KW - Hypoglycemic Agents KW - Insulin KW - Monosaccharide Transport Proteins KW - Propylamines KW - Slc2a1 protein, rat KW - Tritium KW - 10028-17-8 KW - 2-N-(4-(1-azitrifluoroethyl)benzoyl)-1,3-bis-(mannos-4-yloxy)-2-propylamine KW - 129461-18-3 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Photochemistry KW - Animals KW - Rats KW - Rats, Sprague-Dawley KW - Male KW - Diabetes Mellitus, Experimental -- physiopathology KW - Hypoglycemia -- metabolism KW - Hyperglycemia -- metabolism KW - Glucose -- metabolism KW - Blood-Brain Barrier -- physiology KW - Monosaccharide Transport Proteins -- physiology KW - Hypoglycemia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69557575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+elevated+mutagenesis+in+the+spleen+with+genetic+susceptibility+to+induced+plasmacytoma+development+in+mice.&rft.au=Felix%2C+K%3BKelliher%2C+K%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1616&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 - 1999-01-21 N1 - Date created - 1999-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The measurement of cadmium in biological materials, using graphite furnace atomic absorption spectrometry with Zeeman background correction. AN - 69556583; 9864420 AB - Cadmium (Cd), a toxic heavy metal and probable carcinogen in humans, appears to have potential anti-cancer activity in pre-clinical systems. This observation led us to develop a method for measuring cellular Cd and DNA-bound Cd following micromolar exposures to cadmium dichloride. Cultured human ovarian cancer cell lines were used. Following low level exposures to cadmium dichloride (CdCl2), atomic absorption spectrometry with Zeeman background correction was used to measure total cell associated Cd in wet-ashed cells, and the lower limits of detection was at 100 pg of Cd per 106 cells. In cellular DNA isolated by cesium chloride density gradient centrifugation, levels of 1.5 Cd lesions (Cd molecules) per 106 nucleotides were reproducibly detected. Standard curves with samples yielded 76.4 6.7% recovery when using picogram quantities of Cd. Manipulation of the total amount of biological material used, can further improve detection limits. Thus, this method is suitable for the detection of Cd in biological matrixes after low levels of Cd exposure, and shows good performance in terms of the level of sensitivity and reproducibility. JF - Oncology reports AU - Abernathy, T V AU - Lee, K B AU - Parker, R J AU - Reed, E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA. PY - 1999 SP - 155 EP - 159 VL - 6 IS - 1 SN - 1021-335X, 1021-335X KW - DNA, Neoplasm KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - DNA, Neoplasm -- chemistry KW - Tumor Cells, Cultured -- chemistry KW - Humans KW - Cadmium Chloride -- pharmacology KW - Specimen Handling KW - Calibration KW - Ovarian Neoplasms -- chemistry KW - Female KW - Spectrophotometry, Atomic -- methods KW - Spectrophotometry, Atomic -- instrumentation KW - Cadmium -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69556583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=The+measurement+of+cadmium+in+biological+materials%2C+using+graphite+furnace+atomic+absorption+spectrometry+with+Zeeman+background+correction.&rft.au=Abernathy%2C+T+V%3BLee%2C+K+B%3BParker%2C+R+J%3BReed%2C+E&rft.aulast=Abernathy&rft.aufirst=T&rft.date=1999-01-01&rft.volume=6&rft.issue=1&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-22 N1 - Date created - 1999-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eight inhibitory monoclonal antibodies define the role of individual P-450s in human liver microsomal diazepam, 7-ethoxycoumarin, and imipramine metabolism. AN - 69554706; 9884317 AB - Eight inhibitory monoclonal antibodies (MAbs) individually specific to human cytochrome P-450 (P-450) 1A1, 1A2, 2A6, 2B6, 2C subfamily (2C8, 2C9, 2C18 and 2C19), 2D6, 2E1, and 3A4/5 were used to define the role of single P-450s in the metabolism of diazepam (DZ), 7-ethoxycoumarin (7-EC), and imipramine (IMI) in human liver microsomes (HLM). The MAbs were added combinatorially to six HLM samples. With DZ as a substrate, more than 80% of temazepam (TMZ) formation was inhibited in all six samples by the addition of MAb to 3A4/5, indicating an 80% contribution of 3A4/5 to TMZ formation. Nordiazepam formation was inhibited with MAbs to 2B6 (6-23%), 2C subfamily (12-61%) and 3A4/5 (14-45%). The MAbs to 1A1, 1A2, 2A6, 2D6, and 2E1 did not inhibit TMZ or nordiazepam formation; this indicates their noninvolvement in DZ metabolism. The MAb-defined P-450 contribution to 7-EC Odeethylation in six HLM samples was 17 to 60% for 2E1, 15 to 46% for 2A6, and 5 to 22% for 1A2, reflecting the role and variation of each P-450 in this activity. MAbs to 1A1, the 2C subfamily, 2D6, and 3A4/5 did not affect 7-EC metabolism in the HLM samples. IMI is metabolized mainly to 2-hydroxyimipramine by expressed 2C19 and 2D6, and desipramine (DIM) by expressed 1A2, 2C18, 2C19 and 2D6. Expressed 1A1, 2C9, and 3A4 showed low activities for the formation of DIM. Of six HLM samples, five showed IMI hydroxylation activity (0.35-2.6 nmol/min/nmol P-450) while one (HL43) lacked hydroxylation activity. All six HLM samples showed N-deethylation activity (0.74-1.4 nmol/min/nmol P-450). The MAb-determined contribution of 2D6 and 2C19 to 2-hydroxyimipramine formation ranged from 47 to 90% and from 0 to 49%, respectively, while HL43 did not show 2-hydroxylation. The role of P-450s involved in DIM formation varied for 2C19 (13-50%), 1A2 (23-41%), and 3A4 (8-26%). These studies demonstrate a system for identifying the quantitative metabolic role of single P-450s and their interindividual variability in a tissue containing multiple P-450s. The system using inhibitory MAbs is simple, precise, and applicable to any P-450-mediated catalytic activity including that for drugs, carcinogens, mutagens, toxic chemicals and endobiotics. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Yang, T J AU - Krausz, K W AU - Sai, Y AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 102 EP - 109 VL - 27 IS - 1 SN - 0090-9556, 0090-9556 KW - Antibodies, Monoclonal KW - 0 KW - Coumarins KW - Cytochrome P-450 Enzyme Inhibitors KW - 7-ethoxycoumarin KW - 31005-02-4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Imipramine KW - OGG85SX4E4 KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Humans KW - Diazepam -- metabolism KW - Microsomes, Liver -- metabolism KW - Coumarins -- metabolism KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- metabolism KW - Imipramine -- metabolism KW - Antibodies, Monoclonal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Eight+inhibitory+monoclonal+antibodies+define+the+role+of+individual+P-450s+in+human+liver+microsomal+diazepam%2C+7-ethoxycoumarin%2C+and+imipramine+metabolism.&rft.au=Yang%2C+T+J%3BKrausz%2C+K+W%3BSai%2C+Y%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Yang&rft.aufirst=T&rft.date=1999-01-01&rft.volume=27&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&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 - An action plan for mouse genomics. AN - 69554330; 9916794 AB - The mouse has become the leading animal model for studying biological processes in mammals. Creation of additional genomic and genetic resources will make the mouse an even more useful model for the research community. On the basis of recommendations from the scientific community, the National Institutes of Health (NIH) plans to support grants to generate a 'working draft' sequence of the mouse genome by 2003, systematic mutagenesis and phenotyping centres, repositories for mouse strain maintenance, distribution and cryopreservation and training fellowships in mouse pathobiology. JF - Nature genetics AU - Battey, J AU - Jordan, E AU - Cox, D AU - Dove, W AD - National Institute on Deafness and Other Communication Disorders, NIH Building 31, Bethesda, Maryland 20892, USA. batteyj@nidcd.nih.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 73 EP - 75 VL - 21 IS - 1 SN - 1061-4036, 1061-4036 KW - Index Medicus KW - United States KW - Animals KW - National Institutes of Health (U.S.) KW - Genome KW - Mice -- genetics KW - Research Support as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+action+plan+for+mouse+genomics.&rft.au=Battey%2C+J%3BJordan%2C+E%3BCox%2C+D%3BDove%2C+W&rft.aulast=Battey&rft.aufirst=J&rft.date=1999-01-01&rft.volume=21&rft.issue=1&rft.spage=73&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 - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetics of substance abuse vulnerability: a current approach. AN - 69554075; 9885780 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 3 EP - 9 VL - 20 IS - 1 SN - 0893-133X, 0893-133X KW - Receptors, Drug KW - 0 KW - Index Medicus KW - Pedigree KW - Animals KW - Humans KW - Disease Models, Animal KW - Receptors, Drug -- genetics KW - Genetic Predisposition to Disease KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Molecular+genetics+of+substance+abuse+vulnerability%3A+a+current+approach.&rft.au=Uhl%2C+G+R&rft.aulast=Uhl&rft.aufirst=G&rft.date=1999-01-01&rft.volume=20&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-15 N1 - Date created - 1999-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of neuroendocrine hormones to promote reconstitution after bone marrow transplantation. AN - 69553770; 9876237 AB - A survey of the previous literature and the data shown here indicate that neuroendocrine hormones such as growth hormone and prolactin may be of potential clinical use after bone marrow transplantation (BMT) to promote hematopoietic and immune recovery. The amounts of hormones used in our model do not promote weight gain suggesting that their lymphohematopoietic actions were independent of their anabolic effects. While the hormones may not produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. IL-2 or G-CSF), their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in the post-BMT setting. However, more work needs to be performed to understand the mechanism(s) of their action, particularly with regard to T-cell function and development. JF - Neuroimmunomodulation AU - Woody, M A AU - Welniak, L A AU - Richards, S AU - Taub, D D AU - Tian, Z AU - Sun, R AU - Longo, D L AU - Murphy, W J AD - Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Md. 21702-1201, USA. PY - 1999 SP - 69 EP - 80 VL - 6 IS - 1-2 SN - 1021-7401, 1021-7401 KW - Prolactin KW - 9002-62-4 KW - Growth Hormone KW - 9002-72-6 KW - Index Medicus KW - Animals KW - Immune System -- drug effects KW - Hematopoiesis -- drug effects KW - Humans KW - T-Lymphocytes -- physiology KW - Immune System -- physiology KW - Growth Hormone -- therapeutic use KW - Prolactin -- therapeutic use KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69553770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+neuroendocrine+hormones+to+promote+reconstitution+after+bone+marrow+transplantation.&rft.au=Woody%2C+M+A%3BWelniak%2C+L+A%3BRichards%2C+S%3BTaub%2C+D+D%3BTian%2C+Z%3BSun%2C+R%3BLongo%2C+D+L%3BMurphy%2C+W+J&rft.aulast=Woody&rft.aufirst=M&rft.date=1999-01-01&rft.volume=6&rft.issue=1-2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-11 N1 - Date created - 1999-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the hydrophobic tail of the human immunodeficiency virus type 1 p6(Gag) protein produces a mutant that fails to package its envelope protein. AN - 69553100; 9847302 AB - The p6(Gag) protein of human immunodeficiency virus type 1 (HIV-1) is produced as the carboxyl-terminal sequence within the Gag polyprotein. The amino acid composition of this protein is high in hydrophilic and polar residues except for a patch of relatively hydrophobic amino acids found in the carboxyl-terminal 16 amino acids. Internal cleavage of p6(Gag) between Y36 and P37, apparently by the HIV-1 protease, removes this hydrophobic tail region from approximately 30% of the mature p6(Gag) proteins in HIV-1MN. To investigate the importance of this cleavage and the hydrophobic nature of this portion of p6(Gag), site-directed mutations were made at the minor protease cleavage site and within the hydrophobic tail. The results showed that all of the single-amino-acid-replacement mutants exhibited either reduced or undetectable cleavage at the site yet almost all were nearly as infectious as wild-type virus, demonstrating that processing at this site is not important for viral replication. However, one exception, Y36F, was 300-fold as infectious the wild type. In contrast to the single-substitution mutants, a virus with two substitutions in this region of p6(Gag), Y36S-L41P, could not infect susceptible cells. Protein analysis showed that while the processing of the Gag precursor was normal, the double mutant did not incorporate Env into virus particles. This mutant could be complemented with surface glycoproteins from vesicular stomatitis virus and murine leukemia virus, showing that the inability to incorporate Env was the lethal defect for the Y36S-L41P virus. However, this mutant was not rescued by an HIV-1 Env with a truncated gp41(TM) cytoplasmic domain, showing that it is phenotypically different from the previously described MA mutants that do not incorporate their full-length Env proteins. Cotransfection experiments with Y36S-L41P and wild-type proviral DNAs revealed that the mutant Gag dominantly blocked the incorporation of Env by wild-type Gag. These results show that the Y36S-L41P p6(Gag) mutation dramatically blocks the incorporation of HIV-1 Env, presumably acting late in assembly and early during budding. JF - Journal of virology AU - Ott, D E AU - Chertova, E N AU - Busch, L K AU - Coren, L V AU - Gagliardi, T D AU - Johnson, D G AD - AIDS Vaccine Program, SAIC/Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. ott@avpvx1.ncifcrf.gov Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 19 EP - 28 VL - 73 IS - 1 SN - 0022-538X, 0022-538X KW - Gene Products, env KW - 0 KW - Gene Products, gag KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Mutagenesis, Site-Directed KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Virus Assembly KW - Gene Products, env -- chemistry KW - Gene Products, env -- physiology KW - Gene Products, gag -- physiology KW - Gene Products, gag -- chemistry KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69553100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+the+hydrophobic+tail+of+the+human+immunodeficiency+virus+type+1+p6%28Gag%29+protein+produces+a+mutant+that+fails+to+package+its+envelope+protein.&rft.au=Ott%2C+D+E%3BChertova%2C+E+N%3BBusch%2C+L+K%3BCoren%2C+L+V%3BGagliardi%2C+T+D%3BJohnson%2C+D+G&rft.aulast=Ott&rft.aufirst=D&rft.date=1999-01-01&rft.volume=73&rft.issue=1&rft.spage=19&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1991 Jan;65(1):162-9 [1845882] Biotechniques. 1990 May;8(5):528-35 [2357375] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9 [2014240] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4528-32 [2034693] J Biol Chem. 1991 Aug 5;266(22):14554-61 [1860861] J Virol. 1992 Apr;66(4):1856-65 [1548743] J Virol. 1992 Apr;66(4):2232-9 [1548759] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Oct;66(10):6107-16 [1326661] J Virol. 1992 Nov;66(11):6304-13 [1383561] J Virol. 1995 Jun;69(6):3824-30 [7745730] J Virol. 1995 Sep;69(9):5455-60 [7636991] J Virol. 1995 Oct;69(10):6106-14 [7666514] J Virol. 1995 Nov;69(11):6873-9 [7474102] J Virol. 1996 Jan;70(1):159-64 [8523520] J Virol. 1996 Jan;70(1):341-51 [8523546] Nature. 1995 Dec 14;378(6558):743-7 [7501025] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Biol Chem. 1996 Mar 1;271(9):4709-17 [8617736] Nature. 1996 Jun 27;381(6585):744-5 [8657277] Curr Top Microbiol Immunol. 1996;214:65-94 [8791725] EMBO J. 1996 Nov 1;15(21):5783-8 [8918455] J Virol. 1997 Apr;71(4):3341-5 [9060707] J Virol. 1997 Aug;71(8):5871-7 [9223476] J Virol. 1997 Sep;71(9):6541-6 [9261374] Virology. 1998 Feb 15;241(2):224-33 [9499797] J Virol. 1998 Apr;72(4):2832-45 [9525603] J Biol Chem. 1998 Mar 27;273(13):7177-80 [9516405] J Virol. 1998 Jun;72(6):4667-77 [9573230] Biochim Biophys Acta. 1993 Sep 8;1182(2):157-61 [8357847] Annu Rev Biochem. 1993;62:543-85 [8352596] J Virol. 1995 Nov;69(11):6810-8 [7474093] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8033-7 [8396259] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Aug;68(8):4857-61 [8035484] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Oct;68(10):6782-6 [8084015] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 May;69(5):2759-64 [7707498] AIDS Res Hum Retroviruses. 1995 Jan;11(1):55-64 [7734197] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] J Gen Virol. 1982 Nov;63 (Pt 1):15-24 [6757385] J Virol. 1987 Jan;61(1):209-13 [3640832] J Virol. 1987 Apr;61(4):1116-24 [3029406] Cell. 1987 Jun 5;49(5):659-68 [3107838] EMBO J. 1988 Feb;7(2):513-8 [3259178] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90 [3290901] Biochem Biophys Res Commun. 1988 Oct 14;156(1):297-303 [3052448] Cell. 1989 Oct 6;59(1):113-20 [2676192] Science. 1990 Feb 16;247(4944):848-52 [2305256] J Gen Virol. 1990 Apr;71 ( Pt 4):767-73 [2157795] J Virol. 1990 May;64(5):2298-308 [1691314] J Virol. 1990 Jul;64(7):3207-11 [2191147] Biochemistry. 1991 Feb 12;30(6):1600-9 [1993177] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antioxidant effects of nitric oxide. AN - 69550849; 9919590 JF - Methods in enzymology AU - Wink, D A AU - Vodovotz, Y AU - Grisham, M B AU - DeGraff, W AU - Cook, J C AU - Pacelli, R AU - Krishna, M AU - Mitchell, J B AD - Tumor Biology Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 413 EP - 424 VL - 301 SN - 0076-6879, 0076-6879 KW - Antioxidants KW - 0 KW - Free Radicals KW - Oxidants KW - Reactive Oxygen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Humans KW - Oxidative Stress KW - Oxidants -- metabolism KW - Antioxidants -- metabolism KW - Nitric Oxide -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69550849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=Antioxidant+effects+of+nitric+oxide.&rft.au=Wink%2C+D+A%3BVodovotz%2C+Y%3BGrisham%2C+M+B%3BDeGraff%2C+W%3BCook%2C+J+C%3BPacelli%2C+R%3BKrishna%2C+M%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1999-01-01&rft.volume=301&rft.issue=&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&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 - Fiber-type-specific transcription of the troponin I slow gene is regulated by multiple elements. AN - 69548926; 9858575 AB - The regulatory elements that restrict transcription of genes encoding contractile proteins specifically to either slow- or fast-twitch skeletal muscles are unknown. As an initial step towards understanding the mechanisms that generate muscle diversity during development, we have identified a 128-bp troponin I slow upstream element (SURE) and a 144-bp troponin I fast intronic element (FIRE) that confer fiber type specificity in transgenic mice (M. Nakayama et al., Mol. Cell. Biol. 16:2408-2417, 1996). SURE and FIRE have maintained the spatial organization of four conserved motifs (3' to 5'): an E box, an AT-rich site (A/T2) that binds MEF-2, a CACC site, and a novel CAGG motif. Troponin I slow (TnIs) constructs harboring mutations in these motifs were analyzed in transiently and stably transfected Sol8 myocytes and in transgenic mice to assess their function. Mutations of the E-box, A/T2, and CAGG motifs completely abolish transcription from the TnI SURE. In contrast, mutation of the CACC motif had no significant effect in transfected myocytes or on the slow-specific transcription of the TnI SURE in transgenic mice. To assess the role of E boxes in fiber type specificity, a chimeric enhancer was constructed in which the E box of SURE was replaced with the E box from FIRE. This TnI E box chimera, which lacks the SURE NFAT site, confers essentially the same levels of transcription in transgenic mice as those conferred by wild-type SURE and is specifically expressed in slow-twitch muscles, indicating that the E box on its own cannot determine the fiber-type-specific expression of the TnI promoter. The importance of the 5' half of SURE, which bears little homology to the TnI FIRE, in muscle-specific expression was analyzed by deletion and linker scanning analyses. Removal of the 5' half of SURE (-846 to -811) results in the loss of expression in stably transfected but not in transiently expressing myocytes. Linker scanning mutations identified sequences in this region that are necessary for the function of SURE when integrated into chromatin. One of these sites (GTTAATCCG), which is highly homologous to a bicoid consensus site, binds to nuclear proteins from several mesodermal cells. These results show that multiple elements are involved in the muscle-specific activity of the TnIs promoter and that interactions between upstream and downstream regions of SURE are important for transcription in the context of native chromatin. JF - Molecular and cellular biology AU - Calvo, S AU - Venepally, P AU - Cheng, J AU - Buonanno, A AD - Unit on Molecular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 515 EP - 525 VL - 19 IS - 1 SN - 0270-7306, 0270-7306 KW - Troponin I KW - 0 KW - Index Medicus KW - Animals KW - Conserved Sequence KW - Transfection KW - Genes, Reporter KW - Mice KW - Gene Expression Regulation KW - Mice, Transgenic KW - Structure-Activity Relationship KW - Mutagenesis KW - Muscle Fibers, Skeletal KW - Transcription, Genetic KW - Troponin I -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69548926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+replication-deficient+vaccinia+virus%2FT7+RNA+polymerase+hybrid+expression%3A+effect+of+T7+RNA+polymerase+levels+and+alpha-amanitin.&rft.au=Engleka%2C+K+A%3BLewis%2C+E+W%3BHoward%2C+B+H&rft.aulast=Engleka&rft.aufirst=K&rft.date=1998-04-10&rft.volume=243&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1991 Feb 15;251(4995):761-6 [1846704] Nucleic Acids Res. 1990 Dec 25;18(24):7433-8 [2259632] J Biol Chem. 1991 Oct 15;266(29):19659-65 [1918073] Science. 1991 Nov 29;254(5036):1385-7 [1683715] Genes Dev. 1991 Dec;5(12A):2327-41 [1748287] Nature. 1990 Aug 16;346(6285):663-5 [2385294] Mol Cell Biol. 1989 Apr;9(4):1397-405 [2725509] Mol Cell Biol. 1991 Jan;11(1):267-80 [1846022] Science. 1992 Mar 20;255(5051):1581-4 [1549784] Genes Dev. 1989 May;3(5):628-40 [2473006] Mol Cell Biol. 1989 Nov;9(11):5022-33 [2601707] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1089-93 [2300571] Genes Dev. 1989 Dec;3(12B):2050-61 [2560751] Nature. 1990 Aug 2;346(6283):485-8 [1974036] Trends Genet. 1992 Apr;8(4):144-8 [1321521] Mol Cell Biol. 1992 Sep;12(9):3665-77 [1324403] Genes Dev. 1992 Sep;6(9):1783-98 [1516833] Nucleic Acids Res. 1992 Oct 11;20(19):5105-13 [1329039] Curr Opin Genet Dev. 1993 Apr;3(2):265-74 [8389217] Mol Cell Biol. 1993 Oct;13(10):6469-78 [8413246] Mol Cell Biol. 1993 Nov;13(11):7019-28 [8413291] Development. 1993 Aug;118(4):1137-47 [8269844] Mol Cell Biol. 1994 Mar;14(3):1870-85 [8114720] Dev Dyn. 1993 Nov;198(3):214-24 [8136525] J Biol Chem. 1994 Apr 8;269(14):10651-9 [8144655] Mol Cell Biol. 1994 Jul;14(7):4596-605 [8007964] Mol Cell Biol. 1994 Dec;14(12):7758-69 [7969117] Mol Cell Biol. 1995 Apr;15(4):1870-8 [7891680] Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6185-9 [7597099] J Biol Chem. 1995 Sep 8;270(36):21420-7 [7673178] Mol Cell Biol. 1995 Nov;15(11):6169-77 [7565769] J Mol Biol. 1995 Oct 13;253(1):17-31 [7473711] Mol Cell Biol. 1996 Jan;16(1):76-85 [8524331] Physiol Rev. 1996 Apr;76(2):371-423 [8618961] Development. 1996 Apr;122(4):1195-206 [8620846] Genes Dev. 1996 May 15;10(10):1284-95 [8675014] Mol Cell Biol. 1996 Jul;16(7):3909-22 [8668209] Mol Cell Biol. 1996 Sep;16(9):5058-68 [8756664] Dev Genet. 1996;19(2):95-107 [8900042] Dev Genet. 1996;19(2):169-81 [8900050] Mol Cell Biol. 1997 Feb;17(2):656-66 [9001219] Genes Dev. 1997 Feb 15;11(4):436-50 [9042858] Mech Dev. 1997 Jan;61(1-2):151-63 [9076685] Development. 1997 Jul;124(14):2807-17 [9226452] J Biol Chem. 1998 Jun 12;273(24):15217-26 [9614136] Genes Dev. 1998 Aug 15;12(16):2499-509 [9716403] Mol Cell Biol. 1996 May;16(5):2408-17 [8628309] Virology. 1973 Apr;52(2):456-67 [4705382] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Methods Enzymol. 1983;101:582-98 [6888276] Mol Cell Biol. 1985 Feb;5(2):410-3 [2983194] Annu Rev Biophys Biophys Chem. 1987;16:535-59 [2954560] Mol Cell Biol. 1987 Sep;7(9):3065-75 [3670306] Cell. 1987 Dec 24;51(6):987-1000 [3690668] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5728-32 [2456580] Cell. 1989 Feb 24;56(4):607-17 [2537150] Mol Cell Biol. 1988 Dec;8(12):5072-9 [3244349] EMBO J. 1989 Mar;8(3):701-9 [2721498] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5847-51 [2062862] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transdifferentiation of NRP-152 rat prostatic basal epithelial cells toward a luminal phenotype: regulation by glucocorticoid, insulin-like growth factor-I and transforming growth factor-beta. AN - 69548689; 9858470 AB - The role of basal epithelial cells in prostatic function, development and carcinogenesis is unknown. The ability of basal prostatic epithelial cells to acquire a luminal phenotype was explored in vitro using the NRP-152 rat dorsal-lateral prostate epithelial cell line as a model system. NRP-152, which was spontaneously immortalized and clonally derived, is an androgen-responsive and nontumorigenic cell line that has a basal cell phenotype under normal growth conditions. However, when placed in mitogen-deficient media, these cells undergo a dramatic morphological change to a luminal phenotype. Under these growth-restrictive conditions, immunocytochemical analysis shows that NRP-152 cells acquire the luminal markers Z0-1 (a tight-junction associated protein), occludin (integral tight-junction protein), and cytokeratin 18, and lose the basal markers cytokeratins 5 and 14. Total protein and mRNA levels of cytokeratins 8, 18, c-CAM 105 (the calcium-independent cell adhesion molecule) and Z0-1, as detected by western and/or northern blot analyses, respectively, are induced, while cytokeratin 5 and 15 are lost, and occludin is unchanged. Concomitant with this differentiation, expression of transforming growth factor-beta2 (TGF-beta2), TGF-beta3, and TGF-beta receptor type II (TbetaRII) is induced, while those of TGF-beta1 and TbetaRI remain essentially unchanged. Mitogens, such as insulin-like growth factor-I and dexamethasone inhibit luminal differentiation, while exogenous TGF-beta induces such differentiation. These data together with TGF-beta neutralization experiments using pan-specific antibody implicate an important role for autocrine TGF-beta in the induction of the luminal differentiation. JF - Journal of cell science AU - Danielpour, D AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 169 EP - 179 VL - 112 ( Pt 2) SN - 0021-9533, 0021-9533 KW - Biomarkers KW - 0 KW - Glucocorticoids KW - Transforming Growth Factor beta KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Glucocorticoids -- metabolism KW - Dexamethasone -- pharmacology KW - Insulin-Like Growth Factor I -- metabolism KW - Insulin-Like Growth Factor I -- pharmacology KW - Rats KW - Phenotype KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Apoptosis -- drug effects KW - Cell Differentiation -- drug effects KW - Transforming Growth Factor beta -- metabolism KW - Immunohistochemistry KW - Male KW - Cell Line KW - Prostate -- drug effects KW - Prostate -- metabolism KW - Prostate -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69548689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transdifferentiation+of+NRP-152+rat+prostatic+basal+epithelial+cells+toward+a+luminal+phenotype%3A+regulation+by+glucocorticoid%2C+insulin-like+growth+factor-I+and+transforming+growth+factor-beta.&rft.au=Danielpour%2C+D&rft.aulast=Danielpour&rft.aufirst=D&rft.date=1999-01-01&rft.volume=112+%28+Pt+2%29&rft.issue=&rft.spage=169&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 - 1999-03-15 N1 - Date created - 1999-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of site-directed mutagenesis of Escherichia coli heat-labile enterotoxin on ADP-ribosyltransferase activity and interaction with ADP-ribosylation factors. AN - 69546258; 9864224 AB - Escherichia coli heat-labile enterotoxin (LT), an oligomeric protein with one A subunit (LTA) and five B subunits, exerts its effects via the ADP-ribosylation of Gsalpha, a guanine nucleotide-binding (G) protein that activates adenylyl cyclase. LTA also ADP-ribosylates simple guanidino compounds (e.g., arginine) and catalyzes its own auto-ADP-ribosylation. All LTA-catalyzed reactions are enhanced by ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins. Replacement of arginine-7 (R7K), valine-53 (V53D), serine-63 (S63K), valine 97 (V97K), or tyrosine-104 (Y104K) in LTA resulted in fully assembled but nontoxic proteins. S63K, V53D, and R7K are catalytic-site mutations, whereas V97K and Y104K are amino acid replacements adjacent to and outside of the catalytic site, respectively. The effects of mutagenesis were quantified by measuring ADP-ribosyltransferase activity (i.e., auto-ADP-ribosylation and ADP-ribosylagmatine synthesis) and interaction with ARF (i.e., inhibition of ARF-stimulated cholera toxin ADP-ribosyltransferase activity and effects of ARF on mutant auto-ADP-ribosylation). All mutants were inactive in the ADP-ribosyltransferase assay; however, auto-ADP-ribosylation in the presence of recombinant human ARF6 was detected, albeit much less than that of native LT (Y104K > V53D > V97K > R7K, S63K). Based on the lack of inhibition by free ADP-ribose, the observed auto-ADP-ribosylation activity was enzymatic and not due to the nonenzymatic addition of free ADP-ribose. V53D, S63K, and R7K were more effective than Y104K or V97K in blocking ARF stimulation of cholera toxin ADP-ribosyltransferase. Based on these data, it appears that ARF-binding and catalytic sites are not identical and that a region outside the NAD cleft may participate in the LTA-ARF interaction. JF - Infection and immunity AU - Stevens, L A AU - Moss, J AU - Vaughan, M AU - Pizza, M AU - Rappuoli, R AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 259 EP - 265 VL - 67 IS - 1 SN - 0019-9567, 0019-9567 KW - Bacterial Toxins KW - 0 KW - Enterotoxins KW - Escherichia coli Proteins KW - heat-labile enterotoxin, E coli KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Tyrosine KW - 42HK56048U KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Valine KW - HG18B9YRS7 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Humans KW - Tyrosine -- genetics KW - Valine -- genetics KW - Binding Sites -- genetics KW - Lysine -- genetics KW - Enzyme Activation -- genetics KW - Catalysis KW - Mutagenesis, Site-Directed KW - Bacterial Toxins -- genetics KW - Bacterial Toxins -- metabolism KW - Enterotoxins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Escherichia coli -- genetics KW - Enterotoxins -- genetics KW - Adenosine Diphosphate Ribose -- metabolism KW - Poly(ADP-ribose) Polymerases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69546258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+site-directed+mutagenesis+of+Escherichia+coli+heat-labile+enterotoxin+on+ADP-ribosyltransferase+activity+and+interaction+with+ADP-ribosylation+factors.&rft.au=Stevens%2C+L+A%3BMoss%2C+J%3BVaughan%2C+M%3BPizza%2C+M%3BRappuoli%2C+R&rft.aulast=Stevens&rft.aufirst=L&rft.date=1999-01-01&rft.volume=67&rft.issue=1&rft.spage=259&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1988 Feb 5;263(4):1768-72 [3123477] J Biol Chem. 1987 Jun 25;262(18):8707-11 [2885323] Biochem Biophys Res Commun. 1988 May 16;152(3):957-61 [3132159] Infect Immun. 1989 Nov;57(11):3549-54 [2807535] Biochim Biophys Acta. 1990 May 16;1034(2):195-9 [2112955] J Biol Chem. 1990 Dec 25;265(36):22520-5 [2266142] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] J Clin Invest. 1991 May;87(5):1780-6 [1902492] Nature. 1991 May 30;351(6325):371-7 [2034287] Infect Immun. 1991 Sep;59(9):2870-9 [1908825] J Biol Chem. 1992 Sep 5;267(25):17766-72 [1517219] J Biol Chem. 1993 Mar 25;268(9):6383-7 [8454609] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6238-41 [8327504] J Biol Chem. 1993 Aug 25;268(24):17878-82 [8349672] J Biol Chem. 1993 Nov 5;268(31):23215-8 [8226842] FEBS Lett. 1994 Jan 3;337(1):88-92 [8276119] J Exp Med. 1994 Dec 1;180(6):2147-53 [7964489] Nature. 1994 Nov 3;372(6501):55-63 [7969419] Mol Microbiol. 1994 Oct;14(1):51-60 [7830560] Protein Sci. 1997 Dec;6(12):2650-4 [9416617] Mol Microbiol. 1994 Oct;14(1):41-50 [7830559] Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1644-8 [7878032] J Biol Chem. 1995 May 26;270(21):12327-30 [7759471] Infect Immun. 1995 Jun;63(6):2356-60 [7768621] Nat Struct Biol. 1995 Apr;2(4):269-72 [7796260] Biochemistry. 1995 Sep 5;34(35):10996-1004 [7669757] Infect Immun. 1996 Dec;64(12):5434-8 [8945604] Infect Immun. 1997 Jan;65(1):331-4 [8975934] Curr Opin Cell Biol. 1997 Aug;9(4):484-7 [9261053] J Biol Chem. 1979 Jul 10;254(13):5855-61 [221485] J Infect Dis. 1979 Jun;139(6):674-80 [448194] J Biol Chem. 1981 Dec 25;256(24):12861-5 [6273411] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] Proc Natl Acad Sci U S A. 1984 Jun;81(11):3307-11 [6145155] Adv Enzymol Relat Areas Mol Biol. 1988;61:303-79 [3128060] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of constitutive and ras-inducible phosphorylation sites of KSR: implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression. AN - 69545386; 9858547 AB - Genetic and biochemical studies have identified kinase suppressor of Ras (KSR) to be a conserved component of Ras-dependent signaling pathways. To better understand the role of KSR in signal transduction, we have initiated studies investigating the effect of phosphorylation and protein interactions on KSR function. Here, we report the identification of five in vivo phosphorylation sites of KSR. In serum-starved cells, KSR contains two constitutive sites of phosphorylation (Ser297 and Ser392), which mediate the binding of KSR to the 14-3-3 family of proteins. In the presence of activated Ras, KSR contains three additional sites of phosphorylation (Thr260, Thr274, and Ser443), all of which match the consensus motif (Px[S/T]P) for phosphorylation by mitogen-activated protein kinase (MAPK). Further, we find that treatment of cells with the MEK inhibitor PD98059 blocks phosphorylation of the Ras-inducible sites and that activated MAPK associates with KSR in a Ras-dependent manner. Together, these findings indicate that KSR is an in vivo substrate of MAPK. Mutation of the identified phosphorylation sites did not alter the ability of KSR to facilitate Ras signaling in Xenopus oocytes, suggesting that phosphorylation at these sites may serve other functional roles, such as regulating catalytic activity. Interestingly, during the course of this study, we found that the biological effect of KSR varied dramatically with the level of KSR protein expressed. In Xenopus oocytes, KSR functioned as a positive regulator of Ras signaling when expressed at low levels, whereas at high levels of expression, KSR blocked Ras-dependent signal transduction. Likewise, overexpression of Drosophila KSR blocked R7 photoreceptor formation in the Drosophila eye. Therefore, the biological function of KSR as a positive effector of Ras-dependent signaling appears to be dependent on maintaining KSR protein expression at low or near-physiological levels. JF - Molecular and cellular biology AU - Cacace, A M AU - Michaud, N R AU - Therrien, M AU - Mathes, K AU - Copeland, T AU - Rubin, G M AU - Morrison, D K AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 229 EP - 240 VL - 19 IS - 1 SN - 0270-7306, 0270-7306 KW - 14-3-3 Proteins KW - 0 KW - Proteins KW - Serine KW - 452VLY9402 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Protein Kinases KW - EC 2.7.- KW - KSR-1 protein kinase KW - EC 2.7.1.- KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Mice KW - Rabbits KW - Protein Binding KW - Binding Sites KW - Phosphorylation KW - Drosophila melanogaster KW - Cell Line, Transformed KW - Mutation KW - Cell Line KW - Protein Kinases -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Kinases -- genetics KW - ras Proteins -- metabolism KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69545386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+constitutive+and+ras-inducible+phosphorylation+sites+of+KSR%3A+implications+for+14-3-3+binding%2C+mitogen-activated+protein+kinase+binding%2C+and+KSR+overexpression.&rft.au=Cacace%2C+A+M%3BMichaud%2C+N+R%3BTherrien%2C+M%3BMathes%2C+K%3BCopeland%2C+T%3BRubin%2C+G+M%3BMorrison%2C+D+K&rft.aulast=Cacace&rft.aufirst=A&rft.date=1999-01-01&rft.volume=19&rft.issue=1&rft.spage=229&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 - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1994 Apr 1;13(7):1610-9 [8157000] Cell. 1995 Dec 15;83(6):889-901 [8521513] Curr Opin Genet Dev. 1994 Feb;4(1):71-6 [8193543] Curr Opin Genet Dev. 1994 Feb;4(1):82-9 [8193545] J Biol Chem. 1994 Jul 22;269(29):19067-73 [8034665] Cell. 1995 Dec 15;83(6):879-88 [8521512] Nature. 1993 May 13;363(6425):133-40 [8483497] Cell. 1995 Dec 15;83(6):903-13 [8521514] Cell. 1996 Mar 22;84(6):889-97 [8601312] Genetics. 1996 May;143(1):315-29 [8722784] Curr Opin Cell Biol. 1996 Apr;8(2):197-204 [8791426] Curr Opin Cell Biol. 1996 Apr;8(2):231-8 [8791421] Cell. 1996 Nov 15;87(4):619-28 [8929531] Curr Opin Cell Biol. 1996 Dec;8(6):795-804 [8939679] Genes Dev. 1996 Nov 1;10(21):2684-95 [8946910] Curr Opin Cell Biol. 1997 Apr;9(2):174-9 [9069260] Curr Biol. 1997 May 1;7(5):294-300 [9115393] Science. 1997 Jun 13;276(5319):1702-5 [9180081] Science. 1997 Sep 5;277(5331):1501-5 [9278512] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] Mol Cell Biol. 1993 Nov;13(11):7170-9 [7692235] Genes Dev. 1994 Feb 1;8(3):313-27 [8314085] Nature. 1994 Feb 24;367(6465):686 [8107861] Cell. 1994 Aug 12;78(3):499-512 [8062390] Cell. 1995 Jan 27;80(2):179-85 [7834738] Cell. 1995 Jan 27;80(2):187-97 [7834739] Curr Opin Genet Dev. 1995 Feb;5(1):44-50 [7749324] Nature. 1995 Jul 13;376(6536):188-91 [7603573] Nature. 1995 Jul 13;376(6536):191-4 [7603574] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12792-6 [9371754] Science. 1997 Dec 19;278(5346):2075-80 [9405336] Curr Biol. 1998 Jan 1;8(1):46-55 [9427625] Curr Biol. 1998 Jan 1;8(1):56-64 [9427629] J Biol Chem. 1998 Mar 27;273(13):7743-8 [9516483] Dev Biol. 1987 Sep;123(1):264-75 [17985474] Cell. 1978 Jul;14(3):725-31 [210957] Science. 1982 Oct 22;218(4570):341-7 [6289435] Annu Rev Biochem. 1987;56:779-827 [3304147] Cell. 1989 Jan 13;56(1):5-8 [2535967] J Biol Chem. 1991 Aug 15;266(23):15180-4 [1907971] J Biol Chem. 1991 Aug 15;266(23):15277-85 [1651323] Cell. 1991 Nov 15;67(4):701-16 [1934068] J Biol Chem. 1991 Nov 25;266(33):22159-63 [1939237] Methods Enzymol. 1991;200:3-37 [1835513] Nature. 1992 Mar 26;356(6367):340-4 [1372395] Nature. 1992 Dec 10;360(6404):600-3 [1461284] Trends Genet. 1994 Feb;10(2):44-8 [8191584] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review). AN - 69536000; 9863015 AB - A brief summary of recent research, primarily from the authors' laboratory, on polycyclic aromatic hydrocarbon carcinogens with respect to their DNA adduct formation, the mutational properties of these adducts and the effects of hydrocarbon dihydrodiol epoxide metabolites on the passage of cells through the cell cycle is presented. The concept of stealth properties of potent carcinogens, i.e. their ability to damage DNA without inducing a G1 arrest, is discussed. Also, mutation studies with dihydrodiol epoxide metabolites, the sequence-dependence of site-specific mutation, as well as the selectivity of hydrocarbon-DNA adduct formation are summarized. JF - International journal of oncology AU - Dipple, A AU - Khan, Q A AU - Page, J E AU - Pontén, I AU - Szeliga, J AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 103 EP - 111 VL - 14 IS - 1 SN - 1019-6439, 1019-6439 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Epoxy Compounds KW - Mutagens KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Animals KW - Humans KW - Epoxy Compounds -- toxicity KW - Cell Cycle -- drug effects KW - Polycyclic Aromatic Hydrocarbons -- toxicity KW - Carcinogens -- metabolism KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Polycyclic Aromatic Hydrocarbons -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69536000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=DNA+reactions%2C+mutagenic+action+and+stealth+properties+of+polycyclic+aromatic+hydrocarbon+carcinogens+%28review%29.&rft.au=Dipple%2C+A%3BKhan%2C+Q+A%3BPage%2C+J+E%3BPont%C3%A9n%2C+I%3BSzeliga%2C+J&rft.aulast=Dipple&rft.aufirst=A&rft.date=1999-01-01&rft.volume=14&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral and cognitive effects of smoking: relationship to nicotine addiction. AN - 69517243; 11768172 AB - Nicotine addiction is an extremely complex process that involves biological, psychological, behavioral, and cultural factors. Three factors that influence smoking and that are influenced by smoking are performance, stress, and body weight. We know that if nicotine-addicted smokers are deprived of nicotine, attentional and cognitive abilities can be impaired, and such deficits can be reversed if the person smokes or is given nicotine. In nonsmokers and nondeprived smokers, nicotine enhances finger tapping, focused and sustained attention, recognition memory, and reasoning. Stress results in increased smoking, but there is little empirical evidence that smoking reduces stress. Stress reduction from smoking is likely the relief of withdrawal-induced negative mood that is experienced between cigarettes. Smokers weigh on average 3-4 kg less than nonsmokers, and the weight-gain seen after quitting smoking also averages 3-4 kg. Changes in eating and energy expenditure are responsible for the body weight changes seen during smoking cessation and relapse. We need to know the full range of conditions under which nicotine affects behavior. The mechanisms by which stress functions to maintain nicotine addiction are not well understood. We do not know what interventions are effective in addressing the stress experienced during smoking cessation. Because no effective interventions have been developed to prevent weight-gain after quitting, research should focus on the concern or perception of weight-gain. We need to understand how and why body weight concerns vary across gender, age, and ethnicity because of the implications for designing effective smoking-cessation programs. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Heishman, S J AD - Clinical Pharmacology & Therapeutics Branch, National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland 21224, USA. sheish@intra.nida.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - S143 EP - 7; discussion S165-6 VL - 1 Suppl 2 SN - 1462-2203, 1462-2203 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Cognition -- drug effects KW - Humans KW - Attention -- drug effects KW - Tobacco Use Disorder -- metabolism KW - Psychomotor Performance -- drug effects KW - Nicotine -- pharmacology KW - Body Weight -- drug effects KW - Smoking -- metabolism KW - Tobacco Use Disorder -- psychology KW - Smoking -- psychology KW - Stress, Psychological -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69517243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Behavioral+and+cognitive+effects+of+smoking%3A+relationship+to+nicotine+addiction.&rft.au=Heishman%2C+S+J&rft.aulast=Heishman&rft.aufirst=S&rft.date=1999-01-01&rft.volume=1+Suppl+2&rft.issue=&rft.spage=S143&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-05-22 N1 - Date created - 2001-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic factors regulating experimental arthritis in mice and rats. AN - 69506217; 11791440 JF - Current directions in autoimmunity AU - Wilder, R L AU - Remmers, E F AU - Kawahito, Y AU - Gulko, P S AU - Cannon, G W AU - Griffiths, M M AD - Inflammatory Joint Diseases Section, Arthritis Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md., USA. wilderr@arb.niams.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 121 EP - 165 VL - 1 SN - 1422-2132, 1422-2132 KW - Diamines KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Freund's Adjuvant KW - 9007-81-2 KW - avridine KW - P9J7O7YNSW KW - Index Medicus KW - Rats KW - Freund's Adjuvant -- adverse effects KW - Animals KW - Diamines -- adverse effects KW - Mice KW - Genetic Predisposition to Disease KW - Species Specificity KW - Terpenes -- adverse effects KW - Arthritis, Experimental -- genetics KW - Arthritis, Rheumatoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69506217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+directions+in+autoimmunity&rft.atitle=Genetic+factors+regulating+experimental+arthritis+in+mice+and+rats.&rft.au=Wilder%2C+R+L%3BRemmers%2C+E+F%3BKawahito%2C+Y%3BGulko%2C+P+S%3BCannon%2C+G+W%3BGriffiths%2C+M+M&rft.aulast=Wilder&rft.aufirst=R&rft.date=1999-01-01&rft.volume=1&rft.issue=&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Current+directions+in+autoimmunity&rft.issn=14222132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2002-01-31 N1 - Date created - 2002-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcoholism treatment in the United States. An overview. AN - 69489597; 10890799 AB - On any given day, more than 700,000 people in the United States receive alcoholism treatment in either inpatient or outpatient settings. For many of those patients, detoxification--with or without pharmacotherapy--is the first step of treatment. The major behavioral approaches currently used in alcoholism treatment include cognitive-behavioral therapy, motivational enhancement therapy, and Alcoholics Anonymous (AA) or related 12-step programs. Clinical studies, such as the Project MATCH trial, have compared the effectiveness of these approaches. Overall, that study detected no significant differences among the three treatments in patient outcome, although certain treatment methodologies may be most appropriate for patients with certain characteristics. Pharmacotherapy with aversive or anticraving medications may supplement behavioral treatment approaches. Brief interventions that are delivered by primary health care providers also have been shown to reduce drinking levels, particularly in nondependent drinkers. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Fuller, R K AU - Hiller-Sturmhöfel, S AD - Division of Clinical and Prevention Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 69 EP - 77 VL - 23 IS - 2 SN - 1535-7414, 1535-7414 KW - Alcohol Deterrents KW - 0 KW - Narcotic Antagonists KW - Naltrexone KW - 5S6W795CQM KW - Index Medicus KW - Narcotic Antagonists -- therapeutic use KW - Humans KW - Treatment Outcome KW - United States -- epidemiology KW - Alcohol Deterrents -- therapeutic use KW - Naltrexone -- therapeutic use KW - Alcoholism -- epidemiology KW - Cognitive Therapy KW - Alcoholism -- therapy KW - Alcoholics Anonymous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69489597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Alcoholism+treatment+in+the+United+States.+An+overview.&rft.au=Fuller%2C+R+K%3BHiller-Sturmh%C3%B6fel%2C+S&rft.aulast=Fuller&rft.aufirst=R&rft.date=1999-01-01&rft.volume=23&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-14 N1 - Date created - 2000-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional imaging of craving. AN - 69488575; 10890814 AB - To visualize brain activity associated with mental states, such as craving for alcohol and other drugs (AODs), researchers have begun to use functional imaging techniques. Three commonly used techniques are single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Studies using these three approaches have been reviewed in order to evaluate the validity of a proposed model of the brain regions involved in alcoholism and the craving for alcohol. This model suggests a central role for a connected group of brain regions that include the basal ganglia, thalamus, and orbital cortex. A study using SPECT technology in alcoholics, however, found altered brain activity in only some of those regions during craving. Additional studies in alcoholics, as well as cocaine users, identified several other brain regions whose activities appeared to change in response to craving. These studies have led to the development of a revised model of brain regions involved in craving for AODs. Numerous questions remain, however, that must be answered before the brain areas involved in craving can be identified conclusively. JF - Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism AU - Hommer, D W AD - Section of Brain Electrophysiology and Imaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 187 EP - 196 VL - 23 IS - 3 SN - 1535-7414, 1535-7414 KW - Index Medicus KW - Animals KW - Tomography, Emission-Computed, Single-Photon -- methods KW - Magnetic Resonance Imaging -- methods KW - Humans KW - Tomography, Emission-Computed -- methods KW - Brain Mapping KW - Cocaine-Related Disorders -- physiopathology KW - Behavior, Addictive -- physiopathology KW - Alcoholism -- physiopathology KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69488575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.atitle=Functional+imaging+of+craving.&rft.au=Hommer%2C+D+W&rft.aulast=Hommer&rft.aufirst=D&rft.date=1999-01-01&rft.volume=23&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Alcohol+research+%26+health+%3A+the+journal+of+the+National+Institute+on+Alcohol+Abuse+and+Alcoholism&rft.issn=15357414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-10 N1 - Date created - 2000-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Roles for insulin-like growth factor-1 in mediating the anti-carcinogenic effects of caloric restriction. AN - 69485222; 10885804 AB - This paper focuses on the role of insulin-like growth factor-1 (IGF-1) and its associated regulatory apparatus as a key endocrine, autocrine, and paracrine signalling system involved in mediating the anti-carcinogenic activity of dietary restriction. Literature is reviewed showing that the inhibitory action of dietary restriction on carcinogenesis is global and pervasive--it is effective in several laboratory species, for a variety of tumor types, and for both spontaneous tumors and tumors caused by different types of tumor-inducing agents. Evidence is presented showing the IGF-1 pathway responds appropriately to nutritional interventions including diet restriction. Recent evidence points to an obligatory role for the IGF-1 receptor in the establishment and maintenance of the transformed phenotype and reveals that IGF-1 in concert with insulin-like binding protein 3 and p53 is involved in autocrine/paracrine growth signaling pathways as adaptive responses to environmental stimuli. Considered together these works show that the IGF-1 pathway is uniquely poised to influence cellular transformation leading to the malignant phenotype by modulating the balance of cellular proliferation and cell death (apoptosis) in precancerous and cancerous cells and by influencing metastasis of nascent tumors. We evaluated these hypotheses directly using animal models of mononuclear cell leukemia, bladder transitional cell carcinogenesis, and breast cancer. Our studies demonstrate that manipulation of IGF-1 level through dietary intervention influences tumor growth and metastasis. Upregulation of this pathway demonstrated that increased IGF-1 stimulates tumor proliferation, progression and metastasis. Conversely, downregulation of this pathway in vivo as a consequence of dietary restriction results in antitumorigenic activity. We found that the functional disruption of IGF-1R markedly influences breast cancer metastasis in nude mice by suppressing cellular adhesion, invasion, and metastasis of breast cancer cells to the lung, lymph nodes, and lymph vessels. Epidemiological observations and clinical oncology results support the involvement of IGF-1 in carcinogenesis and anticarcinogenesis. This leads to the hypothesis that factors such as IGF-1 which regulate body size and composition may be related to human cancer incidence or prognosis. Additional understanding of this pathway and its interactions with other signaling pathways will advance our ability to develop new interventions towards decreased cancer risk in humans. JF - The journal of nutrition, health & aging AU - Kari, F W AU - Dunn, S E AU - French, J E AU - Barrett, J C AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 92 EP - 101 VL - 3 IS - 2 SN - 1279-7707, 1279-7707 KW - Tumor Suppressor Protein p53 KW - 0 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Humans KW - Apoptosis -- drug effects KW - Rodentia KW - Aging -- metabolism KW - Insulin-Like Growth Factor I -- physiology KW - Energy Intake -- physiology KW - Neoplasms, Experimental -- prevention & control KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69485222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+health+%26+aging&rft.atitle=Roles+for+insulin-like+growth+factor-1+in+mediating+the+anti-carcinogenic+effects+of+caloric+restriction.&rft.au=Kari%2C+F+W%3BDunn%2C+S+E%3BFrench%2C+J+E%3BBarrett%2C+J+C&rft.aulast=Kari&rft.aufirst=F&rft.date=1999-01-01&rft.volume=3&rft.issue=2&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=The+journal+of+nutrition%2C+health+%26+aging&rft.issn=12797707&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-25 N1 - Date created - 2000-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of interaction involving identified genes: available study designs. AN - 69484023; 10854486 AB - Advances in molecular genetic techniques have led to an increased ability to examine gene-environment interactions. Studies to detect gene-environment interactions are motivated by different situations, including 1) most identified cancer genes having associated lifetime risks less than 100% (i.e., incomplete penetrance), 2) hereditary factors that control the metabolism of carcinogens that may modulate risk of disease as hypothesized in pharmacogenetics, and 3) inconsistent associations across studies between a cancer and a suspected risk factor. The above situations and others have led to increased study of interaction between genetic and environmental factors. Less studied so far, but with increased potential for the future, is interaction between identified genes. Gene-gene interaction studies would also be motivated by the situations described above. Approaches to detect gene-environment and gene-gene interactions are reviewed. Available risk estimates, required types of subjects, and feasibility of the proposed study designs are discussed; efficiency and power for interaction assessment are summarized where available. In general, most designs allow for estimating risk associated with a genetic factor, environmental factor, and interaction effect. Although power and efficiency for detecting interactions have been assessed for specific situations in some of the methods, further investigations are needed to define the efficiency spectra of each design. JF - Journal of the National Cancer Institute. Monographs AU - Goldstein, A M AU - Andrieu, N AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7236, USA. ag26o@nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 49 EP - 54 IS - 26 SN - 1052-6773, 1052-6773 KW - Index Medicus KW - Humans KW - Environmental Exposure KW - Case-Control Studies KW - Family KW - Genes KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69484023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Monographs&rft.atitle=Detection+of+interaction+involving+identified+genes%3A+available+study+designs.&rft.au=Goldstein%2C+A+M%3BAndrieu%2C+N&rft.aulast=Goldstein&rft.aufirst=A&rft.date=1999-01-01&rft.volume=&rft.issue=26&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute.+Monographs&rft.issn=10526773&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-17 N1 - Date created - 2000-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of HMG-14/-17-containing chromatin. AN - 69478693; 10804520 JF - Methods in molecular biology (Clifton, N.J.) AU - Postnikov, Y V AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 303 EP - 310 VL - 119 SN - 1064-3745, 1064-3745 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Index Medicus KW - Animals KW - Humans KW - Chromatin -- metabolism KW - Chromatin -- chemistry KW - Chromatin -- isolation & purification KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69478693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.atitle=Analysis+of+HMG-14%2F-17-containing+chromatin.&rft.au=Postnikov%2C+Y+V%3BBustin%2C+M&rft.aulast=Postnikov&rft.aufirst=Y&rft.date=1999-01-01&rft.volume=119&rft.issue=&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+biology+%28Clifton%2C+N.J.%29&rft.issn=10643745&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-06 N1 - Date created - 2000-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain imaging studies of cocaine abuse: implications for medication development. AN - 69477353; 10803636 AB - Contemporary in vivo brain imaging techniques confer the ability to assess brain function and structure noninvasively, and thereby can yield information to help guide the development of new treatments for substance abuse. The advantages and limitations of the major imaging modalities (positron emission tomography [PET], single photon emission computed tomography [SPECT], structural and functional magnetic resonance imaging [MRI, fMRI, respectively]) are discussed with respect to their applicability to research on cocaine abuse. The effects of acute administration of cocaine have been studied using PET and fMRI, with PET manifesting decreases in cerebral glucose metabolism and blood flow, and fMRI revealing regional effects that are correlated temporally with subjective responses. In addition, studies of drug abusers, abstinent from cocaine for various lengths of time, have revealed persistent differences in brain function and structure, especially in the frontal cortex, when compared with parameters in the brains of subjects who do not use illicit drugs of abuse. PET studies also have revealed abnormalities in markers for dopaminergic and opioid systems during withdrawal from cocaine. Moreover, studies of cue-elicited craving for cocaine demonstrate a connection between the response to drug-related stimuli and neural elements of cognition and emotion. The future directions of in vivo brain imaging to identify functional and structural alterations in the brains of cocaine abusers are discussed in relation to the development of medications to treat cocaine dependence. JF - Critical reviews in neurobiology AU - London, E D AU - Bonson, K R AU - Ernst, M AU - Grant, S AD - The Brain Imaging Center, National Institute on Drug Abuse, Baltimore, MD 21224, USA. elondon@tracer.org Y1 - 1999 PY - 1999 DA - 1999 SP - 227 EP - 242 VL - 13 IS - 3 SN - 0892-0915, 0892-0915 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Brain Mapping KW - Tomography, Emission-Computed, Single-Photon KW - Humans KW - Tomography, Emission-Computed KW - Brain -- physiopathology KW - Cocaine-Related Disorders -- pathology KW - Brain -- pathology KW - Cocaine-Related Disorders -- drug therapy KW - Cocaine-Related Disorders -- physiopathology KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69477353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+neurobiology&rft.atitle=Brain+imaging+studies+of+cocaine+abuse%3A+implications+for+medication+development.&rft.au=London%2C+E+D%3BBonson%2C+K+R%3BErnst%2C+M%3BGrant%2C+S&rft.aulast=London&rft.aufirst=E&rft.date=1999-01-01&rft.volume=13&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+neurobiology&rft.issn=08920915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-02 N1 - Date created - 2000-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA topoisomerase I poisons. AN - 69471279; 10800479 JF - Cancer chemotherapy and biological response modifiers AU - Takimoto, C H AU - Kieffer, L V AU - Kieffer, M E AU - Arbuck, S G AU - Wright, J AD - NCI-Navy Medical Oncology Branch, Naval Hospital Bethesda, MD 20889-5105, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 81 EP - 124 VL - 18 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents KW - 0 KW - Antiviral Agents KW - Enzyme Inhibitors KW - Radiation-Sensitizing Agents KW - Topoisomerase I Inhibitors KW - irinotecan KW - 0H43101T0J KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Topotecan KW - 7M7YKX2N15 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - DNA Topoisomerases, Type I -- chemistry KW - Animals KW - Topotecan -- pharmacology KW - Radiation-Sensitizing Agents -- pharmacology KW - Humans KW - Antiviral Agents -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Drug Resistance, Neoplasm KW - Camptothecin -- pharmacology KW - Camptothecin -- pharmacokinetics KW - Camptothecin -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Camptothecin -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69471279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemotherapy+and+biological+response+modifiers&rft.atitle=DNA+topoisomerase+I+poisons.&rft.au=Takimoto%2C+C+H%3BKieffer%2C+L+V%3BKieffer%2C+M+E%3BArbuck%2C+S+G%3BWright%2C+J&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1999-01-01&rft.volume=18&rft.issue=&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-18 N1 - Date created - 2000-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxanes and other microtubule stabilizing agents. AN - 69469313; 10800478 JF - Cancer chemotherapy and biological response modifiers AU - Sackett, D L AU - Fojo, T AD - Department of Health and Human Services, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 59 EP - 80 VL - 18 SN - 0921-4410, 0921-4410 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Humans KW - Drug Resistance, Neoplasm KW - Paclitaxel -- adverse effects KW - Paclitaxel -- pharmacokinetics KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Microtubules -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69469313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemotherapy+and+biological+response+modifiers&rft.atitle=Taxanes+and+other+microtubule+stabilizing+agents.&rft.au=Sackett%2C+D+L%3BFojo%2C+T&rft.aulast=Sackett&rft.aufirst=D&rft.date=1999-01-01&rft.volume=18&rft.issue=&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+biological+response+modifiers&rft.issn=09214410&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-18 N1 - Date created - 2000-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophils, ribonucleases and host defense: solving the puzzle. AN - 69461353; 10741866 AB - The eosinophil ribonucleases eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3) are among the major secretory effector proteins of human eosinophilic leukocytes, cells whose role in host defense remains controversial and poorly understood. We have recently described the unusual manner in which this ribonuclease lineage has evolved, with extraordinary diversification observed in primate as well as in rodent EDNs and ECPs. The results of our evolutionary studies suggest that the EDN/ ECP ribonucleases are in the process of being tailored for a specific, ribonuclease-related goal. With this in mind, we have begun to look carefully at some of the intriguing associations that link eosinophils and their ribonucleases to disease caused by the single-stranded RNA viral pathogen, respiratory syncytial virus (RSV). Recent work in our laboratory has demonstrated that eosinophils can mediate a direct, ribonuclease-dependent reduction in infectivity of RSV in vitro, and that EDN can function alone as an independent antiviral agent. The results of this work have led us to consider the possibility that the EDN/ECP ribonucleases represent a heretofore unrecognized element of innate and specific antiviral host defense. JF - Immunologic research AU - Rosenberg, H F AU - Domachowske, J B AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hr2k@nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 261 EP - 274 VL - 20 IS - 3 SN - 0257-277X, 0257-277X KW - Antiviral Agents KW - 0 KW - Blood Proteins KW - Eosinophil Granule Proteins KW - Proteins KW - Recombinant Proteins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Space life sciences KW - Respiratory Syncytial Viruses -- drug effects KW - Animals KW - Recombinant Proteins -- pharmacology KW - Immunity, Active -- immunology KW - Immunity, Innate -- immunology KW - Biological Evolution KW - Dose-Response Relationship, Drug KW - Humans KW - Amino Acid Sequence KW - Proteins -- genetics KW - Blood Proteins -- genetics KW - Proteins -- pharmacology KW - Sequence Alignment KW - Antiviral Agents -- pharmacology KW - Restriction Mapping KW - Molecular Sequence Data KW - Ribonuclease, Pancreatic -- genetics KW - Ribonucleases -- pharmacology KW - Eosinophils -- enzymology KW - Ribonucleases -- genetics KW - Ribonucleases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69461353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunologic+research&rft.atitle=Eosinophils%2C+ribonucleases+and+host+defense%3A+solving+the+puzzle.&rft.au=Rosenberg%2C+H+F%3BDomachowske%2C+J+B&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1999-01-01&rft.volume=20&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Immunologic+research&rft.issn=0257277X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-31 N1 - Date created - 2000-05-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of streamline chelating for capture and purification of poly-His-tagged recombinant proteins. AN - 69457915; 10734566 AB - Expression of recombinant proteins with poly-histidine tags enables their convenient capture and purification using immobilized metal affinity chromatography (IMAC). The 6 x His-tagged protein binds to a chelating resin charged with metal ions such as Ni2+, Cu2+ or Zn2+, and can therefore be separated from proteins which have lower, or no, affinity for the resin. Two recombinant proteins, a malaria transmission-blocking vaccine candidate secreted extracellularly by S. cerevisiae and a modified diphtheria toxin produced intracellularly by E. coli, were expressed with 6 x His tags and could therefore be purified using IMAC. In an effort to further simplify the initial capture of these proteins, an expanded bed adsorption technique using a chelating resin (Streamline Chelating) was introduced. It was possible to capture the intracellular diphtheria protein from E. coli directly after cell lysis, without prior centrifugation or filtration. The extracellular malaria vaccine candidate was also directly captured from a high cell density yeast culture. Detailed information on the experimental work performed, and the capture processes developed, is provided. JF - Bioseparation AU - Noronha, S AU - Kaufman, J AU - Shiloach, J AD - Biotechnology Unit, NIDDK, NIH, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 145 EP - 151 VL - 8 IS - 1-5 SN - 0923-179X, 0923-179X KW - Chelating Agents KW - 0 KW - Diphtheria Toxin KW - Malaria Vaccines KW - Recombinant Proteins KW - Histidine KW - 4QD397987E KW - Index Medicus KW - Recombinant Proteins -- isolation & purification KW - Electrophoresis, Polyacrylamide Gel KW - Diphtheria Toxin -- chemistry KW - Malaria Vaccines -- isolation & purification KW - Malaria Vaccines -- chemistry KW - Adsorption KW - Escherichia coli -- genetics KW - Recombinant Proteins -- chemistry KW - Diphtheria Toxin -- isolation & purification KW - Histidine -- chemistry KW - Chelating Agents -- chemistry KW - Chromatography, Affinity -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69457915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioseparation&rft.atitle=Use+of+streamline+chelating+for+capture+and+purification+of+poly-His-tagged+recombinant+proteins.&rft.au=Noronha%2C+S%3BKaufman%2C+J%3BShiloach%2C+J&rft.aulast=Noronha&rft.aufirst=S&rft.date=1999-01-01&rft.volume=8&rft.issue=1-5&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Bioseparation&rft.issn=0923179X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Labeled kynurenine pharmacokinetic modeling studies in gerbils. Nonequilibrium between infused and endogenous kynurenine. AN - 69454603; 10721071 AB - In order to complete pharmacokinetic studies on the central vs. peripheral origin of several tryptophan metabolites, we infused gerbils with labelled kynurenine (2H4 or 15N2). Osmotic minipumps charged with kynurenine solutions were surgically implanted subcutaneously in adult female gerbils (50-60 g). After a variable number of hours, the gerbils were sacrificed and organs taken for determination of labelled/unlabelled kynurenine ratios using mass spectrometric assay of a pentafluorobenzyl derivative as described previously. Surprisingly high ratios of 2H to 1H-kynurenine were measured in the kidney (0.25-0.40) and urine (4.0-8.0), although the ratio of deuterium labelled to endogenous kynurenine remained below detection limits (< 0.05) in serum and other tissues. Infusion of greater quantities of 2H4-kynurenine confirmed these observations in gerbils in which ratios of 2H4-to-1H kynurenine were measurable in serum and tissues. Synthesis and infusion of 15N2-kynurenine demonstrated that these effects were not due to deuterium isotope substitution. The data demonstrate a non-equilibrium between infused and endogenous kynurenine, which is related to differential rates of protein binding and the rapid clearance of free, infused kynurenine by kidney. JF - Advances in experimental medicine and biology AU - Kita, T AU - Heyes, M P AU - Morrison, P F AU - Markey, S P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 315 EP - 320 VL - 467 SN - 0065-2598, 0065-2598 KW - Nitrogen Isotopes KW - 0 KW - Kynurenine KW - 343-65-7 KW - Deuterium KW - AR09D82C7G KW - Index Medicus KW - Gerbillinae KW - Animals KW - Kidney -- metabolism KW - Infusions, Intravenous KW - Gas Chromatography-Mass Spectrometry KW - Brain -- metabolism KW - Tissue Distribution KW - Time Factors KW - Female KW - Kynurenine -- metabolism KW - Kynurenine -- pharmacokinetics KW - Kynurenine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69454603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Labeled+kynurenine+pharmacokinetic+modeling+studies+in+gerbils.+Nonequilibrium+between+infused+and+endogenous+kynurenine.&rft.au=Kita%2C+T%3BHeyes%2C+M+P%3BMorrison%2C+P+F%3BMarkey%2C+S+P&rft.aulast=Kita&rft.aufirst=T&rft.date=1999-01-01&rft.volume=467&rft.issue=&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-09 N1 - Date created - 2000-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment and cloning of mouse Arhgap7 to chromosome 8A4-B2, a conserved syntenic region of human chromosome 8p22-->p21. AN - 69452901; 10702663 JF - Cytogenetics and cell genetics AU - Yuan, B Z AU - Yang, Y AU - Keck-Waggoner, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 189 EP - 190 VL - 87 IS - 3-4 SN - 0301-0171, 0301-0171 KW - DLC-1 (deleted in liver cancer) protein, mouse KW - 0 KW - DLC1 protein, human KW - DNA, Complementary KW - GTPase-Activating Proteins KW - Proteins KW - Tumor Suppressor Proteins KW - rho GTPase-activating protein KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Humans KW - Molecular Sequence Data KW - In Situ Hybridization, Fluorescence KW - Mice KW - Amino Acid Sequence KW - Cloning, Molecular KW - GTPase-Activating Proteins -- genetics KW - GTPase-Activating Proteins -- chemistry KW - Conserved Sequence -- genetics KW - Proteins -- chemistry KW - Physical Chromosome Mapping KW - Chromosomes, Human, Pair 8 -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69452901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetics+and+cell+genetics&rft.atitle=Assignment+and+cloning+of+mouse+Arhgap7+to+chromosome+8A4-B2%2C+a+conserved+syntenic+region+of+human+chromosome+8p22--%26gt%3Bp21.&rft.au=Yuan%2C+B+Z%3BYang%2C+Y%3BKeck-Waggoner%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Yuan&rft.aufirst=B&rft.date=1999-01-01&rft.volume=87&rft.issue=3-4&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Cytogenetics+and+cell+genetics&rft.issn=03010171&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-04-12 N1 - Date created - 2000-04-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF178078; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term chemical carcinogenesis bioassays predict human cancer hazards. Issues, controversies, and uncertainties. AN - 69432878; 10676409 AB - Long-term carcinogenesis bioassays are the most valued and predictive means for identifying potential carcinogenic hazards of various agents to humans. Agents may be chemicals, chemical mixtures, multiple chemicals, combinations of chemicals, residues and contaminants, commercial products and formulations, and various exposure circumstances. Life-styles, dietary factors, and occupational exposure circumstances are very difficult, but not totally impossible, to evaluate experimentally. Historically, the first chemical bioassay took place in the early part of this century: Yamagiwa and Ichikawa in 1915, showed that coal tar applied experimentally to rabbit ears caused skin carcinomas. Since then, nearly 1500-2000 bioassays of one sort or another have been carried out. Importantly, however, some of these bioassays must be considered inadequate for judging the absence of carcinogenicity, since there were various limitations on the way they were performed: too few animals, too short a duration, too low exposure concentrations, too limited pathology, as examples. Thus, each bioassay must be critically evaluated, especially those reported to be negative, because "false negatives" are certainly more hazardous to human health than are "false positives". Likewise, one must be careful not to discount bioassay results simply because a target organ in rodents may not have a direct counterpart in humans (e.g., Zymbal glands), or because an organ site in rodents may not be a major site of cancers in humans (e.g., mouse liver). The design and conduct of a bioassay is not simple, however, and one must be fully aware of possible pitfalls as well as viable and often necessary alternatives. Similarly, evaluating results and interpreting findings must be approached with the utmost objectivity and consistency. These and other select issues, controversies, and uncertainties possibly encountered in long-term bioassays are covered in this paper. One fact remains abundantly clear: for every known human carcinogen that has been tested adequately in laboratory animals, the findings of carcinogenicity are concordant. JF - Annals of the New York Academy of Sciences AU - Huff, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. huff1@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 56 EP - 79 VL - 895 SN - 0077-8923, 0077-8923 KW - Carcinogens KW - 0 KW - Xenobiotics KW - Index Medicus KW - False Negative Reactions KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Xenobiotics -- adverse effects KW - Rabbits KW - Predictive Value of Tests KW - Mice KW - Research Design KW - Risk Assessment KW - False Positive Reactions KW - Biological Assay KW - Cell Transformation, Neoplastic KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69432878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Long-term+chemical+carcinogenesis+bioassays+predict+human+cancer+hazards.+Issues%2C+controversies%2C+and+uncertainties.&rft.au=Huff%2C+J&rft.aulast=Huff&rft.aufirst=J&rft.date=1999-01-01&rft.volume=895&rft.issue=&rft.spage=56&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 - 2000-03-01 N1 - Date created - 2000-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The regulation of cerebral blood flow during intravenous cocaine administration in cocaine abusers. AN - 69432766; 10668454 AB - Cocaine abuse is associated with heightened risk of life-threatening neurological complications such as strokes, seizures, and transient ischemic attacks. We used transcranial Doppler (TCD) sonography, a continuous measure of cerebral blood flow velocity, to better understand the changes in cerebral hemodynamics produced by cocaine administration, which may lead to an increased risk for stroke in cocaine abusers. Heart rate and blood pressure were also measured. Blood flow velocity of seven cocaine abusers was studied during placebo, 10-, 25-, and 50-mg intravenous (i.v.) injections of cocaine. A significant increase in mean and systolic velocity which lasted for about two minutes was observed with all doses of cocaine, with no change in the placebo condition. This increase in systolic velocity indicates that cocaine produces an immediate and brief period of vasoconstriction in large arteries of the brain. The present results elucidate the time course of cocaine's acute cerebrovascular effects and provide a better understanding of etiology of cocaine-related stroke and transient ischemic attacks. JF - Annals of the New York Academy of Sciences AU - Herning, R I AU - Better, W AU - Nelson, R AU - Gorelick, D AU - Cadet, J L AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. rherning@intra.nida.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 489 EP - 494 VL - 890 SN - 0077-8923, 0077-8923 KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Humans KW - Blood Flow Velocity -- drug effects KW - Adult KW - Male KW - Female KW - Cerebrovascular Circulation -- drug effects KW - Cocaine-Related Disorders -- physiopathology KW - Blood Pressure -- drug effects KW - Cocaine -- pharmacology KW - Narcotics -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69432766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+regulation+of+cerebral+blood+flow+during+intravenous+cocaine+administration+in+cocaine+abusers.&rft.au=Herning%2C+R+I%3BBetter%2C+W%3BNelson%2C+R%3BGorelick%2C+D%3BCadet%2C+J+L&rft.aulast=Herning&rft.aufirst=R&rft.date=1999-01-01&rft.volume=890&rft.issue=&rft.spage=489&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 - 2000-03-15 N1 - Date created - 2000-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progress in cancer chemoprevention. AN - 69431419; 10668477 AB - More than 40 promising agents and agent combinations are being evaluated clinically as chemopreventive drugs for major cancer targets. A few have been in vanguard, large-scale intervention trials--for example, the studies of tamoxifen and fenretinide in breast, 13-cis-retinoic acid in head and neck, vitamin E and selenium in prostate, and calcium in colon. These and other agents are currently in phase II chemoprevention trials to establish the scope of their chemopreventive efficacy and to develop intermediate biomarkers as surrogate end points for cancer incidence in future studies. In this group are fenretinide, 2-difluoromethylornithine, and oltipraz. Nonsteroidal anti-inflammatories (NSAID) are also in this group because of their colon cancer chemopreventive effects in clinical intervention, epidemiological, and animal studies. New agents are continually considered for development as chemopreventive drugs. Preventive strategies with antiandrogens are evolving for prostate cancer. Anti-inflammatories that selectively inhibit inducible cyclooxygenase (COX)-2 are being investigated in colon as alternatives to the NSAID, which inhibit both COX-1 and COX-2 and derive their toxicity from COX-1 inhibition. Newer retinoids with reduced toxicity, increased efficacy, or both (e.g., 9-cis-retinoic acid) are being investigated. Promising chemopreventive drugs are also being developed from dietary substances (e.g., green and black tea polyphenols, soy isoflavones, curcumin, phenethyl isothiocyanate, sulforaphane, lycopene, indole-3-carbinol, perillyl alcohol). Basic and translational research necessary to progress in chemopreventive agent development includes, for example, (1) molecular and genomic biomarkers that can be used for risk assessment and as surrogate end points in clinical studies, (2) animal carcinogenesis models that mimic human disease (including transgenic and gene knockout mice), and (3) novel agent treatment regimens (e.g., local delivery to cancer targets, agent combinations, and pharmacodynamically guided dosing). JF - Annals of the New York Academy of Sciences AU - Kelloff, G J AU - Crowell, J A AU - Steele, V E AU - Lubet, R A AU - Boone, C W AU - Malone, W A AU - Hawk, E T AU - Lieberman, R AU - Lawrence, J A AU - Kopelovich, L AU - Ali, I AU - Viner, J L AU - Sigman, C C AD - National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland 20892, USA. kelloffg@dcpcepn.nci.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 1 EP - 13 VL - 889 SN - 0077-8923, 0077-8923 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms, Experimental -- pathology KW - Neoplasm Metastasis -- prevention & control KW - Neoplasms -- pathology KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69431419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Progress+in+cancer+chemoprevention.&rft.au=Kelloff%2C+G+J%3BCrowell%2C+J+A%3BSteele%2C+V+E%3BLubet%2C+R+A%3BBoone%2C+C+W%3BMalone%2C+W+A%3BHawk%2C+E+T%3BLieberman%2C+R%3BLawrence%2C+J+A%3BKopelovich%2C+L%3BAli%2C+I%3BViner%2C+J+L%3BSigman%2C+C+C&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1999-01-01&rft.volume=889&rft.issue=&rft.spage=1&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 - 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 - Tardive dyskinesia: possible involvement of free radicals and treatment with vitamin E. AN - 69430338; 10667743 AB - A decade ago a hypothesis introduced to explain tardive dyskinesia (TD) implicated free radicals generated secondary to neuroleptic treatment. Since then many preclinical and clinical studies have investigated this possibility. These studies suggest that free radicals are probably involved in the pathogenesis of TD and that vitamin E could be efficacious in its treatment. JF - Schizophrenia bulletin AU - Elkashef, A M AU - Wyatt, R J AD - Medications Development Division, National Institute on Drug Abuse, Bethesda, MD 20892-9551, USA. ae8a@nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 731 EP - 740 VL - 25 IS - 4 SN - 0586-7614, 0586-7614 KW - Antioxidants KW - 0 KW - Free Radicals KW - Vitamin E KW - 1406-18-4 KW - Index Medicus KW - Nerve Degeneration -- complications KW - Humans KW - Nerve Degeneration -- pathology KW - Free Radicals -- metabolism KW - Dyskinesia, Drug-Induced -- metabolism KW - Dyskinesia, Drug-Induced -- complications KW - Dyskinesia, Drug-Induced -- drug therapy KW - Antioxidants -- therapeutic use KW - Vitamin E -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69430338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+bulletin&rft.atitle=Tardive+dyskinesia%3A+possible+involvement+of+free+radicals+and+treatment+with+vitamin+E.&rft.au=Elkashef%2C+A+M%3BWyatt%2C+R+J&rft.aulast=Elkashef&rft.aufirst=A&rft.date=1999-01-01&rft.volume=25&rft.issue=4&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+bulletin&rft.issn=05867614&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 - Cyclooxygenase-deficient mice. A summary of their characteristics and susceptibilities to inflammation and carcinogenesis. AN - 69429611; 10668482 AB - Cyclooxygenase (COX)-1- and COX-2-deficient mice have unique physiological differences that have allowed investigation into the individual biological roles of the COX isoforms. In the following, the phenotypes of the two COX knockout mice are summarized, and recent studies to investigate the effects of COX deficiency on inflammatory responses and cancer susceptibility are discussed. The data suggest that both isoforms have important roles in the maintenance of physiological homeostasis and that such designations as house-keeping and/or response gene may not be entirely accurate. Furthermore, data from COX-deficient mice indicate that both isoforms can contribute to the inflammatory response and that both isoforms have significant roles in carcinogenesis. JF - Annals of the New York Academy of Sciences AU - Langenbach, R AU - Loftin, C D AU - Lee, C AU - Tiano, H AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. langenbach@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 52 EP - 61 VL - 889 SN - 0077-8923, 0077-8923 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - Prostaglandin-Endoperoxide Synthases KW - Ptgs1 protein, mouse KW - Index Medicus KW - Animals KW - Mice KW - Genetic Predisposition to Disease KW - Neoplasms, Experimental -- etiology KW - Neoplasms, Experimental -- genetics KW - Inflammation -- etiology KW - Inflammation -- genetics KW - Disease Models, Animal KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69429611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cyclooxygenase-deficient+mice.+A+summary+of+their+characteristics+and+susceptibilities+to+inflammation+and+carcinogenesis.&rft.au=Langenbach%2C+R%3BLoftin%2C+C+D%3BLee%2C+C%3BTiano%2C+H&rft.aulast=Langenbach&rft.aufirst=R&rft.date=1999-01-01&rft.volume=889&rft.issue=&rft.spage=52&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 - 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 - Neuroprotective properties of nitric oxide. AN - 69428172; 10668435 AB - The discoveries of physiological roles of nitric oxide (.NO) as the mediator of endothelium-derived relaxing factor (EDRF) action and the activator of guanylyl cyclase to increase cyclic guanosine monophosphate (cGMP), which lead to vasorelaxation in the cardiovascular system, have been awarded with the 1998 Nobel Prize of Medicine. The present review discusses putative beneficial effects of .NO in the central nervous system (CNS). In addition to its prominent roles of the regulation of cerebral blood flow and the modulation of cell to cell communication in the brain, recent in vitro and in vivo results indicated that .NO is a potent antioxidative agent. .NO terminates oxidant stress in the brain by (i) suppressing iron-induced generation of hydroxyl radicals (.OH) via the Fenton reaction, (ii) interrupting the chain reaction of lipid peroxidation, (iii) augmenting the antioxidative potency of reduced glutathione (GSH) and (iv) inhibiting cysteine proteases. It is apparent that .NO--a relative long half-life nitrogen-centered weak radical--scavenges those short-lived, highly reactive free radicals such as superoxide anion (O2.-), .OH, peroxyl lipid radicals (LOO.) and thiyl radicals (i.e., GS.), yielding reactive nitrogen species including nitrites, nitrates, S-nitrosoglutathione (GSNO) and peroxynitrite (ONOO-). GSNO is 100-fold more potent than GSH; it completely inhibits the weak peroxidative effect of ONOO-. Moreover, CO2 and .NO neutralize prooxidative effects of ONOO-. CO2 prevents protein oxidation but not 3-nitrotyrosine formation caused by ONOO-. Finally, neuroprotective effects of GSNO and .NO have been demonstrated in brain preparations in vivo. These novel neuroprotective properties of .NO and GSNO may have their physiological significance, since oxidative stress depletes GSH while increasing GS. and .NO formation in astroglial and endothelial cells, resulting in the generation of a more potent antioxidant GSNO and providing additional neuro-protection at microM concentrations. This putative GSNO pathway (GSH-->GS.-->GSNO-->.NO + GSSG-->GSH) may be an important part of endogenous antioxidative defense system, which could protect neurons and other brain cells against oxidative stress caused by oxidants, iron complexes, proteases and cytokines. In conclusion, .NO is a potent antioxidant against oxidative damage caused by reactive oxygen species, which are generated by Fenton reaction or other mechanisms in the brain via redox cycling of iron complexes. JF - Annals of the New York Academy of Sciences AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, National Institute of Mental Health, NIH Clinical Center, Bethesda, Maryland 20892-1264, USA. chiueh@helix.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 301 EP - 311 VL - 890 SN - 0077-8923, 0077-8923 KW - Free Radical Scavengers KW - 0 KW - Nitrates KW - Nitric Oxide Donors KW - Nitroso Compounds KW - Oxidants KW - Reactive Oxygen Species KW - peroxynitric acid KW - 26404-66-0 KW - Nitric Oxide KW - 31C4KY9ESH KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Oxidants -- pharmacology KW - Humans KW - Nitrates -- metabolism KW - Nitrates -- pharmacology KW - Oxidants -- metabolism KW - Free Radical Scavengers -- metabolism KW - Nitric Oxide Donors -- pharmacology KW - Reactive Oxygen Species -- metabolism KW - Oxidative Stress -- physiology KW - Nitroso Compounds -- metabolism KW - Glutathione -- metabolism KW - Oxidative Stress -- drug effects KW - Nitroso Compounds -- pharmacology KW - Nitric Oxide -- physiology KW - Nitric Oxide Donors -- metabolism KW - Glutathione -- pharmacology KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69428172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuroprotective+properties+of+nitric+oxide.&rft.au=Chiueh%2C+C+C&rft.aulast=Chiueh&rft.aufirst=C&rft.date=1999-01-01&rft.volume=890&rft.issue=&rft.spage=301&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 - 2000-03-15 N1 - Date created - 2000-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials. AN - 69427520; 10665481 AB - The discovery and cloning of the cyclin-dependent kinases (cdks), main regulators of cell cycle progression, allowed several investigators to design novel modulators of cdk activity. Flavopiridol (HMR 1275, L86-8275), a flavonoid derived from an indigenous plant from India, demonstrated potent and specific in vitro inhibition of all cdks tested (cdks 1, 2, 4 and 7) with clear block in cell cycle progression at the G1/S and G2/M boundaries. Moreover, preclinical studies demonstrated the capacity of flavopiridol to induce programmed cell death, promote differentiation, inhibit angiogenic processes and modulate transcriptional events. The relationship between the latter effects and cdk inhibition is still unclear. Initial testing in early clinical human trials with infusional flavopiridol showed activity in some patients with non-Hodgkin's lymphoma, renal, prostate, colon and gastric carcinomas. Main side effects were secretory diarrhea and a pro-inflammatory syndrome associated with hypotension. Biologically active plasma concentrations of flavopiridol (approximately 300-500 nM) are easily achievable in patients receiving infusional flavopiridol. Phase 2 trials with infusional flavopiridol in several tumor types, other schedules and combination with standard chemotherapies are being assessed. In conclusion, flavopiridol is the first cdk inhibitor to be tested in clinical trials. Although important questions remain to be answered, this positive experience will stimulate the development of novel cdk modulators for cancer therapy. JF - Investigational new drugs AU - Senderowicz, A M AD - DTP Clinical Trials Unit, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis. National Cancer Institute, Bethesda, MD 20892, USA. sendero@helix.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 313 EP - 320 VL - 17 IS - 3 SN - 0167-6997, 0167-6997 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Cell Cycle -- drug effects KW - Piperidines -- pharmacology KW - Neoplasms -- drug therapy KW - Piperidines -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Flavonoids -- adverse effects KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Flavonoids -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Piperidines -- adverse effects KW - Flavonoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69427520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Flavopiridol%3A+the+first+cyclin-dependent+kinase+inhibitor+in+human+clinical+trials.&rft.au=Senderowicz%2C+A+M&rft.aulast=Senderowicz&rft.aufirst=A&rft.date=1999-01-01&rft.volume=17&rft.issue=3&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&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 - The possible involvement of 15-lipoxygenase/leukocyte type 12-lipoxygenase in colorectal carcinogenesis. AN - 69426163; 10667387 JF - Advances in experimental medicine and biology AU - Kamitani, H AU - Geller, M AU - Eling, T AD - Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 593 EP - 598 VL - 469 SN - 0065-2598, 0065-2598 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Arachidonate 12-Lipoxygenase KW - EC 1.13.11.31 KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 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 - Leukocytes -- enzymology KW - Tumor Cells, Cultured KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Humans KW - Gene Expression KW - HT29 Cells KW - Caco-2 Cells KW - Mutation KW - Isoenzymes -- metabolism KW - Genes, APC KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Arachidonate 15-Lipoxygenase -- genetics KW - Arachidonate 12-Lipoxygenase -- metabolism KW - Colorectal Neoplasms -- etiology KW - Arachidonate 12-Lipoxygenase -- genetics KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69426163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=The+possible+involvement+of+15-lipoxygenase%2Fleukocyte+type+12-lipoxygenase+in+colorectal+carcinogenesis.&rft.au=Kamitani%2C+H%3BGeller%2C+M%3BEling%2C+T&rft.aulast=Kamitani&rft.aufirst=H&rft.date=1999-01-01&rft.volume=469&rft.issue=&rft.spage=593&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&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 - Indomethacin inhibition of pristane plasmacytomagenesis in genetically susceptible inbred mice. AN - 69426068; 10667324 JF - Advances in experimental medicine and biology AU - Potter, M AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 151 EP - 156 VL - 469 SN - 0065-2598, 0065-2598 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Carcinogens KW - Prostaglandins KW - Reactive Oxygen Species KW - Terpenes KW - Sulindac KW - 184SNS8VUH KW - pristane KW - 26HZV48DT1 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Peritoneal Neoplasms -- chemically induced KW - Peritoneal Neoplasms -- prevention & control KW - Colon -- drug effects KW - Sulindac -- pharmacology KW - Prostaglandins -- biosynthesis KW - Peritoneal Neoplasms -- genetics KW - Mice KW - Mice, Inbred BALB C KW - Terpenes -- toxicity KW - Plasmacytoma -- prevention & control KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Carcinogens -- toxicity KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69426068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+experimental+medicine+and+biology&rft.atitle=Indomethacin+inhibition+of+pristane+plasmacytomagenesis+in+genetically+susceptible+inbred+mice.&rft.au=Potter%2C+M&rft.aulast=Potter&rft.aufirst=M&rft.date=1999-01-01&rft.volume=469&rft.issue=&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Advances+in+experimental+medicine+and+biology&rft.issn=00652598&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 - Project MATCH. AN - 69423852; 10665095 JF - Addiction (Abingdon, England) AU - Gordis, E AU - Fuller, R AD - National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD 20892-7003, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 57 EP - 59 VL - 94 IS - 1 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - United States KW - Sensitivity and Specificity KW - Multicenter Studies as Topic KW - Humans KW - Treatment Outcome KW - Follow-Up Studies KW - Sample Size KW - Controlled Clinical Trials as Topic KW - Alcoholism -- rehabilitation KW - Psychotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69423852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction+%28Abingdon%2C+England%29&rft.atitle=Project+MATCH.&rft.au=Gordis%2C+E%3BFuller%2C+R&rft.aulast=Gordis&rft.aufirst=E&rft.date=1999-01-01&rft.volume=94&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Addiction+%28Abingdon%2C+England%29&rft.issn=09652140&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 - Strategies for molecular intervention in esophageal cancers and their precursor lesions. AN - 69400095; 10631909 AB - Molecular analysis of malignant transformation in Barrett's epithelium provides insight into the temporal nature and significance of individual genetic events during multistep esophageal carcinogenesis. Potential targets for intervention in esophageal neoplasms include mutations involving retinoblastoma (Rb) and p53 tumor-suppressor pathways as well as tyrosine kinase cascades, which are known to promote cell cycle progression. Data from recent experiments provide the preclinical rationale for novel pharmacologic interventions in established esophageal cancers, and suggest strategies for chemoprevention in patients at risk for the development of these neoplasms. JF - Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus AU - Schrump, D S AU - Nguyen, D M AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 181 EP - 185 VL - 12 IS - 3 SN - 1120-8694, 1120-8694 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Index Medicus KW - Adenoviridae KW - Piperidines -- therapeutic use KW - Genes, p53 KW - Humans KW - Genetic Vectors KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Cell Transformation, Neoplastic KW - Flavonoids -- therapeutic use KW - Adenocarcinoma -- pathology KW - Precancerous Conditions -- genetics KW - Barrett Esophagus -- pathology KW - Barrett Esophagus -- genetics KW - Esophageal Neoplasms -- genetics KW - Precancerous Conditions -- drug therapy KW - Precancerous Conditions -- pathology KW - Esophageal Neoplasms -- pathology KW - Esophageal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69400095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diseases+of+the+esophagus+%3A+official+journal+of+the+International+Society+for+Diseases+of+the+Esophagus&rft.atitle=Strategies+for+molecular+intervention+in+esophageal+cancers+and+their+precursor+lesions.&rft.au=Schrump%2C+D+S%3BNguyen%2C+D+M&rft.aulast=Schrump&rft.aufirst=D&rft.date=1999-01-01&rft.volume=12&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Diseases+of+the+esophagus+%3A+official+journal+of+the+International+Society+for+Diseases+of+the+Esophagus&rft.issn=11208694&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-02 N1 - Date created - 2000-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and pharmacodynamics of moist snuff in humans. AN - 69399890; 10629244 AB - Four brands of moist snuff and a non-tobacco mint snuff were tested. Subjects reported to the laboratory for five experimental sessions. After baseline measurement of dependent variables, each subject placed 2 g of one of the brands of snuff (or one Skoal Bandits pouch) between the cheek and gum for 30 minutes. The subjects remained in the experimental laboratory for an additional 60 minutes. Ten volunteers who were daily users of smokeless tobacco. Plasma nicotine concentration, cardiovascular effects, and subjective effects. Large amounts of nicotine were delivered rapidly to the bloodstream. The amount of nicotine absorbed and the rate of absorption were related to the pH of the snuff product in aqueous suspension. Cardiovascular and subjective effects were related to the amount of nicotine absorbed. Snuff products are capable of rapidly delivering high doses of nicotine, which can lead to dependence. Long-term use of snuff can lead to a number of adverse health effects including oral cancers, cardiovascular diseases, and gingival diseases. For these reasons, it is important that the public health community considers oral snuff use as a burden on public health in the same way that cigarette smoking is recognised. JF - Tobacco control AU - Fant, R V AU - Henningfield, J E AU - Nelson, R A AU - Pickworth, W B AD - National Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland, USA. rfant@pinneyassociates.com Y1 - 1999 PY - 1999 DA - 1999 SP - 387 EP - 392 VL - 8 IS - 4 SN - 0964-4563, 0964-4563 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Heart Rate -- drug effects KW - Humans KW - Adult KW - Middle Aged KW - Blood Pressure -- drug effects KW - Male KW - Tobacco, Smokeless -- pharmacokinetics KW - Plants, Toxic KW - Nicotine -- pharmacokinetics KW - Nicotine -- adverse effects KW - Nicotine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69399890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Pharmacokinetics+and+pharmacodynamics+of+moist+snuff+in+humans.&rft.au=Fant%2C+R+V%3BHenningfield%2C+J+E%3BNelson%2C+R+A%3BPickworth%2C+W+B&rft.aulast=Fant&rft.aufirst=R&rft.date=1999-01-01&rft.volume=8&rft.issue=4&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=09644563&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 - Elevated prolactin in pediatric patients on typical and atypical antipsychotics. AN - 69396749; 10630453 AB - As part of systematic treatment trials of haloperidol, clozapine, and olanzapine with a total of 35 children and adolescents with early onset psychosis, prolactin was measured at baseline and week 6 of treatment. The National Institute of Mental Health patients--13 females, 22 males (mean age, 14.1+/-2.3 years; range, 9.1-19 years) with childhood onset schizophrenia (n = 32), or Psychotic Disorder not otherwise specified (NOS) (n = 3) with onset of psychosis before age 13--were recruited for open or double-blind trials of haloperidol, clozapine, or olanzapine. Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment. Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs; however, on clozapine, mean prolactin remained within the normal range. Prolactin was increased above the upper limit of normal for 100% of 10 patients on haloperidol, 70% of 10 patients on olanzapine, and 0% of 15 patients on clozapine (chi2 analyses: H > C, p = 0.004; O > C, p = 0.001). Given the potential endocrine and possible cardiac correlates of hyperprolactinemia, these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger samples to establish treatment safety of atypical antipsychotics in adolescents. JF - Journal of child and adolescent psychopharmacology AU - Wudarsky, M AU - Nicolson, R AU - Hamburger, S D AU - Spechler, L AU - Gochman, P AU - Bedwell, J AU - Lenane, M C AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1600, USA. wudarsky@codon.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 239 EP - 245 VL - 9 IS - 4 SN - 1044-5463, 1044-5463 KW - Antipsychotic Agents KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - Prolactin KW - 9002-62-4 KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Sex Factors KW - Double-Blind Method KW - Humans KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Haloperidol -- adverse effects KW - Prolactin -- blood KW - Pirenzepine -- analogs & derivatives KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Pirenzepine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69396749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+child+and+adolescent+psychopharmacology&rft.atitle=Elevated+prolactin+in+pediatric+patients+on+typical+and+atypical+antipsychotics.&rft.au=Wudarsky%2C+M%3BNicolson%2C+R%3BHamburger%2C+S+D%3BSpechler%2C+L%3BGochman%2C+P%3BBedwell%2C+J%3BLenane%2C+M+C%3BRapoport%2C+J+L&rft.aulast=Wudarsky&rft.aufirst=M&rft.date=1999-01-01&rft.volume=9&rft.issue=4&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Journal+of+child+and+adolescent+psychopharmacology&rft.issn=10445463&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 - Co-stimulation of cyclic-AMP-linked metabotropic glutamate receptors in rat striatum attenuates excitotoxin-induced nuclear factor-kappaB activation and apoptosis. AN - 69390635; 10625054 AB - Interactions between glutamatergic mechanisms mediated by receptors of the ionotropic and metabotropic classes in the central nervous system are complex and incompletely understood. To explore the consequences of these interactions on excitotoxicity, we examined the influence of group II and group III selective metabotropic glutamate receptor agonists on the N-methyl-D-aspartate-induced apoptotic destruction of GABAergic neurons in rat striatum. The intrastriatal administration of a group III metabotropic glutamate receptor agonist (amino-4-phosphonobutyric acid, 900-1800 nmol), but not of a group II agonist [(2S,1'S,2'S)-(carboxycyclopropyl)glycine, 100-1800 nmol] produced internucleosomal DNA fragmentation. Similarly, amino-4-phosphonobutyric acid (600 nmol) but not (2S,1'S,2'S)-(carboxycyclopropyl)glycine (100-1800 nmol) destroyed some striatal neurons as indicated by a loss of D1 dopamine receptors and 67,000 mol. wt glutamate decarboxylase (glutamate decarboxylase-67) messenger RNA. On the other hand, the intensity of internucleosomal DNA fragmentation induced by N-methyl-D aspartate (150 nmol) was substantially decreased by the intrastriatal co-administration of either (2S,1'S,2'S)-(carboxycyclopropyl)glycine or amino-4-phosphonobutyric acid (100-600 nmol). Both (2S, 1'S,2'S)-(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also reduced the N-methyl-D-aspartate-induced loss of striatal D1 dopamine receptors by 67% and 68% (both P < 0.001), and glutamate decarboxylase-67 messenger RNA by 68% and 61%, respectively. Furthermore, both (2S,1'S,2'S)-(carboxycyclopropyl)glycine and amino-4-phosphonobutyric acid also attenuated the N-methyl-D-aspartate-induced decline in striatal IKB-alpha protein levels by 62% and 37%, as well as the increase in nuclear transcription factor nuclear factor-kappaB binding activity by 135% and 94% (both P < 0.001), and the subsequent rise in p53 and c-Myc protein levels. These results suggest that stimulation of cyclic-AMP-linked metabotropic glutamate receptors inhibits ionotropic glutamate receptor-mediated activation of apoptotic cascades involving IkappaB-alpha degradation and nuclear factor-kappaB nuclear translocation, as well as p53 and c-Myc induction. Certain selective metabotropic glutamate receptor agonists might thus find utility as adjuncts to N-methyl-D-aspartate antagonists in the protection against the neurotoxicity initiated by excessive ionotropic glutamate receptor stimulation. JF - Neuroscience AU - Wang, Y AU - Qin, Z H AU - Nakai, M AU - Chen, R W AU - Chuang, D M AU - Chase, T N AD - Experimental Therapeutics Branch, NINDS, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 1153 EP - 1162 VL - 94 IS - 4 SN - 0306-4522, 0306-4522 KW - Amino Acids, Dicarboxylic KW - 0 KW - Aminobutyrates KW - I-kappa B Proteins KW - NF-kappa B KW - Neurotoxins KW - Nucleosomes KW - Receptors, Metabotropic Glutamate KW - (alpha-carboxycyclopropyl)glycine KW - 22255-17-0 KW - 2-amino-4-phosphonobutyric acid KW - 6323-99-5 KW - N-Methylaspartate KW - 6384-92-5 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - Cell Death -- physiology KW - Nucleosomes -- physiology KW - Cell Nucleus -- metabolism KW - I-kappa B Proteins -- metabolism KW - Cell Death -- drug effects KW - Biological Transport -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Amino Acids, Dicarboxylic -- pharmacology KW - Aminobutyrates -- pharmacology KW - Nucleosomes -- drug effects KW - N-Methylaspartate -- pharmacology KW - Neurons -- physiology KW - I-kappa B Proteins -- antagonists & inhibitors KW - DNA Fragmentation KW - Male KW - Corpus Striatum -- cytology KW - Corpus Striatum -- physiology KW - Corpus Striatum -- metabolism KW - Apoptosis -- physiology KW - Receptors, Metabotropic Glutamate -- metabolism KW - Cyclic AMP -- metabolism KW - Neurotoxins -- pharmacology KW - Corpus Striatum -- drug effects KW - NF-kappa B -- physiology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69390635?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Co-stimulation+of+cyclic-AMP-linked+metabotropic+glutamate+receptors+in+rat+striatum+attenuates+excitotoxin-induced+nuclear+factor-kappaB+activation+and+apoptosis.&rft.au=Wang%2C+Y%3BQin%2C+Z+H%3BNakai%2C+M%3BChen%2C+R+W%3BChuang%2C+D+M%3BChase%2C+T+N&rft.aulast=Wang&rft.aufirst=Y&rft.date=1999-01-01&rft.volume=94&rft.issue=4&rft.spage=1153&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&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 - Evaluation of 2-(methylaminosulfonyl)-1-(arylsulfonyl)hydrazines as anticancer agents. AN - 69383573; 10613605 AB - Seven new 2-(methylaminosulfonyl)- 1-(arylsulfonyl)hydrazines were prepared and evaluated as potential antitumor agents in vivo against murine Ehrlich ascites carcinoma (EAC). Borderline in vivo activity in EAC was exhibited by two compounds. All of them were screened in vitro against a battery of human tumor cell lines at the National Cancer Institute (NCI), USA. One of them, namely compound 2f(NSC No. 649 752) displayed highly significant specificity in two different cell lines as non-small cell lung cancer line HOP-18 and in CNS cancer line SNB-19. The compounds assessed in vitro for anti-HIV activity also at the NCI, however, have not reached the criteria of significant activity. The alkylating activity of the compounds was determined by measuring the absorbance of the alkylated product of 4-(4-nitrobenzyl)pyridine. It was found that they are capable of acting as chemical alkylating agents. JF - Neoplasma AU - Ghosh, M AU - Dutta, S AU - Sanyal, U AD - Department of Anticancer Drug Development and Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1999 PY - 1999 DA - 1999 SP - 242 EP - 245 VL - 46 IS - 4 SN - 0028-2685, 0028-2685 KW - Anti-HIV Agents KW - 0 KW - Antineoplastic Agents KW - Hydrazines KW - Index Medicus KW - AIDS/HIV KW - Drug Screening Assays, Antitumor KW - Animals KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Lung Neoplasms KW - Humans KW - Anti-HIV Agents -- pharmacology KW - Mice KW - Carcinoma, Non-Small-Cell Lung KW - Male KW - Hydrazines -- toxicity KW - Hydrazines -- therapeutic use KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- chemical synthesis KW - Hydrazines -- chemical synthesis KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69383573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Evaluation+of+2-%28methylaminosulfonyl%29-1-%28arylsulfonyl%29hydrazines+as+anticancer+agents.&rft.au=Ghosh%2C+M%3BDutta%2C+S%3BSanyal%2C+U&rft.aulast=Ghosh&rft.aufirst=M&rft.date=1999-01-01&rft.volume=46&rft.issue=4&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&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 - Biosynthesis of selenophosphate. AN - 69379591; 10609888 AB - Selenophosphate synthetase, the product of the selD gene, produces the highly active selenium donor, monoselenophosphate, from selenide and ATP. Positional isotope exchange experiments have shown hydrolysis of ATP occurs by way of a phosphoryl-enzyme intermediate. Although, mutagenesis studies have demonstrated Cys17 in the Escherichia coli enzyme is essential for catalytic activity the nucleophile in catalysis has not been identified. Recently, selenophosphate synthetase enzymes have been identified from other organisms. The human enzyme which contains a threonine residue corresponding to Cys17 in the E. coli enzyme, has been overexpressed in E. coli. The purified enzyme shows no detectable activity in the in vitro selenophosphate synthetase assay. In contrast, when the human enzyme is expressed to complement a selD mutation in E. coli, in the presence of 75Se, incorporation of 75Se into bacterial selenoproteins is observed. The inactive purified human enzyme together with the very low determined specific activity of the E. coli enzyme (83 nmol/min/mg) suggest an essential component for the formation of selenophosphate has not been identified. JF - BioFactors (Oxford, England) AU - Lacourciere, G M AD - Laboratory of Biochemistry, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 237 EP - 244 VL - 10 IS - 2-3 SN - 0951-6433, 0951-6433 KW - Drosophila Proteins KW - 0 KW - Phosphates KW - Selenium Compounds KW - selenophosphate KW - 12509-41-0 KW - Phosphotransferases KW - EC 2.7.- KW - selenophosphate synthetase KW - EC 2.7.9.3 KW - Index Medicus KW - Animals KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Models, Chemical KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Phosphotransferases -- genetics KW - Phosphates -- metabolism KW - Bacteria -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Phosphotransferases -- metabolism KW - Selenium Compounds -- metabolism KW - Phosphotransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69379591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioFactors+%28Oxford%2C+England%29&rft.atitle=Biosynthesis+of+selenophosphate.&rft.au=Lacourciere%2C+G+M&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=1999-01-01&rft.volume=10&rft.issue=2-3&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=BioFactors+%28Oxford%2C+England%29&rft.issn=09516433&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-01 N1 - Date created - 2000-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Angiogenesis a putative new approach in glutamine related therapy. AN - 69374006; 10607927 AB - Angiogenesis or the generation of new blood vessels, is an important factor regarding the growth of a tumor. Hence, it becomes a necessary parameter of any kind in therapeutic studies. Glutamine is an essential nutrient of tumor tissue and glutamine related therapy involves clearance of circulatory glutamine by glutaminase. So, whether this enzyme has any effect on angiogenesis of a tumor or not becomes an obvious question. To address this question, this study has been carried out with different murine tumor models. The results indicate that purified glutaminase reduces tumor volume as well as restricts the generation of new blood vessels. Glutaminase is effective in the case of solid as well as ascites tumor models. In the case of induced cancer, the host exhibits delayed onset of neoplasia following enzyme treatment and tumor host interactions determine the intensity of the neovascularisation process. Therefore, it can be concluded that this enzyme might be an effective agent against cancer metastasis. JF - Pathology oncology research : POR AU - Maity, P AU - Chakraborty, S AU - Bhattacharya, P AD - Chittaranjan National Cancer Institute, Department of Metabolic Regulation 37, S. P. Mukherjee Road, Calcutta, 700026, India. cncinstegiasceos@vsul.net.in. Y1 - 1999 PY - 1999 DA - 1999 SP - 309 EP - 314 VL - 5 IS - 4 SN - 1219-4956, 1219-4956 KW - Glutamine KW - 0RH81L854J KW - Methylcholanthrene KW - 56-49-5 KW - Glutaminase KW - EC 3.5.1.2 KW - Index Medicus KW - Uterine Cervical Dysplasia -- pathology KW - Cervix Uteri -- pathology KW - Cervix Uteri -- drug effects KW - Animals KW - Neovascularization, Physiologic KW - Methylcholanthrene -- toxicity KW - Liver -- metabolism KW - Cervix Uteri -- blood supply KW - Mice KW - Uterine Cervical Dysplasia -- chemically induced KW - Male KW - Female KW - Carcinoma, Ehrlich Tumor -- blood supply KW - Glutamine -- metabolism KW - Sarcoma 180 -- drug therapy KW - Glutamine -- blood KW - Carcinoma, Ehrlich Tumor -- pathology KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Sarcoma 180 -- pathology KW - Glutaminase -- therapeutic use KW - Neovascularization, Pathologic -- prevention & control KW - Sarcoma 180 -- blood supply KW - Neovascularization, Pathologic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69374006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pathology+oncology+research+%3A+POR&rft.atitle=Angiogenesis+a+putative+new+approach+in+glutamine+related+therapy.&rft.au=Maity%2C+P%3BChakraborty%2C+S%3BBhattacharya%2C+P&rft.aulast=Maity&rft.aufirst=P&rft.date=1999-01-01&rft.volume=5&rft.issue=4&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Pathology+oncology+research+%3A+POR&rft.issn=12194956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-21 N1 - Date created - 2000-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II trial of gallium nitrate in patients with androgen-metastatic prostate cancer. AN - 69369687; 10592501 AB - Due to in vitro data suggesting antitumor activity with gallium nitrate, we sought to evaluate the safety and activity in patients with androgen-independent prostate cancer. Patients were eligible for this study if they had an ECOG performance status of < or = 2, stage D2 metastatic prostate cancer that was progressing following combined androgen ablation (medical or surgical castration plus antiandrogen) and had failed antiandrogen withdrawal. Therapy consisted of gallium nitrate (200 mg/m(2)/day) as a continuous infusion for 7 days, administered every 21 days, with hydration (100 ml/m(2)/h). Individuals that had previously received suramin were treated at a dose of 150 mg/m(2)/day of gallium nitrate. Eight patients were enrolled: 4 patients at the 200 mg/m(2)/day dose level and 4 patients at the lower dosage (150 mg/m(2)/day). One of 8 patients had a >75% decline in prostate-specific antigen (PSA), 3 patients had stable PSA values for 17, 18 and 22 weeks, and 4 patients had progression by PSA (>50% increase over baseline). Anemia requiring transfusion occurred in 5 of 8 patients (63%). Two patients (25%) developed grade 4 toxicity: 1 patient developed complete blindness with partial reversal over 12 months, and another patient had pulmonary infiltrates, hypoxemia, and fever. Serious adverse events were not correlated to prior suramin exposure, or gallium plasma concentrations (total or free), but appeared to be related to cumulative cycles of gallium nitrate. Remaining adverse events were grade 1 or 2. No patients developed renal or neurological toxicity. This trial was prematurely terminated because repeated administration of gallium nitrate was poorly tolerated in an elderly population with androgen-independent prostate cancer. Gallium had modest clinical activity in this disease. Copyright 1999 S. Karger AG, Basel JF - Urologia internationalis AU - Senderowicz, A M AU - Reid, R AU - Headlee, D AU - Abornathy, T AU - Horti, J AU - Lush, R M AU - Reed, E AU - Figg, W D AU - Sausville, E A AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 120 EP - 125 VL - 63 IS - 2 SN - 0042-1138, 0042-1138 KW - Antineoplastic Agents KW - 0 KW - Gallium KW - CH46OC8YV4 KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - gallium nitrate KW - VRA0C6810N KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Prostate-Specific Antigen -- blood KW - Middle Aged KW - Male KW - Blindness -- chemically induced KW - Gallium -- adverse effects KW - Antineoplastic Agents -- administration & dosage KW - Gallium -- administration & dosage KW - Prostatic Neoplasms -- drug therapy KW - Gallium -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69369687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urologia+internationalis&rft.atitle=A+phase+II+trial+of+gallium+nitrate+in+patients+with+androgen-metastatic+prostate+cancer.&rft.au=Senderowicz%2C+A+M%3BReid%2C+R%3BHeadlee%2C+D%3BAbornathy%2C+T%3BHorti%2C+J%3BLush%2C+R+M%3BReed%2C+E%3BFigg%2C+W+D%3BSausville%2C+E+A&rft.aulast=Senderowicz&rft.aufirst=A&rft.date=1999-01-01&rft.volume=63&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Urologia+internationalis&rft.issn=00421138&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of phenotype variation on detection of linkage in the COGA data. AN - 69363453; 10597413 AB - Error in phenotypic measurement can significantly compromise ability to detect linkage. We assessed the impact of introducing phenotypic measurement error on our ability to detect a quantitative trait locus in the Collaborative Study on the Genetics of Alcoholism (COGA) data. The impact of introducing three different types of errors was evaluated: 1) errors generated by sampling from a normal distribution; 2) errors generated by permuting phenotype values between subjects; and 3) errors generated by sampling from a uniform error distribution. JF - Genetic epidemiology AU - Birznieks, G AU - Ghosh, S AU - Watanabe, R M AU - Mitchell, B D AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - S61 EP - S66 VL - 17 Suppl 1 SN - 0741-0395, 0741-0395 KW - Index Medicus KW - Sensitivity and Specificity KW - Quantitative Trait, Heritable KW - Phenotype KW - Genetic Testing KW - Reproducibility of Results KW - Lod Score KW - Humans KW - Genome KW - Genetic Linkage KW - Genetic Variation KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69363453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=The+effect+of+phenotype+variation+on+detection+of+linkage+in+the+COGA+data.&rft.au=Birznieks%2C+G%3BGhosh%2C+S%3BWatanabe%2C+R+M%3BMitchell%2C+B+D&rft.aulast=Birznieks&rft.aufirst=G&rft.date=1999-01-01&rft.volume=17+Suppl+1&rft.issue=&rft.spage=S61&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&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 - Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential. AN - 69362946; 10597430 AB - Our goal was to detect genes contributing to the P300 component of the event related potential (ERP). We found that all of the ERP traits were highly correlated. Most of them distinguished alcoholics from nonalcoholics. To have one summary variable for the ERP traits, we calculated the first principal component (PRIN1). After adjusting for age and sex, we screened for linkage of PRIN1 to all of the markers using the two-point Haseman-Elston sib-pair test. We compared results obtained from computing a moving average of two-point p-values ("regional" inference) in an approximately 10 cM region with those obtained from single, two-point tests. Different "suggestive" and "significant" linkage regions were found using the two methods. Based on the regional method, areas on chromosomes 2 and 5 should be followed up in future studies. JF - Genetic epidemiology AU - Goldin, L R AU - Chase, G A AD - Genetic Epidemiology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-7236, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - S163 EP - S167 VL - 17 Suppl 1 SN - 0741-0395, 0741-0395 KW - Index Medicus KW - Genotype KW - Software KW - Genetic Testing KW - Age Factors KW - Chromosomes, Human, Pair 2 KW - Sex Factors KW - Humans KW - Chromosome Mapping KW - Male KW - Female KW - Chromosomes, Human, Pair 5 KW - Genetic Linkage KW - Event-Related Potentials, P300 -- genetics KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69362946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=Comparison+of+two+linkage+inference+procedures+for+genes+related+to+the+P300+component+of+the+event+related+potential.&rft.au=Goldin%2C+L+R%3BChase%2C+G+A&rft.aulast=Goldin&rft.aufirst=L&rft.date=1999-01-01&rft.volume=17+Suppl+1&rft.issue=&rft.spage=S163&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&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 - Possible linkage of alcoholism, monoamine oxidase activity and P300 amplitude to markers on chromosome 12q24. AN - 69362299; 10597435 AB - Multipoint linkage analysis was used to screen for evidence of linkage between alcoholism and five alcoholism-related quantitative traits. The results suggest that a susceptibility locus that influences monoamine oxidase activity and P300 amplitude at the Pz lead, and increases the risk of alcohol dependence may be linked to markers in the 12q24 region. Furthermore, the susceptibility for alcoholism may be associated with allele 3 (allele size 144) of D12S392. JF - Genetic epidemiology AU - Juo, S H AU - Pugh, E W AU - Baffoe-Bonnie, A AU - Kingman, A AU - Sorant, A J AU - Klein, A P AU - O'Neill, J AU - Mathias, R A AU - Wilson, A F AU - Bailey-Wilson, J E AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - S193 EP - S198 VL - 17 Suppl 1 SN - 0741-0395, 0741-0395 KW - Genetic Markers KW - 0 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Index Medicus KW - Quantitative Trait, Heritable KW - Genetic Testing KW - Lod Score KW - Humans KW - Genome KW - Chromosome Mapping KW - Statistics, Nonparametric KW - Genetic Linkage KW - Alcoholism -- enzymology KW - Alcoholism -- epidemiology KW - Event-Related Potentials, P300 -- genetics KW - Alcoholism -- physiopathology KW - Alcoholism -- genetics KW - Chromosomes, Human, Pair 12 KW - Monoamine Oxidase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69362299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=Possible+linkage+of+alcoholism%2C+monoamine+oxidase+activity+and+P300+amplitude+to+markers+on+chromosome+12q24.&rft.au=Juo%2C+S+H%3BPugh%2C+E+W%3BBaffoe-Bonnie%2C+A%3BKingman%2C+A%3BSorant%2C+A+J%3BKlein%2C+A+P%3BO%27Neill%2C+J%3BMathias%2C+R+A%3BWilson%2C+A+F%3BBailey-Wilson%2C+J+E&rft.aulast=Juo&rft.aufirst=S&rft.date=1999-01-01&rft.volume=17+Suppl+1&rft.issue=&rft.spage=S193&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&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 - A genome-wide search for loci contributing to smoking and alcoholism. AN - 69359522; 10597412 AB - Using the Collaborative Study on the Genetics of Alcoholism (COGA) data, we performed a sib-pair linkage analysis of two smoking-related traits and one alcoholism phenotype. The first trait, EVRNVR, was a dichotomous one we constructed based on epidemiological definitions of smoking. The second trait, PKYRS, used the quantitative pack-year history provided, and the third trait was the COGA alcoholism classification, ALDX1. There was some evidence for linkage of the EVRNVR trait to regions-on chromosomes 6, 9, and 14. Smaller numbers of loci provided nominal evidence for linkage to PKYRS, although some candidate gene regions were identified. The number of loci identified using EVRNVR suggests that a threshold-based phenotype may better identify loci affecting smoking history. Approximately one-third of the loci that showed evidence for linkage to EVRNVR at a nominal significance level (p < 0.01) also showed evidence for linkage to ALDX1. Some of these regions may represent loci increasing vulnerability to both smoking and alcoholism. JF - Genetic epidemiology AU - Bergen, A W AU - Korczak, J F AU - Weissbecker, K A AU - Goldstein, A M AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20852, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - S55 EP - S60 VL - 17 Suppl 1 SN - 0741-0395, 0741-0395 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Phenotype KW - Genetic Linkage KW - Age Factors KW - Sex Factors KW - Humans KW - Chromosomes, Human, Pair 9 KW - Chromosomes, Human, Pair 6 KW - Chromosomes, Human, Pair 14 KW - Family Health KW - Male KW - Female KW - Genetic Testing KW - Smoking -- genetics KW - Alcoholism -- genetics KW - Genome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69359522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=A+genome-wide+search+for+loci+contributing+to+smoking+and+alcoholism.&rft.au=Bergen%2C+A+W%3BKorczak%2C+J+F%3BWeissbecker%2C+K+A%3BGoldstein%2C+A+M&rft.aulast=Bergen&rft.aufirst=A&rft.date=1999-01-01&rft.volume=17+Suppl+1&rft.issue=&rft.spage=S55&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&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 - Folding funnels and conformational transitions via hinge-bending motions. AN - 69339390; 10593256 AB - In this article we focus on presenting a broad range of examples illustrating low-energy transitions via hinge-bending motions. The examples are divided according to the type of hinge-bending involved; namely, motions involving fragments of the protein chains, hinge-bending motions involving protein domains, and hinge-bending motions between the covalently unconnected subunits. We further make a distinction between allosterically and nonallosterically regulated proteins. These transitions are discussed within the general framework of folding and binding funnels. We propose that the conformers manifesting such swiveling motions are not the outcome of "induced fit" binding mechanism; instead, molecules exist in an ensemble of conformations that are in equilibrium in solution. These ensembles, which populate the bottoms of the funnels, a priori contain both the "open" and the "closed" conformational isomers. Furthermore, we argue that there are no fundamental differences among the physical principles behind the folding and binding funnels. Hence, there is no basic difference between funnels depicting ensembles of conformers of single molecules with fragment, or domain motions, as compared to subunits in multimeric quaternary structures, also showing such conformational transitions. The difference relates only to the size and complexity of the system. The larger the system, the more complex its corresponding fused funnel(s). In particular, funnels associated with allosterically regulated proteins are expected to be more complicated, because allostery is frequently involved with movements between subunits, and consequently is often observed in multichain and multimolecular complexes. This review centers on the critical role played by flexibility and conformational fluctuations in enzyme activity. Internal motions that extend over different time scales and with different amplitudes are known to be essential for the catalytic cycle. The conformational change observed in enzyme-substrate complexes as compared to the unbound enzyme state, and in particular the hinge-bending motions observed in enzymes with two domains, have a substantial effect on the enzymatic catalytic activity. The examples we review span the lipolytic enzymes that are particularly interesting, owing to their activation at the water-oil interface; an allosterically controlled dehydrogenase (lactate dehydrogenase); a DNA methyltransferase, with a covalently-bound intermediate; large-scale flexible loop motions in a glycolytic enzyme (TIM); domain motion in PGK, an enzyme which is essential in most cells, both for ATP generation in aerobes and for fermentation in anaerobes; adenylate kinase, showing large conformational changes, owing to their need to shield their catalytic centers from water; a calcium-binding protein (calmodulin), involved in a wide range of cellular calcium-dependent signaling; diphtheria toxin, whose large domain motion has been shown to yield "domain swapping;" the hexameric glutamate dehydrogenase, which has been studied both in a thermophile and in a mesophile; an allosteric enzyme, showing subunit motion between the R and the T states (aspartate transcarbamoylase), and the historically well-studied lac repressor. Nonallosteric subunit transitions are also addressed, with some examples (aspartate receptor and BamHI endonuclease). Hence, using this enzyme-catalysis-centered discussion, we address energy funnel landscapes of large-scale conformational transitions, rather than the faster, quasi-harmonic, thermal fluctuations. JF - Cell biochemistry and biophysics AU - Kumar, S AU - Ma, B AU - Tsai, C J AU - Wolfson, H AU - Nussinov, R AD - Intramural Research Support Program-SAIC, Laboratory of Experimental and Computational Biology, NCI-FCRDC, Frederick, MD, 21702, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 141 EP - 164 VL - 31 IS - 2 SN - 1085-9195, 1085-9195 KW - Calmodulin KW - 0 KW - Chaperonin 60 KW - Diphtheria Toxin KW - Receptors, Amino Acid KW - Repressor Proteins KW - aspartic acid receptor KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Glutamate Dehydrogenase KW - EC 1.4.1.2 KW - DNA modification methylase HhaI KW - EC 2.1.1.- KW - DNA-Cytosine Methylases KW - Aspartate Carbamoyltransferase KW - EC 2.1.3.2 KW - Phosphoglycerate Kinase KW - EC 2.7.2.3 KW - Adenylate Kinase KW - EC 2.7.4.3 KW - Lipase KW - EC 3.1.1.3 KW - Deoxyribonuclease BamHI KW - EC 3.1.21.- KW - Triose-Phosphate Isomerase KW - EC 5.3.1.1 KW - Index Medicus KW - Lipase -- chemistry KW - Adenylate Kinase -- chemistry KW - Diphtheria Toxin -- chemistry KW - Models, Molecular KW - Calmodulin -- chemistry KW - DNA-Cytosine Methylases -- chemistry KW - L-Lactate Dehydrogenase -- chemistry KW - Deoxyribonuclease BamHI -- chemistry KW - Repressor Proteins -- chemistry KW - Aspartate Carbamoyltransferase -- chemistry KW - Models, Biological KW - Phosphoglycerate Kinase -- chemistry KW - Receptors, Amino Acid -- chemistry KW - Glutamate Dehydrogenase -- chemistry KW - Chaperonin 60 -- chemistry KW - Triose-Phosphate Isomerase -- chemistry KW - Protein Folding KW - Protein Binding KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69339390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biochemistry+and+biophysics&rft.atitle=Folding+funnels+and+conformational+transitions+via+hinge-bending+motions.&rft.au=Kumar%2C+S%3BMa%2C+B%3BTsai%2C+C+J%3BWolfson%2C+H%3BNussinov%2C+R&rft.aulast=Kumar&rft.aufirst=S&rft.date=1999-01-01&rft.volume=31&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Cell+biochemistry+and+biophysics&rft.issn=10859195&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 - Molecular epidemiology of lung cancer. AN - 69334297; 10582132 AB - Lung cancer occurs through a complex multistage process that results from the combination of carcinogen exposure and genetic susceptibilities. The primary etiology of lung cancer is tobacco smoking, but an understanding of why some smokers develop lung cancer, and others do not, remains unclear. Current studies focus on genetic susceptibilities to lung cancer, and how they modify the effects of tobacco smoke carcinogens. New assays are being developed to study other contributors to cancer risk, such as interindividual differences in DNA repair. There is current evidence to suggest that the risk of lung cancer for women, compared to men, is higher for the same level of smoking. Several biological differences for the types of lung cancer have been observed in women and men. Also, there appear to be differences in lung cancer between Caucasians and African-Americans. Molecular epidemiology tools are uniquely suited to study these biological differences. These studies will improve cancer risk assessments and focus cancer prevention strategies. Other studies also are focusing on tobacco addiction, in order to lead to improved smoking cessation strategies. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Shields, P G AD - Molecular Epidemiology Section, National Cancer Institute, Bethesda, MD, USA. Peter_G_Shields@nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - S7 EP - 11 VL - 10 Suppl 5 SN - 0923-7534, 0923-7534 KW - Carcinogens KW - 0 KW - Index Medicus KW - DNA Repair KW - Sex Factors KW - African Continental Ancestry Group -- genetics KW - Humans KW - Smoking Cessation KW - European Continental Ancestry Group -- genetics KW - Male KW - Female KW - Risk Assessment KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Smoking -- adverse effects KW - Lung Neoplasms -- genetics KW - Genetic Predisposition to Disease KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69334297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+epidemiology+of+lung+cancer.&rft.au=Shields%2C+P+G&rft.aulast=Shields&rft.aufirst=P&rft.date=1999-01-01&rft.volume=144&rft.issue=4&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&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 plasma pharmacokinetics and cerebrospinal fluid penetration of the thymidylate synthase inhibitor raltitrexed (Tomudex) in a nonhuman primate model. AN - 69242101; 10550563 AB - Raltitrexed (Tomudex), ZD1694) is a novel quinazoline folate analog that selectively inhibits thymidylate synthase. Intracellularly, raltitrexed is polyglutamated to its active form which can be retained in cells for prolonged periods. The pharmacokinetics of raltitrexed in plasma and cerebrospinal fluid (CSF) were studied in a nonhuman primate model. Animals received 3 mg/m(2) (n = 1), 6 mg/m(2) (n = 3), or 10 mg/m(2) (n = 3) i.v. over 15 min, and frequent plasma samples were obtained over 48 h. CSF samples were drawn from an indwelling 4th ventricular Ommaya reservoir over 48 h. Plasma and CSF raltitrexed concentrations were measured with a novel, sensitive enzyme inhibition assay with a lower limit of quantification of 0.005 microM. A three-compartment pharmacokinetic model was fitted to the raltitrexed plasma concentration-time data. The plasma concentration-time profile of raltitrexed was triexponential with a rapid initial decline and a prolonged terminal elimination phase (t(1/2) > 24 h), which was related to retention of raltitrexed in a deep tissue compartment. At the peak approximately 30% of the administered dose was in the deep tissue compartment, and 24 h after the dosing >20% of the administered dose remained in the body with >99% in the deep tissue compartment. The mean peak (end of infusion) plasma concentrations after the 3, 6, and 10 mg/m(2) doses were 1.5, 2.4 and 4.8 microM, respectively. The clearance of raltitrexed ranged from 110 to 165 ml/min per m(2), and the steady-state volume of distribution exceeded 200 l/m(2). The CSF penetration of raltitrexed was limited (0.6 to 2.0%) and drug could only be detected in the CSF following a 10 mg/m(2 )dose. The elimination of raltitrexed is triexponential with a prolonged terminal elimination phase. The pharmacokinetic profile is consistent with extensive polyglutamation and intracellular retention of ralitrexed. The three-compartment model presented here may be useful for the analysis of the pharmacokinetics of raltitrexed in humans. JF - Cancer chemotherapy and pharmacology AU - Widemann, B C AU - Balis, F M AU - Godwin, K S AU - McCully, C AU - Adamson, P C AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1928, USA. widemanb@pbmac.nci.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 439 EP - 443 VL - 44 IS - 6 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Quinazolines KW - Thiophenes KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - raltitrexed KW - FCB9EGG971 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Infusions, Intravenous KW - Half-Life KW - Metabolic Clearance Rate KW - Macaca mulatta KW - Models, Biological KW - Male KW - Quinazolines -- pharmacokinetics KW - Thymidylate Synthase -- antagonists & inhibitors KW - Thiophenes -- cerebrospinal fluid KW - Antimetabolites, Antineoplastic -- cerebrospinal fluid KW - Thiophenes -- pharmacokinetics KW - Thiophenes -- blood KW - Antimetabolites, Antineoplastic -- blood KW - Quinazolines -- blood KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Quinazolines -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69242101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemotherapy+and+pharmacology&rft.atitle=The+plasma+pharmacokinetics+and+cerebrospinal+fluid+penetration+of+the+thymidylate+synthase+inhibitor+raltitrexed+%28Tomudex%29+in+a+nonhuman+primate+model.&rft.au=Widemann%2C+B+C%3BBalis%2C+F+M%3BGodwin%2C+K+S%3BMcCully%2C+C%3BAdamson%2C+P+C&rft.aulast=Widemann&rft.aufirst=B&rft.date=1999-01-01&rft.volume=44&rft.issue=6&rft.spage=439&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&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 - Molecular recognition in P2 receptors: ligand development aided by molecular modeling and mutagenesis. AN - 69237067; 10550992 JF - Progress in brain research AU - Jacobson, K A AU - Hoffmann, C AU - Kim, Y C AU - Camaioni, E AU - Nandanan, E AU - Jang, S Y AU - Guo, D P AU - Ji, X D AU - von Kügelgen, I AU - Moro, S AU - Ziganshin, A U AU - Rychkov, A AU - King, B F AU - Brown, S G AU - Wildman, S S AU - Burnstock, G AU - Boyer, J L AU - Mohanram, A AU - Harden, T K AD - Molecular Recognition Section, LBC, NIDDK, NIH, Bethesda, MD 20892, USA. kajacobs@helix.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 119 EP - 132 VL - 120 SN - 0079-6123, 0079-6123 KW - Ligands KW - 0 KW - Receptors, Purinergic P2 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Conformation KW - Receptors, Purinergic P2 -- genetics KW - Adenosine Triphosphate -- chemical synthesis KW - Adenosine Triphosphate -- analogs & derivatives KW - Receptors, Purinergic P2 -- chemistry KW - Receptors, Purinergic P2 -- physiology KW - Adenosine Triphosphate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69237067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+brain+research&rft.atitle=Molecular+recognition+in+P2+receptors%3A+ligand+development+aided+by+molecular+modeling+and+mutagenesis.&rft.au=Jacobson%2C+K+A%3BHoffmann%2C+C%3BKim%2C+Y+C%3BCamaioni%2C+E%3BNandanan%2C+E%3BJang%2C+S+Y%3BGuo%2C+D+P%3BJi%2C+X+D%3Bvon+K%C3%BCgelgen%2C+I%3BMoro%2C+S%3BZiganshin%2C+A+U%3BRychkov%2C+A%3BKing%2C+B+F%3BBrown%2C+S+G%3BWildman%2C+S+S%3BBurnstock%2C+G%3BBoyer%2C+J+L%3BMohanram%2C+A%3BHarden%2C+T+K&rft.aulast=Jacobson&rft.aufirst=K&rft.date=1999-01-01&rft.volume=120&rft.issue=&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Progress+in+brain+research&rft.issn=00796123&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 - Characterization of new transgenic Big Blue(R) mouse and rat primary fibroblast cell strains for use in molecular toxicology studies. AN - 69209432; 10529731 AB - We have established and characterized primary mouse and rat cell strains for studies designed to complement in vivo gene mutation assays using the Big Blue(R) mouse or rat. Primary fibroblast cell strains, designated BBM1 and BBR1, were derived from a transgenic male Big Blue(R) B6C3F1 mouse and from a male Big Blue(R) Fischer-344 rat, respectively. Both BBM1 and BBR1 are genetically stable and mostly diploid. Both cell strains have low spontaneous frequencies of mutation at the lacI and cII loci as well as low frequencies of sister chromatid exchange and micronuclei formation. In addition, N-ethyl-N-nitrosourea (ENU) induces mutations at the cII locus in both BBM1 and BBR1 cells. These new primary Big Blue(R) mouse (BBM1) and rat (BBR1) fibroblast cell strains represent useful new models for molecular toxicology studies. Environ. Mol. Mutagen. 34:90-96, 1999 Published 1999 Wiley-Liss, Inc. JF - Environmental and molecular mutagenesis AU - Erexson, G L AU - Watson, D E AU - Tindall, K R AD - Molecular Mutagenesis Group, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999 PY - 1999 DA - 1999 SP - 90 EP - 96 VL - 34 IS - 2-3 SN - 0893-6692, 0893-6692 KW - Mutagens KW - 0 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Ethylnitrosourea -- toxicity KW - Mutagens -- toxicity KW - Mice KW - Mice, Transgenic KW - Male KW - Mutagenicity Tests -- methods KW - Cell Line UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69209432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+molecular+mutagenesis&rft.atitle=Characterization+of+new+transgenic+Big+Blue%28R%29+mouse+and+rat+primary+fibroblast+cell+strains+for+use+in+molecular+toxicology+studies.&rft.au=Erexson%2C+G+L%3BWatson%2C+D+E%3BTindall%2C+K+R&rft.aulast=Erexson&rft.aufirst=G&rft.date=1999-01-01&rft.volume=34&rft.issue=2-3&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Environmental+and+molecular+mutagenesis&rft.issn=08936692&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 - Reproductive Endocrine Disruption by Environmental Xenobiotics that Modulate the Estrogen-Signaling Pathway, Particularly Tetrachlorodibenzo-p-dioxin (TCDD) AN - 20723392; 7837466 AB - Environmental pollutants are known to exert endocrine-disrupting effects on several hormonal axes of animals, including reproduction and development. Many of these xenobiotics modulate the estrogen-receptor signaling pathway(s) in agonistic or antagonistic ways. Some of the compounds are themselves estrogenic (so- called xenoestrogens, environmental estrogens, or ecoestrogens), and are classified as synthetic estrogens, phyto- or fungal estrogens, alkylphenol ethoxylates; certain non-coplanar polyclorinated biphenyls (PCBs), etc. Other molecules are anti-androgenic, e.g., p, p-dichloro-diphenyl-dichloroethylene (DDE); while still others disrupt estrogen function in a manner that is dose, species and tissue specific, e.g., certain co- planar PCBs and dioxin-like molecules (e.g., tetrachlorodibenzo-p-dioxin [TCDD]). Exposure to some compounds has been correlated with skewing of sex ratios in aquatic species, and feminization and demasculinization of male animals; declines in human sperm counts; and overall diminution in fertility of birds, fish, and mammals. This review will cover these various xenobiotics and evaluate them for their estrogen-modulating effects; and then further concentrate on TCDD specifically. Dioxins are produced as by-products of herbicide overuse, from paper bleaching, plastics manufacture, and waste incineration. TCDD has been correlated with altered fecundity and endometriosis in monkeys, and with certain cancers in experimental animals and humans. TCDD is also correlated with reproductive deficits in many laboratory species. In summary, we believe that some of the reproductive deficits from endocrine-disrupting xenobiotics may be attributable to the modulation of the estrogen-signaling pathway, in positive and negative manners, depending on dose, species, and tissue specificity. JF - Journal of Reproduction and Development AU - J., Hutz Reinhold AD - Department of Biological Sciences, NIEHS Marine and Freshwater Biomedical Sciences Center, University of Wisconsin-Milwaukee, Lapham Hall, Room 308, 3209 N. Maryland Avenue, Milwaukee, WI 53211-0413, USA Y1 - 1999///0, PY - 1999 DA - 0, 1999 SP - 1 EP - 12 PB - The Japanese Society of Animal Reproduction VL - 45 IS - 1 SN - 0916-8818, 0916-8818 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts KW - Xenobiotic estrogens KW - Dioxin KW - Endocrine disruption KW - Fertility KW - endocrine disruptors KW - Endocrine disruptors KW - Pollution effects KW - Endometriosis KW - Xenobiotics KW - Sperm KW - Xenoestrogens KW - Pollutants KW - Chemical pollution KW - Plastics KW - PCB KW - Estrogens KW - Bleaching KW - Sex ratio KW - DDE KW - Wastes KW - TCDD KW - Herbicides KW - Cancer KW - Biphenyl KW - alkylphenols KW - polychlorinated biphenyls KW - Fecundity KW - Reviews KW - Reproduction KW - Signal transduction KW - K 03410:Animal Diseases KW - X 24330:Agrochemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20723392?accountid=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+Reproduction+and+Development&rft.atitle=Reproductive+Endocrine+Disruption+by+Environmental+Xenobiotics+that+Modulate+the+Estrogen-Signaling+Pathway%2C+Particularly+Tetrachlorodibenzo-p-dioxin+%28TCDD%29&rft.au=J.%2C+Hutz+Reinhold&rft.aulast=J.&rft.aufirst=Hutz&rft.date=1999-01-01&rft.volume=45&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Reproduction+and+Development&rft.issn=09168818&rft_id=info:doi/10.1262%2Fjrd.45.1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-11-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Fertility; Endocrine disruptors; Endometriosis; Sperm; Xenobiotics; Xenoestrogens; Pollutants; Plastics; PCB; Estrogens; Sex ratio; Bleaching; DDE; Wastes; TCDD; Herbicides; Cancer; Biphenyl; alkylphenols; Fecundity; polychlorinated biphenyls; Reviews; Reproduction; Dioxin; Signal transduction; endocrine disruptors; Pollution effects; Chemical pollution DO - http://dx.doi.org/10.1262/jrd.45.1 ER - TY - JOUR T1 - Threading Analysis of Prospero-Type Homeodomains AN - 20035399; 8720596 AB - The homeodomain is a common structural motif found in many transcription factors involved in cell fate determination during development. We have used threading analysis techniques to predict whether the atypical homeodomain of prospero (pros) family members could form the three-helical homeodomain structural motif, even though these proteins are not statistically similar to canonical homeodomains as assessed by BLAST searches. Amino acid sequences of these divergent homeodomain proteins were threaded through the X-ray coordinates of the Drosophila engrailed homeodomain protein [23]. The analysis confirms that the prospero class of homeodomain proteins is indeed capable of forming the homeodomain structure despite its low degree of sequence identity to the canonical homeodomain. Energy calculations indicate that the homeodomain structure is stabilized primarily by hydrophobic interactions between residues at the helical interfaces. Although the atypical prospero-type homeodomain shows very little sequence similarity when compared to other homeodomain proteins, the critical amino acids responsible for maintaining the three-dimensional structure are highly conserved. A number of other homeodomain proteins, such as PHO2p from Saccharomyces and Pax6 from human, were also included in the threading analysis and were shown to be able to form the engrailed structure, indicating that there are no rigid overall sequence requirements for the formation of the homeodomain structural motif. Based on the threading experiments and the subsequent structural alignment, a new amino acid signature that unambiguously identifies the prospero-type proteins was deduced. JF - In Silico Biology AU - Banerjee-Basu, Sharmila AU - Landsman, David AU - Baxevanis, Andreas D AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892 USA Y1 - 1999 PY - 1999 DA - 1999 SP - 163 EP - 173 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 3 SN - 1386-6338, 1386-6338 KW - Entomology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - homeodomain KW - prospero KW - protein threading KW - structure prediction KW - Pax6 protein KW - Amino acids KW - Prospero protein KW - Homeobox KW - Hydrophobicity KW - Development KW - Saccharomyces KW - Ionizing radiation KW - Transcription factors KW - Energy KW - Conserved sequence KW - Cell fate KW - Drosophila KW - Amino acid sequence KW - Z 05300:General KW - K 03310:Genetics & Taxonomy KW - W 30900:Methods KW - G 07780:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20035399?accountid=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=In+Silico+Biology&rft.atitle=Threading+Analysis+of+Prospero-Type+Homeodomains&rft.au=Banerjee-Basu%2C+Sharmila%3BLandsman%2C+David%3BBaxevanis%2C+Andreas+D&rft.aulast=Banerjee-Basu&rft.aufirst=Sharmila&rft.date=1999-01-01&rft.volume=1&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Pax6 protein; Amino acids; Energy; Transcription factors; Ionizing radiation; Prospero protein; Conserved sequence; Hydrophobicity; Homeobox; Development; Cell fate; Amino acid sequence; Saccharomyces; Drosophila ER - TY - JOUR T1 - An Evolutionary Classification of the Metallo--Lactamase Fold Proteins AN - 19882950; 8720601 AB - All the detectable metallo--lactamase fold proteins were identified in the publicly available sequence databases and complete genome sequences using iterative profile searches with the PSI-BLAST program and motif searches with position specific weight matrices. The catalytic site/mechanism and the corresponding structural elements were characterized for these proteins based on the available structure of the Bacillus zinc-dependent -lactamase. Based on pair-wise sequence and phylogenetic analysis an evolutionary classification for enzymes of this fold was developed and discussed in terms of implications for substrate specificity. Finally, some predicted inactive members which have been recruited for non-enzymatic functions such as microtubule binding in a cytoskeletal MAP1 are described. JF - In Silico Biology AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bldg. 38A, Bethesda, MD 20894, USA, and Department of Biology - * BSBW, Texas A University, College Station, Texas 77843, USA,, aravind@ncbi.nlm.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 69 EP - 91 PB - IOS Press, Nieuwe Hemweg 6B VL - 1 IS - 2 SN - 1386-6338, 1386-6338 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts KW - -lactamase KW - metal dependent hydrolases KW - poly-A specific RNA processing KW - DNA repair KW - inactive enzymes KW - Genomes KW - Phylogeny KW - Microtubules KW - Nucleotide sequence KW - Substrate specificity KW - Enzymes KW - Cytoskeleton KW - Computer programs KW - Databases KW - Active sites KW - Bacillus KW - Evolution KW - J 02310:Genetics & Taxonomy KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19882950?accountid=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=In+Silico+Biology&rft.atitle=An+Evolutionary+Classification+of+the+Metallo--Lactamase+Fold+Proteins&rft.au=Aravind%2C+L&rft.aulast=Aravind&rft.aufirst=L&rft.date=1999-01-01&rft.volume=1&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-01-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Cytoskeleton; Phylogeny; Genomes; Databases; Computer programs; Microtubules; Nucleotide sequence; Enzymes; Substrate specificity; Active sites; Evolution; Bacillus ER - TY - JOUR T1 - Strategies for chemoprevention of prostate cancer. AN - 1859389305; 12496854 AB - Because prostate cancer has a long latency and high incidence, it is a good target for chemoprevention by agents such as retinoids, antiandrogens, antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are frequently conducted on cohorts of patients with previous cancers or premalignant lesions who are scheduled for prostate cancer surgery; such trials are currently in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of men with high-grade PIN (HGPIN) are particularly useful in that they require a much smaller cohort of 200-400 patients instead of the 18 000 patients required for typical Phase III trials. Even with a smaller sample size, statistically significant evidence of cancer prevention is achieved due to the high probability of HGPIN progressing to cancer (35-55%). A Bayesian sequential monitoring system allows interim analysis of biomarker modulation as early as the completion of 30 patients. Putting all these strategies together will help inhibit, delay, or modulate the natural history of prostate carcinogenesis. JF - Prostate cancer and prostatic diseases AU - Kelloff, G J AU - Lieberman, R AU - Brawer, M K AU - Crawford, E D AU - Labrie, F AU - Miller, G J AD - Chemoprevention Branch, Division of Cancer Prevention, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. Y1 - 1999/01// PY - 1999 DA - January 1999 SP - 27 EP - 33 VL - 2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859389305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostate+cancer+and+prostatic+diseases&rft.atitle=Strategies+for+chemoprevention+of+prostate+cancer.&rft.au=Kelloff%2C+G+J%3BLieberman%2C+R%3BBrawer%2C+M+K%3BCrawford%2C+E+D%3BLabrie%2C+F%3BMiller%2C+G+J&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1999-01-01&rft.volume=2&rft.issue=&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Prostate+cancer+and+prostatic+diseases&rft.issn=1476-5608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2002-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malignancy: Current Clinical Practice: Treatment of Hairy Cell Leukemia at the Close of the 20th Century. AN - 1859354265; 11399570 AB - In the last half of this century, hairy cell leukemia was recognized as a distinct B-cell malignancy, accounting for 2% of all leukemias. Characteristics include splenomegaly, pancytopenia, a usually indolent course, and responsiveness to both interferon and purine analog therapy. Accurate diagnosis requires the demonstration of malignant cells in the bone marrow and peripheral blood which contain cytoplasmic projections and characteristic surface antigens. Splenectomy was identified early as a palliative therapy, and in 1984 systemic treatment with interferon alpha was first reported to induce complete remissions. Soon thereafter, the purine analog deoxycoformycin was found to induce more durable complete remissions in a higher percentage of patients. In 1990, 2-Chlorodeoxyadenosine, a new purine analog therapy, was reported to be capable of inducing long-term durable responses in most patients after a single cycle. Current challenges include identifying which purine analog is the least toxic since both appear similarly effective, and neither appear to add to the already increased rate of second malignancies occurring in these patients. Moreover, up to 25% of patients with hairy cell leukemia fail initially or eventually to respond to standard therapy, making the development of new approaches necessary. The characteristic bright expression of several B-cell antigens on the malignant cells, including CD20, CD22 and CD25, has led to the development of targeted biotherapeutic approaches. A recombinant immunotoxin targeting CD25 has recently been reported to induce major responses and it is likely that other successful targeted approaches will be reported early in the new century. JF - Hematology (Amsterdam, Netherlands) AU - Kreitman, ROBERT J. AU - Cheson, BRUCE D. AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1999 PY - 1999 DA - 1999 SP - 283 EP - 303 VL - 4 IS - 4 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859354265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology+%28Amsterdam%2C+Netherlands%29&rft.atitle=Malignancy%3A+Current+Clinical+Practice%3A+Treatment+of+Hairy+Cell+Leukemia+at+the+Close+of+the+20th+Century.&rft.au=Kreitman%2C+ROBERT+J.%3BCheson%2C+BRUCE+D.&rft.aulast=Kreitman&rft.aufirst=ROBERT&rft.date=1999-01-01&rft.volume=4&rft.issue=4&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Hematology+%28Amsterdam%2C+Netherlands%29&rft.issn=1607-8454&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of Cigarette Smoking with Amyotrophic Lateral Sclerosis AN - 18023404; 4678463 AB - We explored the relationship between amyotrophic lateral sclerosis (ALS) and cigarette smoking in a case-control study conducted in New England from 1993 to 1996. Recently diagnosed ALS cases (n = 109) were recruited from two major referral centers. Population controls (n = 256) were identified by random telephone screening. Data were analyzed by logistic regression. After adjusting for age, sex, region and education, ever having smoked cigarettes was associated with an increase in risk for ALS (odds ratio 1.7; 95% confidence interval 1.0-2.8). Average cigarettes smoked per day, years smoked and pack-years were all greater in cases than controls, but dose-response trends were not observed. Similar numbers of cases and controls had ever used alcohol, and only a small, nonsignificant association of drinks per month with ALS was observed. The association of cigarette smoking with ALS was not affected by adjusting for alcohol use. In contrast, the weak relationship of ALS with alcohol use was apparently due to confounding by smoking. JF - Neuroepidemiology AU - Kamel, F AU - Umbach, D M AU - Munsat, T L AU - Shefner, J M AU - Sandler, D P AD - National Institute of Environmental Health Sciences, Research Triangle Park, N.C., USA Y1 - 1999 PY - 1999 DA - 1999 SP - 194 EP - 202 VL - 18 IS - 4 SN - 0251-5350, 0251-5350 KW - man KW - USA, New England KW - amyotrophic lateral sclerosis KW - CSA Neurosciences Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Amyotrophic lateral sclerosis KW - Neurotoxicity KW - Cigarette smoking KW - Regression analysis KW - Ethanol KW - H 11000:Diseases/Injuries/Trauma KW - X 24180:Social poisons & drug abuse KW - N3 11105:Primates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18023404?accountid=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=Neuroepidemiology&rft.atitle=Association+of+Cigarette+Smoking+with+Amyotrophic+Lateral+Sclerosis&rft.au=Kamel%2C+F%3BUmbach%2C+D+M%3BMunsat%2C+T+L%3BShefner%2C+J+M%3BSandler%2C+D+P&rft.aulast=Kamel&rft.aufirst=F&rft.date=1999-01-01&rft.volume=18&rft.issue=4&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Neuroepidemiology&rft.issn=02515350&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 - Cigarette smoking; Amyotrophic lateral sclerosis; Regression analysis; Ethanol; Neurotoxicity ER - TY - JOUR T1 - Stem Trace: an interactive visual tool for comparative RNA structure analysis AN - 17902628; 5148267 AB - Stem Trace is one of the latest tools available in STRUCTURELAB, an RNA structure analysis computer workbench. The paradigm used in STRUCTURELAB views RNA structure determination as a problem of dealing with a database of a large number of computationally generated structures. Stem Trace provides the capability to analyze this data set in a novel, visually driven, interactive and exploratory way. In addition to providing graphs at a high level of ion, it is also connected with complementary visualization tools which provide orthogonal views of the same data, as well as drawing of structures represented by a stem trace. Thus, on top of being an analysis tool, Stem Trace is a graphical user interface to an RNA structural information database. We illustrate Stem Trace's capabilities with several examples of the analysis of RNA folding data performed on 24 strains of HIV-1, HIV-2 and SIV sequences around the HIV dimerization region. This dimer linkage site has been found to play a role in encapsidation, reverse transcription, recombination, and inhibition of translation. Our examples show how Stem Trace elucidates preservation of structures in this region across the various strains of HIV. JF - Bioinformatics AU - Kasprzak, W AU - Shapiro, B AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute/FCRDC, Bldg 469, Rm 150C, MD 21702, USA, kasprzak@ncifcrf.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 16 EP - 31 VL - 15 IS - 1 SN - 1367-4803, 1367-4803 KW - human immunodeficiency virus 1 KW - human immunodeficiency virus 2 KW - simian immunodeficiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Databases KW - RNA KW - Nucleotide sequence KW - Bioinformatics KW - 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/17902628?accountid=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=Bioinformatics&rft.atitle=Stem+Trace%3A+an+interactive+visual+tool+for+comparative+RNA+structure+analysis&rft.au=Kasprzak%2C+W%3BShapiro%2C+B&rft.aulast=Kasprzak&rft.aufirst=W&rft.date=1999-01-01&rft.volume=15&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&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 - Bioinformatics; Computer applications; RNA; Nucleotide sequence; Databases ER - TY - JOUR T1 - Centrifugal precipitation chromatography applied to fractionation of proteins with ammonium sulfate AN - 17641043; 4675542 AB - A novel chromatographic system introduced here internally generates a concentration gradient of ammonium sulfate (AS) along a long channel to fractionate proteins according to their solubility in AS solution. The separation column consists of a pair of discs with mutually mirror-imaged spiral channels that are separated by a semipermeable membrane. The disc assembly is mounted on a sealless continuous flow centrifuge. A concentrated AS solution is introduced into the upper channel while a water solution is passed through the lower channel in the opposite direction in a rotating column. A mixture of proteins injected into the water channel moves along an AS gradient of increasing concentration that has been established in the water solution. Each protein species precipitates at a different AS concentration along the gradient. By decreasing the concentration of the AS solution its concentration in the water is decreased, causing the protein to redissolve and to reprecipitate further down the channel. The eluate is continuously monitored and collected using a fraction collector. The method has been demonstrated on separation of serum proteins and applied to purification of a recombinant ketosteroid isomerase from a crude E. coli lysate by adding an affinity ligand to the sample solution. A possible mechanism involved in this affinity separation is discussed. The method may be applied to other biopolymers such as DNA and RNA. JF - Journal of Liquid Chromatography & Related Technologies AU - Ito, Y AD - Laboratory of Biophysical Chemistry National Heart, Lung, and Blood Institute National Institutes of Health, Bldg. 10, Room 7N322 10 Center Drive, MSC 1676 Bethesda, MD 20892-1676, USA Y1 - 1999 PY - 1999 DA - 1999 SP - 2825 EP - 2836 VL - 22 IS - 18 SN - 1082-6076, 1082-6076 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Centrifugation KW - Ammonium sulfate KW - Escherichia coli KW - Column chromatography KW - Precipitation KW - A 01002:Acids, amino acids, peptides & proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17641043?accountid=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+Liquid+Chromatography+%26+Related+Technologies&rft.atitle=Centrifugal+precipitation+chromatography+applied+to+fractionation+of+proteins+with+ammonium+sulfate&rft.au=Ito%2C+Y&rft.aulast=Ito&rft.aufirst=Y&rft.date=1999-01-01&rft.volume=22&rft.issue=18&rft.spage=2825&rft.isbn=&rft.btitle=&rft.title=Journal+of+Liquid+Chromatography+%26+Related+Technologies&rft.issn=10826076&rft_id=info:doi/10.1081%2FJLC-100102062 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Precipitation; Column chromatography; Centrifugation; Ammonium sulfate DO - http://dx.doi.org/10.1081/JLC-100102062 ER - TY - JOUR T1 - The Role of Social Work in HIV/AIDS Clinical Trials AN - 1761726169; 199905350 AB - Drawing on experiences at the National Instits of Health, discussed is how the social worker can facilitate screening, retention, & patient adherence in clinical trials for HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome). After summarizing the process & its key vocabulary, three case studies are used to demonstrate how social workers can assist clients who may wish to participate in, or are already enrolled in, a clinical trial. After examining six major issues that affect the client in a clinical trial (informed consent; treatment vs research; risks & side effects; altruism; the role of family members; & gender, race, & class issues), interventions at the screening level are detailed, along with concrete services & psychosocial interventions for study participants. 19 References. Adapted from the source document. JF - Social Work in Health Care AU - Williams, Judith K AU - Boykin, Fred AD - HIV Counseling Program, National Instits Health, Bldg 10 Rm 1N252 9000 Rockville Pike, Bethesda MD 20892 jwilliams@nih.gov Y1 - 1999///0, PY - 1999 DA - 0, 1999 SP - 35 EP - 56 VL - 29 IS - 1 SN - 0098-1389, 0098-1389 KW - Client Relations KW - Occupational Roles KW - Acquired Immune Deficiency Syndrome KW - Social Workers KW - Medical Research KW - Research Subjects KW - article KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1761726169?accountid=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=Social+Work+in+Health+Care&rft.atitle=The+Role+of+Social+Work+in+HIV%2FAIDS+Clinical+Trials&rft.au=Williams%2C+Judith+K%3BBoykin%2C+Fred&rft.aulast=Williams&rft.aufirst=Judith&rft.date=1999-01-01&rft.volume=29&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Social+Work+in+Health+Care&rft.issn=00981389&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2016-02-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Social Workers; Occupational Roles; Acquired Immune Deficiency Syndrome; Research Subjects; Medical Research; Client Relations ER - TY - JOUR T1 - Rational design of live-attenuated recombinant vaccine virus for human respiratory syncytial virus by reverse genetics AN - 17525585; 4714237 AB - "Reverse genetics" is the reconstitution of biological components from cDNA. It is now possible to produce infectious recombinant (r) RSV entirely from cDNA. Thus, one can introduce predetermined changes into RSV through the cDNA intermediate. This provides a powerful tool for studies of molecular biology, viral pathogenesis, and the host immune response, as well as a method for the rational design of live-attenuated viral vaccine candidates. This article will describe the use of reverse genetics to prepare and characterize live-attenuated recombinant versions of the RSV A2 strain (antigenic subgroup A). JF - Advances in Virus Research AU - Collins, P L AU - Whitehead, S S AU - Bukreyev, A AU - Fearns, R AU - Teng, M N AU - Juhasz, K AU - Chanock, R M AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0720, USA Y1 - 1999 PY - 1999 DA - 1999 SP - 423 EP - 452 VL - 54 SN - 0065-3527, 0065-3527 KW - pathogenesis KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Attenuation KW - Human respiratory syncytial virus KW - Recombinants KW - Respiratory tract diseases KW - Immune response KW - Vaccines KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17525585?accountid=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=Advances+in+Virus+Research&rft.atitle=Rational+design+of+live-attenuated+recombinant+vaccine+virus+for+human+respiratory+syncytial+virus+by+reverse+genetics&rft.au=Collins%2C+P+L%3BWhitehead%2C+S+S%3BBukreyev%2C+A%3BFearns%2C+R%3BTeng%2C+M+N%3BJuhasz%2C+K%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Collins&rft.aufirst=P&rft.date=1999-01-01&rft.volume=54&rft.issue=&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Advances+in+Virus+Research&rft.issn=00653527&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 respiratory syncytial virus; Respiratory tract diseases; Vaccines; Recombinants; Attenuation; Immune response ER - TY - JOUR T1 - Carcinogenic Chemical-Response "Fingerprint" for Male F344 Rats Exposed to a Series of 195 Chemicals: Implications for Predicting Carcinogens With Transgenic Models AN - 17451522; 4663344 AB - Transgenic model systems have recently been advocated as replacements for traditional methods of testing chemicals for carcinogenicity in rodents. To shed light on the diversity of responses induced by chemicals in natural whole animal systems, a type of "fingerprint" is devised and, in turn, applied to describe the results of testing approximately 200 chemicals in male F344 rats. Such focus helps develop an appreciation of the complexity involved in the chemical carcinogenic response. When we ask transgenic systems to serve as replacements for natural whole animals, for predicting the risk of chemically induced cancer, we are asking them somehow to reflect or express this complexity so that the effects of exposure in humans can be realistically appraised. For the fingerprint, a graphic data display is used to represent the different tissues and organs that show statistically significant, chemically related tumor increases. Chemicals vary extensively according to the particular sites and the array of sites that display a carcinogenic response; but any given site may also show a carcinogenic response to a variety of different chemicals. The data suggest that a large number of different genetic factors may underlie the determination of the chemical carcinogenic response. This apparent genotypic variability and complexity in phenotypic expression would seem to make it quite difficult, if not impossible, to decide on the specific performance requirements of transgenic systems for detecting carcinogens. Unless this and other obstacles can be overcome, the transgenic approach to identifying carcinogenic chemicals for regulatory purposes may best be abandoned. JF - Environmental and Molecular Mutagenesis AU - Johnson, F M AD - Environmental Toxicology Program, EC-14 Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, johnson1@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 234 EP - 245 VL - 34 IS - 4 SN - 0893-6692, 0893-6692 KW - chemicals KW - rats KW - Genetics Abstracts; Toxicology Abstracts KW - Chemicals KW - Transgenic animals KW - Genetic factors KW - Carcinogenesis KW - Carcinogens KW - Toxicity testing KW - X 24240:Miscellaneous KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17451522?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Carcinogenic+Chemical-Response+%22Fingerprint%22+for+Male+F344+Rats+Exposed+to+a+Series+of+195+Chemicals%3A+Implications+for+Predicting+Carcinogens+With+Transgenic+Models&rft.au=Johnson%2C+F+M&rft.aulast=Johnson&rft.aufirst=F&rft.date=1999-01-01&rft.volume=34&rft.issue=4&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&rft_id=info:doi/10.1002%2F%28SICI%291098-2280%281999%2934%3A43.3.CO%3B2-U LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Transgenic animals; Toxicity testing; Genetic factors; Carcinogens; Chemicals DO - http://dx.doi.org/10.1002/(SICI)1098-2280(1999)34:4<234::AID-EM3>3.3.CO;2-U ER - TY - JOUR T1 - Study design for a case-control investigation of cellular telephones and other risk factors for brain tumours in adults AN - 17442293; 4657713 AB - The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case-control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age greater than or equal to 18y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene-environment interactions. JF - Radiation Protection Dosimetry AU - Inskip, P D AU - Hatch, EE AU - Stewart, P A AU - Heineman, E F AU - Ziegler, R G AU - Dosemeci, M AU - Parry, D AU - Rothman, N AU - Boice, JD Jr AU - Wilcosky, T C AU - Watson, D J AU - Shapiro, W R AU - Selker, R G AU - Fine, HA AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA Y1 - 1999 PY - 1999 DA - 1999 SP - 45 EP - 52 VL - 86 IS - 1 SN - 4144-8420, 4144-8420 KW - man KW - cellular telephones KW - tumors KW - Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Diets KW - Consumer products KW - Tumorigenesis KW - Brain KW - Electromagnetic fields KW - Telephones KW - Ionizing radiation KW - H 9000:Consumer and Recreation Safety KW - R2 23020:Technological risks KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17442293?accountid=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=Radiation+Protection+Dosimetry&rft.atitle=Study+design+for+a+case-control+investigation+of+cellular+telephones+and+other+risk+factors+for+brain+tumours+in+adults&rft.au=Inskip%2C+P+D%3BHatch%2C+EE%3BStewart%2C+P+A%3BHeineman%2C+E+F%3BZiegler%2C+R+G%3BDosemeci%2C+M%3BParry%2C+D%3BRothman%2C+N%3BBoice%2C+JD+Jr%3BWilcosky%2C+T+C%3BWatson%2C+D+J%3BShapiro%2C+W+R%3BSelker%2C+R+G%3BFine%2C+HA&rft.aulast=Inskip&rft.aufirst=P&rft.date=1999-01-01&rft.volume=86&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Radiation+Protection+Dosimetry&rft.issn=41448420&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 - Consumer products; Electromagnetic fields; Ionizing radiation; Brain; Tumorigenesis; Diets; Telephones; Risk assessment ER - TY - JOUR T1 - Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature AN - 17419016; 4641391 AB - Lipid peroxidation is a normal phenomenon that occurs continuously at low levels in all humans. These peroxidation reactions are toxic to cells and cell membranes; however, they are normally controlled by countervailing biologic mechanisms. Uncontrolled peroxidation has been associated with cell injury and death. During pregnancy, excess lipid peroxidation has been associated with preeclampsia and other reproductive complications, but there is only scattered information about baseline levels in healthy pregnant women. The purpose of this paper is to review what is known about lipid peroxidation in uncomplicated pregnancies. We begin with an overview of the lipid peroxidation process and its association with disease. We then describe the markers most commonly used to measure it. The balance of the paper is devoted to a review and summary of the literature. JF - Reproductive Toxicology AU - Little, R E AU - Gladen, B C AD - National Institute of Environmental Health Sciences, Epidemiology Branch A3-05, NIEHS, Box 12233, 111 Alexander Drive, Research Triangle Park, NC 27709, USA, little1@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 347 EP - 352 VL - 13 IS - 5 SN - 0890-6238, 0890-6238 KW - man KW - Toxicology Abstracts KW - Reviews KW - Lipid peroxidation KW - Pregnancy KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17419016?accountid=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=Reproductive+Toxicology&rft.atitle=Levels+of+lipid+peroxides+in+uncomplicated+pregnancy%3A+a+review+of+the+literature&rft.au=Little%2C+R+E%3BGladen%2C+B+C&rft.aulast=Little&rft.aufirst=R&rft.date=1999-01-01&rft.volume=13&rft.issue=5&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2FS0890-6238%2899%2900033-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lipid peroxidation; Reviews; Pregnancy DO - http://dx.doi.org/10.1016/S0890-6238(99)00033-7 ER - TY - JOUR T1 - Characterization of New Transgenic Big Blue super(+) Mouse and Rat Primary Fibroblast Cell Strains for Use in Molecular Toxicology Studies AN - 17394507; 4630368 AB - We have established and characterized primary mouse and rat cell strains for studies designed to complement in vivo gene mutation assays using the Big Blue super(+) mouse or rat. Primary fibroblast cell strains, designated BBM1 and BBR1, were derived from a transgenic male Big Blue super(+) B6C3F1 mouse and from a male Big Blue super(+) Fischer-344 rat, respectively. Both BBM1 and BBR1 are genetically stable and mostly diploid. Both cell strains have low spontaneous frequencies of mutation at the lacI and cII loci as well as low frequencies of sister chromatid exchange and micronuclei formation. In addition, N-ethyl-N-nitrosourea (ENU) induces mutations at the cII locus in both BBM1 and BBR1 cells. These new primary Big Blue super(+) mouse (BBM1) and rat (BBR1) fibroblast cell strains represent useful new models for molecular toxicology studies. JF - Environmental and Molecular Mutagenesis AU - Erexson, G L AU - Watson, DE AU - Tindall, K R AD - Molecular Mutagenesis Group, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, tindall@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 90 EP - 96 VL - 34 IS - 2-3 SN - 0893-6692, 0893-6692 KW - mice KW - rats KW - Big Blue super(+) mouse KW - Big Blue super(+) rat KW - cII gene KW - lacI gene KW - Toxicology Abstracts; Genetics Abstracts KW - Big Blue@u+ mouse KW - Big Blue@u+ rat KW - N-Ethyl-N-nitrosourea KW - Sister chromatid exchange KW - Genotoxicity KW - Genotoxicity testing KW - G 07220:General theory/testing systems KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17394507?accountid=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+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Isolated+hepatic+perfusion+with+tumor+necrosis+factor+and+melphalan+for+unresectable+cancers+confined+to+the+liver.&rft.au=Alexander%2C+H+R%3BBartlett%2C+D+L%3BLibutti%2C+S+K%3BFraker%2C+D+L%3BMoser%2C+T%3BRosenberg%2C+S+A&rft.aulast=Alexander&rft.aufirst=H&rft.date=1998-04-01&rft.volume=16&rft.issue=4&rft.spage=1479&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 - Genotoxicity; Sister chromatid exchange; N-Ethyl-N-nitrosourea; Genotoxicity testing DO - http://dx.doi.org/10.1002/(SICI)1098-2280(1999)34:2/3<90::AID-EM6>3.3.CO;2-N ER - TY - JOUR T1 - Genotoxicity Biomarkers in the Assessment of Heavy Metal Effects in Mussels: Experimental Studies AN - 17367840; 4572726 AB - Heavy metals are stable and persistent environmental contaminants. The range of metal concentrations is generally below acute thresholds in coastal areas, where recognition of chronic sublethal effects is more relevant. Evidence of long-term adverse effects, such as cancer, due to heavy metals in marine animals comes from a number of field and experimental studies. The mechanism of metal carcinogenicity remains largely unknown, although several lines of experimental evidence suggest that a genotoxic effect may be involved. The aim of our study was to evaluate the sensitivity of genotoxicity tests, alkaline elution and micronucleus test, as biomarkers for the detection of heavy metals in mussels as the sentinel species. Experimental studies were carried out on Mytilus galloprovincialis exposed in aquarium (5 days) to different concentrations of three selected metal salts, CuCl sub(2) (5, 10, 20, 40, 80 mu g/l/a), CdCl sub(2) (1.84, 18.4, 184 mu g/l/a), and HgCl sub(2) (32 mu g/l/a), and to a mixture of equimolar doses of the three metals to study the results of their joint action. Metallothionein quantitation was used as a marker of metal exposure. Lysosomal membrane stability was applied to evaluate the influence of physiological status on genotoxic damage. The ranking of genotoxic potential was in decreasing order: Hg > Cu > Cd. Cu and Hg caused an increase of DNA single-strand breaks and micronuclei frequency. Cd induced a statistical increase of DNA damage, but gave negative results with the micronucleus test. A relationship between genotoxic effects and metallothionein content was observed. Reduction in lysosomal membrane stability with the increasing concentration of heavy metals was also evident. JF - Environmental and Molecular Mutagenesis AU - Bolognesi, C AU - Landini, E AU - Roggieri, P AU - Fabbri, R AU - Viarengo, A AD - Toxicological Evaluation Unit, National Cancer Institute, Largo Rosanna Benzi, 10, 16132, Genoa, Italy, blgcld@hp380.ist.unige.it Y1 - 1999 PY - 1999 DA - 1999 SP - 287 EP - 292 VL - 33 IS - 4 SN - 8093-6692, 8093-6692 KW - Mytilus galloprovincialis KW - cadmium chloride KW - copper chloride KW - cupric chloride KW - mercuric chloride KW - metallothionein KW - Genetics Abstracts; Pollution Abstracts; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Toxicology Abstracts KW - Bioindicators KW - Heavy metals KW - Genotoxicity KW - Genotoxicity testing KW - Pollution effects KW - Copper KW - Genetic abnormalities KW - DNA damage KW - Metallothioneins KW - DNA KW - Marine organisms KW - Mercury KW - Cadmium KW - Mollusca KW - Pollution indicators KW - Organometallic complexes KW - Indicator species KW - Q5 08504:Effects on organisms KW - X 24165:Biochemistry KW - Q1 08265:Genetics and evolution KW - P 6000:TOXICOLOGY AND HEALTH KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17367840?accountid=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=Environmental+and+Molecular+Mutagenesis&rft.atitle=Genotoxicity+Biomarkers+in+the+Assessment+of+Heavy+Metal+Effects+in+Mussels%3A+Experimental+Studies&rft.au=Bolognesi%2C+C%3BLandini%2C+E%3BRoggieri%2C+P%3BFabbri%2C+R%3BViarengo%2C+A&rft.aulast=Bolognesi&rft.aufirst=C&rft.date=1999-01-01&rft.volume=33&rft.issue=4&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=80936692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Metallothioneins; Heavy metals; DNA; Mercury; Pollution effects; Cadmium; Copper; Genetic abnormalities; Pollution indicators; Organometallic complexes; Indicator species; DNA damage; Genotoxicity; Bioindicators; Marine organisms; Genotoxicity testing; Mollusca ER - TY - JOUR T1 - Evaluation of super(99m)Tc-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin AN - 17359487; 4503850 AB - We evaluated super(99m)Tc-labeled mercaptoacetyltriglycine ( super(99m)Tc-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (r sub(max)) and half clearance time (HCT) with those of super(99m)Tc-labeled diisopropyl-iminodiacetic acid ( super(99m)Tc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent ( super(99m)Tc-MAG3-biocytin or super(99m)Tc-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma-camera equipped with a pinhole collimator. Dynamic images showed rapid hepatic uptake of super(99m)Tc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas super(99m)Tc-disofenin coinjected with bilirubin showed a higher blood background than super(99m)Tc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, r sub(max) and HCT. The r sub(max) was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. super(99m)Tc-MAG3-biocytin without bilirubin coinjection showed an r sub(max) of 8.9 plus or minus 1.3 and an HCT of 399 plus or minus 36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for super(99m)Tc-disofenin with bilirubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinjection: r sub(max) was decreased from 7.9 plus or minus 2.5 to 1.4 plus or minus 0.2 and HCT was increased from 292 plus or minus 32 s to 782 plus or minus 133 s. super(99m)Tc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels. JF - Nuclear Medicine and Biology AU - Kim, Meyoung-kon AU - Seidel, J AU - Le, N AU - Kim, In-Sook AU - Yoo, Tae-Moo AU - Barker, C AU - Kobayashi, H AU - Green, M V AU - Carrasquillo, JA AU - Paik, CH AD - Department of Nuclear Medicine (Building 21, Room 136), Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA, paik@nmdhst.cc.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 43 EP - 49 VL - 26 IS - 1 SN - 0969-8051, 0969-8051 KW - mice KW - bilirubin KW - biocytin KW - imaging agents KW - mercaptoacetyltriglycine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Heart KW - Liver KW - Biliary tract KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17359487?accountid=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=Nuclear+Medicine+and+Biology&rft.atitle=Evaluation+of+super%2899m%29Tc-mercaptoacetyltriglycine-biocytin+as+a+new+hepatobiliary+imaging+agent+in+mice+coinjected+with+bilirubin&rft.au=Kim%2C+Meyoung-kon%3BSeidel%2C+J%3BLe%2C+N%3BKim%2C+In-Sook%3BYoo%2C+Tae-Moo%3BBarker%2C+C%3BKobayashi%2C+H%3BGreen%2C+M+V%3BCarrasquillo%2C+JA%3BPaik%2C+CH&rft.aulast=Kim&rft.aufirst=Meyoung-kon&rft.date=1999-01-01&rft.volume=26&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Nuclear+Medicine+and+Biology&rft.issn=09698051&rft_id=info:doi/10.1016%2FS0969-8051%2898%2900077-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Biliary tract; Heart DO - http://dx.doi.org/10.1016/S0969-8051(98)00077-8 ER - TY - JOUR T1 - Adherence of Candida albicans to bladder mucosa: development and application of a tissue explant assay TT - Entwicklung und Anwendung eines Gewebs-Explant Assays zur experimentellen Untersuchung der Adhaerenz von Candida albicans an Urothelzellen AN - 17337870; 4610585 AB - In order to study the interactions between Candida species and uroepithelial tissue, a tissue explant assay was developed using bladder mucosa harvested from New Zealand white rabbits. Blastoconidia of Candida albicans, Candida tropicalis and Candida glabrata attached to the uroepithelial tissue in similar quantities. However, there was significantly more adherence to the uroepithelium by pre-germinated C. albicans compared with C. albicans blastoconidia. Furthermore, the amount of uroepithelial tissue injury was directly related to the length of exposure of the tissue to Candida. Thus, this tissue explant assay may provide a useful method for investigating properties related to fungal adherence to transitional uroepithelium and organism-mediated tissue injury. JF - Mycoses AU - Lyman, CA AU - Navarro, E AU - Garrett, K F AU - Roberts, D D AU - Pizzo, P A AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Building 10, Room 13N240, Bethesda, MD 20892, USA Y1 - 1999 PY - 1999 DA - 1999 SP - 255 EP - 259 VL - 42 IS - 4 SN - 0933-7407, 0933-7407 KW - adherence KW - rabbits KW - tissue explant assay KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Candidiasis KW - Urinary bladder KW - Mucosa KW - Tissue culture KW - Candida albicans KW - Bioassays KW - K 03069:Fungi KW - A 01117:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17337870?accountid=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=Mycoses&rft.atitle=Adherence+of+Candida+albicans+to+bladder+mucosa%3A+development+and+application+of+a+tissue+explant+assay&rft.au=Lyman%2C+CA%3BNavarro%2C+E%3BGarrett%2C+K+F%3BRoberts%2C+D+D%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Lyman&rft.aufirst=CA&rft.date=1999-01-01&rft.volume=42&rft.issue=4&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Mycoses&rft.issn=09337407&rft_id=info:doi/ LA - German DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Candida albicans; Mucosa; Bioassays; Candidiasis; Tissue culture; Urinary bladder ER - TY - JOUR T1 - Protease inhibitors: resistance, cross-resistance, fitness and the choice of initial and salvage therapies AN - 17336425; 4604961 JF - AIDS AU - Erickson, J W AU - Gulnik, S V AU - Markowitz, M AD - NCI-FCRDC, SAIC-Frederick, PO Box B, Frederick, MD 21702, USA, erickson@ncifcrf.gov Y1 - 1999 PY - 1999 DA - 1999 SP - S189 EP - S204 VL - 13 SN - 0269-9370, 0269-9370 KW - HIV KW - man KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Drug resistance KW - Chemotherapy KW - Proteinase inhibitors KW - Antiviral agents KW - Human immunodeficiency virus KW - Cross-resistance KW - A 01068:Antiviral & viricidal KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17336425?accountid=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=AIDS&rft.atitle=Protease+inhibitors%3A+resistance%2C+cross-resistance%2C+fitness+and+the+choice+of+initial+and+salvage+therapies&rft.au=Erickson%2C+J+W%3BGulnik%2C+S+V%3BMarkowitz%2C+M&rft.aulast=Erickson&rft.aufirst=J&rft.date=1999-01-01&rft.volume=13&rft.issue=&rft.spage=S189&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&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; Chemotherapy; Acquired immune deficiency syndrome; Drug resistance; Antiviral agents; Cross-resistance; Proteinase inhibitors ER - TY - JOUR T1 - New approaches to managing opportunistic infections AN - 17335145; 4604964 JF - AIDS AU - Lundgren, J AU - Masur, H AD - Clinical Center 7D43, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1999 PY - 1999 DA - 1999 SP - S227 EP - S234 VL - 13 SN - 0269-9370, 0269-9370 KW - HIV KW - man KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Opportunist infection KW - Human immunodeficiency virus KW - Immunocompromised hosts KW - J 02855:Human Bacteriology: Others KW - V 22004:AIDS: Clinical aspects KW - K 03092:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17335145?accountid=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=AIDS&rft.atitle=New+approaches+to+managing+opportunistic+infections&rft.au=Lundgren%2C+J%3BMasur%2C+H&rft.aulast=Lundgren&rft.aufirst=J&rft.date=1999-01-01&rft.volume=13&rft.issue=&rft.spage=S227&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&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; Opportunist infection; Acquired immune deficiency syndrome; Immunocompromised hosts ER - TY - JOUR T1 - Pneumococcal disease and the role of conjugate vaccines AN - 17319110; 4576774 AB - Streptococcus pneumoniae (pneumococcus) in the postantibiotic era, remains a major cause of morbidity and mortality both in the United States and throughout the developing world. Current concerns about the epidemiology and pathogenesis of pneumococci include changing patterns of virulence and antimicrobial susceptibility and the increased opportunity for spread in communal settings such as day care centers. The concerns about changing patterns of pneumococcal infection may be balanced by the recent introduction of conjugate vaccine technology. The development of conjugate vaccines against S. pneumoniae represents a significant strategy to offset drug resistance and protect against the spread of uncontrolled invasive strains of this pathogen. This effort has been a high priority among vaccine manufacturers to help prevent dramatic increases in morbidity and mortality due to S. pneumoniae. JF - Microbial Drug Resistance AU - Klein, D L AD - Bacterial Respiratory Disease Program Officer, Respiratory Diseases Branch, DMID/NIAID, National Institutes of Health, 6700-B Rockledge Dr., Room 3130, Bethesda, MD 20892, USA, DK27A@nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 147 EP - 157 VL - 5 IS - 2 SN - 1076-6294, 1076-6294 KW - conjugate vaccines KW - man KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Streptococcus pneumoniae KW - Epidemiology KW - Vaccines KW - Pneumonia KW - Antibiotic resistance 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/17319110?accountid=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=Microbial+Drug+Resistance&rft.atitle=Pneumococcal+disease+and+the+role+of+conjugate+vaccines&rft.au=Klein%2C+D+L&rft.aulast=Klein&rft.aufirst=D&rft.date=1999-01-01&rft.volume=5&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Microbial+Drug+Resistance&rft.issn=10766294&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 - Streptococcus pneumoniae; Antibiotic resistance; Vaccines; Pneumonia; Epidemiology ER - TY - JOUR T1 - Preparation and in vitro Studies of [ super(125)I]IUDR-T101 Antibody Conjugate AN - 17308093; 4548134 AB - Idoxuridine labeled with super(125)I was conjugated to polylysine. This conjugate was then coupled to the carbohydrate side chains of T101 monoclonal antibodiy (anti-CD5). The immunoreactivity, cell retention, cytotoxicity, and intracellular localization of this conjugate was tested in CCRF-CEM cells (CD5 positive). The conjugate had 68% immunoreactivity. The retention of super(125)I by CCRF-CEM cells was higher for the conjugate than for T101 directly labeled with super(125)I and more of it localized in the nucleus than did the super(125)I-labeled T101. The super(125)I IUDR-polylysine-T101 conjugate was more cytotoxic than the super(125)I-labeled T101. In conclusion, the conjugation of [ super(125)I]IUDR to T101 is feasible, and preferential targeting of the super(125)I to the nucleus is obtained. JF - Cancer Biotherapy and Radiopharmaceuticals AU - Chakrabarti, M C AU - Paik, CH AU - Carrasquillo, JA AD - Department of Nuclear Medicine, CC, National Institutes of Health, 10 Center Dr., MSC 1180, Bld. 10/1C-401, Bethesda, MD 20892-1180, USA Y1 - 1999 PY - 1999 DA - 1999 SP - 91 EP - 98 VL - 14 IS - 2 SN - 1084-9785, 1084-9785 KW - CCRF-CEM cells KW - idoxuridine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Monoclonal antibodies KW - Carbohydrates KW - Nuclei KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17308093?accountid=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+Biotherapy+and+Radiopharmaceuticals&rft.atitle=Preparation+and+in+vitro+Studies+of+%5B+super%28125%29I%5DIUDR-T101+Antibody+Conjugate&rft.au=Chakrabarti%2C+M+C%3BPaik%2C+CH%3BCarrasquillo%2C+JA&rft.aulast=Chakrabarti&rft.aufirst=M&rft.date=1999-01-01&rft.volume=14&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Cancer+Biotherapy+and+Radiopharmaceuticals&rft.issn=10849785&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 - Nuclei; Monoclonal antibodies; Carbohydrates ER - TY - JOUR T1 - Computer-Aided Analysis of Mutagenicity and Cell Transformation Data for Assessing Their Relationship With Carcinogenicity AN - 17258564; 4547959 AB - Using a computer-aided approach, the tests for Salmonella mutagenicity and transformation in established cell lines were compared for the qualitative bases of their carcinogenicity predictions. For this purpose, a database of 145 chemicals was prepared in which rodent carcinogenicity data and results of the Ames' and transformation tests were available. Using a software program for connectivity analysis (previously developed and validated by us), we assayed the molecular structures of these chemicals for the presence of fragments relatable to their positive (i.e., biophores) or negative (i.e., biophobes) response to the tests in question. These fragments were then studied for their association with genotoxic and nongenotoxic carcinogenicity. The philosophy adopted was that the type and number of molecular fragments chosen by the software to describe the chemicals correctly predicted by the tests could be related to the type of carcinogenic effects to which the tests themselves were sensitive. The classifications made by the software were interpreted by human expertise and the biophores found were compared with the acknowledged structural alerts to DNA reactivity as formalized by Ashby and co-workers [(1991): Mutat Res 257:229-306; (1993): Mutat Res 286: 3-74]. The results show that, in quantitative terms, the overall ability to predict carcinogenicity is about the same for both the Salmonella and transformation test. However, in qualitative terms the transformation test appears to be sensitive to effects that are more heterogeneous than those inducing mutation, some of which are presumably related to nongenotoxic carcinogenic activities. This study illustrates a possible, innovative model of analysis of chemical structures that, using an automated approach along with the biologist's judgment, could contribute to the detection of complementarities among short-term test endpoints. JF - Environmental and Molecular Mutagenesis AU - Taningher, M AU - Malacarne, D AU - Perrotta, A AU - Parodi, S AD - National Cancer Institute (IST), Largo R. Benzi No. 10, I-16132 Genoa, Italy, parodis@hp380.ist.unige.it Y1 - 1999 PY - 1999 DA - 1999 SP - 226 EP - 239 VL - 33 IS - 3 SN - 8093-6692, 8093-6692 KW - Toxicology Abstracts KW - Transformation KW - Mutagenicity KW - Mathematical models KW - Carcinogenicity KW - Genotoxicity testing KW - Computer applications KW - Ames test KW - Salmonella KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17258564?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Computer-Aided+Analysis+of+Mutagenicity+and+Cell+Transformation+Data+for+Assessing+Their+Relationship+With+Carcinogenicity&rft.au=Taningher%2C+M%3BMalacarne%2C+D%3BPerrotta%2C+A%3BParodi%2C+S&rft.aulast=Taningher&rft.aufirst=M&rft.date=1999-01-01&rft.volume=33&rft.issue=3&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=80936692&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; Carcinogenicity; Ames test; Transformation; Mutagenicity; Mathematical models; Computer applications; Genotoxicity testing ER - TY - JOUR T1 - Occupation and Pancreatic Cancer Risk in Shanghai, China AN - 17239512; 4524222 AB - Any association between occupation and pancreatic cancer risk has not been conclusively demonstrated. A population-based case-control study was conducted to examine occupational risks of pancreatic cancer in Shanghai, China. The study included 451 pancreatic cancer patients newly diagnosed in 1990-1993 and 1,552 controls randomly selected from Shanghai residents. Information on a lifetime job history and other factors was obtained in a face-to-face interview. Among men, an increased risk of pancreatic cancer was associated with employment as an electrician, and a positive trend in risk with increasing duration of employment was apparent. Exposure to electric magnetic fields (EMF) as measured by a job exposure matrix also was associated with an increased risk among electricians. Threefold risks were observed for men with the highest level of intensity and for those with the highest probability of EMF exposure, although women with heavy EMF exposure did not experience increased risk. Among men, elevated risks also were found for metal workers; toolmakers; plumbers and welders; and glass manufacturers, potters, painters, and construction workers. Among women, textile workers experienced an increased risk. Our results suggest that occupations associated with exposures to metal and textile dusts or certain chemicals may increase the risk of pancreatic cancer. The elevated risk among electricians may warrant further study to evaluate the possible role of EMF or other exposures. JF - American Journal of Industrial Medicine AU - Ji, Bu-Tian AU - Silverman, D T AU - Dosemeci, M AU - Dai, Qi AU - Gao, Yu-Tang AU - Blair, A AD - National Cancer Institute, 6130 Executive Blvd., EPN 415, Rockville, MD 20852, USA, jib@exchange.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 76 EP - 81 VL - 35 IS - 1 SN - 0271-3586, 0271-3586 KW - China, Shanghai KW - Pancreas KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Dust KW - Hazards KW - Occupational exposure KW - Electromagnetic fields KW - Cancer 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/17239512?accountid=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=Occupation+and+Pancreatic+Cancer+Risk+in+Shanghai%2C+China&rft.au=Ji%2C+Bu-Tian%3BSilverman%2C+D+T%3BDosemeci%2C+M%3BDai%2C+Qi%3BGao%2C+Yu-Tang%3BBlair%2C+A&rft.aulast=Ji&rft.aufirst=Bu-Tian&rft.date=1999-01-01&rft.volume=35&rft.issue=1&rft.spage=76&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dust; Occupational exposure; Cancer; Risk assessment; Hazards; Electromagnetic fields ER - TY - JOUR T1 - Peritoneal Cancer and Occupational Exposure to Asbestos: Results From the Application of a Job-Exposure Matrix AN - 17236666; 4524214 AB - Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied, particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the International Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate. From a large database containing information on the 1984-1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender, race, and 5-year age group. This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information, disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful results among women. JF - American Journal of Industrial Medicine AU - Cocco, P AU - Dosemeci, M AD - Occupational Studies Section, National Cancer Institute, 6130 Executive Boulevard, EPN room 418, Bethesda, MD 20892, USA, dosemecm@epndce.nci.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 9 EP - 14 VL - 35 IS - 1 SN - 0271-3586, 0271-3586 KW - Health & Safety Science Abstracts KW - Risk assessment KW - Asbestos 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/17236666?accountid=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=Peritoneal+Cancer+and+Occupational+Exposure+to+Asbestos%3A+Results+From+the+Application+of+a+Job-Exposure+Matrix&rft.au=Cocco%2C+P%3BDosemeci%2C+M&rft.aulast=Cocco&rft.aufirst=P&rft.date=1999-01-01&rft.volume=35&rft.issue=1&rft.spage=9&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Asbestos; Occupational exposure; Cancer; Risk assessment ER - TY - JOUR T1 - Therapy of Colon Cancer with Oncolytic Adenovirus Is Enhanced by the Addition of Herpes Simplex Virus-thymidine kinase AN - 17223982; 4503759 AB - A major obstacle to the successful application of suicide gene therapy strategies that rely on in situ transduction of tumor cells is the poor distribution of the vector throughout the tumor mass. To address this problem, we evaluated the use of Ad.TK super(RC), an E1b M sub(r) 55,000 deleted replicating adenoviral vector engineered to express the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) as a treatment for human colon cancer xenografts in nude mice. We compared the efficacy of this system with that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK) in mice bearing LS180 tumors. In this system, Ad.TK super(RC) alone was as effective as a traditional Ad.TK vector in combination with GCV. The addition of GCV significantly enhanced the antitumor effect of Ad.TK super(RC). Furthermore, we demonstrated that the survival of HT-29 human colon cancer xenografted mice treated with Ad.TK super(RC) and GCV was prolonged compared with Ad.TK super(RC) alone or with administration of a single cycle of topotecan. These data demonstrate that the addition of direct viral oncolysis to the HSV-tk/GCV suicide gene system resulted in a striking improvement in treatment efficacy and that it may offer advantages over the use of chemotherapeutic agents for treatment of localized disease. JF - Cancer Research AU - Wildner, O AU - Blaese, R M AU - Morris, J C AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, NIH, 10 Center Drive, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA, owildner@nhgri.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 410 EP - 413 VL - 59 IS - 2 SN - 0008-5472, 0008-5472 KW - Adenovirus KW - herpes simplex virus 1 KW - man KW - nude mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Colon KW - Gene therapy KW - Thymidine kinase KW - Carcinoma KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17223982?accountid=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=Therapy+of+Colon+Cancer+with+Oncolytic+Adenovirus+Is+Enhanced+by+the+Addition+of+Herpes+Simplex+Virus-thymidine+kinase&rft.au=Wildner%2C+O%3BBlaese%2C+R+M%3BMorris%2C+J+C&rft.aulast=Wildner&rft.aufirst=O&rft.date=1999-01-01&rft.volume=59&rft.issue=2&rft.spage=410&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; Carcinoma; Colon; Thymidine kinase ER - TY - JOUR T1 - Variability of lipid hydroperoxides in pregnant and nonpregnant women AN - 17212327; 4492379 AB - Lipid peroxidation is thought to be important in numerous disease states, including pregnancy complications. Study of its role requires markers, but the variability of available markers in non-diseased populations has not been well-characterized. We examined the variability over time of blood lipid hydroperoxides, as measured by iodometric analysis, in 49 healthy young women, 21 nonpregnant and 28 pregnant. Lipid hydroperoxides from the same woman were very similar from one day to the next but were less stable over periods of a month or more. The correlation between measurements on consecutive days was 0.98; the correlation between measurements a month or more apart was 0.11. Variability over time was not attributable to seasonal effects or, among the pregnant women, to differences over the course of pregnancy. Knowledge of the variability of this and other markers of oxidative damage enables the development of appropriate study designs. JF - Reproductive Toxicology AU - Gladen, B C AU - Tabacova, S AU - Baird, D D AU - Little, R E AU - Balabaeva, L AD - Biostatistics Branch, Mail Drop A3-03, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, gladen@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 41 EP - 44 VL - 13 IS - 1 SN - 0890-6238, 0890-6238 KW - lipid hydroperoxides KW - man KW - Toxicology Abstracts KW - Toxicity testing KW - Lipid peroxidation KW - Pregnancy KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17212327?accountid=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=Reproductive+Toxicology&rft.atitle=Variability+of+lipid+hydroperoxides+in+pregnant+and+nonpregnant+women&rft.au=Gladen%2C+B+C%3BTabacova%2C+S%3BBaird%2C+D+D%3BLittle%2C+R+E%3BBalabaeva%2C+L&rft.aulast=Gladen&rft.aufirst=B&rft.date=1999-01-01&rft.volume=13&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&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; Lipid peroxidation; Toxicity testing ER - TY - JOUR T1 - Induction of Micronucleated Erythrocytes in Rodents by Diisopropylcarbodiimide and Dicyclohexylcarbodiimide: Dependence on Exposure Protocol AN - 17208917; 4495867 AB - The induction of micronucleated erythrocytes by diisopropylcarbodiimide (DIC) and dicyclohexylcarbodiimide (DCC) was investigated as part of a U.S. National Toxicology Program (NTP) evaluation of the subchronic toxicity of these chemicals. Analysis of peripheral blood smears from male and female B6C3F sub(1) mice exposed to 17.5-140.0 mg DIC/kg/day by skin painting for 13 weeks revealed dose-related increases in the frequency of micronucleated normochromatic erythrocytes (MN-NCE) in both sexes. Results of a similar 13-week peripheral blood micronucleus (MN) test with DCC (1.5-12.0 mg/kg/day) were also positive, although the increases in MN-NCE were not as great as those abserved with DIC. In contrast to the positive results of the subchronic skin-painting studies in mice, acute bone marrow MN studies with DIC and DCC in male F344 rats, using intraperitoneal (i.p.) injection, yielded negative results. Both the acute and the subchronic exposures included doses that produced clinical signs of toxicity. Acute mouse bone marrow MN tests with DIC administered in single or triple i.p. injection protocols were subsequently conducted to determine if the differing responses between mice and rats were due to species or protocol differences. The results of these acute tests were negative or equivocal. Because the subchronic studies produced positive results, it was hypothesized that these carbodiimides required multiple treatments over an extended period of time to produce an increase in MN-erythrocytes. To confirm the original response, a second dermal subchronic study was conducted with DIC; the protocol was modified to include sequential blood samplings to permit monitoring MN frequencies over time. The data demonstrated a small but consistent induction of micronucleated erythrocytes in mice treated with DIC by skin painting. JF - Environmental and Molecular Mutagenesis AU - Witt, K L AU - Tice, R R AU - Shelby, MD AU - Chhabra, R S AU - Zeiger, E AD - Integrated Laboratory Systems, P.O. Box 13501, Research Triangle Park, NC 27709, witt@niehs.nih.gov Y1 - 1999 PY - 1999 DA - 1999 SP - 65 EP - 74 VL - 33 IS - 1 SN - 8093-6692, 8093-6692 KW - dicyclohexylcarbodiimide KW - dicyclohexylcarbodimide KW - diisopropylcarbodiimide KW - mice KW - micronuclei KW - rats KW - Toxicology Abstracts; Genetics Abstracts KW - Micronuclei KW - Erythrocytes KW - X 24240:Miscellaneous KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17208917?accountid=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+and+Molecular+Mutagenesis&rft.atitle=Induction+of+Micronucleated+Erythrocytes+in+Rodents+by+Diisopropylcarbodiimide+and+Dicyclohexylcarbodiimide%3A+Dependence+on+Exposure+Protocol&rft.au=Witt%2C+K+L%3BTice%2C+R+R%3BShelby%2C+MD%3BChhabra%2C+R+S%3BZeiger%2C+E&rft.aulast=Witt&rft.aufirst=K&rft.date=1999-01-01&rft.volume=33&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=80936692&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 - Erythrocytes; Micronuclei ER - TY - JOUR T1 - Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli AN - 17200358; 4490783 AB - Efficient repression of the two promoters P1 and P2 of the gal operon requires the formation of a DNA loop encompassing the promoters. In vitro, DNA loopingmediated repression involves binding of the Gal repressor (GalR) to two gal operators (O sub(E) and O sub(l)) and binding of the histone-like protein HU to a specific locus (hbs) about the midpoint between O sub(E) and O sub(I), and supercoiled DNA. Without DNA looping, GalR binding to O sub(E) partially represses P1 and stimulates P2. We investigated the requirement for DNA supercoiling and HU in repression of the gal promoters in vivo in strains containing a fusion of a reporter gene, gusA or lacZ, to each promoter individually. While the P1 promoter was found to be repressible in the absence of DNA supercoiling and HU, the repression of P2 was entirely dependent upon DNA supercoiling in vivo. The P2 promoter was fully derepressed when supercoiling was inhibited by the addition of coumermycin in cells. P2, but not P1, was also totally derepressed by the absence of HU or the O sub(I) operator. From these results, we propose that the repression of the gal promoters in vivo is mediated by the formation of a higher order DNA-multiprotein complex containing GalR, HU and supercoiled DNA. In the absence of this complex, P1 but not P2 is still repressed by GalR binding to O sub(E). The specific nucleoprotein complexes involving histone-like proteins, which repress promoter activity while remaining sensitive to inducing signals, as discussed, may occur more generally in bacterial nucleoids. JF - Molecular Microbiology AU - Lewis, DEA AU - Geanacopoulos, M AU - Adhya, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA, sadhya@helix.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 451 EP - 461 VL - 31 IS - 2 SN - 0950-382X, 0950-382X KW - GalR protein KW - HU protein KW - double prime HU protein KW - gal operon KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Supercoiling KW - Gene regulation KW - DNA KW - Escherichia coli KW - J 02725:DNA KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17200358?accountid=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=Role+of+HU+and+DNA+supercoiling+in+transcription+repression%3A+specialized+nucleoprotein+repression+complex+at+gal+promoters+in+Escherichia+coli&rft.au=Lewis%2C+DEA%3BGeanacopoulos%2C+M%3BAdhya%2C+S&rft.aulast=Lewis&rft.aufirst=DEA&rft.date=1999-01-01&rft.volume=31&rft.issue=2&rft.spage=451&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; DNA; Gene regulation; Supercoiling ER - TY - JOUR T1 - Processive antitermination AN - 17173576; 4471074 AB - After initiating synthesis of RNA at a promoter, RNA polymerase (RNAP) normally continues to elongate the transcript until it reaches a termination site. Important elements of termination sites are transcribed before polymerase translocation stops, and the resulting RNA is an active element of the termination pathway. Nascent transcripts of intrinsic sites can halt transcription without the assistance of additional factors, and those of Rho-dependent sites recruit the Rho termination protein to the elongation complex. In both cases, RNAP, the transcript, and the template dissociate. Termination is rarely, if ever, completely efficient, and the expression of downstream genes can be controlled by altering the efficiency of terminator readthrough. Two distinct mechanisms of elongation control have been reported for bacterial RNA polymerases. In one, exemplified by attenuation of the his and trp operons of Salmonella typhimurium and Escherichia coli, respectively, a single terminator is inactivated by interaction with an upstream sequence in the transcript, with a terminator-specific protein, or with a translating ribosome that follows closely behind RNAP. In a second, whose prototype is antitermination of phage lambda early transcription, polymerase is stably modified to a terminator-resistant form after it leaves the promoter. In this case, the modified enzyme not only transcribes through sequential downstream terminators, but also it is less sensitive to the pause sites that normally delay transcript elongation. Both pathways are widespread in nature, but in this minireview we consider only the second, which is known as processive antitermination. The recent explosive growth in our understanding of transcription elongation make this an especially appropriate time to survey regulatory elements that target the transcription elongation complex. JF - Journal of Bacteriology AU - Weisberg, R A AU - Gottesman, ME AD - Section on Microbial Genetics, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2785, USA, wia@cu.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 359 EP - 367 VL - 181 IS - 2 SN - 0021-9193, 0021-9193 KW - his operon KW - trp operon KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Phage lambda KW - Transcription KW - Salmonella typhimurium KW - Modification KW - Elongation KW - Promoters KW - DNA-directed RNA polymerase KW - Escherichia coli KW - Termination factors KW - J 02726:RNA and ribosomes KW - V 22044:Viral nucleic acid synthesis & synthesis of virus-coded proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17173576?accountid=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=Processive+antitermination&rft.au=Weisberg%2C+R+A%3BGottesman%2C+ME&rft.aulast=Weisberg&rft.aufirst=R&rft.date=1999-01-01&rft.volume=181&rft.issue=2&rft.spage=359&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; Phage lambda; Salmonella typhimurium; Termination factors; DNA-directed RNA polymerase; Promoters; Transcription; Elongation; Modification ER - TY - JOUR T1 - Identification of Common Lipooligosaccharide Types in Isolates from Patients with Otitis Media by Monoclonal Antibodies against Nontypeable Haemophilus influenzae 9274 AN - 17155566; 4446506 AB - Twenty-one murine monoclonal antibodies (MAbs) were induced by nontypeable Haemophilus influenzae (NTHi) 9274. Nineteen MAbs were specific for the lipooligosaccharide (LOS) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. When the MAbs were assayed with five LOS prototype strains by ELISA, all bound to strain 3198 LOS (type III), while six of the MAbs were also reactive with LOSs from strain 1479 (type I), 5657 (type IV), or 7502 (type V). Ten MAbs had complement-mediated bactericidal activity, and three MAbs were opsonophagocytic against the homologous strain. Five LOS MAbs with different specificities were used to analyze 155 NTHi clinical isolates from the United States and from Japan. These isolates were classified into nine groups by ELISA. Only four isolates (2.6%) were not recognized by any of the five MAbs. Most of the isolates (91.6%) were in four groups which bound three of the five MAbs. One of three MAbs, 6347C11, had strong activity against the homologous strain and was also bactericidal to 45 clinical isolates (29%) which belonged to the four common patterns (25 belonged to pattern 1). These data indicate that these MAbs can be used for LOS typing in which almost all NTHi strains can be typed according to the LOS antigenicity. Among NTHi, at least one conserved LOS epitope which is a target of bactericidal antibodies exists. We conclude that strain 9274 LOS, which is the target for bactericidal antibodies, is a candidate for LOS-based NTHi vaccines. JF - Clinical and Diagnostic Laboratory Immunology AU - Ueyama, T AU - Gu, Xin-Xing AU - Tsai, Chao-Ming AU - Karpas, AB AU - Lim, D J AD - NIDCD, NIH, 5 Research Ct., 2A31, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 96 EP - 100 VL - 6 IS - 1 SN - 1071-412X, 1071-412X KW - Haemophilus influenzae KW - Japan KW - USA KW - lipooligosaccharides KW - man KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Enzyme-linked immunosorbent assay KW - Monoclonal antibodies KW - Complement KW - Vaccines KW - J 02831:Techniques and reagents KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17155566?accountid=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+and+Diagnostic+Laboratory+Immunology&rft.atitle=Identification+of+Common+Lipooligosaccharide+Types+in+Isolates+from+Patients+with+Otitis+Media+by+Monoclonal+Antibodies+against+Nontypeable+Haemophilus+influenzae+9274&rft.au=Ueyama%2C+T%3BGu%2C+Xin-Xing%3BTsai%2C+Chao-Ming%3BKarpas%2C+AB%3BLim%2C+D+J&rft.aulast=Ueyama&rft.aufirst=T&rft.date=1999-01-01&rft.volume=6&rft.issue=1&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Clinical+and+Diagnostic+Laboratory+Immunology&rft.issn=1071412X&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; Enzyme-linked immunosorbent assay; Vaccines; Monoclonal antibodies; Complement ER - TY - JOUR T1 - Transplantation of transduced nonhuman primate CD34 super(+) cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34 super(+) cells AN - 17150468; 4449113 AB - The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34 super(+) cells and colony-forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaL V) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34 super(+) cells transduced with the GaL V envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34 super(+) cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50000/ mu l and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 x 10 super(7) or greater of cytokine-mobilized CD34 super(+) PB cell/kg. Reverse transcriptase(RT)-PCR analysis of CD34 super(+) subsets for both the GaL V and amphotropic receptor were performed. The expression of the GaL V receptor was determined to be restricted to CD34 super(+) Thy-1 super(+) cells, and both CD34 super(+) CD38 super(+) and CD34 super(+) CD38dim cells, while the amphotropic receptor was present on all CD34 super(+) cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34 super(+) cells as only CD34 super(+) Thy-1 super(+) cells express the GaLV receptor. JF - Gene Therapy AU - Bunnell, BA AU - Kluge, KA AU - Lee-Lin, S-Q AU - Byrne, E R AU - Orlic, D AU - Metzger, ME AU - Agricola, BA AU - Wersto, R P AU - Bodine, D M AU - Morgan, R A AU - Donahue, R E AD - Hematology Branch, National Heart, Lung, and Blood Institute, 5 Research Court, Rockville, MD 20850, USA Y1 - 1999/01// PY - 1999 DA - Jan 1999 SP - 48 EP - 56 VL - 6 IS - 1 SN - 0969-7128, 0969-7128 KW - CD34 antigen KW - Gibbon ape leukemia virus KW - Macaca mulatta KW - Moloney murine leukemia virus KW - Rhesus macaque KW - gibbon ape leukemia virus receptors KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Transplantation KW - Gene transfer KW - Moloney leukemia virus KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - G 07419:Primates (except man) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17150468?accountid=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=Transplantation+of+transduced+nonhuman+primate+CD34+super%28%2B%29+cells+using+a+gibbon+ape+leukemia+virus+vector%3A+restricted+expression+of+the+gibbon+ape+leukemia+virus+receptor+to+a+subset+of+CD34+super%28%2B%29+cells&rft.au=Bunnell%2C+BA%3BKluge%2C+KA%3BLee-Lin%2C+S-Q%3BByrne%2C+E+R%3BOrlic%2C+D%3BMetzger%2C+ME%3BAgricola%2C+BA%3BWersto%2C+R+P%3BBodine%2C+D+M%3BMorgan%2C+R+A%3BDonahue%2C+R+E&rft.aulast=Bunnell&rft.aufirst=BA&rft.date=1999-01-01&rft.volume=6&rft.issue=1&rft.spage=48&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 - Gibbon ape leukemia virus; Macaca mulatta; Moloney leukemia virus; Gene transfer; Transplantation ER - TY - JOUR T1 - Polyethylene glycol-mediated infection of non-permissive mammalian cells with Semliki Forest virus: application to signal transduction studies AN - 17128799; 4434253 AB - Semliki Forest Virus (SFV) vectors allow the subcloning of a gene of interest directly in the expression vector, thus avoiding the need to select and purify viral recombinants, making this viral expression system attractive over many others for mammalian protein expression. We now describe a novel and generally applicable method for infection of non-permissive mammalian cells with SFV, that greatly enhances the utility of this expression system. We demonstrate that the hygroscopic polymer poly (ethylene glycol), PEG, promotes the infectivity of cells by SFV under conditions that did not promote cell-cell fusion. We also found that the PEG-induced infection and expression of an exogenous protein (green fluorescent protein, GFP) did not elevate the basal tyrosine kinase activity, induce a stress-activated responses, or result in aberrant cell responses. Expression of GFP tagged-Vav, an activator of stress-activated protein kinase (SAPK/JNK), resulted in the expected induction of JNK activity and in the normal redistribution of Vav in response to engagement of the high affinity receptor for IgE (Fc epsilon RI). Thus, our findings that PEG allows the infection of non-permissive cells by SFV makes this system extremely attractive for expression of proteins in mammalian cells, and studies on signal transduction and cellular localization in immune and non-immune cells. JF - Journal of Immunological Methods AU - Arudchandran, R AU - Brown, MJ AU - Song, J S AU - Wank, SA AU - Haleem-Smith, H AU - Rivera, J AD - Section on Chemical Immunology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA Y1 - 1999/01/01/ PY - 1999 DA - 1999 Jan 01 SP - 197 EP - 208 PB - Elsevier Science B.V. VL - 222 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Semliki Forest virus KW - double prime Fc receptors KW - green fluorescent protein KW - polyethylene glycol KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell fusion KW - Mammalian cells KW - Cloning vectors KW - Stress KW - Immunoglobulin E KW - Signal transduction KW - W3 33240:Immunology KW - V 22091:Immunological techniques & reagents KW - F 06731:Other methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17128799?accountid=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=Polyethylene+glycol-mediated+infection+of+non-permissive+mammalian+cells+with+Semliki+Forest+virus%3A+application+to+signal+transduction+studies&rft.au=Arudchandran%2C+R%3BBrown%2C+MJ%3BSong%2C+J+S%3BWank%2C+SA%3BHaleem-Smith%2C+H%3BRivera%2C+J&rft.aulast=Arudchandran&rft.aufirst=R&rft.date=1999-01-01&rft.volume=222&rft.issue=1-2&rft.spage=197&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 - Semliki Forest virus; Cloning vectors; Stress; Immunoglobulin E; Cell fusion; Mammalian cells; Signal transduction ER - TY - JOUR T1 - Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation. AN - 69177289; 10030673 AB - The mitogen activated protein (MAP) kinases or extracellular signal-regulated kinases (Erks) are activated in response to Ras expression or exposure to tumor promoters or to growth factors, and have been implicated in AP-1 transactivation in some models. We have shown that tumor promoter induced activation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model. Jun and Fos family protein levels have been found not to be limiting for AP-1 response. The present study asks whether activation of Erks1 and 2 is required for AP-1 transactivation and transformation of JB6 cells and whether Erks might be targeted for cancer prevention. Expression of either of two different dominant negative kinase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells substantially inhibited the tumor promoter induced activation of Erks1 and 2 and of AP-1 measured by a collagenase-luciferase reporter. Multiple mutant Erk2 expressing clonal lines were also rendered non-responsive to induced neoplastic transformation. These observations, together with our recent finding attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and/or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progression model, and suggest the utility of Erks as a prevention target. JF - Oncogene AU - Watts, R G AU - Huang, C AU - Young, M R AU - Li, J J AU - Dong, Z AU - Pennie, W D AU - Colburn, N H AD - National Cancer Institute-FCRDC, Laboratory of Biochemical Physiology, Frederick, Maryland 21702-1201, USA. Y1 - 1998/12/31/ PY - 1998 DA - 1998 Dec 31 SP - 3493 EP - 3498 VL - 17 IS - 26 SN - 0950-9232, 0950-9232 KW - Carcinogens KW - 0 KW - Recombinant Proteins KW - Transcription Factor AP-1 KW - Epidermal Growth Factor KW - 62229-50-9 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 - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Carcinogens -- pharmacology KW - Cell Line -- metabolism KW - Cell Line -- drug effects KW - Epidermis -- cytology KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Recombinant Proteins -- genetics KW - Mice, Inbred BALB C KW - Gene Expression Regulation, Neoplastic KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mutation KW - Calcium-Calmodulin-Dependent Protein Kinases -- genetics KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Genes, Dominant KW - Transcription Factor AP-1 -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- drug effects KW - Transcriptional Activation -- genetics KW - Transcription Factor AP-1 -- drug effects KW - Transcription Factor AP-1 -- genetics KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69177289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+dominant+negative+Erk2+inhibits+AP-1+transactivation+and+neoplastic+transformation.&rft.au=Watts%2C+R+G%3BHuang%2C+C%3BYoung%2C+M+R%3BLi%2C+J+J%3BDong%2C+Z%3BPennie%2C+W+D%3BColburn%2C+N+H&rft.aulast=Watts&rft.aufirst=R&rft.date=1998-12-31&rft.volume=17&rft.issue=26&rft.spage=3493&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-12 N1 - Date created - 1999-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of human cancer. AN - 69169028; 10022257 AB - A challenging goal of molecular epidemiology is to identify an individual's risk of cancer. Molecular epidemiology integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Molecular dosimetry of carcinogen exposure is an important facet of molecular epidemiology and cancer risk assessment. Carcinogen macromolecular adduct levels, cytogenetic alterations and somatic cell mutations can be measured to determine the biologically-effective doses of carcinogens. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolism, DNA repair, and epigenetic and genetic alterations in tumor suppressor genes. p53 is a prototype tumor suppressor gene and is well suited for analysis of mutational spectrum in human cancer. The analyses of germline and somatic mutation spectra of the p53 tumor suppressor gene provide important clues for cancer risk assessment in molecular epidemiology. For example, characteristic p53 mutation spectra have been associated with: dietary aflatoxin B1 exposure and hepatocellular carcinoma; sunlight exposure and skin carcinoma; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal-expansion advantage during the multistep process of carcinogenesis. The p53 gene encodes a multifunctional protein involved in the cellular response to stress including DNA damage and hypoxia. Certain p53 mutants lose tumor suppressor activity and gain oncogenic activity, which is one explanation for the commonality of p53 mutations in human cancer. Molecular epidemiological results can be evaluated for causation by inference of the Bradford-Hill criteria, i.e. strength of association (consistency, specificity and temporality) and biological plausibility, which utilizes the 'weight of the evidence principle'. JF - Toxicology letters AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 219 EP - 225 VL - 102-103 SN - 0378-4274, 0378-4274 KW - Index Medicus KW - Animals KW - Genes, p53 KW - Genes, Tumor Suppressor KW - DNA Damage KW - Humans KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69169028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+letters&rft.atitle=Molecular+epidemiology+of+human+cancer.&rft.au=Hussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=1998-12-28&rft.volume=102-103&rft.issue=&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&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 - The study of xenobiotic-metabolizing enzymes and their role in toxicity in vivo using targeted gene disruption. AN - 69168322; 10022249 AB - Most of the chemicals that cause toxicity in animals are metabolized and this metabolism can either increase or decrease the extent of toxicity. A large number of enzymes are involved in the metabolism of xenobiotics. Cytochromes P450 are among the most important and these enzymes are primarily involved in metabolic activation through oxidative metabolism. Transferases, including the glutathione S-transferases, N-acetyltransferases, UDP-glucuronosyltransferases, microsomal and cytosolic epoxide hydrolases, and NAD(P)H quinone oxidoreductase are also significant in xenobiotic metabolism and can play a role in chemical sensitivities. Polymorphisms in P450s and transferases have been found in experimental animals and humans in which a certain segment of the population, usually greater than 1%, are lacking expression of a particular enzyme. In humans, polymorphisms have been associated with adverse drug reactions but have not been shown to cause any serious developmental or physiological defects thus suggesting that in mammals, xenobiotic-metabolizing enzymes may only be required for metabolism of foreign chemicals and have no other critical role. To determine the roles of xenobiotic-metabolizing enzymes in mammalian development and physiological homeostasis, and in sensitivities to chemical toxicity and carcinogenesis, targeted gene disruption was carried out to produce gene knockout mice. Several lines of mice were produced and characterized and these are discussed. JF - Toxicology letters AU - Gonzalez, F J AD - National Cancer Institute, National of Health, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 161 EP - 166 VL - 102-103 SN - 0378-4274, 0378-4274 KW - Xenobiotics KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Transgenic KW - Gene Targeting KW - Acetaminophen -- toxicity KW - NAD(P)H Dehydrogenase (Quinone) -- physiology KW - Cytochrome P-450 CYP1A2 -- physiology KW - NAD(P)H Dehydrogenase (Quinone) -- genetics KW - Cytochrome P-450 CYP1A2 -- genetics KW - Xenobiotics -- metabolism KW - Cytochrome P-450 CYP2E1 -- physiology KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69168322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+letters&rft.atitle=The+study+of+xenobiotic-metabolizing+enzymes+and+their+role+in+toxicity+in+vivo+using+targeted+gene+disruption.&rft.au=Gonzalez%2C+F+J&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1998-12-28&rft.volume=102-103&rft.issue=&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&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 - CONF T1 - Genetic susceptibility: Significance in risk assessment AN - 17584636; 4564374 AB - Polymorphisms in metabolism and DNA-repair genes can increase the risks of cancer associated with exposure to chemical and physical agents in the environment. These types of gene-environment interactions may alter our view of dose-response patterns and how to characterize risk in an exposed population. Depending upon the action of the different forms of these genes, differing patterns of dose-response may be seen in a study population and these patterns can effect our interpretation of the degree of hazard as well as the risk in the general population. This short report describes some of the key issues associated with how variation in genetic make-up can result in different dose-response patterns for cancer following exposure to environmental agents. JF - Toxicology Letters AU - Portier, C J AU - Bell, DA Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 185 EP - 189 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 102-103 IS - 1-3 KW - dose-response effects KW - Toxicology Abstracts KW - Risk assessment KW - Population genetics KW - Gene polymorphism KW - DNA repair KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17584636?accountid=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+Letters&rft.atitle=Genetic+susceptibility%3A+Significance+in+risk+assessment&rft.au=Portier%2C+C+J%3BBell%2C+DA&rft.aulast=Portier&rft.aufirst=C&rft.date=1998-12-28&rft.volume=102-103&rft.issue=1-3&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - CONF T1 - Oxidative DNA damage processing and changes with aging AN - 17275443; 4564353 AB - Living organisms are constantly exposed to oxidative stress from environmental agents and from endogenous metabolic processes. The resulting oxidative modifications occur in proteins, lipids and DNA. Since proteins and lipids are readily degraded and resynthesized, the most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability. Many different DNA base changes have been seen following some form of oxidative stress, and these lesions are widely considered as instigators for the development of cancer and are also implicated in the process of aging. Several studies have documented that oxidative DNA lesions accumulate with aging, and it appears that the major site of this accumulation is mitochondrial DNA rather than nuclear DNA. The DNA repair mechanisms involved in the removal of oxidative DNA lesions are much more complex than previously considered. They involve base excision repair (BER) pathways and nucleotide excision repair (NER) pathways, and there is currently a great deal of interest in clarification of the pathways and their interactions. We have used a number of different approaches to explore the mechanism of the repair processes, and we are able to examine the repair of different types of lesions and to measure different steps of the repair processes. Furthermore, we can measure the DNA damage processing in the nuclear DNA and separately, in the mitochondrial DNA. Contrary to widely held notions, mitochondria have efficient DNA repair of oxidative DNA damage and we are exploring the mechanisms. In a human disorder, Cockayne syndrome (CS), characterized by premature aging, there appear to be deficiencies in the repair of oxidative DNA damage in the nuclear DNA, and this may be the major underlying cause of the disease. JF - Toxicology Letters AU - Bohr, V AU - Anson, R M AU - Mazur, S AU - Dianov, G Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 47 EP - 52 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 102-103 IS - 1-3 KW - Toxicology Abstracts KW - DNA damage KW - Oxidative stress KW - Free radicals KW - Aging KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17275443?accountid=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+Letters&rft.atitle=Oxidative+DNA+damage+processing+and+changes+with+aging&rft.au=Bohr%2C+V%3BAnson%2C+R+M%3BMazur%2C+S%3BDianov%2C+G&rft.aulast=Bohr&rft.aufirst=V&rft.date=1998-12-28&rft.volume=102-103&rft.issue=1-3&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - CONF T1 - Recent discoveries in pharmacokinetics of drugs of abuse AN - 17271390; 4564361 AB - Controlled human dosing studies with drugs of abuse have revealed the importance of the chosen route of administration on the delivery of drugs to the bloodstream and to their site of action. Recently, the intranasal and smoked routes have become favored by some populations for the administration of illicit drugs. Research studies with experienced heroin and cocaine users indicated that an intranasally administered drug generally provided lower blood concentrations of drug and a slower onset of action compared to the intravenous route; however, intranasal doses are easily manipulated by the user and adequate bioavailability and desired drug effects can be achieved. In addition, the trauma of needle use is avoided and disease exposure is reduced by this route. For marijuana, the smoked route of administration has always been the preferred route. In recent studies with smoked marijuana, it was revealed that single puffs of marijuana smoke produced detectable blood concentrations of tetrahydrocannabinol, the active ingredient of marijuana. Continued smoking produced rapid increases in blood concentrations with peak concentrations and effects occurring before or near the end of smoking, demonstrating the rapidity and efficacy of the smoking route for marijuana. The smoked route has also become popular with cocaine and heroin users. This route provided equivalent peak blood concentrations and time of onset of drug effects as the intravenous route. In addition, arterial boli drug concentrations reaching the brain are likely to be higher following the smoked route compared to the intravenous route. Overall, these studies demonstrated that the smoked and intranasal routes are highly efficacious for the delivery of illicit drugs and produce a similar profile of drug action to the intravenous route of administration. JF - Toxicology Letters AU - Cone, E J Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 97 EP - 101 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 102-103 IS - 1-3 KW - pharmacokinetics KW - Toxicology Abstracts KW - Heroin KW - Reviews KW - Cannabis KW - Cocaine KW - Drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17271390?accountid=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+Letters&rft.atitle=Recent+discoveries+in+pharmacokinetics+of+drugs+of+abuse&rft.au=Cone%2C+E+J&rft.aulast=Cone&rft.aufirst=E&rft.date=1998-12-28&rft.volume=102-103&rft.issue=1-3&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - CONF T1 - The transgenic Tg.AC mouse model for identification of chemical carcinogens AN - 17267408; 4564419 AB - The Tg.AC (zetaglobin promoted v-Ha-ras) transgenic mouse is being evaluated as a short-term carcinogenicity bioassay. In order to harmonize the evaluation effort in diverse laboratories, an operational bioassay protocol has been established. Data, based principally on retrospective assay of known carcinogens or tumor promoters and non-carcinogens, are presented that support the operational protocol. The Laboratory of Environmental Carcinogenesis and Mutagenesis at the NIEHS has been evaluating transgenic rodent models for utility in differentiating carcinogens from non-carcinogens. Our main approach in this method development effort has been to retrospectively study responses of the models to chemicals of known rodent carcinogenic potential. To this end we have tested mainly chemicals that have been previously studied in chronic rat and/or mouse bioassays by the National Toxicology Program. Development of the data base and assessment of the utility of the models will be immeasurably aided by the availability of a standardized experimental protocol. The purpose of this communication is to present the elements of the Laboratory of Environmental Carcinogenesis and Mutagenesis Tg.AC mouse bioassay protocol and to show experimental results that led to the development of our study design. JF - Toxicology Letters AU - Tennant, R W AU - Tice, R R AU - Spalding, J W Y1 - 1998/12/28/ PY - 1998 DA - 1998 Dec 28 SP - 465 EP - 471 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 102-103 IS - 1-3 KW - TgAC mouse model KW - Toxicology Abstracts KW - Carcinogenicity KW - Carcinogens KW - Transgenic mice KW - Toxicity testing KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17267408?accountid=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+Letters&rft.atitle=The+transgenic+Tg.AC+mouse+model+for+identification+of+chemical+carcinogens&rft.au=Tennant%2C+R+W%3BTice%2C+R+R%3BSpalding%2C+J+W&rft.aulast=Tennant&rft.aufirst=R&rft.date=1998-12-28&rft.volume=102-103&rft.issue=1-3&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. AN - 69144112; 9916991 AB - The tumor suppressor gene p53 plays a major role in regulation of the mammalian cellular stress response, in part through the transcriptional activation of genes involved in cell cycle control, DNA repair, and apoptosis. Many factors contribute to control of the activation of p53, and the downstream response to its activation may also vary depending on the cellular environment or other modifying factors in the cell. The complexity of the p53 response makes this an ideal system for application of newly emerging rapid throughput analysis techniques and informatics analysis. JF - Oncogene AU - Amundson, S A AU - Myers, T G AU - Fornace, A J AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/24/ PY - 1998 DA - 1998 Dec 24 SP - 3287 EP - 3299 VL - 17 IS - 25 SN - 0950-9232, 0950-9232 KW - Mutagens KW - 0 KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Spindle Apparatus -- genetics KW - Animals KW - DNA Damage -- physiology KW - Computer Simulation KW - Humans KW - Cell Cycle -- physiology KW - DNA -- genetics KW - Cell Division -- drug effects KW - Transcription, Genetic KW - Gene Expression Regulation KW - Computational Biology KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Mutagens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69144112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Roles+for+p53+in+growth+arrest+and+apoptosis%3A+putting+on+the+brakes+after+genotoxic+stress.&rft.au=Amundson%2C+S+A%3BMyers%2C+T+G%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=1998-12-24&rft.volume=17&rft.issue=25&rft.spage=3287&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals AN - 17199628; 4488409 AB - Objectives: Expert panels have developed several guidelines for initiating highly active antiretroviral therapy (HAART) in patients with HIV infection. To evaluate these guidelines, we simulated their application in a cohort of HIV-infected patients established and followed before HAART was available, and determined how long such patients survived without disease progression in the absence of HAART. Methods: Longitudinal data was used that had been collected from 1982 to 1995 on a prospective cohort of 133 homosexual men with known or closely approximated dates of HIV-1 seroconversion and negligible antiretroviral exposure. The main definition of disease progression was CD4 cell count less than or equal to 300 X 10 super(6)/l or development of clinical AIDS diagnosis within 12 months. Results: The mean number of years between the recommended initiation of therapy and when disease progression occurred in the absence of HAART were as follows: initiation of treatment at first visit, 4.81 years [median, 3.78 years; interquartile range (IQR), 1.85-6.59 years]; CD4 cell count 5000 copies/ml (at least 10 000 copies/ml fresh plasma), 4.35 years (median, 3.22 years; IQR, 1.56-6.19 years); CD4 cells 20 000 copies/ml (at least 40 000 copies/ml fresh plasma), 3.61 years (median, 2.70 years; IQR, 1.40-5.11 years); and CD4 cells < 500 X 10 super(6)/l, 2.72 years (median, 2.17 years; IQR, 0.81-4.25 years). The percentage of patients who had disease progression before HAART would have been recommended was 0.8, 1.6, 3.2 and 13.6% with each of these four approaches, respectively. Conclusions: Implementation of recommended treatment guidelines will result in a substantial proportion of patients being treated for long periods before immunologic or clinical disease progression would have occurred in the absence of HAART. These findings should be considered in the clinical care of HIV-infected patients and in future recommendations for the initiation of HAART. JF - AIDS AU - Ioannidis, JPA AU - O'Brien, T R AU - Goedert, J J AD - Viral Epidemiology Branch, DCEG, NCI, NIH, EPN/434, 6130 Executive Blvd, Rockville, MD 20852, USA Y1 - 1998/12/24/ PY - 1998 DA - 1998 Dec 24 SP - 2417 EP - 2423 VL - 12 IS - 18 SN - 0269-9370, 0269-9370 KW - CD4 antigen KW - HIV KW - man KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Antiviral agents KW - Human immunodeficiency virus KW - Lymphocytes T KW - A 01068:Antiviral & viricidal KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17199628?accountid=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=AIDS&rft.atitle=Evaluation+of+guidelines+for+initiation+of+highly+active+antiretroviral+therapy+in+a+longitudinal+cohort+of+HIV-infected+individuals&rft.au=Ioannidis%2C+JPA%3BO%27Brien%2C+T+R%3BGoedert%2C+J+J&rft.aulast=Ioannidis&rft.aufirst=JPA&rft.date=1998-12-24&rft.volume=12&rft.issue=18&rft.spage=2417&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&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; Antiviral agents; Lymphocytes T ER - TY - JOUR T1 - Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment AN - 17197808; 4488407 AB - Objective: To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly. Design and methods: Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)- alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy. Results: At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy. Conclusions: After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts. JF - AIDS AU - Chougnet, C AU - Fowke, K R AU - Mueller, BU AU - Smith, S AU - Zuckerman, J AU - Jankelevitch, S AU - Steinberg, S M AU - Luban, N AU - Pizzo, P A AU - Shearer, G M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 4B17, 9000 Rockville Pike, Bethesda MD 20892, USA Y1 - 1998/12/24/ PY - 1998 DA - 1998 Dec 24 SP - 2397 EP - 2406 VL - 12 IS - 18 SN - 0269-9370, 0269-9370 KW - HIV KW - proteinase inhibitors KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Children KW - Immune response (cell-mediated) KW - Antiviral agents KW - Human immunodeficiency virus KW - Lymphocytes T KW - A 01068:Antiviral & viricidal KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17197808?accountid=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=AIDS&rft.atitle=Protease+inhibitor+and+triple-drug+therapy%3A+cellular+immune+parameters+are+not+restored+in+pediatric+AIDS+patients+after+6+months+of+treatment&rft.au=Chougnet%2C+C%3BFowke%2C+K+R%3BMueller%2C+BU%3BSmith%2C+S%3BZuckerman%2C+J%3BJankelevitch%2C+S%3BSteinberg%2C+S+M%3BLuban%2C+N%3BPizzo%2C+P+A%3BShearer%2C+G+M&rft.aulast=Chougnet&rft.aufirst=C&rft.date=1998-12-24&rft.volume=12&rft.issue=18&rft.spage=2397&rft.isbn=&rft.btitle=&rft.title=AIDS&rft.issn=02699370&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; Children; Acquired immune deficiency syndrome; Immune response (cell-mediated); Antiviral agents; Lymphocytes T ER - TY - JOUR T1 - Genetic studies in Borrelia burgdorferi. AN - 69177040; 10048165 AB - Borrelia burgdorferi, the agent of Lyme disease, has recently joined a growing number of micro-organisms for which the entire genomic sequence is known. Despite this wealth of information, little is known about the contribution of specific spirochetal components to the pathogenesis of Lyme disease or their function in the normal life cycle of the organism. This discrepancy is due in part to the lack of a well-developed genetic system in B. burgdorferi, which in turn can be attributed to its relatively recent isolation and the dissimilarity of Borrelia from other genetically tractable bacteria. We are interested in several plasmid-encoded gene products in B. burgdorferi that may play a role in sensing and adaptation to the different environments the spirochete encounters as it completes an infectious cycle between the tick vector and the mammalian host. We are developing genetic tools with which to test the roles of specific B. burgdorferi gene products in the transmission cycle in an animal model of Lyme disease. We have demonstrated targeted gene inactivation by allelic exchange, using the gyrBr gene encoding coumermycin-resistant topoisomerase as a selectable marker. Spirochetes are transformed by electroporation and coumermycin-resistant colonies are screened by PCR for allelic exchange at the targeted locus. We have successfully inactivated several genes of interest in the type strain B31. We are investigating the utility of additional antibiotic resistance genes as selectable markers in B. burgdorferi. Targeted gene inactivation is a powerful tool with which to investigate the role of particular proteins in the basic biology and virulence of a pathogenic microorganism. We have made significant advances in our ability to genetically manipulate B. burgdorferi in order to address these issues. However, the available methods are incomplete and far from routine. We are currently improving existing methods as well as developing additional genetic tools with which to augment genetic studies in B. burgdorferi. JF - Wiener klinische Wochenschrift AU - Rosa, P AU - Bono, J AU - Elias, A AU - Errett, J AU - Kupko, J AU - Stevenson, B AU - Taylor, G AU - Tilly, K AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. patricia_rosa@nih.gov Y1 - 1998/12/23/ PY - 1998 DA - 1998 Dec 23 SP - 859 EP - 862 VL - 110 IS - 24 SN - 0043-5325, 0043-5325 KW - DNA, Bacterial KW - 0 KW - Index Medicus KW - Genes, Bacterial KW - Genome, Bacterial KW - Transformation, Genetic KW - Genetic Complementation Test KW - Mutagenesis, Insertional KW - Borrelia burgdorferi Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69177040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Wiener+klinische+Wochenschrift&rft.atitle=Genetic+studies+in+Borrelia+burgdorferi.&rft.au=Rosa%2C+P%3BBono%2C+J%3BElias%2C+A%3BErrett%2C+J%3BKupko%2C+J%3BStevenson%2C+B%3BTaylor%2C+G%3BTilly%2C+K&rft.aulast=Rosa&rft.aufirst=P&rft.date=1998-12-23&rft.volume=110&rft.issue=24&rft.spage=859&rft.isbn=&rft.btitle=&rft.title=Wiener+klinische+Wochenschrift&rft.issn=00435325&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 - Probing the topography of HIV-1 nucleocapsid protein with the alkylating agent N-ethylmaleimide. AN - 69153954; 9922156 AB - Retroviral nucleocapsid (NC) proteins contain one or two zinc fingers (ZFs) consisting of a CCHC peptide motif that coordinates Zn(II). Mutational and biochemical analyses have shown that NC ZFs are directly involved in multiple stages of viral replication, including genomic RNA encapsidation, virus maturation, and the early infection process. The multiple roles of the conserved retroviral ZFs make them attractive targets for antiviral agents. We have previously shown that a variety of chemical compounds can inactivate the whole virus by attacking NC ZFs. For the enhancement of the specificity of antiviral reagents, it is desirable to have a detailed knowledge of the spatial organization of reactive sites on the NC protein in its free and oligonucleotide-bound states. A method has been developed using chemical probes to assess the reactivity of specific Cys residues in the NC protein, and is being used to investigate the topography of ZFs in different contexts. In this study we focus on the reaction mechanism of N-ethylmaleimide (NEM) with free HIV-1 NCp7 protein. Our results show that the conformation of free NCp7 restricts the initial site of attack to Cys-49 (the most distal Cys residue in the second ZF) and that the reactivity of thiols in full-length protein differs from that of the isolated ZF peptides. A moderate to near complete reduction in reaction rate was observed when NCp7 was complexed with different oligonucleotides. These findings provide a set of experimentally determined parameters that can serve to guide computational modeling of the NC protein and will be useful for the rational design of drugs directed against retroviral ZFs. JF - Biochemistry AU - Chertova, E N AU - Kane, B P AU - McGrath, C AU - Johnson, D G AU - Sowder, R C AU - Arthur, L O AU - Henderson, L E AD - AIDS Vaccine Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. chertova@avpvx1.ncifcrf.gov Y1 - 1998/12/22/ PY - 1998 DA - 1998 Dec 22 SP - 17890 EP - 17897 VL - 37 IS - 51 SN - 0006-2960, 0006-2960 KW - Alkylating Agents KW - 0 KW - Capsid Proteins KW - Gene Products, gag KW - NCP7 protein, Human immunodeficiency virus 1 KW - Oligonucleotides KW - Peptide Fragments KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - Cysteine KW - K848JZ4886 KW - Ethylmaleimide KW - O3C74ACM9V KW - Index Medicus KW - AIDS/HIV KW - Cysteine -- chemistry KW - Peptide Fragments -- chemistry KW - Fluorescence Polarization KW - Sequence Analysis KW - Hydrogen-Ion Concentration KW - Molecular Sequence Data KW - Zinc Fingers KW - Amino Acid Sequence KW - Oligonucleotides -- metabolism KW - Protein Conformation KW - HIV-1 -- chemistry KW - Ethylmaleimide -- chemistry KW - Capsid -- metabolism KW - Alkylating Agents -- chemistry KW - Gene Products, gag -- chemistry KW - Capsid -- chemistry KW - Gene Products, gag -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69153954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Probing+the+topography+of+HIV-1+nucleocapsid+protein+with+the+alkylating+agent+N-ethylmaleimide.&rft.au=Chertova%2C+E+N%3BKane%2C+B+P%3BMcGrath%2C+C%3BJohnson%2C+D+G%3BSowder%2C+R+C%3BArthur%2C+L+O%3BHenderson%2C+L+E&rft.aulast=Chertova&rft.aufirst=E&rft.date=1998-12-22&rft.volume=37&rft.issue=51&rft.spage=17890&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-11 N1 - Date created - 1999-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the regulatory phosphorylation site in Acanthamoeba myosin IC by using site-directed mutagenesis. AN - 69100242; 9860946 AB - The actin-activated ATPase activity of Acanthamoeba myosin IC is stimulated 15- to 20-fold by phosphorylation of Ser-329 in the heavy chain. In most myosins, either glutamate or aspartate occupies this position, which lies within a surface loop that forms part of the actomyosin interface. To investigate the apparent need for a negative charge at this site, we mutated Ser-329 to alanine, asparagine, aspartate, or glutamate and coexpressed the Flag-tagged wild-type or mutant heavy chain and light chain in baculovirus-infected insect cells. Recombinant wild-type myosin IC was indistinguishable from myosin IC purified from Acanthamoeba as determined by (i) the dependence of its actin-activated ATPase activity on heavy-chain phosphorylation, (ii) the unusual triphasic dependence of its ATPase activity on the concentration of F-actin, (iii) its Km for ATP, and (iv) its ability to translocate actin filaments. The Ala and Asn mutants had the same low actin-activated ATPase activity as unphosphorylated wild-type myosin IC. The Glu mutant, like the phosphorylated wild-type protein, was 16-fold more active than unphosphorylated wild type, and the Asp mutant was 8-fold more active. The wild-type and mutant proteins had the same Km for ATP. Unphosphorylated wild-type protein and the Ala and Asn mutants were unable to translocate actin filaments, whereas the Glu mutant translocated filaments at the same velocity, and the Asp mutant at 50% the velocity, as phosphorylated wild-type proteins. These results demonstrate that an acidic amino acid can supply the negative charge in the surface loop required for the actin-dependent activities of Acanthamoeba myosin IC in vitro and indicate that the length of the side chain that delivers this charge is important. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wang, Z Y AU - Wang, F AU - Sellers, J R AU - Korn, E D AU - Hammer, J A AD - Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/12/22/ PY - 1998 DA - 1998 Dec 22 SP - 15200 EP - 15205 VL - 95 IS - 26 SN - 0027-8424, 0027-8424 KW - Actins KW - 0 KW - DNA Primers KW - Isoenzymes KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Myosin Heavy Chains KW - EC 3.6.4.1 KW - Myosins KW - Index Medicus KW - Isoenzymes -- chemistry KW - Animals KW - Spodoptera KW - Actins -- metabolism KW - Amino Acid Sequence KW - Isoenzymes -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Amino Acid Substitution KW - Cell Line KW - Myosins -- metabolism KW - Myosin Heavy Chains -- chemistry KW - Acanthamoeba -- metabolism KW - Myosins -- chemistry KW - Myosin Heavy Chains -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69100242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+regulatory+phosphorylation+site+in+Acanthamoeba+myosin+IC+by+using+site-directed+mutagenesis.&rft.au=Wang%2C+Z+Y%3BWang%2C+F%3BSellers%2C+J+R%3BKorn%2C+E+D%3BHammer%2C+J+A&rft.aulast=Wang&rft.aufirst=Z&rft.date=1998-12-22&rft.volume=95&rft.issue=26&rft.spage=15200&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF051353; GENBANK N1 - SuppNotes - Cited By: J Biol Chem. 1997 Dec 5;272(49):30623-6 [9388196] Mol Biol Cell. 1998 Jan;9(1):75-88 [9436992] J Biol Chem. 1998 Jun 5;273(23):14644-8 [9603982] Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15206-11 [9860947] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8533-8 [9238011] J Biol Chem. 1971 Aug 10;246(15):4866-71 [4254541] Proc Natl Acad Sci U S A. 1984 Sep;81(17):5345-9 [6382262] J Biol Chem. 1985 Apr 25;260(8):4543-6 [3157680] J Biol Chem. 1985 Sep 15;260(20):11174-9 [3161891] J Biol Chem. 1985 Sep 15;260(20):11183-9 [4030787] J Biol Chem. 1986 Dec 25;261(36):17156-62 [2946692] J Biol Chem. 1987 Oct 5;262(28):13842-9 [2958454] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6720-4 [3477803] J Biol Chem. 1988 Jan 5;263(1):427-35 [2961746] J Biol Chem. 1989 Jun 15;264(17):10243-50 [2524493] Nature. 1989 Aug 17;340(6234):565-8 [2770861] J Cell Biol. 1989 Oct;109(4 Pt 1):1519-28 [2793931] J Biol Chem. 1989 Nov 15;264(32):19333-9 [2530229] J Biol Chem. 1989 Nov 15;264(32):19340-8 [2530230] Gene. 1989 Oct 30;82(2):269-80 [2511079] J Biol Chem. 1990 Mar 5;265(7):3591-4 [2154483] Nature. 1990 Sep 6;347(6288):37-44 [2395459] Methods Enzymol. 1991;196:12-23 [1851936] J Cell Biol. 1992 Jun;117(6):1241-9 [1607386] Methods Enzymol. 1993;217:270-9 [8474334] Science. 1993 Jul 2;261(5117):50-8 [8316857] J Biol Chem. 1993 Aug 25;268(24):17995-8001 [8394357] Nature. 1993 Oct 28;365(6449):841-3 [8413668] FEBS Lett. 1994 Apr 4;342(2):197-202 [8143877] J Muscle Res Cell Motil. 1994 Feb;15(1):1-10 [8182104] J Biol Chem. 1995 May 19;270(20):11776-82 [7744826] J Cell Biol. 1995 Aug;130(3):591-603 [7622560] Cell Motil Cytoskeleton. 1995;31(2):87-92 [7553910] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):21-6 [8552606] Protein Profile. 1995;2(12):1323-1423 [8665326] J Biol Chem. 1996 Jul 19;271(29):16983-6 [8707782] J Biol Chem. 1996 Oct 25;271(43):27044-8 [8900194] J Biol Chem. 1996 Oct 25;271(43):27056-62 [8900196] J Biol Chem. 1996 Dec 13;271(50):31787-90 [8943216] J Cell Biol. 1997 Feb 10;136(3):633-47 [9024693] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1092-5 [9037011] J Muscle Res Cell Motil. 1997 Jun;18(3):395-8 [9172081] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient translesion replication in the absence of Escherichia coli Umu proteins and 3'-5' exonuclease proofreading function. AN - 69099299; 9861001 AB - Translesion replication (TR) past a cyclobutane pyrimidine dimer in Escherichia coli normally requires the UmuD'2C complex, RecA protein, and DNA polymerase III holoenzyme (pol III). However, we find that efficient TR can occur in the absence of the Umu proteins if the 3'-5' exonuclease proofreading activity of the pol III epsilon-subunit also is disabled. TR was measured in isogenic uvrA6 DeltaumuDC strains carrying the dominant negative dnaQ allele, mutD5, or DeltadnaQ spq-2 mutations by transfecting them with single-stranded M13-based vectors containing a specifically located cis-syn T-T dimer. As expected, little TR was observed in the DeltaumuDC dnaQ+ strain. Surprisingly, 26% TR occurred in UV-irradiated DeltaumuDC mutD5 cells, one-half the frequency found in a uvrA6 umuDC+mutD5 strain. lexA3 (Ind-) derivatives of the strains showed that this TR was contingent on two inducible functions, one LexA-dependent, responsible for approximately 70% of the TR, and another LexA-independent, responsible for the remaining approximately 30%. Curiously, the DeltaumuDC DeltadnaQ spq-2 strain exhibited only the LexA-independent level of TR. The cause of this result appears to be the spq-2 allele, a dnaE mutation required for viability in DeltadnaQ strains, since introduction of spq-2 into the DeltaumuDC mutD5 strain also reduces the frequency of TR to the LexA-independent level. The molecular mechanism responsible for the LexA-independent TR is unknown but may be related to the UVM phenomenon [Palejwala, V. A., Wang, G. E., Murphy, H. S. & Humayun, M. Z. (1995) J. Bacteriol. 177, 6041-6048]. LexA-dependent TR does not result from the induction of pol II, since TR in the DeltaumuDC mutD5 strain is unchanged by introduction of a DeltapolB mutation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Vandewiele, D AU - Borden, A AU - O'Grady, P I AU - Woodgate, R AU - Lawrence, C W 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 - 1998/12/22/ PY - 1998 DA - 1998 Dec 22 SP - 15519 EP - 15524 VL - 95 IS - 26 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - LexA protein, Bacteria KW - Pyrimidine Dimers KW - Recombinant Proteins KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - dnaQ protein, E coli KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Index Medicus KW - Genotype KW - Alleles KW - Serine Endopeptidases -- metabolism KW - Transfection KW - Serine Endopeptidases -- genetics KW - Recombinant Proteins -- metabolism KW - Transduction, Genetic KW - DNA Polymerase III -- genetics KW - Escherichia coli -- metabolism KW - Bacterial Proteins -- genetics KW - DNA Damage KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Exodeoxyribonucleases -- genetics KW - Exodeoxyribonucleases -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69099299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+translesion+replication+in+the+absence+of+Escherichia+coli+Umu+proteins+and+3%27-5%27+exonuclease+proofreading+function.&rft.au=Vandewiele%2C+D%3BBorden%2C+A%3BO%27Grady%2C+P+I%3BWoodgate%2C+R%3BLawrence%2C+C+W&rft.aulast=Vandewiele&rft.aufirst=D&rft.date=1998-12-22&rft.volume=95&rft.issue=26&rft.spage=15519&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 - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1974 Feb;117(2):477-87 [4590472] J Bacteriol. 1997 Dec;179(23):7507-14 [9393717] Proc Natl Acad Sci U S A. 1978 Jul;75(7):3037-41 [356043] Proc Natl Acad Sci U S A. 1983 Apr;80(8):2189-92 [6340117] J Mol Biol. 1983 Apr 25;165(4):669-82 [6222198] Mol Gen Genet. 1985;199(1):64-9 [3158798] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6614-8 [2995974] Proc Natl Acad Sci U S A. 1986 Feb;83(3):619-23 [3456159] Mol Gen Genet. 1986 Oct;205(1):9-13 [3540531] Mutat Res. 1987 Jan;183(1):31-7 [3025722] Nucleic Acids Res. 1987 Jun 11;15(11):4645-53 [3035498] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4195-9 [3295877] J Biol Chem. 1987 Aug 5;262(22):10518-23 [2956258] Mol Gen Genet. 1987 Jul;208(3):542-8 [3312950] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8141-5 [3054882] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9124-7 [3057500] J Biol Chem. 1988 Dec 15;263(35):18946-52 [3058691] J Mol Biol. 1988 Oct 5;203(3):635-41 [3062176] Mol Gen Genet. 1988 Nov;214(3):467-73 [2851096] J Bacteriol. 1989 Jun;171(6):3144-51 [2542218] J Bacteriol. 1989 Oct;171(10):5572-80 [2551891] J Bacteriol. 1989 Oct;171(10):5581-6 [2676978] Mutat Res. 1990 Mar;229(1):79-87 [2179713] J Bacteriol. 1990 Apr;172(4):2105-12 [2180917] J Mol Biol. 1990 Mar 5;212(1):79-96 [2108251] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9755-60 [9707548] Mol Cell. 1998 Aug;2(2):191-9 [9734356] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13114-9 [9789050] Mutagenesis. 1990 Jan;5(1):31-4 [2184308] Mutagenesis. 1990 Jan;5(1):35-8 [2184309] Mol Gen Genet. 1990 Jun;222(1):166-8 [2233676] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9211-5 [2251267] Biochemistry. 1990 Sep 18;29(37):8858-66 [2271562] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1251-5 [1847514] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 Apr;174(8):2517-24 [1556072] J Bacteriol. 1993 Jul;175(13):4260-2 [8320242] J Bacteriol. 1994 Feb;176(3):815-21 [8300534] Genetics. 1994 Feb;136(2):439-48 [7908652] Mol Gen Genet. 1995 Apr 20;247(2):216-21 [7753031] J Bacteriol. 1995 Oct;177(20):5979-86 [7592352] Annu Rev Biochem. 1995;64:171-200 [7574479] J Bacteriol. 1995 Nov;177(21):6041-8 [7592365] Cell. 1996 Jan 12;84(1):5-8 [8548826] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2856-61 [8610131] J Bacteriol. 1996 May;178(9):2559-63 [8626322] Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4380-5 [8633075] J Bacteriol. 1996 Jun;178(12):3550-6 [8655553] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):946-51 [9023362] J Bacteriol. 1997 Dec;179(23):7435-45 [9393709] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monoclonal Antibody-Resistant Mutants Selected with a Respiratory Syncytial Virus-Neutralizing Human Antibody Fab Fragment (Fab 19) Define a Unique Epitope on the Fusion (F) Glycoprotein AN - 17159909; 4461375 AB - A recombinant human antibody fragment, designated RSV Fab 19, efficiently neutralizes respiratory syncytial virus (RSV). Here we report the results of our sequence analysis of antibody escape mutants that identified F glycoprotein amino acids critical for binding of human or murine RSV F-neutralizing antibodies. JF - Virology AU - Crowe, JE Jr AU - Firestone, C AU - Crim, R AU - Beeler, JA AU - Coelingh, K L AU - Barbas, CF III AU - Burton AU - Chanock, R M AU - Murphy, B R AD - Respiratory Viruses Section, National Institutes of Health, Bethesda, MD 20892-0720 USA, james.e.crowe@vanderbilt.edu Y1 - 1998/12/20/ PY - 1998 DA - 1998 Dec 20 SP - 373 EP - 375 PB - Academic Press VL - 252 IS - 2 SN - 0042-6822, 0042-6822 KW - Fab KW - Fab 19 antibody KW - glycoprotein F KW - respiratory syncytial virus KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Monoclonal antibodies KW - Antibodies KW - Fusion protein KW - Glycoproteins KW - W3 33375:Antibodies KW - V 22099:Immune response & immune mechanisms 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/17159909?accountid=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=Virology&rft.atitle=Monoclonal+Antibody-Resistant+Mutants+Selected+with+a+Respiratory+Syncytial+Virus-Neutralizing+Human+Antibody+Fab+Fragment+%28Fab+19%29+Define+a+Unique+Epitope+on+the+Fusion+%28F%29+Glycoprotein&rft.au=Crowe%2C+JE+Jr%3BFirestone%2C+C%3BCrim%2C+R%3BBeeler%2C+JA%3BCoelingh%2C+K+L%3BBarbas%2C+CF+III%3BBurton%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=JE&rft.date=1998-12-20&rft.volume=252&rft.issue=2&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&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; Antibodies; Monoclonal antibodies; Fusion protein ER - TY - JOUR T1 - Identification of the sites of N-linked glycosylation on the human calcium receptor and assessment of their role in cell surface expression and signal transduction. AN - 70113385; 9852126 AB - The human calcium receptor (hCaR) is a G-protein-coupled receptor containing 11 potential N-linked glycosylation sites in the large extracellular domain. The number of potential N-linked glycosylation sites actually modified, and the effect on cell surface expression and signal transduction of blocking glycosylation at these sites, was examined by site-directed mutagenesis. Asparagine residues of the consensus sequences (Asn-Xaa-Ser/Thr) for N-linked glycosylation were mutated to glutamine individually and in various combinations to disrupt the potential N-linked glycosylation sites in the context of the full-length receptor. The cDNA constructs were transiently transfected into HEK-293 cells lacking endogeneous hCaR, and expressed receptors were analyzed by mobility differences on immunoblots, glycosidase digestion, intact cell enzyme-linked immunoassay, and extracellular calcium-stimulated phosphoinositide hydrolysis assay. Immunoblot analyses and glycosidase digestion studies of the wild type versus mutant receptors demonstrate that, of the 11 potential sites for N-linked glycosylation, eight sites (Asn-90, -130, -261, -287, -446, -468, -488, and -541) are glycosylated; the three remaining sites (Asn-386, -400, and -594) may not be efficiently glycosylated in the native receptor. Sequential mutagenesis of multiple N-linked glycosylation sites and analyses by immunoblotting, immunofluorescence, biotinylation of cell surface proteins, and intact cell enzyme-linked immunoassay indicated that disruption of as few as three glycosylation sites impairs proper processing and expression of the receptor at the cell surface. Disruption of five glycosylation sites reduced cell surface expression by 50-90% depending on which five sites were disrupted. Phosphoinositide hydrolysis assay results for various glycosylation-defective mutant receptors in general correlated well with the level of cell surface expression. Our results demonstrate that among 11 potential N-linked glycosylation sites on the hCaR, eight sites are actually utilized; glycosylation of at least three sites is critical for cell surface expression of the receptor, but glycosylation does not appear to be critical for signal transduction. JF - The Journal of biological chemistry AU - Ray, K AU - Clapp, P AU - Goldsmith, P K AU - Spiegel, A M AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/18/ PY - 1998 DA - 1998 Dec 18 SP - 34558 EP - 34567 VL - 273 IS - 51 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Recombinant Proteins KW - Asparagine KW - 7006-34-0 KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Models, Molecular KW - Humans KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Enzyme-Linked Immunosorbent Assay KW - Recombinant Proteins -- chemistry KW - Cell Membrane -- metabolism KW - Signal Transduction KW - Amino Acid Substitution KW - Cell Line KW - Calcium -- metabolism KW - Protein Structure, Secondary KW - Calcium-Binding Proteins -- physiology KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70113385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+sites+of+N-linked+glycosylation+on+the+human+calcium+receptor+and+assessment+of+their+role+in+cell+surface+expression+and+signal+transduction.&rft.au=Ray%2C+K%3BClapp%2C+P%3BGoldsmith%2C+P+K%3BSpiegel%2C+A+M&rft.aulast=Ray&rft.aufirst=K&rft.date=1998-12-18&rft.volume=273&rft.issue=51&rft.spage=34558&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 - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1. AN - 70104712; 9852104 AB - The fibrous sheath is a unique cytoskeletal structure in the sperm flagellum believed to modulate sperm motility. FSC1 is the major structural protein of the fibrous sheath. The yeast two-hybrid system was used to identify other proteins that contribute to the structure of the fibrous sheath or participate in sperm motility. When FSC1 was used as the bait to screen a mouse testis cDNA library, two clones were isolated encoding the type Ialpha regulatory subunit (RIalpha) of cAMP-dependent protein kinase. Deletion analysis using the yeast two-hybrid system and in vitro binding assays with glutathione S-transferase-FSC1 fusion proteins identified two RIalpha tethering domains on FSC1. A domain located at residues 219-232 (termed domain A) corresponds to the reported tethering domain for a type II regulatory subunit (RII) of cAMP-dependent protein kinase, indicating that this binding domain has dual specificity to RI and RII. Another RIalpha tethering site (termed domain B) at residues 335-344 shows specific binding of RIalpha and had no significant sequence homology with known RII tethering domains. However, helical wheel projection analysis indicates that domain B is likely to form an amphipathic helix, the secondary structure of RII tethering domains of protein kinase A anchoring proteins. This was supported by the finding that site-directed mutagenesis to disrupt the amphipathic helix eliminated RIalpha binding. This is apparently the first report of an RIalpha-specific protein kinase A anchoring protein tethering domain. JF - The Journal of biological chemistry AU - Miki, K AU - Eddy, E M AD - Gamete Biology Group, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/12/18/ PY - 1998 DA - 1998 Dec 18 SP - 34384 EP - 34390 VL - 273 IS - 51 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Macromolecular Substances KW - Proteins KW - Recombinant Proteins KW - Seminal Plasma Proteins KW - Cyclic AMP-Dependent Protein Kinase Type II KW - EC 2.7.11.11 KW - Cyclic AMP-Dependent Protein Kinases KW - Index Medicus KW - Animals KW - Testis -- metabolism KW - Amino Acid Sequence KW - Mice KW - Sperm Motility KW - Saccharomyces cerevisiae KW - Mutagenesis KW - Binding Sites KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Escherichia coli KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Male KW - Sequence Deletion KW - Gene Library KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Proteins -- chemistry KW - Sperm Tail -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- chemistry KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70104712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+tethering+domains+for+protein+kinase+A+type+Ialpha+regulatory+subunits+on+sperm+fibrous+sheath+protein+FSC1.&rft.au=Miki%2C+K%3BEddy%2C+E+M&rft.aulast=Miki&rft.aufirst=K&rft.date=1998-12-18&rft.volume=273&rft.issue=51&rft.spage=34384&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 - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U10341; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiation of the discriminative-stimulus effects of methamphetamine by the histamine H3 receptor antagonist thioperamide in rats. AN - 69126006; 9881573 AB - In order to assess the role of histamine H3 receptors in the discriminative-stimulus effects of methamphetamine, rats were trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food presentation. The histamine H3 receptor antagonist thioperamide (1.0 mg/kg s.c.), which facilitates histamine release, significantly shifted the methamphetamine dose-response curve to the left when tested together with different doses of methamphetamine and markedly extended the time-course of methamphetamine's discriminative-stimulus effects. The histamine H3 receptor agonist R-alpha-methylhistamine (3.0 mg/kg i.p.), which blocks histamine release, did not produce any effects when given alone, but it attenuated the effects of thioperamide on the methamphetamine dose-response curve when both drugs were given together. Thus, methamphetamine's discriminative-stimulus effects are markedly potentiated by the blockade of histamine H3 receptors by thioperamide. This is likely due to thioperamide's actions at histamine H3 autoreceptors on histaminergic neurons to facilitate release of histamine by methamphetamine or at histamine H3 heteroreceptors on other monoaminergic neurons (e.g., dopaminergic, serotonergic or noradrenergic) to facilitate release of other neurotransmitters. JF - European journal of pharmacology AU - Munzar, P AU - Nosál, R AU - Goldberg, S R AD - Preclinical Pharmacology Laboratory, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore MD 21224, USA. Y1 - 1998/12/18/ PY - 1998 DA - 1998 Dec 18 SP - 93 EP - 101 VL - 363 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Central Nervous System Stimulants KW - 0 KW - Histamine Agonists KW - Histamine Antagonists KW - Methylhistamines KW - Piperidines KW - Receptors, Histamine H3 KW - Methamphetamine KW - 44RAL3456C KW - alpha-methylhistamine KW - 6986-90-9 KW - Histamine KW - 820484N8I3 KW - thioperamide KW - II4319BWUI KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Histamine Agonists -- pharmacology KW - Methylhistamines -- pharmacology KW - Histamine -- metabolism KW - Drug Synergism KW - Time Factors KW - Male KW - Receptors, Histamine H3 -- metabolism KW - Piperidines -- pharmacology KW - Discrimination Learning -- drug effects KW - Receptors, Histamine H3 -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Histamine Antagonists -- pharmacology KW - Methamphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69126006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Potentiation+of+the+discriminative-stimulus+effects+of+methamphetamine+by+the+histamine+H3+receptor+antagonist+thioperamide+in+rats.&rft.au=Munzar%2C+P%3BNos%C3%A1l%2C+R%3BGoldberg%2C+S+R&rft.aulast=Munzar&rft.aufirst=P&rft.date=1998-12-18&rft.volume=363&rft.issue=2-3&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&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 - [Is caffeine addictive? The most widely used psychoactive substance in the world affects same parts of the brain as cocaine]. TT - Ar koffein beroendeframkallande? Världens mest nyttjade psykoaktiva substans påverkar samma delar av hjärnan som kokain. AN - 69137626; 9889511 AB - Caffeine is the most widely used psychoactive substance in the world. In Western society, at least 80 per cent of the adult population consumes caffeine in amounts large enough to have an effect on the brain. Is this due to caffeine dependence? The article reviews the abuse potential of caffeine in relation to its mechanisms of action. Caffeine affects the same parts of the brain as cocaine, but in completely different ways. There is evidence for caffeine withdrawal symptoms, and caffeine does act as a weak reinforcer, but neither effect is as pronounced as those associated with cocaine. Nor does caffeine use appear to pose any threat to the individual or to society. There is thus no need to add diagnosis "caffeine dependence" to the psychiatric manuals. JF - Lakartidningen AU - Daly, J W AU - Holmén, J AU - Fredholm, B B AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. Y1 - 1998/12/16/ PY - 1998 DA - 1998 Dec 16 SP - 5878 EP - 5883 VL - 95 IS - 51-52 SN - 0023-7205, 0023-7205 KW - Central Nervous System Stimulants KW - 0 KW - Receptors, Purinergic KW - Caffeine KW - 3G6A5W338E KW - Index Medicus KW - Animals KW - Drug Interactions KW - Substance Withdrawal Syndrome -- etiology KW - Humans KW - Adult KW - Receptors, Purinergic -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Caffeine -- administration & dosage KW - Brain -- drug effects KW - Substance-Related Disorders -- etiology KW - Caffeine -- pharmacology KW - Caffeine -- adverse effects KW - Central Nervous System Stimulants -- adverse effects KW - Central Nervous System Stimulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69137626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lakartidningen&rft.atitle=%5BIs+caffeine+addictive%3F+The+most+widely+used+psychoactive+substance+in+the+world+affects+same+parts+of+the+brain+as+cocaine%5D.&rft.au=Daly%2C+J+W%3BHolm%C3%A9n%2C+J%3BFredholm%2C+B+B&rft.aulast=Daly&rft.aufirst=J&rft.date=1998-12-16&rft.volume=95&rft.issue=51-52&rft.spage=5878&rft.isbn=&rft.btitle=&rft.title=Lakartidningen&rft.issn=00237205&rft_id=info:doi/ LA - Swedish DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-25 N1 - Date created - 1999-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens AN - 17158464; 4446724 AB - The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. In phase I studies, 54 patients received escalating doses (between 10 super(7) and 10 super(11) plaqueforming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. JF - Journal of the National Cancer Institute AU - Rosenberg, SA AU - Zhai, Y AU - Yang, J C AU - Schwartzentruber, D J AU - Hwu, P AU - Marincola, F M AU - Topalian, S L AU - Restifo, N P AU - Seipp, CA AU - Einhorn, J H AU - Roberts, B AU - White, DE AD - National Institutes of Health, Bldg. 10, Rm. 2B42, Bethesda, MD 20892, USA Y1 - 1998/12/16/ PY - 1998 DA - 1998 Dec 16 SP - 1894 EP - 1900 VL - 90 IS - 24 SN - 0027-8874, 0027-8874 KW - MART-1 antigen KW - glycoprotein gp100 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Interleukin 2 KW - Antigen (tumor-associated) KW - Vaccines KW - Melanoma KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17158464?accountid=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=Immunizing+Patients+With+Metastatic+Melanoma+Using+Recombinant+Adenoviruses+Encoding+MART-1+or+gp100+Melanoma+Antigens&rft.au=Rosenberg%2C+SA%3BZhai%2C+Y%3BYang%2C+J+C%3BSchwartzentruber%2C+D+J%3BHwu%2C+P%3BMarincola%2C+F+M%3BTopalian%2C+S+L%3BRestifo%2C+N+P%3BSeipp%2C+CA%3BEinhorn%2C+J+H%3BRoberts%2C+B%3BWhite%2C+DE&rft.aulast=Rosenberg&rft.aufirst=SA&rft.date=1998-12-16&rft.volume=90&rft.issue=24&rft.spage=1894&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 - Melanoma; Antigen (tumor-associated); Vaccines; Interleukin 2 ER - TY - JOUR T1 - Construction and Characterization of a Triple-Recombinant Vaccinia Virus Encoding B7-1, Interleukin 12, and a Model Tumor Antigen AN - 17154197; 4446723 AB - Construction of recombinant viruses that can serve as vaccines for the treatment of experimental murine tumors has recently been achieved. The cooperative effects of immune system modulators, including cytokines such as interleukin 12 (IL-12) and costimulatory molecules such as B7-1, may be necessary for activation of cytotoxic T lymphocytes. Thus, we have explored the feasibility and the efficacy of inclusion of these immunomodulatory molecules in recombinant virus vaccines in an experimental antitumor model in mice that uses Escherichia coli beta -galactosidase as a target antigen. We developed a "cassette" system in which three loci of the vaccinia virus genome were used for homologous recombination. A variety of recombinant vaccinia viruses were constructed, including one virus, vB7/ beta /IL-12, that contains the following five transgenes: murine B7-1, murine IL-12 subunit p35, murine IL-12 subunit p40, E. coli lacZ (encodes beta -galactosidase, the model antigen), and E. coli gpt (xanthine-guanine phosphoribosyltransferase, a selection gene). The effects of the recombinant viruses on lung metastases and survival were tested in animals that had been given an intravenous injection of beta -galactosidase-expressing murine colon carcinoma cells 3 days before they received the recombinant virus by intravenous inoculation. Expression of functional B7-1 and IL-12 by virally infected cells was demonstrated in vitro. Lung tumor nodules (i.e., metastases) were reduced in mice by more than 95% after treatment with the virus vB7/ beta /IL-12; a further reduction in lung tumor nodules was observed when exogenous IL-12 was also given. Greatest survival of tumor-bearing mice was observed in those treated with viruses encoding beta -galactosidase and B7-1 plus exogenous IL-12. This study shows the feasibility of constructing vaccinia viruses that express tumor antigens and multiple immune cofactors to create unique immunologic microenvironments that can modulate immune responses to cancer. JF - Journal of the National Cancer Institute AU - Carroll, M W AU - Overwijk, W W AU - Surman AU - Tsung, K AU - Moss, B AU - Restifo, N P AD - National Institutes of Health, Bldg. 10, Rm. 2B42, Bethesda, MD 20892-1502, USA, restifo@pop.nci.nih.gov Y1 - 1998/12/16/ PY - 1998 DA - 1998 Dec 16 SP - 1881 EP - 1887 VL - 90 IS - 24 SN - 0027-8874, 0027-8874 KW - double prime B7-1 antigen KW - cancer vaccines KW - vaccinia virus KW - xanthine-guanine phosphoribosyltransferase KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Tumors KW - Expression vectors KW - Interleukin 12 KW - Lung KW - Antigen (tumor-associated) 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/17154197?accountid=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=Construction+and+Characterization+of+a+Triple-Recombinant+Vaccinia+Virus+Encoding+B7-1%2C+Interleukin+12%2C+and+a+Model+Tumor+Antigen&rft.au=Carroll%2C+M+W%3BOverwijk%2C+W+W%3BSurman%3BTsung%2C+K%3BMoss%2C+B%3BRestifo%2C+N+P&rft.aulast=Carroll&rft.aufirst=M&rft.date=1998-12-16&rft.volume=90&rft.issue=24&rft.spage=1881&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 - Antigen (tumor-associated); Expression vectors; Interleukin 12; Tumors; Lung ER - TY - JOUR T1 - Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. AN - 69105602; 9865727 AB - Resveratrol, a compound present in a variety of plants, was recently shown to have potent chemopreventive activity against aryl hydrocarbon-induced tumorigenesis in mice. Therefore, in the present study, we examined the effect of resveratrol on the function of the aryl hydrocarbon receptor (AHR) and the transcription of CYP1A1 in human HepG2 hepatoma cells. Resveratrol inhibited the increase in cytochrome P450 (CYP) 1A1 mRNA caused by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a concentration-dependent manner. The induction of transcription of an aryl hydrocarbon-responsive reporter vector containing the CYP1A1 promoter by TCDD was likewise inhibited by resveratrol. Resveratrol also inhibited the constitutive level of CYP1A1 mRNA and reporter vector transcription in HepG2 cells. The increase in CYP1A1 enzyme activity induced by TCDD was inhibited by resveratrol. Resveratrol prevented the TCDD-induced transformation of the cytosolic AHR to its nuclear DNA-binding form. However, resveratrol had no effect on the binding of TCDD to the cytosolic AHR. These data demonstrate that resveratrol inhibits CYP1A1 expression in vitro, and that it does this by preventing the binding of the AHR to promoter sequences that regulate CYP1A1 transcription. This activity may be an important part of the chemopreventive activity of resveratrol. JF - Cancer research AU - Ciolino, H P AU - Daschner, P J AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Divsion of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Maryland 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1998/12/15/ PY - 1998 DA - 1998 Dec 15 SP - 5707 EP - 5712 VL - 58 IS - 24 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Stilbenes KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - resveratrol KW - Q369O8926L KW - Index Medicus KW - Cytosol -- metabolism KW - Promoter Regions, Genetic KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Humans KW - Polychlorinated Dibenzodioxins -- metabolism KW - Stilbenes -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69105602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Resveratrol+inhibits+transcription+of+CYP1A1+in+vitro+by+preventing+activation+of+the+aryl+hydrocarbon+receptor.&rft.au=Ciolino%2C+H+P%3BDaschner%2C+P+J%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1998-12-15&rft.volume=58&rft.issue=24&rft.spage=5707&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 - 1999-01-25 N1 - Date created - 1999-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thiol oxidation and loss of mitochondrial complex I precede excitatory amino acid-mediated neurodegeneration. AN - 69081184; 9852566 AB - Human ingestion of "chickling peas" from the plant Lathyrus sativus, which contains an excitatory amino acid, L-BOAA (L-beta-N-oxalylamino-L-alanine), leads to a progressive corticospinal neurodegenerative disorder, neurolathyrism. Exposure to L-BOAA, but not its optical enantiomer D-BOAA, causes mitochondrial dysfunction as evidenced by loss of complex I activity in vitro in male mouse brain slices and in vivo in selected regions of mouse CNS (lumbosacral cord and motor cortex). Loss of complex I activity in lumbosacral cord after L-BOAA administration to mice was accompanied by concurrent loss of glutathione. The inhibited complex I activity in mitochondria isolated from lumbosacral cord of animals treated with L-BOAA rebounded after incubation with the thiol-reducing agent dithiothreitol, indicating that oxidation of protein thiols to disulfides was responsible for enzyme inhibition. The inhibition of complex I could be abolished by pretreatment with antioxidant thiols such as glutathione ester and alpha-lipoic acid. Chronic treatment of male mice, but not female mice, with L-BOAA resulted in loss of complex I activity and vacuolation and dendritic swelling of neurons in the motor cortex and lumbar cord, paralleling the regionality of the aforementioned biochemical effects on CNS mitochondria. These results support the view that thiol oxidation and concomitant mitochondrial dysfunction (also implicated in other neurodegenerative disorders), occurring downstream of glutamate receptor activation by L-BOAA, are primary events leading to neurodegeneration. Maintenance of protein thiol homeostasis by thiol delivery agents could potentially offer protection against excitotoxic insults such as those seen with L-BOAA. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Sriram, K AU - Shankar, S K AU - Boyd, M R AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India. Y1 - 1998/12/15/ PY - 1998 DA - 1998 Dec 15 SP - 10287 EP - 10296 VL - 18 IS - 24 SN - 0270-6474, 0270-6474 KW - Amino Acids, Diamino KW - 0 KW - Excitatory Amino Acid Agonists KW - Excitatory Amino Acids KW - Neurotoxins KW - Sulfhydryl Compounds KW - oxalyldiaminopropionic acid KW - 7554-90-7 KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - Glutathione KW - GAN16C9B8O KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Animals KW - Motor Cortex -- cytology KW - Brain -- cytology KW - Brain -- drug effects KW - Neurotoxins -- pharmacology KW - Motor Cortex -- drug effects KW - Rats KW - Motor Cortex -- pathology KW - In Vitro Techniques KW - Mitochondria -- drug effects KW - Spinal Cord -- pathology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Time Factors KW - Male KW - Spinal Cord -- cytology KW - Oxidation-Reduction -- drug effects KW - Dose-Response Relationship, Drug KW - Glutathione -- metabolism KW - Lathyrism -- chemically induced KW - Mice KW - Glutathione -- pharmacology KW - Lathyrism -- pathology KW - Amino Acids, Diamino -- pharmacology KW - Brain -- pathology KW - Spinal Cord -- drug effects KW - Dithiothreitol -- pharmacology KW - Rats, Wistar KW - Mitochondria -- metabolism KW - Female KW - NAD(P)H Dehydrogenase (Quinone) -- antagonists & inhibitors KW - Neurodegenerative Diseases -- chemically induced KW - Sulfhydryl Compounds -- chemistry KW - Excitatory Amino Acids -- pharmacology KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69081184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thiol+oxidation+and+loss+of+mitochondrial+complex+I+precede+excitatory+amino+acid-mediated+neurodegeneration.&rft.au=Sriram%2C+K%3BShankar%2C+S+K%3BBoyd%2C+M+R%3BRavindranath%2C+V&rft.aulast=Sriram&rft.aufirst=K&rft.date=1998-12-15&rft.volume=18&rft.issue=24&rft.spage=10287&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 - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lon-mediated proteolysis of the Escherichia coli UmuD mutagenesis protein: in vitro degradation and identification of residues required for proteolysis AN - 17154073; 4449158 AB - Most SOS mutagenesis in Escherichia coli is dependent on the UmuD and UmuC proteins. Perhaps as a consequence, the activity of these proteins is exquisitely regulated. The intracellular level of UmuD and UmuC is normally quite low but increases dramatically in lon super(-) strains, suggesting that both proteins are substrates of the Lon protease. We report here that the highly purified UmuD protein is specifically degraded in vitro by Lon in an ATP-dependent manner. To identify the regions of UmuD necessary for Lon-mediated proteolysis, we performed 'alanine-stretch' mutagenesis on umuD and followed the stability of the mutant protein in vivo. Such an approach allowed us to localize the site(s) within UmuD responsible for Lon-mediated proteolysis. The primary signal is located between residues 15 and 18 (FPLF), with an auxiliary site between residues 26 and 29 (FPSP), of the amino terminus of UmuD. Transfer of the amino terminus of UmuD (residues 1-40) to an otherwise stable protein imparts Lon-mediated proteolysis, thereby indicating that the amino terminus of UmuD is sufficient for Lon recognition and the ensuing degradation of the protein. JF - Genes & Development AU - Gonzalez, M AU - Frank, E G 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, woodgate@helix.nih.gov Y1 - 1998/12/15/ PY - 1998 DA - 1998 Dec 15 SP - 3889 EP - 3899 VL - 12 IS - 24 SN - 0890-9369, 0890-9369 KW - SOS mutagenesis KW - UmuD protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - N 14930:Transcription factors KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17154073?accountid=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=Genes+%26+Development&rft.atitle=Lon-mediated+proteolysis+of+the+Escherichia+coli+UmuD+mutagenesis+protein%3A+in+vitro+degradation+and+identification+of+residues+required+for+proteolysis&rft.au=Gonzalez%2C+M%3BFrank%2C+E+G%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=Gonzalez&rft.aufirst=M&rft.date=1998-12-15&rft.volume=12&rft.issue=24&rft.spage=3889&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli ER - TY - JOUR T1 - Chromosomal proteins HMG-14 and HMG-17 are released from mitotic chromosomes and imported into the nucleus by active transport. AN - 70122071; 9852141 AB - The high mobility group 14/17 (HMG-14/-17) proteins form specific complexes with nucleosome core particles and produce distinct footprints on nucleosomal DNA. Therefore, they could be an integral part of the chromatin fiber. Here we show that during the cell cycle these proteins are transiently dissociated from chromatin. They colocalize with the nuclear DNA in interphase and prophase but not in metaphase and anaphase. They relocate into the nucleus and colocalize again with the DNA in late telophase, concomitantly with the appearance of the nuclear envelope. Thus, these nucleosomal binding proteins are not always associated with chromatin. Using reconstituted nuclei and permeabilized cells, we demonstrate that these two small proteins, with a molecular mass <10 kD, are actively imported into the nucleus. We identify the major elements involved in the nuclear import of these chromosomal proteins: HMG-14/-17 proteins contain an intrinsic bipartite nuclear localization signal, and their entry into the nucleus through nuclear pores requires energy and the participation of importin alpha. These findings suggest that the cell cycle-related association of HMG-14/-17 with chromatin is dependent on, and perhaps regulated by, nuclear import processes. JF - The Journal of cell biology AU - Hock, R AU - Scheer, U 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. Y1 - 1998/12/14/ PY - 1998 DA - 1998 Dec 14 SP - 1427 EP - 1436 VL - 143 IS - 6 SN - 0021-9525, 0021-9525 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Tissue Extracts KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Chromatin -- metabolism KW - Nucleosomes -- metabolism KW - Interphase KW - Oocytes -- physiology KW - Mice KW - Nuclear Envelope -- physiology KW - Biological Transport, Active KW - Metaphase KW - Spermatozoa -- physiology KW - Mitosis KW - Xenopus KW - Female KW - Male KW - Cell Nucleus -- metabolism KW - Chromosomes -- metabolism KW - High Mobility Group Proteins -- metabolism KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70122071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chromosomal+proteins+HMG-14+and+HMG-17+are+released+from+mitotic+chromosomes+and+imported+into+the+nucleus+by+active+transport.&rft.au=Hock%2C+R%3BScheer%2C+U%3BBustin%2C+M&rft.aulast=Hock&rft.aufirst=R&rft.date=1998-12-14&rft.volume=143&rft.issue=6&rft.spage=1427&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 - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Sci. 1997 Sep;110 ( Pt 17):2053-63 [9378756] Trends Biochem Sci. 1998 May;23(5):185-9 [9612083] Biotechniques. 1998 Apr;24(4):668-74 [9564542] Cell. 1979 Jan;16(1):181-9 [369705] Proc Natl Acad Sci U S A. 1979 Feb;76(2):630-4 [284387] Biochemistry. 1980 Sep 16;19(19):4466-71 [6157409] Cell. 1984 Sep;38(2):493-9 [6235920] Exp Cell Res. 1985 Feb;156(2):295-310 [3881264] Cell. 1986 Nov 21;47(4):577-87 [3779837] J Cell Biol. 1986 Dec;103(6 Pt 1):2091-102 [3097026] Cell. 1987 Jan 30;48(2):205-17 [3026635] Nature. 1989 Jan 19;337(6204):276-9 [2911368] Chromosoma. 1988 Nov;97(3):193-7 [3064988] Methods Enzymol. 1989;170:214-51 [2770539] J Cell Biol. 1989 Nov;109(5):1975-82 [2808516] J Cell Biol. 1990 Sep;111(3):807-16 [2391365] J Biol Chem. 1990 Nov 25;265(33):20077-80 [2243079] J Cell Biol. 1991 Mar;112(6):1073-82 [1825658] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Exp Cell Res. 1993 Sep;208(1):128-36 [8359213] EMBO J. 1993 Oct;12(10):3855-64 [8404854] Mol Biol Cell. 1993 Oct;4(10):993-1002 [8298196] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Cell. 1994 Feb 25;76(4):609-22 [7510215] Cell. 1994 Dec 2;79(5):767-78 [8001116] EMBO J. 1995 Apr 3;14(7):1478-89 [7729423] Cell. 1995 Oct 6;83(1):29-38 [7553870] 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):247-55 [8562917] Science. 1996 Mar 15;271(5255):1513-8 [8599106] Eur J Cell Biol. 1995 Dec;68(4):345-54 [8690014] Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 [8768072] Genes Dev. 1996 Oct 1;10(19):2389-400 [8843192] J Biol Chem. 1996 Nov 29;271(48):30781-9 [8940058] J Cell Biol. 1997 Apr 7;137(1):19-26 [9105033] Nature. 1997 Apr 24;386(6627):779-87 [9126736] Curr Opin Cell Biol. 1997 Jun;9(3):412-9 [9159081] Biochemistry. 1997 May 20;36(20):5992-9 [9166769] Cell. 1997 May 30;89(5):715-25 [9182759] Mol Cell Biol. 1997 Oct;17(10):5843-55 [9315642] Proc Natl Acad Sci U S A. 1998 May 12;95(10):5468-73 [9576905] J Mol Biol. 1997 Dec 12;274(4):454-65 [9417927] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebral glucose metabolism during opioid withdrawal following methylnaloxonium injection into the locus coeruleus. AN - 70097427; 9838021 AB - Previous studies have demonstrated a widespread stimulation of regional cerebral metabolic rate(s) for glucose (rCMRglc) in morphine-dependent rats subjected to opioid withdrawal precipitated by systemic injection of naloxone. Nonetheless, many of the behavioral signs of opioid withdrawal are produced by intracerebral injections of an opioid antagonist, methylnaloxonium (MN), into the locus coeruleus (LC). The purpose of the present work was to determine the extent to which cerebral metabolic alterations in opioid withdrawal could be initiated by a local action in LC. Intracerebral injections of MN into LC increased rCMRglc in morphine-dependent rats, and the anatomical distribution of this effect was similar to that produced by systemic injections of naloxone. The present data support the view that LC is a major substrate of opioid withdrawal in the brain, and they suggest that LC plays an important role in changing rCMRglc during opioid withdrawal induced by systemic naloxone administration. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Kimes, A S AU - Maldonado, R AU - Ambrosio, E AU - Koob, G F AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. akimes@intra.nida.nih.gov Y1 - 1998/12/14/ PY - 1998 DA - 1998 Dec 14 SP - 1 EP - 12 VL - 814 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Narcotic Antagonists KW - 0 KW - Quaternary Ammonium Compounds KW - Naloxone KW - 36B82AMQ7N KW - N-methylnaloxone KW - 73232-50-5 KW - Morphine KW - 76I7G6D29C KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Animals KW - Locus Coeruleus -- metabolism KW - Rats KW - Body Temperature Regulation -- drug effects KW - Rats, Inbred F344 KW - Amygdala -- metabolism KW - Heart Rate -- drug effects KW - Locus Coeruleus -- drug effects KW - Amygdala -- drug effects KW - Blood Pressure -- drug effects KW - Injections KW - Functional Laterality KW - Male KW - Naloxone -- pharmacology KW - Substance Withdrawal Syndrome KW - Morphine -- adverse effects KW - Glucose -- metabolism KW - Naloxone -- analogs & derivatives KW - Brain -- metabolism KW - Narcotic Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70097427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cerebral+glucose+metabolism+during+opioid+withdrawal+following+methylnaloxonium+injection+into+the+locus+coeruleus.&rft.au=Kimes%2C+A+S%3BMaldonado%2C+R%3BAmbrosio%2C+E%3BKoob%2C+G+F%3BLondon%2C+E+D&rft.aulast=Kimes&rft.aufirst=A&rft.date=1998-12-14&rft.volume=814&rft.issue=1-2&rft.spage=1&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 - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium can disrupt the SNARE protein complex on sea urchin egg secretory vesicles without irreversibly blocking fusion. AN - 70099117; 9837952 AB - The homotypic fusion of sea urchin egg cortical vesicles (CV) is a system in which to correlate the biochemistry and physiology of membrane fusion. Homologues of vesicle-associated membrane protein (VAMP), syntaxin, and SNAP-25 were identified in CV membranes. A VAMP and syntaxin immunoreactive band at a higher apparent molecular mass (approximately 70 kDa) was detected; extraction and analysis confirmed that the band contained VAMP, SNAP-25, and syntaxin. This complex was also identified by immunoprecipitation and by sucrose gradient analysis. VAMP in the complex was insensitive to proteolysis by tetanus toxin. All criteria identify the SNARE complex as that described in other secretory systems. Complexes exist pre-formed on individual CV membranes and form between contacting CV. Most notably, CV SNARE complexes are disrupted in response to [Ca2+]free that trigger maximal fusion. N-Ethylmaleimide, which blocks fusion at or before the Ca2+-triggering step, blocks complex disruption by Ca2+. However, disruption is not blocked by lysophosphatidylcholine, which transiently arrests a late stage of fusion. Since removal of lysophosphatidylcholine from Ca2+-treated CV is known to allow fusion, complex disruption occurs independently from the membrane fusion step. As Ca2+ disrupts rather than stabilizes the complex, the presumably coiled-coil SNARE interactions are not needed at the time of fusion. These findings rule out models of fusion in which SNARE complex formation goes to completion ("zippers-up") after Ca2+ binding removes a "fusion-clamp." JF - The Journal of biological chemistry AU - Tahara, M AU - Coorssen, J R AU - Timmers, K AU - Blank, P S AU - Whalley, T AU - Scheller, R AU - Zimmerberg, J AD - Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/11/ PY - 1998 DA - 1998 Dec 11 SP - 33667 EP - 33673 VL - 273 IS - 50 SN - 0021-9258, 0021-9258 KW - Lipid Bilayers KW - 0 KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Qa-SNARE Proteins KW - R-SNARE Proteins KW - SNARE Proteins KW - Synaptosomal-Associated Protein 25 KW - Tetanus Toxin KW - Vesicular Transport Proteins KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Nerve Tissue Proteins -- metabolism KW - Sea Urchins KW - Tetanus Toxin -- pharmacology KW - Molecular Weight KW - Calcium -- metabolism KW - Membrane Fusion KW - Membrane Proteins -- metabolism KW - Ovum -- metabolism KW - Ovum -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70099117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calcium+can+disrupt+the+SNARE+protein+complex+on+sea+urchin+egg+secretory+vesicles+without+irreversibly+blocking+fusion.&rft.au=Tahara%2C+M%3BCoorssen%2C+J+R%3BTimmers%2C+K%3BBlank%2C+P+S%3BWhalley%2C+T%3BScheller%2C+R%3BZimmerberg%2C+J&rft.aulast=Tahara&rft.aufirst=M&rft.date=1998-12-11&rft.volume=273&rft.issue=50&rft.spage=33667&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 - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF061750; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional activation of transforming growth factor beta1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1. Potential mechanisms for autocrine fibrogenesis in response to injury. AN - 70096822; 9837963 AB - We have explored the regulation of transforming growth factor beta (TGF-beta) activity in tissue repair by examining the interactions of Zf9/core promoter-binding protein, a Kruppel-like zinc finger transcription factor induced early in hepatic stellate cell (HSC) activation, with promoters for TGF-beta1 and TGF-beta receptors, types I and II. Nuclear extracts from culture-activated HSCs bound avidly by electrophoretic mobility shift assay to two tandem GC boxes within the TGF-beta1 promoter but minimally to a single GC box; these results correlated with transactivation by Zf9 of TGF-beta1 promoter-reporters. Zf9 transactivated the full-length TGF-beta1 promoter in either primary HSCs, HSC-T6 cells (an SV40-immortalized rat HSC line), Hep G2 cells, or Drosophila Schneider (S2) cells. Recombinant Zf9-GST also bound to GC box sequences within the promoters for the types I and II TGF-beta receptors. Both type I and type II TGF-beta receptor promoters were also transactivated by Zf9 in mammalian cells but not in S2 cells. In contrast, Sp1 significantly transactivated both receptor promoters in S2 cells. These results suggest that (a) Zf9/core promoter-binding protein may enhance TGF-beta activity through transactivation of both the TGF-beta1 gene and its key signaling receptors, and (b) transactivating potential of Zf9 and Sp1 toward promoters for TGF-beta1 and its receptors are not identical and depend on the cellular context. JF - The Journal of biological chemistry AU - Kim, Y AU - Ratziu, V AU - Choi, S G AU - Lalazar, A AU - Theiss, G AU - Dang, Q AU - Kim, S J AU - Friedman, S L AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/11/ PY - 1998 DA - 1998 Dec 11 SP - 33750 EP - 33758 VL - 273 IS - 50 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Recombinant Proteins KW - Trans-Activators KW - Transforming Growth Factor beta KW - Fibrinogen KW - 9001-32-5 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - Recombinant Proteins -- metabolism KW - Cell Nucleus -- metabolism KW - Liver -- metabolism KW - RNA, Messenger -- genetics KW - Trans-Activators -- metabolism KW - Receptors, Transforming Growth Factor beta -- genetics KW - Fibrinogen -- biosynthesis KW - Transforming Growth Factor beta -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70096822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+transforming+growth+factor+beta1+and+its+receptors+by+the+Kruppel-like+factor+Zf9%2Fcore+promoter-binding+protein+and+Sp1.+Potential+mechanisms+for+autocrine+fibrogenesis+in+response+to+injury.&rft.au=Kim%2C+Y%3BRatziu%2C+V%3BChoi%2C+S+G%3BLalazar%2C+A%3BTheiss%2C+G%3BDang%2C+Q%3BKim%2C+S+J%3BFriedman%2C+S+L&rft.aulast=Kim&rft.aufirst=Y&rft.date=1998-12-11&rft.volume=273&rft.issue=50&rft.spage=33750&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 - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VIP neurotrophism in the central nervous system: multiple effectors and identification of a femtomolar-acting neuroprotective peptide. AN - 69156431; 9928014 AB - Vasoactive intestinal peptide has neurotrophic and growth-regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta-amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial-derived substances released by VIP. These substance include cytokines, protease nexin I, and ADNF, a novel neuroprotective protein with structural similarities to heat-shock protein 60. Antiserum against ADNF produced neuronal cell death and an increase in apoptotic neurons in cell culture. A 14 amino acid peptide (ADNF-14) derived from ADNF has been discovered that mimics the survival-promoting action of the parent protein. These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease. JF - Annals of the New York Academy of Sciences AU - Brenneman, D E AU - Glazner, G AU - Hill, J M AU - Hauser, J AU - Davidson, A AU - Gozes, I AD - Section on Developmental and Molecular Pharmacology, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/11/ PY - 1998 DA - 1998 Dec 11 SP - 207 EP - 212 VL - 865 SN - 0077-8923, 0077-8923 KW - Cytokines KW - 0 KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Neurotoxins KW - Peptide Fragments KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - AIDS/HIV KW - Nerve Tissue Proteins -- physiology KW - Animals KW - Microchemistry KW - Humans KW - Peptide Fragments -- pharmacology KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Neurotoxins -- toxicity KW - Neuroglia -- physiology KW - Nerve Tissue Proteins -- pharmacology KW - Cell Survival KW - Brain -- cytology KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Cytokines -- physiology KW - Brain -- physiology KW - Vasoactive Intestinal Peptide -- physiology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69156431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=VIP+neurotrophism+in+the+central+nervous+system%3A+multiple+effectors+and+identification+of+a+femtomolar-acting+neuroprotective+peptide.&rft.au=Brenneman%2C+D+E%3BGlazner%2C+G%3BHill%2C+J+M%3BHauser%2C+J%3BDavidson%2C+A%3BGozes%2C+I&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1998-12-11&rft.volume=865&rft.issue=&rft.spage=207&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 - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenoassociated Virus-Mediated Transfer of a Functional Water Channel into Salivary Epithelial Cells In Vitro and In Vivo AN - 17130582; 4433569 AB - Aquaporin 1 (AQP1) is the archetypal member of a family of integral membrane proteins that function as water channels. Previously we have shown that this protein can be expressed transiently from a recombinant adenovirus (AdhAQP1) in vitro in different epithelial cell lines, and in vivo in rat submandibular glands. In the present study we have constructed a recombinant adenoassociated virus (rAAV) containing the human aquaporin 1 gene (rAAVhAQP1). rAAVhAQP1 was produced at relatively high titers. approximately 10 super(11)-10 super(12) particles/ml and approximately 10 super(8)-10 super(9) transducing units/ml. We show that the rAAVhAQP1 can transduce in vitro four epithelial cell lines of different origins, at a level sufficient to detect the recombinant hAQP1 protein by either Western blot or confocal microscopic analysis. The recombinant hAQP1 was correctly targeted to the plasma membranes in all cell lines. Function of the recombinant hAQP1 was measured as fluid flow, in response to an osmotic gradient, across a monolayer of transduced epithelial cells. The data show that even at a low level of transduction, typically approximately 10% of the cells in the monolayer, transepithelial fluid movement is enhanced about three-fold above basal levels. In addition, we report that rAAVhAQP1 can transduce epithelial cells in the salivary glands and liver of mice in vivo. These results suggest that rAAVs may be useful gene transfer vectors to direct the production of functional transgenes in salivary epithelial cell types. JF - Human Gene Therapy AU - Braddon, V R AU - Chiorini, JA AU - Wang, S AU - Kotin, R M AU - Baum, B J AD - GTTB/NIDCR/NIH, Building 10, Room 1N-113, Bethesda, MD 20892-1190, USA Y1 - 1998/12/10/ PY - 1998 DA - 1998 Dec 10 SP - 2777 EP - 2785 VL - 9 IS - 18 SN - 1043-0342, 1043-0342 KW - Adeno-associated virus KW - aquaporin 1 KW - aquaporins KW - man KW - mice KW - rAAVhAQP1 gene KW - rats KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Salivary gland 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/17130582?accountid=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=Adenoassociated+Virus-Mediated+Transfer+of+a+Functional+Water+Channel+into+Salivary+Epithelial+Cells+In+Vitro+and+In+Vivo&rft.au=Braddon%2C+V+R%3BChiorini%2C+JA%3BWang%2C+S%3BKotin%2C+R+M%3BBaum%2C+B+J&rft.aulast=Braddon&rft.aufirst=V&rft.date=1998-12-10&rft.volume=9&rft.issue=18&rft.spage=2777&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 - Adeno-associated virus; Gene therapy; Salivary gland; Gene transfer ER - TY - JOUR T1 - Functional topography of nascent RNA in elongation intermediates of RNA polymerase AN - 17148174; 4438213 AB - To determine the dynamics of transcript extrusion from Escherichia coli RNA polymerase (RNAP), we used degradation of the RNA by RNases T1 and A in a series of consecutive elongation complexes (ECs). In intact ECs, even extremely high doses of the RNases were unable to cut the RNA closer than 14-16 nt from the 3' end. Our results prove that all of the cuts detected within the 14-nt zone are derived from the EC that is denatured during inactivation of the RNases. The protected zone monotonously translocates along the RNA after addition of new nucleotides to the transcript. The upstream region of the RNA heading toward the 5' end is cleaved and dissociated from the EC, with no effect on the stability and activity of the EC. Most of the current data suggest that an 8- to 10- nt RNA super(.)DNA hybrid is formed in the EC. Here, we show that an 8- to 10-nt RNA obtained by truncating the RNase-generated products further with either GreB or pyrophosphate is sufficient for the high stability and activity of the EC. This result suggests that the transcript-RNAP interaction that is required for holding the EC together can be limited to the RNA region involved in the 8- to 10-nt RNA super(.)DNA hybrid. JF - Proceedings of the National Academy of Sciences, USA AU - Komissarova, N AU - Kashlev, M AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center Frederick, MD 21702-1201, mkashlev@mail.ncifcrf.gov Y1 - 1998/12/08/ PY - 1998 DA - 1998 Dec 08 SP - 14699 EP - 14704 PB - National Academy of Sciences VL - 95 IS - 25 SN - 0027-8424, 0027-8424 KW - GreB protein KW - pyrophosphate KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - DNA-directed RNA polymerase KW - Transcription elongation KW - Escherichia coli KW - Pancreatic ribonuclease KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17148174?accountid=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=Functional+topography+of+nascent+RNA+in+elongation+intermediates+of+RNA+polymerase&rft.au=Komissarova%2C+N%3BKashlev%2C+M&rft.aulast=Komissarova&rft.aufirst=N&rft.date=1998-12-08&rft.volume=95&rft.issue=25&rft.spage=14699&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; Transcription elongation; Pancreatic ribonuclease; DNA-directed RNA polymerase ER - TY - JOUR T1 - Membrane protein biogenesis: The exception explains the rules AN - 17145691; 4438189 AB - The transport of most proteins across the bacterial inner membrane or its eukaryotic counterpart, the endoplasmic reticulum, is accomplished in a two step reaction. In the first step proteins that are destined to leave the cytoplasm are guided or "targeted" to transport sites in the membrane. The prototypical targeting machine is the signal recognition particle (SRP), a ribonucleoprotein complex that binds to hydrophobic leader peptides and transmembrane domains of ribosome-bound nascent polypeptide chains and releases them only after making contact with its membrane-bound receptor. Although SRP is required for the transport of essentially all proteins across the endoplasmic reticulum membrane in mammalian cells, it plays a much less central role in yeast and so far has been shown to be required only for the insertion of a subset of polytopic membrane proteins in bacteria. In microbes, other targeting factors have been identified that function as chaperones to keep partially or fully synthesized passenger proteins in a conformation that is compatible with their transport across the membrane. In the second step, polypeptides are handed off to a protein conducting channel or "translocon" that facilitates permeation of the membrane barrier. The translocon comprises a conserved heterotrimeric core called the SecY complex (in bacteria) or the Sec61p complex (in eukaryotes) as well as other components that differ in each of the three kingdoms of life. JF - Proceedings of the National Academy of Sciences, USA AU - Bernstein, H D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD 20892-1810 Y1 - 1998/12/08/ PY - 1998 DA - 1998 Dec 08 SP - 14587 EP - 14589 PB - National Academy of Sciences VL - 95 IS - 25 SN - 0027-8424, 0027-8424 KW - Sec61p protein KW - SecY protein KW - bacteria KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Reviews KW - Chaperones KW - Membrane proteins KW - N 14100:Reviews KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17145691?accountid=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=Membrane+protein+biogenesis%3A+The+exception+explains+the+rules&rft.au=Bernstein%2C+H+D&rft.aulast=Bernstein&rft.aufirst=H&rft.date=1998-12-08&rft.volume=95&rft.issue=25&rft.spage=14587&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 - Reviews; Membrane proteins; Chaperones ER - TY - JOUR T1 - Phosphorylation of p53 serine 15 increases interaction with CBP. AN - 70086091; 9830059 AB - p53 exerts its cell cycle regulatory effects through its ability to function as a sequence-specific DNA binding transcription factor. CREB-binding protein (CBP)/p300, through its interaction with the N terminus of p53, acts as a coactivator for p53 and increases the sequence-specific DNA-binding activity of p53 by acetylating its C terminus. The same N-terminal domain of p53 has recently been shown to be phosphorylated at Ser15 in response to gamma-irradiation. Remarkably, we now demonstrate that phosphorylation of p53 at Ser15 increases its ability to recruit CBP/p300. The increase in CBP/p300 binding was followed by an increase in the overall level of acetylation of the C terminus of p53. These results provide a mechanism for the activation of p53-regulated genes following DNA damage, through a signaling pathway linking p53 N-terminal kinase and C-terminal acetyltransferase activities. JF - The Journal of biological chemistry AU - Lambert, P F AU - Kashanchi, F AU - Radonovich, M F AU - Shiekhattar, R AU - Brady, J N AD - Virus Tumor Biology Section, Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/12/04/ PY - 1998 DA - 1998 Dec 04 SP - 33048 EP - 33053 VL - 273 IS - 49 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - Serine KW - 452VLY9402 KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - CREBBP protein, human KW - DNA-Activated Protein Kinase KW - EC 2.7.11.1 KW - PRKDC protein, human KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Acetylation KW - Protein-Serine-Threonine Kinases -- metabolism KW - Phosphorylation KW - HeLa Cells KW - Humans KW - Protein Binding KW - Radiation, Ionizing KW - Trans-Activators -- metabolism KW - Tumor Suppressor Protein p53 -- chemistry KW - Tumor Suppressor Protein p53 -- genetics KW - Nuclear Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Serine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70086091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+p53+serine+15+increases+interaction+with+CBP.&rft.au=Lambert%2C+P+F%3BKashanchi%2C+F%3BRadonovich%2C+M+F%3BShiekhattar%2C+R%3BBrady%2C+J+N&rft.aulast=Lambert&rft.aufirst=P&rft.date=1998-12-04&rft.volume=273&rft.issue=49&rft.spage=33048&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 - 1999-01-08 N1 - Date created - 1999-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unique recombinant human ribonuclease and inhibition of Kaposi's sarcoma cell growth. AN - 70089949; 9839518 AB - Preparations of human chorionic gonadotropin (hCG) have been shown to exhibit anti-Kaposi's sarcoma (KS) activity, but the identity of the responsible agent(s) remains controversial. One candidate agent is an eosinophil-derived neurotoxin (EDN)-like polypeptide that contaminates preparations of hCG. We have genetically engineered a unique form of hEDN, which is a ribonuclease, and have evaluated the cytotoxic effects of the recombinant protein on KS Y-1 cells and on cells of other cancer types. The amino-terminus of hEDN was extended by four amino acid residues, corresponding to the proximal part of the hEDN signal peptide (serine, leucine, histidine, and valine; positions -4 to -1, respectively), by use of the polymerase chain reaction and an hEDN complementary DNA. The recombinant protein was isolated from bacterial inclusion bodies. The cytotoxic activity of this hEDN variant, (-4)rhEDN, was tested on KS Y-1 cells and human glioma, melanoma, breast carcinoma, and renal carcinoma cells. Approximately half of the anti-KS activity in a crude commercial preparation of hCG was associated with a polypeptide that reacted with anti-recombinant-hEDN (rhEDN) polyclonal antibodies. Although rhEDN protein displayed little cytotoxicity against KS Y-1 cells (IC50 [50% inhibition concentration] = >100 microg/mL), (-4)rhEDN markedly inhibited cell viability (IC50 = 6 microg/mL). Neither version of rhEDN inhibited the viability of other tested human cancer cell types. A four amino acid extension of the amino-terminus of rhEDN confers cytotoxicity against KS Y-1 cells in vitro. Design of the (-4)rhEDN variant was based on the sequence of a natural human protein associated with hCG. Our results suggest that (-4)rhEDN is one of the agents in hCG responsible for anti-KS activity. A purified molecule is thus available for in vitro and in vivo mechanistic and, possibly, future clinical studies. JF - Journal of the National Cancer Institute AU - Newton, D L AU - Rybak, S M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1998/12/02/ PY - 1998 DA - 1998 Dec 02 SP - 1787 EP - 1791 VL - 90 IS - 23 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - DNA, Complementary KW - Proteins KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Histidine KW - 4QD397987E KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Leucine KW - GMW67QNF9C KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Kidney Neoplasms -- drug therapy KW - DNA, Complementary -- chemical synthesis KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Leucine -- genetics KW - Genes, Synthetic KW - Valine -- genetics KW - Serine -- genetics KW - Blotting, Western KW - Histidine -- genetics KW - Polymerase Chain Reaction -- methods KW - Recombinant Proteins -- therapeutic use KW - Sarcoma, Kaposi -- drug therapy KW - Sarcoma, Kaposi -- metabolism KW - Proteins -- therapeutic use KW - Ribonuclease, Pancreatic -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70089949?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unique+recombinant+human+ribonuclease+and+inhibition+of+Kaposi%27s+sarcoma+cell+growth.&rft.au=Newton%2C+D+L%3BRybak%2C+S+M&rft.aulast=Newton&rft.aufirst=D&rft.date=1998-12-02&rft.volume=90&rft.issue=23&rft.spage=1787&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 - 1998-12-16 N1 - Date created - 1998-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive Substrates of Thought Disorder, II: Specifying a Candidate Cognitive Mechanism AN - 85688418; 9911543 AB - A possible cognitive mechanism within the semantic system that might produce thought disorder is examined by assessing priming in patients with chronic schizophrenia compared to normal controls (N = 20 & 21, respectively). The patients were divided into subgroups of severe vs mild thought disorder. The word pairs in the priming paradigm differed in their degree of association but shared a categorical membership. The paradigm involved short stimulus onset asynchronies to maximize automatic processing & required pronunciation of words to minimize decision-making. All subjects (Ss) were also administered neuropsychological tests to assess language, executive function, real-world knowledge, & mental status. Controls showed appropriate priming in stepwise fashion at the three different levels of word association, as did the patients with mild thought disorder. The patients with severe thought disorder showed inhibited responses to high & medium associates compared with their baseline reaction times. Correlations between priming & cognitive variables were significant only with measures of semantic processing. Priming abnormalities were uniformly related to ratings of global thought disorder. These results suggest that aberrations in the automatic spread of activation or facilitation in semantic networks may be a candidate cognitive mechanism in semantic accounts of thought disorder. 5 Tables, 1 Figure, 24 References. Adapted from the source document JF - The American Journal of Psychiatry AU - Aloia, Mark S AU - Gourovitch, Monica L AU - Missar, David AU - Pickar, David AU - Weinberger, Daniel R AU - Goldberg, Terry E AD - c/o Goldberg-Clinical Brain Disorders Branch, NIMH, Bldg 10, Room 4S235, MSC 1379, Bethesda, MD 20892-1379 Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1677 EP - 1684 VL - 155 IS - 12 SN - 0002-953X, 0002-953X KW - Schizophrenia (75250) KW - Language Pathology (43250) KW - Language Thought Relationship (44410) KW - Fluency (24910) KW - Semantic Processing (76760) KW - article KW - 6710: linguistics and psychiatry; linguistics and psychiatry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85688418?accountid=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=The+American+Journal+of+Psychiatry&rft.atitle=Cognitive+Substrates+of+Thought+Disorder%2C+II%3A+Specifying+a+Candidate+Cognitive+Mechanism&rft.au=Aloia%2C+Mark+S%3BGourovitch%2C+Monica+L%3BMissar%2C+David%3BPickar%2C+David%3BWeinberger%2C+Daniel+R%3BGoldberg%2C+Terry+E&rft.aulast=Aloia&rft.aufirst=Mark&rft.date=1998-12-01&rft.volume=155&rft.issue=12&rft.spage=1677&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&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 - AJPSAO N1 - SubjectsTermNotLitGenreText - Schizophrenia (75250); Language Thought Relationship (44410); Semantic Processing (76760); Fluency (24910); Language Pathology (43250) ER - TY - JOUR T1 - Cochlear outer hair cell electromotility can provide force for both low and high intensity distortion product otoacoustic emissions. AN - 85418182; pmid-9872135 AB - It is generally believed that the force for the otoacoustic emission (OAE) generation is provided by a mechanism of electromotility, observed in isolated cochlear outer hair cells (OHCs). OHC electromotility is resistant to several ototoxic reagents, it does not depend on ATP hydrolysis, but it can be blocked by specific sulfhydryl reagents: p-chloromercuriphenylsulfonic acid (pCMPS) and p-hydroxymercuriphenylsulfonic acid (pHMPS). We have used these reagents to test whether they also affect OAE. Application of pCMPS and pHMPS on the round window membrane of anesthetized guinea pigs produced a dose-dependent inhibition of the cubic (2F1-F2) distortion product OAE (DPOAE). The inhibition developed progressively from high to low frequencies, reflecting the diffusion of the drugs through the cochlear compartment. The effect of pCMPS and pHMPS was different from the effects of furosemide and lethal anoxia, which impair cochlear function but do not block OHC electromotility. pHMPS suppressed DPOAE completely at all sound intensities tested (45-80 dB SPL), whereas furosemide or lethal anoxia caused DPOAE to disappear at low-level stimulation (45-60 dB SPL) only. Our results suggest that the OHC electromotility might provide the force for DPOAE generation not only at low, but also at high stimulus intensities. JF - Hearing research AU - Frolenkov, G I AU - Belyantseva, I A AU - Kurc, M AU - Mastroianni, M A AU - Kachar, B AD - Section on Structural Cell Biology, Laboratory of Cellular Biology, NIDCD-NIH, Bethesda, MD 20852-3320, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 67 EP - 74 VL - 126 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Oxidants -- pharmacology KW - Guinea Pigs KW - Sulfhydryl Compounds -- pharmacology KW - 4-Chloromercuribenzenesulfonate -- pharmacology KW - Cochlea -- cytology KW - Otoacoustic Emissions, Spontaneous -- physiology KW - Electrophysiology KW - Otoacoustic Emissions, Spontaneous -- drug effects KW - Cell Movement -- physiology KW - Anoxia -- physiopathology KW - Cochlea -- physiology KW - Furosemide -- pharmacology KW - Phenylmercury Compounds -- pharmacology KW - Male KW - Female KW - Hair Cells, Auditory, Outer -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85418182?accountid=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=Cochlear+outer+hair+cell+electromotility+can+provide+force+for+both+low+and+high+intensity+distortion+product+otoacoustic+emissions.&rft.au=Frolenkov%2C+G+I%3BBelyantseva%2C+I+A%3BKurc%2C+M%3BMastroianni%2C+M+A%3BKachar%2C+B&rft.aulast=Frolenkov&rft.aufirst=G&rft.date=1998-12-01&rft.volume=126&rft.issue=1-2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The Corsi block-tapping task: methodological and theoretical considerations. AN - 85411183; pmid-9841789 AB - The Corsi block-tapping task has enjoyed extensive use in clinical and experimental studies for a quarter of a century and is arguably the single most important nonverbal task in neuropsychological research. Nevertheless, there has been considerable inconsistency not only in the administration and scoring of this measure, but also in the physical properties of the test apparatus. In this paper, we survey a wide range of studies that have made use of the block-tapping task during the past 25 years and provide a detailed appraisal of the manifold methodological variations. Additionally, we discuss the historical context in which the Corsi originated and offer a critical examination of the cognitive processing operations purported to underlie performance on this task. (Copyright 1998 Academic Press.) JF - Brain and cognition AU - Berch, D B AU - Krikorian, R AU - Huha, E M AD - National Institutes of Health, 6701 Rockledge Drive, Bethesda, 20892-7848, USA. berchd@drg.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 317 EP - 338 VL - 38 IS - 3 SN - 0278-2626, 0278-2626 KW - Index Medicus; Space life sciences KW - National Library of Medicine KW - Humans KW - Memory -- physiology KW - Space Perception -- physiology KW - Neuropsychological Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85411183?accountid=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=The+Corsi+block-tapping+task%3A+methodological+and+theoretical+considerations.&rft.au=Berch%2C+D+B%3BKrikorian%2C+R%3BHuha%2C+E+M&rft.aulast=Berch&rft.aufirst=D&rft.date=1998-12-01&rft.volume=38&rft.issue=3&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Perception of timing of kinesthetic stimuli. AN - 85280495; pmid-9926837 AB - A psychophysical method was used to estimate the timing of perception of kinesthetic stimuli with different velocities in normal volunteers. A 1 ms auditory click occurred randomly before or after an imposed flexion movement at either 20, 40 or 60 deg/s of the metacarpophalangeal joint. Subjects reported whether the click was perceived before or after the movement onset (experiment 1) or perception of movement velocity (experiment 2). The time at which there was a 50% chance that subjects reported movement or velocity perception after the click was taken as an estimate of the time subjects perceived the stimuli. The difference in time of perceived movement velocity discrimination and movement onset was only significant when the velocity was 20 deg/s (52 ms). This suggests that movement onset and identification of the velocity of the faster movements are perceived nearly simultaneously. JF - Neuroreport AU - Grill, S E AU - Rosenberger, W F AU - Boyle, K AU - Cannon, M AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. PY - 1998 SP - 4001 EP - 4005 VL - 9 IS - 18 SN - 0959-4965, 0959-4965 KW - Human KW - Aged KW - Psychophysics KW - Movement KW - Kinesthesis KW - Discrimination (Psychology) KW - Adult KW - Middle Age KW - Acoustic Stimulation KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280495?accountid=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=Neuroreport&rft.atitle=Perception+of+timing+of+kinesthetic+stimuli.&rft.au=Grill%2C+S+E%3BRosenberger%2C+W+F%3BBoyle%2C+K%3BCannon%2C+M%3BHallett%2C+M&rft.aulast=Grill&rft.aufirst=S&rft.date=1998-12-01&rft.volume=9&rft.issue=18&rft.spage=4001&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Emotion, motivation, and anxiety: brain mechanisms and psychophysiology. AN - 85254621; pmid-9861468 AB - The organization of response systems in emotion is founded on two basic motive systems, appetitive and defensive. The subcortical and deep cortical structures that determine primary motivated behavior are similar across mammalian species. Animal research has illuminated these neural systems and defined their reflex outputs. Although motivated behavior is more complex and varied in humans, the simpler underlying response patterns persist in affective expression. These basic phenomena are elucidated here in the context of affective perception. Thus, the research examines human beings watching uniquely human stimuli--primarily picture media (but also words and sounds) that prompt emotional arousal--showing how the underlying motivational structure is apparent in the organization of visceral and behavioral responses, in the priming of simple reflexes, and in the reentrant processing of these symbolic representations in the sensory cortex. Implications of the work for understanding pathological emotional states are discussed, emphasizing research on psychopathy and the anxiety disorders. JF - Biological Psychiatry AU - Lang, P J AU - Bradley, M M AU - Cuthbert, B N AD - NIMH Center for the Study of Emotion and Attention, University of Florida, Gainesville 32610, USA. PY - 1998 SP - 1248 EP - 1263 VL - 44 IS - 12 SN - 0006-3223, 0006-3223 KW - Emotions KW - Support, U.S. Gov't, P.H.S. KW - Anxiety Disorders KW - Startle Reaction KW - Fear KW - Imagery (Psychotherapy) KW - Psychophysiology KW - Human KW - Animal KW - Brain KW - Support, Non-U.S. Gov't KW - Motivation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85254621?accountid=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=Biological+Psychiatry&rft.atitle=Emotion%2C+motivation%2C+and+anxiety%3A+brain+mechanisms+and+psychophysiology.&rft.au=Lang%2C+P+J%3BBradley%2C+M+M%3BCuthbert%2C+B+N&rft.aulast=Lang&rft.aufirst=P&rft.date=1998-12-01&rft.volume=44&rft.issue=12&rft.spage=1248&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cognitive substrates of thought disorder, I: the semantic system. AN - 85246308; pmid-9842774 AB - OBJECTIVE: Few studies have explored in detail the relation of cognitive deficits in attention, working memory, and semantics to thought disorder. The authors sought to determine whether thought disorder resides in the semantic system or elsewhere. METHOD: Twenty-three normal comparison subjects and 23 patients with schizophrenia participated in the study. All subjects received tests of executive function and working memory, including the Wisconsin Card Sorting Test and the Letter-Number Span test; a test of deployment of attentional resources; and tests of semantic processing and language comprehension, including the Peabody Picture Vocabulary Test, the Speed and Capacity of Language-Processing Test, the Boston Naming Test, and tests of semantic verbal fluency and phonologic verbal fluency, from which was derived a difference score. All patients were also administered the Scale for the Assessment of Thought, Language, and Communication to assess thought disorder. RESULTS: The normal subjects were compared with the schizophrenic patients who were rated as having mild thought disorder (N=13) or moderate to severe thought disorder (N=10). While differences between the schizophrenic subgroups and the comparison subjects were observed on nearly all tests, a large difference in effect size between the two schizophrenic subgroups was apparent only in the verbal fluency difference score. In a series of multiple regression analyses, two variables made significant contributions to the prediction of positive thought disorder: the verbal fluency difference score and the Peabody Picture Vocabulary Test score. CONCLUSIONS: These results suggest that clinically rated thought disorder is associated with and may result from semantic processing abnormalities. In particular, patients with more severe thought disorder may have difficulty accessing semantic items because of disorganization of the semantic systems and, to a more limited degree, may also lack a semantic or conceptual knowledge base. JF - The American Journal of Psychiatry AU - Goldberg, T E AU - Aloia, M S AU - Gourovitch, M L AU - Missar, D AU - Pickar, D AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, Bethesda, MD 20892-1379, USA. PY - 1998 SP - 1671 EP - 1676 VL - 155 IS - 12 SN - 0002-953X, 0002-953X KW - Severity of Illness Index KW - Language Tests KW - Regression Analysis KW - Models, Psychological KW - Human KW - Psychometrics KW - Cognition Disorders KW - Schizophrenia KW - Memory KW - Psychiatric Status Rating Scales KW - Adult KW - Neuropsychological Tests KW - Male KW - Female KW - Schizophrenic Psychology KW - Semantics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85246308?accountid=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=Cognitive+substrates+of+thought+disorder%2C+I%3A+the+semantic+system.&rft.au=Goldberg%2C+T+E%3BAloia%2C+M+S%3BGourovitch%2C+M+L%3BMissar%2C+D%3BPickar%2C+D%3BWeinberger%2C+D+R&rft.aulast=Goldberg&rft.aufirst=T&rft.date=1998-12-01&rft.volume=155&rft.issue=12&rft.spage=1671&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 - Gender and drug abuse research. AN - 79635801; 11279864 JF - The journal of gender-specific medicine : JGSM : the official journal of the Partnership for Women's Health at Columbia AU - Millstein, R A AD - National Institute on Drug Abuse, National Institutes of Health, 5600 Fishers Ln, Room 10-05, Rockville, MD 20857, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 44 EP - 47 VL - 1 IS - 3 SN - 1523-7036, 1523-7036 KW - Index Medicus KW - Sex Factors KW - Risk Factors KW - Humans KW - National Institutes of Health (U.S.) KW - United States -- epidemiology KW - HIV Infections -- epidemiology KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Women's Health KW - Substance-Related Disorders -- metabolism KW - Research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79635801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gender-specific+medicine+%3A+JGSM+%3A+the+official+journal+of+the+Partnership+for+Women%27s+Health+at+Columbia&rft.atitle=Gender+and+drug+abuse+research.&rft.au=Millstein%2C+R+A&rft.aulast=Millstein&rft.aufirst=R&rft.date=1998-12-01&rft.volume=1&rft.issue=3&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=The+journal+of+gender-specific+medicine+%3A+JGSM+%3A+the+official+journal+of+the+Partnership+for+Women%27s+Health+at+Columbia&rft.issn=15237036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-04-19 N1 - Date created - 2001-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Foscarnet. AN - 70123144; 9849068 JF - Pediatrics in review AU - Zeichner, S L AD - HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 399 EP - 400 VL - 19 IS - 12 SN - 0191-9601, 0191-9601 KW - Antiviral Agents KW - 0 KW - Foscarnet KW - 364P9RVW4X KW - Index Medicus KW - Cytomegalovirus Retinitis -- drug therapy KW - Humans KW - Herpesviridae Infections -- drug therapy KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- pharmacology KW - Foscarnet -- pharmacology KW - Antiviral Agents -- adverse effects KW - Foscarnet -- therapeutic use KW - Foscarnet -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70123144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics+in+review&rft.atitle=Foscarnet.&rft.au=Zeichner%2C+S+L&rft.aulast=Zeichner&rft.aufirst=S&rft.date=1998-12-01&rft.volume=19&rft.issue=12&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=Pediatrics+in+review&rft.issn=01919601&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inactivation of the p53 tumor suppressor gene via a novel Alu rearrangement. AN - 70121322; 9850060 AB - Inactivation of the p53 tumor suppressor gene is a common finding in human cancer. In most cases, inactivation is due to a point mutation in the gene, but rearrangement of the p53 gene is sometimes observed. We analyzed the inactivation of p53 in the human pancreas cancer cell line Hs766T, which harbors a structural alteration in the p53 gene. This inactivation was found to be the result of a complex deletion/insertion event involving at least two different Alu elements. The rearrangement eliminated exons 2-4 from the p53 gene, whereas a 175-bp Alu fragment was inserted between the breakpoints of the deletion. DNA sequence analysis of this Alu fragment revealed that it is identical to an Alu element in intron 1 of the p53 gene. This is the first report of p53 inactivation due to a rearrangement involving Alu elements. This type of inactivation may go unnoticed when only traditional methods to detect p53 alterations are used. JF - Cancer research AU - Slebos, R J AU - Resnick, M A AU - Taylor, J A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. slebos@niehs.nih.gov Y1 - 1998/12/01/ PY - 1998 DA - 1998 Dec 01 SP - 5333 EP - 5336 VL - 58 IS - 23 SN - 0008-5472, 0008-5472 KW - DNA Transposable Elements KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Exons KW - Humans KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Pancreatic Neoplasms -- genetics KW - Gene Expression Regulation, Neoplastic KW - Genes, p53 KW - Alu Elements KW - Gene Rearrangement UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70121322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inactivation+of+the+p53+tumor+suppressor+gene+via+a+novel+Alu+rearrangement.&rft.au=Slebos%2C+R+J%3BResnick%2C+M+A%3BTaylor%2C+J+A&rft.aulast=Slebos&rft.aufirst=R&rft.date=1998-12-01&rft.volume=58&rft.issue=23&rft.spage=5333&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 - 1998-12-31 N1 - Date created - 1998-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells. AN - 70117139; 9846573 AB - The finding of frequent nitric oxide synthase expression in human cancers indicates that nitric oxide has a pathophysiological role in carcinogenesis. To determine the role of nitric oxide in tumor progression, we generated human carcinoma cell lines that produced nitric oxide constitutively. Cancer cells expressing inducible nitric oxide synthase that had wild-type p53 had reduced tumor growth in athymic nude mice, whereas those with mutated p53 had accelerated tumor growth associated with increased vascular endothelial growth factor expression and neovascularization. Our data indicate that tumor-associated nitric oxide production may promote cancer progression by providing a selective growth advantage to tumor cells with mutant p53, and that inhibitors of inducible nitric oxide synthase may have therapeutic activity in these tumors. JF - Nature medicine AU - Ambs, S AU - Merriam, W G AU - Ogunfusika, M O AU - Bennett, W P AU - Ishibe, N AU - Hussain, S P AU - Tzeng, E E AU - Geller, D A AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1371 EP - 1376 VL - 4 IS - 12 SN - 1078-8956, 1078-8956 KW - Antigens, CD31 KW - 0 KW - Endothelial Growth Factors KW - Lymphokines KW - Tumor Suppressor Protein p53 KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Animals KW - Apoptosis KW - Gene Transfer Techniques KW - Humans KW - Mice KW - Neoplasm Transplantation KW - Tumor Cells, Cultured KW - Transplantation, Heterologous KW - Neovascularization, Pathologic KW - Antigens, CD31 -- analysis KW - Tumor Suppressor Protein p53 -- physiology KW - Neoplasms, Experimental -- enzymology KW - Nitric Oxide Synthase -- genetics KW - Endothelial Growth Factors -- physiology KW - Neoplasms, Experimental -- pathology KW - Lymphokines -- physiology KW - Nitric Oxide Synthase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70117139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+and+vascular+endothelial+growth+factor+regulate+tumor+growth+of+NOS2-expressing+human+carcinoma+cells.&rft.au=Ambs%2C+S%3BMerriam%2C+W+G%3BOgunfusika%2C+M+O%3BBennett%2C+W+P%3BIshibe%2C+N%3BHussain%2C+S+P%3BTzeng%2C+E+E%3BGeller%2C+D+A%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-12-01&rft.volume=4&rft.issue=12&rft.spage=1371&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 - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The structure of the ITS2-proximal stem is required for pre-rRNA processing in yeast. AN - 70111959; 9848657 AB - Accurate and efficient processing of pre-rRNA is critical to the accumulation of mature functional ribosomal subunits for maintenance of cell growth. Processing requires numerous factors which act in trans as well as RNA sequence/ structural elements which function in cis. To examine the latter, we have used directed mutagenesis and expression of mutated pre-rRNAs in yeast. Specifically, we tested requirements for formation of an ITS2-proximal stem on processing, a structure formed by an interaction between sequences corresponding to the 3' end of 5.8S rRNA and the 5' end of 25S. Pre-rRNA processing is inhibited in templates encoding mutations that prevent the formation of the ITS2-proximal stem. Compensatory, double mutations, which alter the sequence of this region but restore the structure of the stem, also restore processing, although at lower efficiency. This reduction in efficiency is reflected in decreased levels of mature 5.8S and 25S rRNA and increased levels of 35S pre-rRNA and certain processing intermediates. This phenotype is reminiscent of the biochemical depletion of U8 snoRNA in vertebrates for which the ITS2-proximal stem has been proposed as a potential site for interaction with U8 RNP. Thus, formation of the ITS2-proximal stem may be a requirement common to yeast and vertebrate pre-rRNA processing. JF - RNA (New York, N.Y.) AU - Peculis, B A AU - Greer, C L AD - National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Genetics and Biochemistry Branch, Bethesda, Maryland 20892, USA. bp51h@nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1610 EP - 1622 VL - 4 IS - 12 SN - 1355-8382, 1355-8382 KW - RNA Precursors KW - 0 KW - RNA, Fungal KW - RNA, Ribosomal KW - Index Medicus KW - Animals KW - Base Sequence KW - Blotting, Northern KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Mutagenesis KW - Cell Division KW - Saccharomyces cerevisiae -- genetics KW - RNA, Ribosomal -- chemistry KW - RNA Precursors -- metabolism KW - RNA, Ribosomal -- metabolism KW - RNA, Fungal -- metabolism KW - RNA Processing, Post-Transcriptional KW - Saccharomyces cerevisiae -- cytology KW - RNA, Fungal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70111959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=RNA+%28New+York%2C+N.Y.%29&rft.atitle=The+structure+of+the+ITS2-proximal+stem+is+required+for+pre-rRNA+processing+in+yeast.&rft.au=Peculis%2C+B+A%3BGreer%2C+C+L&rft.aulast=Peculis&rft.aufirst=B&rft.date=1998-12-01&rft.volume=4&rft.issue=12&rft.spage=1610&rft.isbn=&rft.btitle=&rft.title=RNA+%28New+York%2C+N.Y.%29&rft.issn=13558382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1990 Dec;9(13):4503-9 [2265615] Nucleic Acids Res. 1996 Aug 1;24(15):2857-67 [8760866] J Mol Biol. 1991 Feb 20;217(4):649-59 [2005617] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3962-6 [2023944] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7026-30 [1871118] EMBO J. 1991 Dec;10(13):4231-9 [1756730] Biochimie. 1991 Jun;73(6):805-12 [1764525] J Biol Chem. 1992 Feb 15;267(5):3008-13 [1737755] Science. 1996 Oct 25;274(5287):546, 563-7 [8849441] EMBO J. 1996 Oct 15;15(20):5701-14 [8896463] Curr Biol. 1996 Nov 1;6(11):1413-5 [8939586] Nucleic Acids Res. 1997 Jan 1;25(1):109-11 [9016515] Curr Opin Cell Biol. 1997 Jun;9(3):337-42 [9159079] Cell. 1997 May 16;89(4):565-73 [9160748] Cell. 1997 May 30;89(5):799-809 [9182768] Mol Cell Biol. 1997 Jul;17(7):3702-13 [9199304] EMBO J. 1987 Dec 20;6(13):4169-75 [3327689] Genes Dev. 1988 Feb;2(2):160-72 [3282992] Mol Cell Biol. 1989 Feb;9(2):551-9 [2540422] Mol Cell Biol. 1990 Mar;10(3):1145-52 [2406561] EMBO J. 1992 Feb;11(2):673-82 [1531632] J Mol Biol. 1992 Feb 20;223(4):899-910 [1538404] EMBO J. 1992 Apr;11(4):1531-42 [1563354] Mol Cell Biol. 1993 Jan;13(1):114-22 [8417319] Mol Cell Biol. 1993 Apr;13(4):2469-77 [8455623] J Biol Chem. 1993 May 25;268(15):10813-9 [8496146] Cell. 1993 Jun 18;73(6):1233-45 [8513505] Nucleic Acids Res. 1993 Jul 1;21(13):3055-74 [8332527] Mol Phylogenet Evol. 1992 Dec;1(4):253-69 [1364170] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):659-63 [8290578] EMBO J. 1994 May 15;13(10):2452-63 [7515008] Mol Biol Evol. 1994 May;11(3):406-16 [8015435] Genes Dev. 1994 Jun 15;8(12):1423-33 [7926742] Genes Dev. 1994 Sep 15;8(18):2241-55 [7958892] Science. 1994 Dec 2;266(5190):1558-61 [7985025] Nucleic Acids Res. 1994 Nov 25;22(23):5139-47 [7800512] J Mol Biol. 1995 Jun 30;250(1):24-36 [7602595] J Mol Evol. 1995 Jun;40(6):640-51 [7643415] Nucleic Acids Res. 1995 Jul 25;23(14):2791-8 [7544463] Trends Biochem Sci. 1995 Jul;20(7):261-4 [7667877] Annu Rev Biochem. 1995;64:897-934 [7574504] RNA. 1996 Jan;2(1):51-62 [8846296] RNA. 1996 Jan;2(1):63-73 [8846297] Science. 1996 Apr 12;272(5259):268-70 [8602511] Biochem Cell Biol. 1995 Nov-Dec;73(11-12):915-24 [8722007] J Cell Biol. 1990 Dec;111(6 Pt 1):2261-74 [2277060] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic enhancement of skin neoplasia by chronic stimulation of growth factors. AN - 70107724; 9846968 AB - Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors, such as transforming growth factor (TGF)-alpha, promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA), a marked increase in the number of skin papillomas occurred in Tg.AC mice, which carry the v-Ha-ras oncogene, that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings, increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and TGF-alpha mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-alpha overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter. JF - The American journal of pathology AU - Germolec, D R AU - Spalding, J AU - Yu, H S AU - Chen, G S AU - Simeonova, P P AU - Humble, M C AU - Bruccoleri, A AU - Boorman, G A AU - Foley, J F AU - Yoshida, T AU - Luster, M I AD - Environmental Immunology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. germolec@niehs.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1775 EP - 1785 VL - 153 IS - 6 SN - 0002-9440, 0002-9440 KW - Antibodies KW - 0 KW - Growth Substances KW - RNA, Messenger KW - Transforming Growth Factor alpha KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Arsenic KW - N712M78A8G KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Skin Diseases -- immunology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- immunology KW - Humans KW - Mice KW - Tissue Distribution KW - Transforming Growth Factor alpha -- metabolism KW - Skin Diseases -- chemically induced KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Papilloma -- immunology KW - RNA, Messenger -- metabolism KW - Antibodies -- pharmacology KW - Transforming Growth Factor alpha -- immunology KW - Tetradecanoylphorbol Acetate -- administration & dosage KW - Immunohistochemistry KW - Papilloma -- chemically induced KW - Female KW - Granulocyte-Macrophage Colony-Stimulating Factor -- metabolism KW - Cell Division KW - Arsenic -- analysis KW - Arsenic -- toxicity KW - Skin Neoplasms -- chemically induced KW - Arsenic -- administration & dosage KW - Skin Neoplasms -- metabolism KW - Growth Substances -- metabolism KW - Growth Substances -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70107724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arsenic+enhancement+of+skin+neoplasia+by+chronic+stimulation+of+growth+factors.&rft.au=Germolec%2C+D+R%3BSpalding%2C+J%3BYu%2C+H+S%3BChen%2C+G+S%3BSimeonova%2C+P+P%3BHumble%2C+M+C%3BBruccoleri%2C+A%3BBoorman%2C+G+A%3BFoley%2C+J+F%3BYoshida%2C+T%3BLuster%2C+M+I&rft.aulast=Germolec&rft.aufirst=D&rft.date=1998-12-01&rft.volume=153&rft.issue=6&rft.spage=1775&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 - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Invest Dermatol. 1994 Oct;103(4):601-4 [7930689] Mutat Res. 1997 Jun;386(3):263-77 [9219564] Cancer Res. 1995 Mar 15;55(6):1296-300 [7882325] Free Radic Biol Med. 1995 Feb;18(2):349-55 [7744320] J Natl Cancer Inst. 1968 Mar;40(3):453-63 [5644201] Cancer Res. 1969 Apr;29(4):892-5 [5777793] Scand J Clin Lab Invest. 1976 Nov;36(7):679-82 [1019579] Environ Mutagen. 1980;2(3):371-9 [6459229] Acta Pharmacol Toxicol (Copenh). 1982 Sep;51(3):253-65 [7136731] EMBO J. 1983;2(11):1877-82 [6605850] Cancer Res. 1985 Nov;45(11 Pt 2):5895-9 [4053060] J Exp Med. 1988 Feb 1;167(2):670-5 [3279155] Science. 1988 Jul 1;241(4861):79-81 [3388020] Science. 1989 Feb 10;243(4892):811-4 [2916128] Int J Cancer. 1989 May 15;43(5):915-21 [2714898] Mol Carcinog. 1988;1(1):7-12 [2475136] Br J Cancer. 1989 Oct;60(4):542-8 [2478181] Cell. 1990 Jun 15;61(6):1121-35 [1693546] Cell. 1990 Jun 15;61(6):1137-46 [2350785] Cell. 1990 Jun 15;61(6):1147-55 [2161707] J Invest Dermatol. 1990 Jun;94(6 Suppl):101S-107S [2161884] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Genes Dev. 1991 May;5(5):714-27 [1709129] Mol Carcinog. 1991;4(3):210-9 [2064727] J Exp Med. 1992 Jun 1;175(6):1717-28 [1588289] Environ Health Perspect. 1992 Jul;97:259-67 [1396465] Mutat Res. 1992 Dec 16;284(2):215-21 [1281272] Carcinogenesis. 1992 Dec;13(12):2367-73 [1473246] Am J Pathol. 1993 Apr;142(4):1199-207 [8475993] Carcinogenesis. 1993 Jul;14(7):1335-41 [8330346] Cancer Res. 1993 Sep 15;53(18):4329-36 [8364928] J Invest Dermatol. 1993 Nov;101(5):701-5 [7693825] Cell Growth Differ. 1993 Dec;4(12):1071-82 [8117621] Carcinogenesis. 1994 Apr;15(4):653-60 [8149476] Carcinogenesis. 1994 May;15(5):1017-29 [8200063] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7822-6 [8052666] Mol Cell Biol. 1995 Sep;15(9):4694-701 [7651386] Clin Exp Dermatol. 1995 May;20(3):208-12 [7671414] Cancer Lett. 1996 Jan 2;98(2):227-31 [8556713] Dermatol Surg. 1996 Mar;22(3):301-4 [8599743] Oncogene. 1996 Aug 15;13(4):757-65 [8761297] Br J Clin Pharmacol. 1996 Jul;42(1):43-52 [8807143] Res Commun Mol Pathol Pharmacol. 1996 Aug;93(2):131-48 [8884985] Toxicol Appl Pharmacol. 1996 Nov;141(1):308-18 [8917704] Environ Health Perspect. 1996 Oct;104 Suppl 5:1095-100 [8933059] J Cutan Pathol. 1997 Jan;24(1):8-13 [9027627] Mol Carcinog. 1997 Mar;18(3):160-70 [9115586] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10907-12 [9380733] Toxicol Pathol. 1998 Jul-Aug;26(4):562-9 [9715516] Arch Environ Health. 1963 Dec;7:668-74 [14077213] Mol Carcinog. 1991;4(1):52-60 [2009135] J Clin Invest. 1997 Jun 15;99(12):3009-17 [9185525] Cell Growth Differ. 1994 Nov;5(11):1235-41 [7848924] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. AN - 70105509; 9850098 AB - Abnormalities in mucin-type glycoprotein expression have been documented in a variety of cancers, identifying these molecules as targets for immunologically based therapies and prognostic/diagnostic assays. We examined the expression of the membrane-bound MUC1 mucin in normal, histologically atypical, and neoplastic lung to determine its potential contribution to lung carcinogenesis. In vivo, intense MUC1 immunoreactivity was present in normal type II pneumocytes as well as in a range of atypical lesions derived from type II cells and >60% of primary and metastatic non-small cell lung cancers. Expression was not associated with altered survival, although it was highly correlated with the adenocarcinoma histology. A carcinogenesis model using 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters revealed that MUC1 mRNA increased prior to the histological appearance of tumors. In vitro studies using MUC1 expressing non-small cell lung cancer cell lines revealed that differentiation away from a type II cell lineage was associated with dramatic down-regulation of MUC1. We propose that MUC1 is a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis. JF - Cancer research AU - Jarrard, J A AU - Linnoila, R I AU - Lee, H AU - Steinberg, S M AU - Witschi, H AU - Szabo, E AD - Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1998/12/01/ PY - 1998 DA - 1998 Dec 01 SP - 5582 EP - 5589 VL - 58 IS - 23 SN - 0008-5472, 0008-5472 KW - Biomarkers, Tumor KW - 0 KW - Carcinogens KW - Histone Deacetylase Inhibitors KW - MUC1 tandem repeat peptide KW - Mucin-1 KW - Nitrosamines KW - Oligopeptides KW - Peptide Fragments KW - RNA, Messenger KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Index Medicus KW - Animals KW - Cell Lineage KW - Humans KW - Lung -- metabolism KW - RNA, Messenger -- metabolism KW - Cell Differentiation -- physiology KW - Down-Regulation KW - Mesocricetus KW - Middle Aged KW - Immunohistochemistry KW - Female KW - Male KW - Cricetinae KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Pulmonary Alveoli -- metabolism KW - Lung Neoplasms -- secondary KW - Oligopeptides -- biosynthesis KW - Pulmonary Alveoli -- cytology KW - Carcinoma, Non-Small-Cell Lung -- secondary KW - Biomarkers, Tumor -- biosynthesis 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/70105509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MUC1+is+a+novel+marker+for+the+type+II+pneumocyte+lineage+during+lung+carcinogenesis.&rft.au=Jarrard%2C+J+A%3BLinnoila%2C+R+I%3BLee%2C+H%3BSteinberg%2C+S+M%3BWitschi%2C+H%3BSzabo%2C+E&rft.aulast=Jarrard&rft.aufirst=J&rft.date=1998-12-01&rft.volume=58&rft.issue=23&rft.spage=5582&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 - 1998-12-31 N1 - Date created - 1998-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of AP-1 and NF-kappaB by manganese-containing superoxide dismutase in human breast cancer cells. AN - 70100332; 9837861 AB - One of the primary antioxidant enzymes, manganese-containing superoxide dismutase (MnSOD), has shown the ability to reverse malignant phenotypes in a variety of human tumor cells that are low or absent in MnSOD expression. We have observed that overexpression of human MnSOD in human breast cancer MCF-7 cells inhibits tumor growth both in vitro and in vivo. The signaling pathway underlying the MnSOD induced tumor suppression is unknown. We demonstrate here that transcriptional and DNA binding ability of AP-1 and NF-kappaB, but not SP-1, were inhibited (by 50%) in the MCF-7 cell line overexpressing MnSOD. When transiently expressing, MnSOD inhibited AP-1 but increased NF-kappaB transactivation, which can be abolished by sodium pyruvate, a hydrogen peroxide scavenger. To analyze the target genes responsible for MnSOD-induced tumor suppression, genes related to tumor growth and responsive to AP-1 or NF-kappaB were analyzed. AP-1 responsive collagenase I, stromelysin I, and NF-kappaB responsive IL-1 and IL-6 were down-regulated in the MnSOD stable transfectants compared to the control cell lines. Since TPA induces differentiation in human breast cancer cells and up-regulates MnSOD gene in HeLa cells, MnSOD expression and AP-1 and NF-kappaB activity were measured under TPA treatment. The results showed that TPA induced endogenous MnSOD expression and inhibited both AP-1 and NF-kappaB. Together, these results suggest that tumor suppression by overexpressing MnSOD is related to a modulation of AP-1 and NF-kappaB, which causes a down-regulation of genes responsible for tumor malignant phenotype. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Li, J J AU - Oberley, L W AU - Fan, M AU - Colburn, N H AD - Gene Regulation Section, Laboratory of Biochemical Physiology, National Cancer Institute, Frederick, Maryland 21702-1201, USA. lij@mail.ncifcrf.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1713 EP - 1723 VL - 12 IS - 15 SN - 0892-6638, 0892-6638 KW - NF-kappa B KW - 0 KW - Recombinant Proteins KW - Transcription Factor AP-1 KW - Manganese KW - 42Z2K6ZL8P KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tumor Cells, Cultured KW - Down-Regulation KW - Recombinant Proteins -- metabolism KW - Humans KW - Genes, Reporter KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Signal Transduction KW - Female KW - Gene Expression Regulation, Neoplastic KW - NF-kappa B -- biosynthesis KW - Transcription Factor AP-1 -- biosynthesis KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- genetics KW - Breast Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70100332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Inhibition+of+AP-1+and+NF-kappaB+by+manganese-containing+superoxide+dismutase+in+human+breast+cancer+cells.&rft.au=Li%2C+J+J%3BOberley%2C+L+W%3BFan%2C+M%3BColburn%2C+N+H&rft.aulast=Li&rft.aufirst=J&rft.date=1998-12-01&rft.volume=12&rft.issue=15&rft.spage=1713&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-07 N1 - Date created - 1999-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. AN - 70099055; 9843216 AB - Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref. 4), which encodes the common cytokine receptor gamma chain (gamma(c)) that is shared by the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal (T(-)B(+)NK(-)SCID). Some SCID patients lack T cells but retain NK cells. Given diminished T-cell development in Il7- or Il7r-deficient mice and that Il/7r-deficient mice have NK cells, we hypothesized that T(-)B(+)NK(+) SCID might result from defective IL-7 signalling, although apparent differences in the role of the IL-7/IL-7R pathway in humans and mice in T-cell and B-cell development have been suggested. We now demonstrate that defective IL7R expression causes T(-)B(+)NK(+) SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling. JF - Nature genetics AU - Puel, A AU - Ziegler, S F AU - Buckley, R H 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 - 1998/12// PY - 1998 DA - December 1998 SP - 394 EP - 397 VL - 20 IS - 4 SN - 1061-4036, 1061-4036 KW - DNA Primers KW - 0 KW - Receptors, Interleukin-7 KW - Index Medicus KW - Animals KW - Humans KW - Infant, Newborn KW - B-Lymphocytes -- immunology KW - Mice KW - Infant KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Signal Transduction -- genetics KW - Molecular Sequence Data KW - T-Lymphocytes -- immunology KW - Killer Cells, Natural -- immunology KW - Receptors, Interleukin-7 -- metabolism KW - Receptors, Interleukin-7 -- genetics KW - Severe Combined Immunodeficiency -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70099055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Defective+IL7R+expression+in+T%28-%29B%28%2B%29NK%28%2B%29+severe+combined+immunodeficiency.&rft.au=Puel%2C+A%3BZiegler%2C+S+F%3BBuckley%2C+R+H%3BLeonard%2C+W+J&rft.aulast=Puel&rft.aufirst=A&rft.date=1998-12-01&rft.volume=20&rft.issue=4&rft.spage=394&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 - 1998-12-21 N1 - Date created - 1998-12-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF043129; GENBANK; AF043127; AF043128; AF043125; AF043126; AF043123; AF043124 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of caspases in immunotoxin-induced apoptosis of cancer cells. AN - 70093970; 9836586 AB - Immunotoxins composed of antibodies linked to plant or bacterial toxins are being evaluated in the treatment of cancer. It is known that the toxin moieties of immunotoxins, including Pseudomonasexotoxin A (PE), diphtheria toxin, and ricin, are capable of inducing apoptosis. Since the efficiency of induction of apoptosis and the apoptosis pathway may have direct effects on the therapeutic usefulness of immunotoxins, we have studied how B3(Fv)-PE38, a genetically engineered immunotoxin in which the Fv fragment of an antibody is fused to a mutated form of PE, induces apoptosis of the MCF-7 breast cancer cell line. We show for the first time that a PE-containing immunotoxin activates ICE/ced-3 proteases, now termed caspases, and causes characteristic cleavage of the "death substrate" poly(ADP)-ribose polymerase (PARP) to an 89 kDa fragment with a time course of cleavage comparable to that induced by TNFalpha. Also the fluorescent substrate, DEVD-AFC, is cleaved 2-4-fold more rapidly by lysates from B3(Fv)-PE38 treated MCF-7 cells than untreated control cells, suggesting that a CPP32-like caspase is involved in B3(Fv)-PE38-mediated apoptosis. B3(Fv)-PE38-induced PARP cleavage is inhibited by several protease inhibitors known to inhibit caspases (zVAD-fmk, zDEVD-fmk, zIETD-fmk) as well as by overexpression of Bcl-2 providing additional evidence for caspase involvement. zVAD-fmk, a broad spectrum inhibitor of most mammalian caspases, prevents the early morphological changes and loss of cell membrane integrity produced by B3(Fv)-PE38, but not its ability to inhibit protein synthesis, arrest cell growth, and subsequently kill cells. Despite inhibition of apoptosis, the immunotoxin is still capable of selective cell killing, which indicates that B3(Fv)-PE38 kills cells by two mechanisms: one requires caspase activation, and the other is due to the arrest of protein synthesis caused by inactivation of elongation factor 2. The fact that an immunotoxin can specifically kill tumor cells without the need of inducing apoptosis makes such agents especially valuable for the treatment of cancers that are protected against apoptosis, e.g., by overexpression of Bcl-2. JF - Biochemistry AU - Keppler-Hafkemeyer, A AU - Brinkmann, U AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, Maryland 20892, USA. Y1 - 1998/12/01/ PY - 1998 DA - 1998 Dec 01 SP - 16934 EP - 16942 VL - 37 IS - 48 SN - 0006-2960, 0006-2960 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antibodies, Monoclonal KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Oligopeptides KW - Peptide Fragments KW - Protein Synthesis Inhibitors KW - Proto-Oncogene Proteins c-bcl-2 KW - Tumor Necrosis Factor-alpha KW - Virulence Factors KW - aspartyl-glutamyl-valyl-aspartal KW - benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - immunotoxin LMB-7 KW - Cycloheximide KW - 98600C0908 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 2 KW - Caspase 3 KW - Caspases KW - Caspase 1 KW - EC 3.4.22.36 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Caspase 1 -- metabolism KW - Enzyme Activation KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Tumor Cells, Cultured KW - Protein Synthesis Inhibitors -- pharmacology KW - Cycloheximide -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Oligopeptides -- pharmacology KW - Pseudomonas aeruginosa KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Female KW - Exotoxins -- pharmacology KW - Apoptosis KW - Breast Neoplasms -- metabolism KW - Bacterial Toxins -- pharmacology KW - Immunotoxins -- pharmacology KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70093970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+caspases+in+immunotoxin-induced+apoptosis+of+cancer+cells.&rft.au=Keppler-Hafkemeyer%2C+A%3BBrinkmann%2C+U%3BPastan%2C+I&rft.aulast=Keppler-Hafkemeyer&rft.aufirst=A&rft.date=1998-12-01&rft.volume=37&rft.issue=48&rft.spage=16934&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-07 N1 - Date created - 1999-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Corepression of the P1 addiction operon by Phd and Doc. AN - 70070348; 9829946 AB - The P1 plasmid addiction operon encodes Doc, a toxin that kills plasmid-free segregants, and Phd, an unstable antidote that neutralizes the toxin. Additionally, these products repress transcription of the operon. The antidote binds to two adjacent sites in the promoter. Here we present evidence concerning the regulatory role of the toxin, which we studied with the aid of a mutation, docH66Y. The DocH66Y protein retained the regulatory properties of the wild-type protein, but not its toxicity. In vivo, DocH66Y enhanced repression by Phd but failed to affect repression in the absence of Phd, suggesting that DocH66Y contacts Phd. In vitro, a MalE-DocH66Y fusion protein was found to bind Phd. Binding of toxin to antidote may be the physical basis for the neutralization of toxin. DocH66Y failed to bind DNA in vitro yet enhanced the affinity, cooperativity, and specificity with which Phd bound the operator. Although DocH66Y enhanced the binding of Phd to two adjacent Phd-binding sites, DocH66Y had relatively little effect on the binding of Phd to a single Phd-binding site, indicating that DocH66Y mediates cooperative interactions between adjacent Phd-binding sites. Several electrophoretically distinct protein-DNA complexes were observed with different amounts of DocH66Y relative to Phd. Maximal repression and specificity of DNA binding were observed with subsaturating amounts of DocH66Y relative to Phd. Analogous antidote-toxin pairs appear to have similar autoregulatory circuits. Autoregulation, by dampening fluctuations in the levels of toxin and antidote, may prevent the inappropriate activation of the toxin. JF - Journal of bacteriology AU - Magnuson, R AU - Yarmolinsky, M B AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4225, USA. roy@sunspot.nci.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 6342 EP - 6351 VL - 180 IS - 23 SN - 0021-9193, 0021-9193 KW - Bacterial Toxins KW - 0 KW - Carrier Proteins KW - DNA Primers KW - DNA, Viral KW - Doc protein, Enterobacteria phage P1 KW - Macromolecular Substances KW - Maltose-Binding Proteins KW - Phd protein, Enterobacteria phage P1 KW - Viral Proteins KW - Index Medicus KW - Plasmids -- metabolism KW - Carrier Proteins -- metabolism KW - Plasmids -- genetics KW - DNA Primers -- genetics KW - Bacterial Toxins -- genetics KW - Promoter Regions, Genetic KW - Base Sequence KW - Bacterial Toxins -- metabolism KW - Half-Life KW - Models, Genetic KW - Molecular Sequence Data KW - Bacterial Toxins -- toxicity KW - Genes, Viral KW - Binding Sites -- genetics KW - Mutation KW - DNA, Viral -- genetics KW - DNA, Viral -- metabolism KW - Viral Proteins -- genetics KW - Operon KW - Viral Proteins -- chemistry KW - Viral Proteins -- metabolism KW - Bacteriophage P1 -- genetics KW - Viral Proteins -- toxicity KW - Bacteriophage P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Corepression+of+the+P1+addiction+operon+by+Phd+and+Doc.&rft.au=Magnuson%2C+R%3BYarmolinsky%2C+M+B&rft.aulast=Magnuson&rft.aufirst=R&rft.date=1998-12-01&rft.volume=180&rft.issue=23&rft.spage=6342&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 - 1998-12-24 N1 - Date created - 1998-12-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1989 May;171(5):2353-60 [2651399] Electrophoresis. 1988 Jun;9(6):255-62 [2466658] Mol Gen Genet. 1989 Sep;218(3):481-6 [2511422] Mol Gen Genet. 1989 Oct;219(1-2):26-32 [2615761] Mol Gen Genet. 1991 Mar;225(3):355-62 [2017133] J Biol Chem. 1991 Jul 25;266(21):13661-71 [1856200] J Biol Chem. 1991 Aug 5;266(22):14328-37 [1860842] Bioessays. 1991 May;13(5):241-2 [1892477] Bioessays. 1991 Oct;13(10):499-503 [1661580] Mol Microbiol. 1991 Nov;5(11):2685-93 [1779758] Methods Enzymol. 1991;208:103-17 [1779832] J Biol Chem. 1992 Jun 15;267(17):12174-81 [1601883] Curr Opin Genet Dev. 1992 Apr;2(2):236-42 [1638117] Mol Microbiol. 1992 Jul;6(14):1981-94 [1508045] J Bacteriol. 1992 Oct;174(19):6138-44 [1400162] Mol Gen Genet. 1993 Feb;237(1-2):81-8 [8455570] J Mol Biol. 1993 Oct 5;233(3):414-28 [8411153] J Biol Chem. 1993 Dec 25;268(36):27109-17 [8262949] Nature. 1994 Jul 21;370(6486):223-6 [7913207] Mol Microbiol. 1994 Apr;12(1):131-41 [8057833] J Mol Biol. 1994 Oct 21;243(2):190-8 [7932749] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11276-80 [7972047] J Mol Biol. 1995 Apr 7;247(4):568-77 [7723014] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3274-7 [7724551] J Bacteriol. 1995 Jul;177(14):4121-30 [7608087] Mol Gen Genet. 1995 Sep 20;248(5):599-609 [7476860] Mol Microbiol. 1995 Jul;17(2):205-10 [7494469] EMBO J. 1995 Nov 1;14(21):5329-37 [7489722] Trends Biochem Sci. 1995 Dec;20(12):517-21 [8571454] J Bacteriol. 1996 Mar;178(5):1420-9 [8631720] J Mol Biol. 1996 Jul 12;260(2):113-9 [8764393] J Biol Chem. 1996 Aug 2;271(31):18705-10 [8702525] Mol Microbiol. 1996 May;20(3):461-6 [8736525] Biochem Biophys Res Commun. 1996 Aug 14;225(2):679-84 [8753818] Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10151-5 [8816767] Nucleic Acids Res. 1997 Feb 15;25(4):873-6 [9016640] Nature. 1997 Apr 10;386(6625):569-77 [9121580] Genes Cells. 1996 Feb;1(2):179-88 [9140062] Cell. 1997 Jun 27;89(7):1101-9 [9215632] EMBO J. 1997 Jun 16;16(12):3666-74 [9218807] Cold Spring Harb Symp Quant Biol. 1968;33:791-8 [4892009] Mol Gen Genet. 1980;177(4):545-52 [6991863] J Mol Biol. 1980 Apr;138(2):179-207 [6997493] Cell. 1981 Sep;25(3):729-36 [7026049] J Bacteriol. 1982 Oct;152(1):63-71 [6749822] Proc Natl Acad Sci U S A. 1983 Jan;80(1):21-5 [6337371] Gene. 1984 Feb;27(2):213-22 [6373503] Proc Natl Acad Sci U S A. 1984 Nov;81(22):6929-33 [6390428] Gene. 1984 Nov;31(1-3):165-71 [6098521] Cell. 1985 Jul;41(3):745-51 [2988785] J Mol Biol. 1985 Sep 20;185(2):261-72 [3903163] Nature. 1986 Aug 21-27;322(6081):697-701 [3018583] Gene. 1987;53(1):85-96 [3596251] Methods Enzymol. 1987;153:461-81 [3323806] Gene. 1988 Dec 30;74(2):365-73 [3073105] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure opportunities of families of farmer pesticide applicators. AN - 70057246; 9816416 AB - Families of farmer pesticide applicators have unusual opportunities for exposure, directly or indirectly, to pesticides. These exposures are not well characterized. Subjects were 26,793 licensed private pesticide applicators enrolled in the Agricultural Health Study, a cohort study being conducted in Iowa and North Carolina. Questionnaires were completed by the applicators and their spouses. Many indirect exposure opportunities exist; for example, 21% of homes are within 50 yards of pesticide mixing areas, 27% of applicators store pesticides in their homes, and 94% of clothing worn for pesticide work is washed in the same machine as other laundry. Direct exposure opportunities also occur; for example, 51% of wives of applicators worked in the fields in the last growing season, 40% of wives have ever mixed or applied pesticides, and over half of children aged 11 or more do farm chores. The extent of the opportunities for exposure of family members of farmer pesticide applicators makes studies of their health important. JF - American journal of industrial medicine AU - Gladen, B C AU - Sandler, D P AU - Zahm, S H AU - Kamel, F AU - Rowland, A S AU - Alavanja, M C AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. gladen@niehs.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 581 EP - 587 VL - 34 IS - 6 SN - 0271-3586, 0271-3586 KW - Pesticides KW - 0 KW - Index Medicus KW - United States KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Occupational Exposure KW - Agriculture KW - Family Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70057246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Exposure+opportunities+of+families+of+farmer+pesticide+applicators.&rft.au=Gladen%2C+B+C%3BSandler%2C+D+P%3BZahm%2C+S+H%3BKamel%2C+F%3BRowland%2C+A+S%3BAlavanja%2C+M+C&rft.aulast=Gladen&rft.aufirst=B&rft.date=1998-12-01&rft.volume=34&rft.issue=6&rft.spage=581&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 - 1999-01-13 N1 - Date created - 1999-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. AN - 70042400; 9806910 AB - Tfeb is a member of the basic Helix-Loop-Helix-Zipper family of transcription factors. In vitro studies have shown that TFEB can bind DNA as a homodimer or as a heterodimer with three closely related family members: MITF, TFE3 and TFEC. While mutations of Mitf have been shown to affect the development of a number of cell types including melanocytes, osteoclasts, and masts cells, little is known about the phenotypic consequences of mutations at Tfe3, Tfeb and Tfec. Here we show that mice with a targeted disruption of Tfeb die between 9.5 and 10.5 days in embryonic development and have severe defects in placental vascularization. Tfeb is expressed at low levels in the embryo but at high levels in the labyrinthine trophoblast cells of the placenta. While labyrinthine cells are present in the mutant Tfeb placenta, they fail to express VEGF, a potent mitogen required for normal vasculogenesis of the embryo and extraembryonic tissues. In Tfeb mutant embryos the embryonic vasculature forms normally but few vessels are seen entering the placenta and those that do enter fail to thrive and branch normally. Our results indicate that Tfeb plays a critical role in the signal transduction processes required for normal vascularization of the placenta. JF - Development (Cambridge, England) AU - Steingrímsson, E AU - Tessarollo, L AU - Reid, S W AU - Jenkins, N A AU - Copeland, N G AD - Mammalian Genetics Laboratory and Neural Development Group, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. eirikurs@rhi.hi.is Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 4607 EP - 4616 VL - 125 IS - 23 SN - 0950-1991, 0950-1991 KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors KW - 0 KW - DNA-Binding Proteins KW - Endothelial Growth Factors KW - Lymphokines KW - Neoplasm Proteins KW - TFEB protein, human KW - Transcription Factors KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Index Medicus KW - Animals KW - Homozygote KW - Exons KW - Dimerization KW - Endothelial Growth Factors -- genetics KW - Mice KW - Stem Cells -- physiology KW - Genomic Library KW - Pregnancy KW - Mutagenesis KW - Mice, Knockout KW - Fetal Death KW - Mice, Inbred Strains KW - Stem Cells -- cytology KW - Helix-Loop-Helix Motifs KW - Lymphokines -- genetics KW - Introns KW - Signal Transduction KW - Female KW - Gene Expression Regulation, Developmental KW - Trophoblasts -- cytology KW - Embryonic and Fetal Development -- physiology KW - DNA-Binding Proteins -- genetics KW - Trophoblasts -- metabolism KW - Neovascularization, Physiologic -- genetics KW - DNA-Binding Proteins -- physiology KW - Placenta -- blood supply KW - Placenta -- cytology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70042400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+bHLH-Zip+transcription+factor+Tfeb+is+essential+for+placental+vascularization.&rft.au=Steingr%C3%ADmsson%2C+E%3BTessarollo%2C+L%3BReid%2C+S+W%3BJenkins%2C+N+A%3BCopeland%2C+N+G&rft.aulast=Steingr%C3%ADmsson&rft.aufirst=E&rft.date=1998-12-01&rft.volume=125&rft.issue=23&rft.spage=4607&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 - 1999-03-18 N1 - Date created - 1999-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excitotoxic lesions of the rat medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage. AN - 70025572; 9803421 AB - Neonatal excitotoxic damage of the ventral hippocampus (VH) is a heuristic model of schizophrenia. We investigated whether: (1) neonatal damage of the medial prefrontal cortex (mPFC) has effects similar to the neonatal VH lesion; and (2) intrinsic mPFC neurons contribute to the abnormal behaviors associated with VH lesions. Neonatal rats were lesioned in the mPFC. In adulthood, they showed attenuated locomotion in response to novelty, amphetamine, and MK-801, and enhanced apomorphine-induced stereotypies as compared to controls. Striatal D1 and D2 receptor mRNAs were unaltered. Another group was lesioned in the VH and additionally in the mPFC in adulthood. Destroying mPFC neurons normalized hyperlocomotion to novelty and amphetamine of the neonatally VH lesioned rats. Thus, neonatal damage of the mPFC does not provide a heuristic model of schizophrenia-like phenomena, in contrast to analogous damage of the VH. However, mPFC intrinsic neurons that have developed in the context of abnormal hippocampal connectivity may be responsible for abnormal behaviors in the neonatally VH lesioned rats. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lipska, B K AU - al-Amin, H A AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, St. Elizabeth's, Washington, DC 20032, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 451 EP - 464 VL - 19 IS - 6 SN - 0893-133X, 0893-133X KW - Dopamine Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Excitatory Amino Acids KW - RNA, Messenger KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Amphetamine KW - CK833KGX7E KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Animals KW - Apomorphine -- pharmacology KW - Dopamine Agents -- pharmacology KW - Disease Models, Animal KW - Stereotyped Behavior -- drug effects KW - RNA, Messenger -- biosynthesis KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Motor Activity -- drug effects KW - Amphetamine -- pharmacology KW - Female KW - Behavior, Animal -- drug effects KW - Hippocampus -- physiology KW - Excitatory Amino Acids -- toxicity KW - Prefrontal Cortex -- drug effects KW - Animals, Newborn -- physiology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Excitotoxic+lesions+of+the+rat+medial+prefrontal+cortex.+Effects+on+abnormal+behaviors+associated+with+neonatal+hippocampal+damage.&rft.au=Lipska%2C+B+K%3Bal-Amin%2C+H+A%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1998-12-01&rft.volume=19&rft.issue=6&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and relative bioavailability of carboxyamido-triazole with respect to food and time of administration: use of a single model for simultaneous determination of changing parameters. AN - 69254530; 10485080 AB - Carboxyamido-triazole (CAI) is an anti-invasive, antimetastatic, antiangiogenic agent in clinical development for cancer treatment. It has been postulated that food might enhance the oral absorption of micronized CAI based on an apparent discrepancy in steady state maximum concentrations when taken without regard to meals vs. fasting. The purpose of this study was to determine if a standardized meal affects the absorption and pharmacokinetics of this agent. Twelve patients with refractory cancers and good end organ function were randomized to receive two doses of CAI (250 mg/m2) with and without a standardized high fat meal. One cohort of 6 patients received these doses at 9 AM, and the remaining 6 patients received CAI at 9 PM. Blood was obtained prior to each dose, and serially thereafter. A series of pharmacokinetic (PK) models were fit to the concentration-time data. PK parameters were ultimately calculated using a model which allows simultaneous estimation of parameters from both test doses using nonlinear least squares analysis with ADAPT II. This model estimates independent absorption rate constants and relative fraction absorbed for each condition. AUC0-t was determined using the trapezoidal method, extrapolated to infinity, and used to calculate the relative bioavailability. No significant differences in PK parameters were noted between the morning and evening cohorts. However, the relative bioavailability, as measured by AUC0-infinity, of CAI was significantly increased when administered with a high fat meal compared to fasting (138.9 vs. 52.2 micrograms * hr/ml; p = 0.0005). The magnitude of the increase in relative bioavailability of CAI taken with food could have profound implications for patients who may inadvertently take this medication shortly after eating. JF - Journal of pharmacokinetics and biopharmaceutics AU - Bauer, K S AU - Kohn, E C AU - Lush, R M AU - Steinberg, S M AU - Davis, P AU - Kohler, D AU - Reed, E AU - Figg, W D AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 673 EP - 687 VL - 26 IS - 6 SN - 0090-466X, 0090-466X KW - Antineoplastic Agents KW - 0 KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Index Medicus KW - Area Under Curve KW - Humans KW - Cohort Studies KW - Adult KW - Cross-Over Studies KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- metabolism KW - Biological Availability KW - Antineoplastic Agents -- pharmacokinetics KW - Food-Drug Interactions KW - Triazoles -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69254530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacokinetics+and+biopharmaceutics&rft.atitle=Pharmacokinetics+and+relative+bioavailability+of+carboxyamido-triazole+with+respect+to+food+and+time+of+administration%3A+use+of+a+single+model+for+simultaneous+determination+of+changing+parameters.&rft.au=Bauer%2C+K+S%3BKohn%2C+E+C%3BLush%2C+R+M%3BSteinberg%2C+S+M%3BDavis%2C+P%3BKohler%2C+D%3BReed%2C+E%3BFigg%2C+W+D&rft.aulast=Bauer&rft.aufirst=K&rft.date=1998-12-01&rft.volume=26&rft.issue=6&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmacokinetics+and+biopharmaceutics&rft.issn=0090466X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-06 N1 - Date created - 1999-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Performance characteristics of a compact position-sensitive LSO detector module. AN - 69179406; 10048853 AB - We assembled a compact detector module comprised of an array of small, individual crystals of lutetium oxyorthosilicate:Ce (LSO) coupled directly to a miniature, metal-can, position-sensitive photomultiplier tube (PSPMT). We exposed this module to sources of 511-keV annihilation radiation and beams of 30- and 140-keV photons and measured spatial linearity; spatial variations in module gain, energy resolution, and event positioning; coincidence timing; the accuracy and sensitivity of identifying the crystal-of-first-interaction at 511 keV; and the effects of intercrystal scatter and LSO background radioactivity. The results suggest that this scintillator/phototube combination should be highly effective in the coincidence mode and can be used, with some limitations, to image relatively low-energy single photon emitters. Photons that are completely absorbed on their first interaction at 511 keV are positioned by the module at the center of a crystal. Intercrystal scatter events, even those that lead to total absorption of the incident photon, are placed by the module in a regular "connect-the-dot" pattern that joins crystal centers. As a result, the accuracy of event positioning can be made to exceed 90%, though at significantly reduced sensitivity, by retaining only events that occur within small regions-of-interest around each crystal center and rejecting events that occur outside these regions in the connect-the-dot pattern. JF - IEEE transactions on medical imaging AU - Vaquero, J J AU - Seidel, J AU - Siegel, S AU - Gandler, W R AU - Green, M V AD - Nuclear Medicine Department, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 967 EP - 978 VL - 17 IS - 6 SN - 0278-0062, 0278-0062 KW - Fluorine Radioisotopes KW - 0 KW - Lutetium KW - 5H0DOZ21UJ KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Equipment Design KW - Scattering, Radiation KW - Electrons KW - Reproducibility of Results KW - Photons KW - Normal Distribution KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Lutetium -- radiation effects KW - Tomography, Emission-Computed -- statistics & numerical data KW - Tomography, Emission-Computed -- instrumentation KW - Tomography, Emission-Computed -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69179406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IEEE+transactions+on+medical+imaging&rft.atitle=Performance+characteristics+of+a+compact+position-sensitive+LSO+detector+module.&rft.au=Vaquero%2C+J+J%3BSeidel%2C+J%3BSiegel%2C+S%3BGandler%2C+W+R%3BGreen%2C+M+V&rft.aulast=Vaquero&rft.aufirst=J&rft.date=1998-12-01&rft.volume=17&rft.issue=6&rft.spage=967&rft.isbn=&rft.btitle=&rft.title=IEEE+transactions+on+medical+imaging&rft.issn=02780062&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 - SuppNotes - Erratum In: IEEE Trans Med Imaging 1999 Feb;18(2):184 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication. AN - 69172105; 10023450 AB - The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of tumor cell lines in vitro, a wide range of sensitivity to bystander killing was found. Since transfer of toxic GCV metabolites from hTK-modified to wild-type tumor cells via gap junctions (GJ) seemed to be a likely mechanism of the BSE, we tested GJ function in these various tumors with a dye transfer technique and pharmacological agents known to affect GJ communication. We confirmed that mixtures of tumor cell resistant to the BSE did not show dye transfer from cell to cell while bystander-sensitive tumor cells did. Dieldrin, a drug known to decrease GJ communication, diminished dye transfer and also inhibited the BSE. Forskolin, an upregulator of cAMP did increase GJ, but directly inhibited hTK and therefore its effect on BSE could not be determined. We conclude that these observations further support port the concept that functional GJ play an important role in the BSE and further suggest that pharmacological manipulation of GJ may influence the outcome of cancer therapy with hTK/GCV. JF - Gene therapy AU - Touraine, R L AU - Ishii-Morita, H AU - Ramsey, W J AU - Blaese, R M AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1705 EP - 1711 VL - 5 IS - 12 SN - 0969-7128, 0969-7128 KW - Antiviral Agents KW - 0 KW - Coloring Agents KW - Fluoresceins KW - Insecticides KW - Organophosphorus Compounds KW - Colforsin KW - 1F7A44V6OU KW - Protein Kinases KW - EC 2.7.- KW - Histidine Kinase KW - EC 2.7.13.1 KW - Dieldrin KW - I0246D2ZS0 KW - Ganciclovir KW - P9G3CKZ4P5 KW - fluorexon KW - V0YM2B16TS KW - Index Medicus KW - Rats KW - Dieldrin -- pharmacology KW - Animals KW - Colforsin -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - Genetic Vectors KW - Retroviridae KW - Mice KW - Insecticides -- pharmacology KW - Antiviral Agents -- therapeutic use KW - Transfection -- methods KW - Gap Junctions -- drug effects KW - Ganciclovir -- therapeutic use KW - Protein Kinases -- genetics KW - Genetic Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69172105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy&rft.atitle=The+bystander+effect+in+the+HSVtk%2Fganciclovir+system+and+its+relationship+to+gap+junctional+communication.&rft.au=Touraine%2C+R+L%3BIshii-Morita%2C+H%3BRamsey%2C+W+J%3BBlaese%2C+R+M&rft.aulast=Touraine&rft.aufirst=R&rft.date=1998-12-01&rft.volume=5&rft.issue=12&rft.spage=1705&rft.isbn=&rft.btitle=&rft.title=Gene+therapy&rft.issn=09697128&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 - Precancerous lesions in two counties of China with contrasting gastric cancer risk. AN - 69170926; 10024186 AB - Gastric cancer (GC) is one of the most common cancers worldwide and shows remarkable geographical variation even within countries such as China. Linqu County in Shandong Province of northeast China has a GC rate that is 15 times higher than that of Cangshan County in Shandong, even though these counties are within 200 miles of each other. In order to evaluate the frequency of precancerous gastric lesions in Linqu and Cangshan Counties we examined 3400 adults in Linqu County and 224 adults in Cangshan County. An endoscopic examination with four biopsies was performed in each individual of the two populations. The prevalence of intestinal metaplasia (IM) and dysplasia (DYS) was 30% and 15.1%, respectively, in Linqu compared to 7.9% and 5.6% in Cangshan (P < 0.01). Within these histological categories, advanced grades were found more often in Linqu than in Cangshan. The prevalences of IM and DYS were more common at each biopsy site in Linqu, where the lesions also tended to affect multiple sites. The findings of this study support the concept that IM and DYS are closely correlated with risks of GC and represent late stages in the multistep process of gastric carcinogenesis. JF - International journal of epidemiology AU - You, W C AU - Zhang, L AU - Gail, M H AU - Li, J Y AU - Chang, Y S AU - Blot, W J AU - Zhao, C L AU - Liu, W D AU - Li, H Q AU - Ma, J L AU - Hu, Y R AU - Bravo, J C AU - Correa, P AU - Xu, G W AU - Fraumeni, J F AD - National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 945 EP - 948 VL - 27 IS - 6 SN - 0300-5771, 0300-5771 KW - Index Medicus KW - Gastroscopy KW - Diagnosis, Differential KW - Rural Population KW - Gastritis, Atrophic -- diagnosis KW - Humans KW - Retrospective Studies KW - Biopsy KW - Gastric Mucosa -- pathology KW - Risk Factors KW - China -- epidemiology KW - Adult KW - Metaplasia -- pathology KW - Middle Aged KW - Gastritis, Atrophic -- epidemiology KW - Female KW - Male KW - Prevalence KW - Precancerous Conditions -- diagnosis KW - Stomach Neoplasms -- epidemiology KW - Stomach Neoplasms -- diagnosis KW - Precancerous Conditions -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69170926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Precancerous+lesions+in+two+counties+of+China+with+contrasting+gastric+cancer+risk.&rft.au=You%2C+W+C%3BZhang%2C+L%3BGail%2C+M+H%3BLi%2C+J+Y%3BChang%2C+Y+S%3BBlot%2C+W+J%3BZhao%2C+C+L%3BLiu%2C+W+D%3BLi%2C+H+Q%3BMa%2C+J+L%3BHu%2C+Y+R%3BBravo%2C+J+C%3BCorrea%2C+P%3BXu%2C+G+W%3BFraumeni%2C+J+F&rft.aulast=You&rft.aufirst=W&rft.date=1998-12-01&rft.volume=27&rft.issue=6&rft.spage=945&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 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 - [Topoisomerases I: new targets for the treatment of cancer and mechanisms of resistance]. TT - Les topo-isomérases I: nouvelles cibles pour le traitement des cancers et mécanismes de résistance. AN - 69165131; 9932078 AB - DNA topoisomerases I are ubiquitous enzymes that play a crucial role in DNA condensation, replication, transcription, and repair. Eukaryotic enzymes are highly conserved and specifically targeted by natural anticancer agents such as camptothecin and its derivatives. These drugs poison top 1 by inhibiting the enzyme via trapping of top 1 clivage complexes, which ultimately generate cell death. New camptothecin derivatives with better pharmacologic characteristics are under development. Understanding top 1 functions and structure will help to discover more specific and less toxic top 1 inhibitors in order to circumvent drug resistance. JF - Bulletin du cancer AU - Pourquier, P AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 5 EP - 10 VL - Spec No SN - 0007-4551, 0007-4551 KW - Antineoplastic Agents KW - 0 KW - Benzimidazoles KW - DNA, Neoplasm KW - Enzyme Inhibitors KW - Intercalating Agents KW - Macromolecular Substances KW - Neoplasm Proteins KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Intercalating Agents -- pharmacology KW - DNA Topoisomerases, Type I -- chemistry KW - Drug Screening Assays, Antitumor KW - Humans KW - Binding Sites -- drug effects KW - Benzimidazoles -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Drug Resistance, Neoplasm KW - Drug Design KW - DNA, Neoplasm -- biosynthesis KW - DNA Replication -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Enzyme Inhibitors -- therapeutic use KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- antagonists & inhibitors KW - Camptothecin -- pharmacology KW - Camptothecin -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Camptothecin -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69165131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bulletin+du+cancer&rft.atitle=%5BTopoisomerases+I%3A+new+targets+for+the+treatment+of+cancer+and+mechanisms+of+resistance%5D.&rft.au=Pourquier%2C+P%3BPommier%2C+Y&rft.aulast=Pourquier&rft.aufirst=P&rft.date=1998-12-01&rft.volume=Spec+No&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Bulletin+du+cancer&rft.issn=00074551&rft_id=info:doi/ LA - fre DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals. AN - 69154866; 9926813 AB - Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic acid) and unoperated controls were tested on object discrimination and reversal, place discrimination and reversal, and spatial scene learning to determine the contribution of these temporal lobe structures to these forms of learning and memory. Rhinal cortex lesions produced a severe deficit in object reversal learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal cortex removals and those with hippocampal lesions were equally impaired on spatial scene learning. None of the lesions impaired place discrimination or reversal. These results argue against the idea that the mnemonic contributions of the rhinal cortex and hippocampus are limited to object and spatial domains, respectively. JF - Behavioral neuroscience AU - Murray, E A AU - Baxter, M G AU - Gaffan, D AD - Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. eam@ln.nimh.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1291 EP - 1303 VL - 112 IS - 6 SN - 0735-7044, 0735-7044 KW - Index Medicus KW - Animals KW - Dominance, Cerebral -- physiology KW - Discrimination Learning -- physiology KW - Brain Mapping KW - Mental Recall -- physiology KW - Macaca mulatta KW - Problem Solving -- physiology KW - Orientation -- physiology KW - Entorhinal Cortex -- physiology KW - Hippocampus -- physiology KW - Reversal Learning -- physiology KW - Pattern Recognition, Visual -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69154866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Monkeys+with+rhinal+cortex+damage+or+neurotoxic+hippocampal+lesions+are+impaired+on+spatial+scene+learning+and+object+reversals.&rft.au=Murray%2C+E+A%3BBaxter%2C+M+G%3BGaffan%2C+D&rft.aulast=Murray&rft.aufirst=E&rft.date=1998-12-01&rft.volume=112&rft.issue=6&rft.spage=1291&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 - 1999-04-30 N1 - Date created - 1999-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutation spectrum in relation to GSTM1, CYP1A1 and CYP2E1 in surgically treated patients with non-small cell lung cancer. AN - 69145199; 9918134 AB - p53 mutation status was analysed in relation to DNA polymorphisms of GSTM1, CYP1A1 and CYP2E1 from 105 surgically resected non-small cell lung cancer cases. Demographic factors, smoking, occupation, family history, tumour histology, grade and stage were taken into account. p53 mutations, detected either directly by DNA sequencing (P = 0.04, adjusted for smoking) or indirectly by immunostaining (P = 0.06), were overrepresented among CYP1A1 variants. Mutations in exon 8 and transitions at CpG sites in the p53 gene were favoured in this subset. There was no relation between the individual gene polymorphisms or p53 mutations and disease-free survival by Kaplan-Meier analysis. The finding of excess CYP1A1 heterozygotes in individuals with p53 mutations after adjustment for smoking suggests that CYP1A1 activation contributes to lung cancer via p53 inactivation. JF - Pharmacogenetics AU - Przygodzki, R M AU - Bennett, W P AU - Guinee, D G AU - Khan, M A AU - Freedman, A AU - Shields, P G AU - Travis, W D AU - Jett, J R AU - Tazelaar, H AU - Pairolero, P AU - Trastek, V AU - Liotta, L A AU - Harris, C C AU - Caporaso, N E AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 503 EP - 511 VL - 8 IS - 6 SN - 0960-314X, 0960-314X KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Lung Neoplasms -- enzymology KW - Disease-Free Survival KW - Homozygote KW - Humans KW - Heterozygote KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- surgery KW - Immunohistochemistry KW - Cytochrome P-450 CYP1A1 -- genetics KW - Genes, p53 KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Glutathione Transferase -- genetics KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Mutation KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69145199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutation+spectrum+in+relation+to+GSTM1%2C+CYP1A1+and+CYP2E1+in+surgically+treated+patients+with+non-small+cell+lung+cancer.&rft.au=Przygodzki%2C+R+M%3BBennett%2C+W+P%3BGuinee%2C+D+G%3BKhan%2C+M+A%3BFreedman%2C+A%3BShields%2C+P+G%3BTravis%2C+W+D%3BJett%2C+J+R%3BTazelaar%2C+H%3BPairolero%2C+P%3BTrastek%2C+V%3BLiotta%2C+L+A%3BHarris%2C+C+C%3BCaporaso%2C+N+E&rft.aulast=Przygodzki&rft.aufirst=R&rft.date=1998-12-01&rft.volume=8&rft.issue=6&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-29 N1 - Date created - 1999-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abuse and acquired immune deficiency syndrome. AN - 69144003; 9895137 AB - Acquired immune deficiency syndrome (AIDS) is a modern plague. The first sign of the disease was the appearance of Pneumocystis carinii and Kaposi's sarcoma among young homosexual patients. The virus transmission is from an infected individual to a susceptible host through blood-related, sexual, and perinatal routes. Exchange of body fluid occurs when sharing syringes, drugs, and drug paraphernalia. Although the largest number of people infected with human immunodeficiency virus (HIV) is in subSaharan Africa, the most rapid growth of HIV infection during the 1990s was seen in South-East Asia. Asia showed a steep increase from 1992. Given the experiences in Thailand, India and China, a similar spread of AIDS in other parts of Asia is possible. The risk behaviors that enable the spread of HIV are present in all Pacific Asian countries. Risk behaviors are considered to be the injection of illicit drugs, male patronage of prostitutes, high rates of sexually transmitted diseases, and low condom use. JF - Psychiatry and clinical neurosciences AU - Sheu, Y AD - Medical Affairs, Division of Clinical Research and Services, National Institute on Drug Abuse, Rockville, Maryland 20857, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - S167 EP - S169 VL - 52 Suppl SN - 1323-1316, 1323-1316 KW - Index Medicus KW - AIDS/HIV KW - Far East -- epidemiology KW - Risk Factors KW - Humans KW - Cross-Cultural Comparison KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Male KW - Female KW - Asia, Southeastern -- epidemiology KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Acquired Immunodeficiency Syndrome -- transmission KW - Substance Abuse, Intravenous -- epidemiology KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69144003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+clinical+neurosciences&rft.atitle=Drug+abuse+and+acquired+immune+deficiency+syndrome.&rft.au=Sheu%2C+Y&rft.aulast=Sheu&rft.aufirst=Y&rft.date=1998-12-01&rft.volume=52+Suppl&rft.issue=&rft.spage=S167&rft.isbn=&rft.btitle=&rft.title=Psychiatry+and+clinical+neurosciences&rft.issn=13231316&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 - Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients. AN - 69137778; 9888619 AB - Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder. JF - Psychopharmacology AU - Greenberg, B D AU - Benjamin, J AU - Martin, J D AU - Keuler, D AU - Huang, S J AU - Altemus, M AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. bdg@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 434 EP - 444 VL - 140 IS - 4 SN - 0033-3158, 0033-3158 KW - Serotonin Antagonists KW - 0 KW - Serotonin Uptake Inhibitors KW - Fluoxetine KW - 01K63SUP8D KW - Metergoline KW - 1501393LY5 KW - Index Medicus KW - Behavior -- drug effects KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Pilot Projects KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Serotonin Uptake Inhibitors -- administration & dosage KW - Metergoline -- pharmacology KW - Serotonin Antagonists -- pharmacology KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Obsessive-Compulsive Disorder -- psychology KW - Fluoxetine -- administration & dosage KW - Obsessive-Compulsive Disorder -- drug therapy KW - Fluoxetine -- therapeutic use KW - Obsessive-Compulsive Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69137778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Delayed+obsessive-compulsive+disorder+symptom+exacerbation+after+a+single+dose+of+a+serotonin+antagonist+in+fluoxetine-treated+but+not+untreated+patients.&rft.au=Greenberg%2C+B+D%3BBenjamin%2C+J%3BMartin%2C+J+D%3BKeuler%2C+D%3BHuang%2C+S+J%3BAltemus%2C+M%3BMurphy%2C+D+L&rft.aulast=Greenberg&rft.aufirst=B&rft.date=1998-12-01&rft.volume=140&rft.issue=4&rft.spage=434&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-29 N1 - Date created - 1999-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Haloperidol-induced extrapyramidal reaction: lack of protective effect by vitamin E. AN - 69137612; 9888616 AB - Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis. Oxidative stress has also been implicated in the extrapyramidal symptoms (EPS) produced by haloperidol. Supporting the oxidative stress hypothesis, vitamin E (antioxidant) has demonstrated therapeutic efficacy in idiopathic parkinsonism. The prophylactic efficacy of vitamin E (antioxidant) on haloperidol-induced EPS was examined in a randomized controlled trial. The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial. All patients received oral haloperidol 10 mg/day. The sample was equally randomized to receive either haloperidol alone or haloperidol + vitamin E (3200 IU/day). EPS was rated at recruitment, both live and with video records, and on days 3, 7, 10 and 14. Psychopathology was rated at recruitment and weekly thereafter. Vitamin E had no prophylactic effect on drug-induced EPS, though it did not interfere with the therapeutic efficacy of haloperidol. JF - Psychopharmacology AU - Eranti, V S AU - Gangadhar, B N AU - Janakiramaiah, N AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 418 EP - 420 VL - 140 IS - 4 SN - 0033-3158, 0033-3158 KW - Antioxidants KW - 0 KW - Antipsychotic Agents KW - Vitamin E KW - 1406-18-4 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Prospective Studies KW - Double-Blind Method KW - Humans KW - Adult KW - Adolescent KW - Time Factors KW - Male KW - Haloperidol -- adverse effects KW - Antioxidants -- therapeutic use KW - Vitamin E -- therapeutic use KW - Basal Ganglia Diseases -- prevention & control KW - Antipsychotic Agents -- adverse effects KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69137612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Haloperidol-induced+extrapyramidal+reaction%3A+lack+of+protective+effect+by+vitamin+E.&rft.au=Eranti%2C+V+S%3BGangadhar%2C+B+N%3BJanakiramaiah%2C+N&rft.aulast=Eranti&rft.aufirst=V&rft.date=1998-12-01&rft.volume=140&rft.issue=4&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-29 N1 - Date created - 1999-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a high-risk area of central Italy. AN - 69135443; 9886570 AB - Examination of p53 mutation spectra may provide clues to molecular mechanisms involved in different histologic types of gastric cancer. A total of 105 gastric cancer cases classified according to the Laurén's system were selected from a high-risk area around Florence, Italy. Exons 5-8 of the p53 gene were examined for mutations by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing, using DNA from formalin-fixed paraffin-embedded tissues. Mutation frequency was similar in intestinal-type (12/28) and unclassified tumors (9/18), but was significantly lower in diffuse cancers (12/57, P A:T transitions at CpG sites were the most common mutations for all the three tumor types with 6 of 11 (55%) in intestinal type, 8 of 12 (67%) in diffuse type, and 5 of 8 (63 %) in unclassified tumors. Frequent p53 mutations in both intestinal-type and unclassified tumors support the hypothesis that unclassified tumors represent variants of the intestinal type and suggest that unclassified tumors, like the intestinal type, may also associate with environmental exposures. The predominance of G:C-->A:T transitions at CpG sites, which are associated with methyltransferase-induced DNA methylation at carbon 5 of cytosine, in all three tumor types suggests that the status of DNA methylation may be the major determinant for p53 mutations and may be also equally important in gastric carcinogenesis regardless of histology. JF - Carcinogenesis AU - Shiao, Y H AU - Palli, D AU - Buzard, G S AU - Caporaso, N E AU - Amorosi, A AU - Saieva, C AU - Fraumeni, J F AU - Anderson, L M AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, NCI-FCRDC, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 2145 EP - 2149 VL - 19 IS - 12 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Risk Factors KW - Humans KW - CpG Islands KW - Adult KW - Aged KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Female KW - Stomach Neoplasms -- pathology KW - Genes, p53 KW - Stomach Neoplasms -- genetics KW - Mutation, Missense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69135443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Implications+of+p53+mutation+spectrum+for+cancer+etiology+in+gastric+cancers+of+various+histologic+types+from+a+high-risk+area+of+central+Italy.&rft.au=Shiao%2C+Y+H%3BPalli%2C+D%3BBuzard%2C+G+S%3BCaporaso%2C+N+E%3BAmorosi%2C+A%3BSaieva%2C+C%3BFraumeni%2C+J+F%3BAnderson%2C+L+M%3BRice%2C+J+M&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1998-12-01&rft.volume=19&rft.issue=12&rft.spage=2145&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-21 N1 - Date created - 1999-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway. AN - 69135275; 9885560 AB - In Drosophila, specification of embryonic terminal cells is controlled by the Torso receptor tyrosine kinase. Here, we analyze the molecular basis of positive (Y630) and negative (Y918) phosphotyrosine (pY) signaling sites on Torso. We find that the Drosophila homolog of RasGAP associates with pY918 and is a negative effector of Torso signaling. Further, we show that the tyrosine phosphatase Corkscrew (CSW), which associates with pY630, specifically dephosphorylates the negative pY918 Torso signaling site, thus identifying Torso to be a substrate of CSW in the terminal pathway. CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation. The opposing actions of CSW and RasGAP modulate the strength of the Torso signal, contributing to the establishment of precise boundaries for terminal structure development. JF - Molecular cell AU - Cleghon, V AU - Feldmann, P AU - Ghiglione, C AU - Copeland, T D AU - Perrimon, N AU - Hughes, D A AU - Morrison, D K AD - Molecular Basis of Carcinogenesis Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 719 EP - 727 VL - 2 IS - 6 SN - 1097-2765, 1097-2765 KW - Drosophila Proteins KW - 0 KW - Gap1 protein, Drosophila KW - Insect Proteins KW - Proteins KW - Repressor Proteins KW - drk protein, Drosophila KW - ras GTPase-Activating Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - torso protein, Drosophila KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatases, Non-Receptor KW - corkscrew protein, Drosophila KW - Index Medicus KW - Animals KW - Phosphotyrosine -- chemistry KW - Phosphotyrosine -- metabolism KW - Protein Binding KW - Binding Sites KW - Tyrosine -- chemistry KW - Phosphorylation KW - Repressor Proteins -- physiology KW - Tyrosine -- metabolism KW - Substrate Specificity KW - Signal Transduction KW - Insect Proteins -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Drosophila -- metabolism KW - Protein Tyrosine Phosphatases -- physiology KW - Receptor Protein-Tyrosine Kinases -- physiology KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - Drosophila -- embryology KW - Proteins -- physiology KW - Drosophila -- physiology KW - Receptor Protein-Tyrosine Kinases -- chemistry KW - Protein Tyrosine Phosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69135275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Opposing+actions+of+CSW+and+RasGAP+modulate+the+strength+of+Torso+RTK+signaling+in+the+Drosophila+terminal+pathway.&rft.au=Cleghon%2C+V%3BFeldmann%2C+P%3BGhiglione%2C+C%3BCopeland%2C+T+D%3BPerrimon%2C+N%3BHughes%2C+D+A%3BMorrison%2C+D+K&rft.aulast=Cleghon&rft.aufirst=V&rft.date=1998-12-01&rft.volume=2&rft.issue=6&rft.spage=719&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 - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypomethylation of an exon I estrogen receptor CpG island in spontaneous and carcinogen-induced mammary tumorigenesis in the rat. AN - 69129579; 9883975 AB - Loss of methylation at a CpG island in exon I of the rat ER gene was observed in 48% of the spontaneous mammary tumors in old female Wistar rats and 22% of the contralateral normal mammary tissues. The majority of the methylation losses were total. Similarly, 50% of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in young Sprague-Dawley rats exhibited a partial or total loss of methylation at this site, while all normal mammary tissues in young rats were fully methylated. Loss of ER methylation also increased with age in normal mammary tissues of tumor-free rats approaching 12.5% in middle-aged and 43% in old rats. In addition, 66% of mammary glands obtained from young rats that are subsequently at an increased risk to develop breast cancer due to manipulation of in utero dietary fat intake, exhibited methylation loss while no methylation changes were observed in rats at no increased risk for breast cancer. Therefore, the loss of ER methylation is more extensive in mammary glands of rats at high than low breast cancer risk, in old than young, and in mammary tumors than in normal tissues. The data suggest that hypomethylation of a growth-associated ER gene may be a common event in mammary tumorigenesis in the rat and may be of predictive value as a marker of increased breast cancer risk in aged individuals. JF - Mechanisms of ageing and development AU - Yenbutr, P AU - Hilakivi-Clarke, L AU - Passaniti, A AD - Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224-6823, USA. Y1 - 1998/12/01/ PY - 1998 DA - 1998 Dec 01 SP - 93 EP - 102 VL - 106 IS - 1-2 SN - 0047-6374, 0047-6374 KW - Carcinogens KW - 0 KW - Receptors, Estrogen KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Rats KW - Carcinogens -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Rats, Wistar KW - Carcinogenicity Tests KW - Female KW - Cell Line KW - Mammary Neoplasms, Experimental -- chemically induced KW - Receptors, Estrogen -- genetics KW - DNA Methylation KW - Exons KW - CpG Islands KW - Mammary Neoplasms, Experimental -- genetics KW - Aging -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69129579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypomethylation+of+an+exon+I+estrogen+receptor+CpG+island+in+spontaneous+and+carcinogen-induced+mammary+tumorigenesis+in+the+rat.&rft.au=Yenbutr%2C+P%3BHilakivi-Clarke%2C+L%3BPassaniti%2C+A&rft.aulast=Yenbutr&rft.aufirst=P&rft.date=1998-12-01&rft.volume=106&rft.issue=1-2&rft.spage=93&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 - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral effects of nicotine, amphetamine and cocaine under a fixed-interval schedule of food reinforcement in rats chronically exposed to caffeine. AN - 69115371; 9877005 AB - Epidemiological surveys demonstrate that caffeine, the main psychoactive ingredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimulants, we examined the effects of chronic caffeine exposure on the behavioral responses to nicotine, amphetamine, cocaine, the selective D1 agonist SKF-82958 and the selective D2 receptor agonist NPA, in rats responding under a fixed interval (FI) schedule of food reinforcement. Following stabilization of rates and temporal patterns of responding (mathematically expressed as quarter-life values, QL), twenty-one Sprague-Dawley rats responding under a 5-min FI schedule of food reinforcement were divided into two groups; one (twelve rats) maintained on tap water (control) and the other (nine rats) on caffeine (3 mg/ml added to the drinking water). Following the substitution of caffeine solution for tap water, behavior was temporarily disrupted as evidenced by decreases in responding and QL values which reached a maximum after 72 h (rate 60% and QL 30% below baseline levels). Rats developed complete tolerance to these effects of caffeine over 5 days of caffeine exposure. After response rate and QL values stabilized, effects of drugs were evaluated. Nicotine (0.01-1.0 mg/kg; SC), amphetamine (0.1-5.6; IP), and cocaine (1.0-17; IP) each produced biphasic dose-dependent changes in response rate with maximum increases in response rate following intermediate doses and decreases in response rates following higher doses. The increase in rates of responding produced by amphetamine or cocaine (but not nicotine) were greater (P0.05) were produced by NPA in both groups. Except for amphetamine, the remaining drugs produced similar (P>0.05) dose-dependent decreases in QL values in water- and caffeine-drinking rats. Amphetamine produced smaller decreases in QL values in caffeine-drinking rats than in water-drinking rats (P<0.05). Chronic exposure to caffeine produced complete insurmountable tolerance to the response-rate increasing (stimulant) effects of acute caffeine (3.0-17 mg/kg; IP) in caffeine-drinking rats. In conclusion, our study revealed that chronic caffeine exposure potentiates the behavioral response to amphetamine and cocaine but not to that of nicotine in rats responding under a FI schedule of food reinforcement. Thus, it is likely that these effects are mediated through different pharmacological mechanisms. JF - Psychopharmacology AU - Jaszyna, M AU - Gasior, M AU - Shoaib, M AU - Yasar, S AU - Goldberg, S R AD - Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD 21224, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 257 EP - 271 VL - 140 IS - 3 SN - 0033-3158, 0033-3158 KW - Central Nervous System Stimulants KW - 0 KW - Caffeine KW - 3G6A5W338E KW - Nicotine KW - 6M3C89ZY6R KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Drinking KW - Animals KW - Rats, Sprague-Dawley KW - Nicotine -- pharmacology KW - Food-Drug Interactions KW - Substance-Related Disorders KW - Cocaine -- pharmacology KW - Amphetamine -- pharmacology KW - Male KW - Central Nervous System Stimulants -- pharmacology KW - Reinforcement Schedule KW - Caffeine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69115371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Behavioral+effects+of+nicotine%2C+amphetamine+and+cocaine+under+a+fixed-interval+schedule+of+food+reinforcement+in+rats+chronically+exposed+to+caffeine.&rft.au=Jaszyna%2C+M%3BGasior%2C+M%3BShoaib%2C+M%3BYasar%2C+S%3BGoldberg%2C+S+R&rft.aulast=Jaszyna&rft.aufirst=M&rft.date=1998-12-01&rft.volume=140&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-21 N1 - Date created - 1999-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The aryl hydrocarbon receptor: studies using the AHR-null mice. AN - 69112652; 9860927 AB - The aryl hydrocarbon receptor (AHR) is believed to mediate the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. AHR is a member of the Per, ARNT, Sim/basic-helix-loop-helix superfamily of ligand-activated transcription factors that also harbors the transcription factors involved in the hypoxia response, development of the central nervous system, and day-night adaptations. To investigate the role of AHR in chemical toxicity and carcinogenesis and to determine any possible function in mammalian development and physiological homeostasis, AHR-null mice were developed. The AHR-null mice were resistant to the acute toxicity of TCDD and had an altered teratogenic response to this compound. These mice were found to have a number of abnormal phenotypes, thus confirming that AHR plays an important developmental and physiological role. Among the most consistent phenotypes was an altered liver pathology that was associated with accelerated rates of apoptosis. Evidence suggests that this may be related to an abnormal accumulation of levels of hepatic retinoic acid that cause an activation of transforming growth factor beta, resulting in stimulation of apoptosis. AHR may directly or indirectly control levels of a cytochrome P450 that is responsible for catabolizing retinoic acid. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Gonzalez, F J AU - Fernandez-Salguero, P AD - Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1194 EP - 1198 VL - 26 IS - 12 SN - 0090-9556, 0090-9556 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Polychlorinated Dibenzodioxins -- toxicity KW - Mice KW - Polychlorinated Dibenzodioxins -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69112652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=The+aryl+hydrocarbon+receptor%3A+studies+using+the+AHR-null+mice.&rft.au=Gonzalez%2C+F+J%3BFernandez-Salguero%2C+P&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1998-12-01&rft.volume=26&rft.issue=12&rft.spage=1194&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-05 N1 - Date created - 1999-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gabapentin does not alter single-dose lithium pharmacokinetics. AN - 69102131; 9864078 AB - Lithium (Li) and gabapentin are both exclusively eliminated by renal excretion. When used in combination, a competitive drug-drug interaction could possibly alter Li renal excretion with important clinical implications considering the rather narrow therapeutic index of Li. This study examined the single-dose pharmacokinetic profiles of Li in 13 patients receiving placebo and then steady-state gabapentin (mean daily dose: 3,646.15 mg). During both phases, a single 600-mg dose of Li was orally administered with serial Li levels obtained at time zero and at 0.25, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, and 72 hours. The pharmacokinetic parameters assessed were the following: area under the concentration time curve (AUC) for Li, maximal concentration of Li (Li Cmax), and time to reach peak Li concentration (Li Tmax). For patients receiving gabapentin, the mean Li AUC at 72 hours was 9.91+/-3.54 mmol x hr/mL and did not differ significantly from the mean Li AUC of 10.19+/-2.89 mmol x hr/mL for patients receiving placebo. The mean Li Cmax was 0.69+/-0.13 mmol/L for gabapentin patients and did not differ from the mean Li Cmax of 0.72+/-0.15 mmol/L for placebo patients. The mean serum Li Tmax was 1.38+/-0.62 hours for gabapentin patients and did not differ significantly from the mean serum Li Tmax of 1.5+/-0.91 hours for placebo patients. These data indicate that gabapentin treatment at this high therapeutic dose does not cause clinically significant alterations in short-term Li pharmacokinetics in patients with normal renal function. These preliminary data warrant further controlled study in a larger, more heterogenous patient sample and a longer duration of assessment, but they do suggest that these two medications may be administered in combination for the management of bipolar disorder. JF - Journal of clinical psychopharmacology AU - Frye, M A AU - Kimbrell, T A AU - Dunn, R T AU - Piscitelli, S AU - Grothe, D AU - Vanderham, E AU - Corá-Locatelli, G AU - Post, R M AU - Ketter, T A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. maf@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 461 EP - 464 VL - 18 IS - 6 SN - 0271-0749, 0271-0749 KW - Acetates KW - 0 KW - Amines KW - Antimanic Agents KW - Cyclohexanecarboxylic Acids KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - gabapentin KW - 6CW7F3G59X KW - Lithium KW - 9FN79X2M3F KW - Index Medicus KW - Drug Interactions KW - Double-Blind Method KW - Humans KW - Metabolic Clearance Rate KW - Antimanic Agents -- pharmacology KW - Lithium -- administration & dosage KW - Depression -- metabolism KW - Bipolar Disorder -- drug therapy KW - Depression -- drug therapy KW - Lithium -- pharmacokinetics KW - Bipolar Disorder -- metabolism KW - Acetates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69102131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychopharmacology&rft.atitle=Gabapentin+does+not+alter+single-dose+lithium+pharmacokinetics.&rft.au=Frye%2C+M+A%3BKimbrell%2C+T+A%3BDunn%2C+R+T%3BPiscitelli%2C+S%3BGrothe%2C+D%3BVanderham%2C+E%3BCor%C3%A1-Locatelli%2C+G%3BPost%2C+R+M%3BKetter%2C+T+A&rft.aulast=Frye&rft.aufirst=M&rft.date=1998-12-01&rft.volume=18&rft.issue=6&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&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 - PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. AN - 69097070; 9865913 AB - Mutation of the PTEN tumor suppressor gene is a frequent event in endometrial cancers. In other types of cancers, PTEN mutation has been associated with metastatic behavior and advanced stage. To examine the relationship between PTEN mutation and clinical features of endometrial cancers, we screened 136 cases for mutations in the nine exons and intronic splice sites of the PTEN gene, using single-strand conformation analysis, and aberrant bands were sequenced. Mutations were noted in 44 of 136 (32%) endometrial cancers, and two mutations were present in 8 cases. There were 36 cases with mutations resulting in truncated protein products, 6 cases with missense mutations in the phosphatase domain, 1 case with an in-frame deletion, and 1 case with a large insertion. Mutation of the PTEN gene correlated most closely with endometrioid histology; mutations were seen in only 5% (1 of 21) of serous/clear cell cancers compared with 37% (43 of 115) of endometrioid cancers (P = 0.004). PTEN mutation was associated with early stage, nonmetastatic disease and more favorable survival in both the entire group of 136 cases and in the 115 endometrioid cases. In addition, PTEN mutation correlated with other molecular features associated with favorable clinical behavior, including microsatellite instability and absence of p53 overexpression. Microsatellite instability was found in 60% of cases with PTEN mutations compared with only 25% of cases without mutations (P = 0.004). Overexpression of p53 was seen in only 14% of cases with PTEN mutations compared to 39% of cases without mutations (P = 0.006). In conclusion, PTEN mutation is associated with endometrioid histology and other favorable pathological, clinical, and molecular features rather than with increased metastatic potential as has been noted in some other types of cancers. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Risinger, J I AU - Hayes, K AU - Maxwell, G L AU - Carney, M E AU - Dodge, R K AU - Barrett, J C AU - Berchuck, A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 3005 EP - 3010 VL - 4 IS - 12 SN - 1078-0432, 1078-0432 KW - Genetic Markers KW - 0 KW - Neoplasm Proteins KW - Tumor Suppressor Proteins KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - PTEN Phosphohydrolase KW - EC 3.1.3.67 KW - PTEN protein, human KW - Index Medicus KW - Survival Rate KW - Genes, Tumor Suppressor KW - Humans KW - Neoplasm Proteins -- genetics KW - Adult KW - Prognosis KW - Aged KW - Middle Aged KW - Female KW - Phosphoric Monoester Hydrolases -- genetics KW - Endometrial Neoplasms -- genetics KW - Mutation KW - Endometrial Neoplasms -- diagnosis KW - Endometrial Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69097070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=PTEN+mutation+in+endometrial+cancers+is+associated+with+favorable+clinical+and+pathologic+characteristics.&rft.au=Risinger%2C+J+I%3BHayes%2C+K%3BMaxwell%2C+G+L%3BCarney%2C+M+E%3BDodge%2C+R+K%3BBarrett%2C+J+C%3BBerchuck%2C+A&rft.aulast=Risinger&rft.aufirst=J&rft.date=1998-12-01&rft.volume=4&rft.issue=12&rft.spage=3005&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 - 1999-03-22 N1 - Date created - 1999-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Formation of DNA adducts of the food-derived mutagen 2-amino-9H-pyrido-[2,3-b]indole (A(alpha)C) and bioassay of mammary gland carcinogenicity in Sprague-Dawley rats. AN - 69095170; 9862644 AB - 2-amino-9H-pyrido[2,3-b]indole (AalphaC) is a heterocyclic amine found at relatively high concentrations in barbecued or grilled meats. In the current study, the mammary gland carcinogenicity of AalphaC was examined in female Sprague-Dawley rats given 10 doses of AalphaC (75 mg/kg, orally, once per day starting at 43 days of age) and placed on a defined high-fat diet (23.5% corn oil), a strong promotional factor for rat mammary gland carcinogenesis. Within 1 year, one out of 20 rats dosed with AalphaC developed a tubulopapillary carcinoma, indicating that the bioassay was largely negative. As DNA adduct formation is considered to play a role in carcinogenesis, AalphaC-DNA adduct levels were measured in the mammary gland and other tissues by the 32P-postlabelling method. Under intensification conditions, one major adduct and up to three minor adducts were detected in isolated mammary gland epithelial cells and other tissues (liver, stomach, small intestine, colon and kidney) of AalphaC-treated rats; the adduct patterns were similar in all tissues examined. The major adduct, comprising 60-100% of total DNA adduct levels in tissues, was chromatographically identical to the principal adduct found in 3'-dGp-AalphaC (synthesized by reacting 3'-phospho-2'-deoxyguanosine (3'-dGp) with N-acetoxy-AalphaC). Of the tissues examined, the highest AalphaC-DNA adduct levels were found in the liver. In male rats given a single dose of AalphaC (75 mg/kg, orally, 3 hr prior to necropsy), no AalphaC-DNA adducts were detected in extrahepatic tissues. In female rats given a single dose or 12 daily doses of AalphaC, hepatic DNA adduct levels were at least 12-13-fold higher than those in any other tissue. Mean total AalphaC-DNA adduct levels in mammary gland epithelial cells and liver from female rats given multiple doses of AalphaC were 3.5 and 50.7 (RAL x 10(7)), respectively. Although factors in addition to DNA adduct formation are likely to play a role in mammary gland carcinogenesis, the results suggest that the weak mammary gland carcinogenicity of AalphaC may in part be associated with low AalphaC-DNA adduct levels in the mammary gland epithelium. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Snyderwine, E G AU - Sadrieh, N AU - King, R S AU - Schut, H A AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1033 EP - 1041 VL - 36 IS - 12 SN - 0278-6915, 0278-6915 KW - Carbolines KW - 0 KW - Carcinogens KW - DNA Adducts KW - 2-amino-9H-pyrido(2,3-b)indole KW - P0GZ1ICS6X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Carcinogenicity Tests KW - Organ Specificity KW - Autoradiography KW - Male KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Adenocarcinoma -- chemically induced KW - DNA Adducts -- chemistry KW - Carcinogens -- chemistry KW - Carcinogens -- toxicity KW - Carbolines -- toxicity KW - Adenocarcinoma -- chemistry KW - Carbolines -- chemistry KW - Mammary Neoplasms, Experimental -- chemistry KW - Mammary Neoplasms, Experimental -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69095170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Formation+of+DNA+adducts+of+the+food-derived+mutagen+2-amino-9H-pyrido-%5B2%2C3-b%5Dindole+%28A%28alpha%29C%29+and+bioassay+of+mammary+gland+carcinogenicity+in+Sprague-Dawley+rats.&rft.au=Snyderwine%2C+E+G%3BSadrieh%2C+N%3BKing%2C+R+S%3BSchut%2C+H+A&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-12-01&rft.volume=36&rft.issue=12&rft.spage=1033&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of the human delta-globin gene promoter in primary adult erythroid cells. AN - 69087344; 9858241 AB - Restoration of the CCAAT box or insertion of an erythroid Krüppel-like factor (EKLF) binding site in the delta promoter activates its expression in several erythroid cell lines. We extended these studies using a novel primary human adult erythroid cell (hAEC) system to investigate these effects at the late erythroblast stage. Restoration of the CCAAT box at -70 bp, or insertion of an EKLF binding site at -85 bp or -95 bp in the promoter significantly increased delta globin gene expression in hAEC. Our results demonstrate that the altered CCAAT box (CCAAC) and the lack of an EKLF binding site in delta-globin contribute to its low level of expression in the hAEC model as well. JF - British journal of haematology AU - Tang, D C AU - Rodgers, G P AD - Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1822, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 835 EP - 838 VL - 103 IS - 3 SN - 0007-1048, 0007-1048 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Kruppel-Like Transcription Factors KW - Transcription Factors KW - erythroid Kruppel-like factor KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Humans KW - Adult KW - Gene Expression KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - Mutagenesis, Insertional KW - DNA-Binding Proteins -- metabolism KW - Erythroblasts -- metabolism KW - Globins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69087344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+the+human+delta-globin+gene+promoter+in+primary+adult+erythroid+cells.&rft.au=Tang%2C+D+C%3BRodgers%2C+G+P&rft.aulast=Tang&rft.aufirst=D&rft.date=1998-12-01&rft.volume=103&rft.issue=3&rft.spage=835&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 - 1999-01-27 N1 - Date created - 1999-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cycloguanil and its parent compound proguanil demonstrate distinct activities against Plasmodium falciparum malaria parasites transformed with human dihydrofolate reductase. AN - 69083723; 9855645 AB - The lack of suitable antimalarial agents to replace chloroquine and pyrimethamine/sulfadoxine threatens efforts to control the spread of drug-resistant strains of the malaria parasite Plasmodium falciparum. Here we describe a transformation system, involving WR99210 selection of parasites transformed with either wild-type or methotrexate-resistant human dihydrofolate reductase (DHFR), that has application for the screening of P. falciparum-specific DHFR inhibitors that are active against drug-resistant parasites. Using this system, we have found that the prophylactic drug cycloguanil has a mode of pharmacological action distinct from the activity of its parent compound proguanil. Complementation assays demonstrate that cycloguanil acts specifically on P. falciparum DHFR and has no other significant target. The target of proguanil itself is separate from DHFR. We propose a strategy of combination chemotherapy incorporating the use of multiple parasite-specific inhibitors that act at the same molecular target and thereby maintain, in combination, their effectiveness against alternative forms of resistance that arise from different sets of point mutations in the target. This approach could be combined with traditional forms of combination chemotherapy in which two or more compounds are used against separate targets. JF - Molecular pharmacology AU - Fidock, D A AU - Nomura, T AU - Wellems, T E AD - Malaria Genetics Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 1140 EP - 1147 VL - 54 IS - 6 SN - 0026-895X, 0026-895X KW - Antimalarials KW - 0 KW - Folic Acid Antagonists KW - Triazines KW - cycloguanil KW - 26RM326WVN KW - Hypoxanthine KW - 2TN51YD919 KW - BRL 6231 KW - 47326-86-3 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Proguanil KW - S61K3P7B2V KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Methotrexate -- pharmacology KW - Folic Acid Antagonists -- pharmacology KW - Humans KW - Hypoxanthine -- metabolism KW - Genetic Complementation Test KW - Inhibitory Concentration 50 KW - Mutation KW - Plasmodium falciparum -- enzymology KW - Antimalarials -- pharmacology KW - Triazines -- pharmacology KW - Plasmodium falciparum -- genetics KW - Proguanil -- pharmacology KW - Tetrahydrofolate Dehydrogenase -- biosynthesis KW - Plasmodium falciparum -- drug effects KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69083723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cycloguanil+and+its+parent+compound+proguanil+demonstrate+distinct+activities+against+Plasmodium+falciparum+malaria+parasites+transformed+with+human+dihydrofolate+reductase.&rft.au=Fidock%2C+D+A%3BNomura%2C+T%3BWellems%2C+T+E&rft.aulast=Fidock&rft.aufirst=D&rft.date=1998-12-01&rft.volume=54&rft.issue=6&rft.spage=1140&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The end of moai quarrying and its effect on Lake Rano Raraku, Easter Island AN - 52468016; 1999-044966 JF - Journal of Paleolimnology AU - Dumont, Henri J AU - Cocquyt, Christine AU - Fontugne, Michel AU - Arnold, Maurice AU - Reyss, Jean-Louis AU - Bloemendal, Jan AU - Oldfield, Frank AU - Steenbergen, Cees L M AU - Korthals, Henk J AU - Zeeb, Barbara A Y1 - 1998/12// PY - 1998 DA - December 1998 SP - 409 EP - 422 PB - Kluwer Academic, Dordrecht - Boston - London VL - 20 IS - 4 SN - 0921-2728, 0921-2728 KW - Porifera KW - Easter Island KW - biogeography KW - magnetic properties KW - Cladocera KW - diatoms KW - geochronology KW - carbon KW - absolute age KW - Invertebrata KW - Lake Rano Raraku KW - Plantae KW - archaeology KW - Quaternary KW - biostratigraphy KW - pigments KW - human activity KW - paleomagnetism KW - East Pacific Ocean Islands KW - Branchiopoda KW - organic compounds KW - Mandibulata KW - palynomorphs KW - Oceania KW - biozones KW - upper Holocene KW - relative age KW - isotopes KW - magnetization KW - algae KW - Ostracoda KW - Holocene KW - cores KW - artifacts KW - Cenozoic KW - radioactive isotopes KW - remanent magnetization KW - dates KW - sediments KW - Chrysophyta KW - paleoindian KW - Pb/Pb KW - migration KW - biodiversity KW - isothermal remanent magnetization KW - Crustacea KW - ornamental materials KW - South America KW - Arthropoda KW - Polynesia KW - C-14 KW - lake sediments KW - 24:Quaternary geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52468016?accountid=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=Journal+of+Paleolimnology&rft.atitle=The+end+of+moai+quarrying+and+its+effect+on+Lake+Rano+Raraku%2C+Easter+Island&rft.au=Dumont%2C+Henri+J%3BCocquyt%2C+Christine%3BFontugne%2C+Michel%3BArnold%2C+Maurice%3BReyss%2C+Jean-Louis%3BBloemendal%2C+Jan%3BOldfield%2C+Frank%3BSteenbergen%2C+Cees+L+M%3BKorthals%2C+Henk+J%3BZeeb%2C+Barbara+A&rft.aulast=Dumont&rft.aufirst=Henri&rft.date=1998-12-01&rft.volume=20&rft.issue=4&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Journal+of+Paleolimnology&rft.issn=09212728&rft_id=info:doi/ L2 - http://www.springerlink.com/(i42ivkufd5oczp45mspwbbyb)/app/home/journal.asp?referrer=parent&backto=linkingpublicationresults,1:100294,1 LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - Number of references - 47 N1 - Document feature - illus. incl. 2 tables, geol. sketch maps N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - absolute age; algae; archaeology; Arthropoda; artifacts; biodiversity; biogeography; biostratigraphy; biozones; Branchiopoda; C-14; carbon; Cenozoic; Chrysophyta; Cladocera; cores; Crustacea; dates; diatoms; East Pacific Ocean Islands; Easter Island; geochronology; Holocene; human activity; Invertebrata; isothermal remanent magnetization; isotopes; Lake Rano Raraku; lake sediments; magnetic properties; magnetization; Mandibulata; migration; Oceania; organic compounds; ornamental materials; Ostracoda; paleoindian; paleomagnetism; palynomorphs; Pb/Pb; pigments; Plantae; Polynesia; Porifera; Quaternary; radioactive isotopes; relative age; remanent magnetization; sediments; South America; upper Holocene ER - TY - JOUR T1 - Current approaches toward chemical mixture studies at the National Institute of Environmental Health Sciences and the U.S. National Toxicology Program. AN - 21250799; 11702179 AB - The National Institute of Environmental Health Sciences (NIEHS) has several new initiatives involving chemical mixtures and has recognized the need to develop new experimental approaches to enhance our efforts in this area. Responding to recent increases in nominations of complex occupational exposures for toxicologic assessment by the U.S. National Toxicology Program, the NIEHS and the National Institute for Occupational Safety and Health have begun a program to characterize exposures through field studies, identify biomarkers of exposure in workers, and recreate relevant mixed exposures in a laboratory setting. A second initiative with the National Center for Environmental Health/Centers for Disease Control and Prevention will examine blood samples from the U.S. National Health and Nutrition Examination Survey population surveys for selected endocrine-disrupting agents and for common patterns of persistent xenobiotics, providing critical information for the design of animal studies to assess risks of relevant chemical mixtures to humans. New toxicology testing methods (lower cost, faster) will enhance our ability to study chemical mixtures (e.g., dioxin and dioxinlike chemicals, combination AIDS therapies). Ongoing method development efforts involve in vitro functional toxicology assays, screens for estrogenic activity, and carcinogenesis studies in transgenic mice. A major scientific initiative with mixtures involves studies of individual and mixtures of dioxin and dioxinlike chemicals to determine if toxic equivalence factors predict carcinogenic potency in traditional and transgenic bioassays. Complementing these studies is an increased emphasis on physiologically based pharmacokinetic modeling, an activity central to the proper interpretation of chemical mixture studies. JF - Environmental Health Perspectives AU - Bucher, J R AU - Lucier, G AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA., bucher@niehs.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 1295 EP - 1298 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 106 IS - Suppl 6 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts; Virology & AIDS Abstracts; Health & Safety Science Abstracts; Risk Abstracts; Environment Abstracts KW - Acquired immune deficiency syndrome KW - endocrine disruptors KW - Endocrine disruptors KW - Occupational safety KW - Physiology KW - Disease control KW - Environmental health KW - Xenobiotics KW - disease control KW - Nutrition KW - Dioxins KW - Carcinogenicity KW - prevention KW - Toxicology KW - Occupational exposure KW - Bioindicators KW - Mice KW - Transgenic mice KW - biomarkers KW - estrogenic activity KW - Pharmacokinetics KW - USA KW - Bioassays KW - Carcinogenesis KW - Dioxin KW - estrogens KW - V 22360:AIDS and HIV KW - H 1000:Occupational Safety and Health KW - R2 23060:Medical and environmental health KW - X 24350:Industrial Chemicals KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21250799?accountid=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=Current+approaches+toward+chemical+mixture+studies+at+the+National+Institute+of+Environmental+Health+Sciences+and+the+U.S.+National+Toxicology+Program.&rft.au=Bucher%2C+J+R%3BLucier%2C+G&rft.aulast=Bucher&rft.aufirst=J&rft.date=1998-12-01&rft.volume=106&rft.issue=Suppl+6&rft.spage=1295&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 - Acquired immune deficiency syndrome; Endocrine disruptors; Carcinogenesis; Disease control; Xenobiotics; Transgenic mice; Nutrition; estrogenic activity; biomarkers; Pharmacokinetics; Dioxin; Occupational exposure; Bioindicators; endocrine disruptors; Physiology; Occupational safety; Environmental health; Mice; disease control; Dioxins; Bioassays; Carcinogenicity; prevention; Toxicology; estrogens; USA ER - TY - JOUR T1 - Re: Arsenic - Evidence of Carcinogenicity in Animals. AN - 1859303940; 10207116 JF - Environmental health perspectives AU - Huff AU - Waalkes AU - Chan AD - National Institute of Environmental Health Sciences. Y1 - 1998/12// PY - 1998 DA - December 1998 SP - A582 EP - A583 VL - 106 IS - 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859303940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Re%3A+Arsenic+-+Evidence+of+Carcinogenicity+in+Animals.&rft.au=Huff%3BWaalkes%3BChan&rft.aulast=Huff&rft.aufirst=&rft.date=1998-12-01&rft.volume=106&rft.issue=12&rft.spage=A582&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=1552-9924&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 - Effect of aeration on biodegradation of petroleum waste AN - 17432685; 4645144 AB - Large amounts of oily sludge are generated as residues by the oil industry, representing a real problem for refineries. This work studied the technical viability of treating oily sludge biologically, through stimulation of native microorganisms, at bench scale. Such microorganisms were able to grow in a medium containing oily sludge as the only carbon and energy sources. Two oily sludge concentrations were studied, 5% (v/v) and 10% (v/v), with a C:N ratio of 100:1. Higher microbial populations were observed in the first case. Substrate inhibition and/or toxic effect took place in the second case. The importance of aeration on the microbial activity and on the biodegradation of the residue was ascertained. In terms of n-paraffins, pristane and phytane consumption, maximum global efficiency of 76.9% (w/w) was achieved, in a medium containing 5% (v/v) of oily sludge. Bacteria of the genus Pseudomonas predominated. Two yeast species were also identified and two filamentous fungi were isolated. JF - Revista de Microbiologia AU - Ururahy, AFP AU - Marins, MDM AU - Vital, R L AU - Gabardo, I T AU - Pereira, N Jr AD - Departamento de Engenharia Bioquimica, Escola de Quimica, Universidade Federal do Rio de Janeiro, CEP 21941-590, Rio de Janeiro, RJ, Brasil, nei@h20.eq.ufrj.br Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 254 EP - 258 VL - 29 IS - 4 SN - 0001-3714, 0001-3714 KW - Pseudomonas KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Pollution Abstracts KW - Yeasts KW - Biodegradation KW - Sludges KW - Waste treatment KW - Aeration KW - Petroleum industry wastes KW - Petroleum KW - Sludge treatment KW - P 3000:SEWAGE & WASTEWATER TREATMENT KW - A 01063:Utilization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17432685?accountid=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=Revista+de+Microbiologia&rft.atitle=Effect+of+aeration+on+biodegradation+of+petroleum+waste&rft.au=Ururahy%2C+AFP%3BMarins%2C+MDM%3BVital%2C+R+L%3BGabardo%2C+I+T%3BPereira%2C+N+Jr&rft.aulast=Ururahy&rft.aufirst=AFP&rft.date=1998-12-01&rft.volume=29&rft.issue=4&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=Revista+de+Microbiologia&rft.issn=00013714&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; Biodegradation; Petroleum industry wastes; Sludge treatment; Waste treatment; Aeration; Petroleum; Sludges; Yeasts ER - TY - JOUR T1 - Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer AN - 17342168; 4612396 AB - Background Cangshan County of Shandong Province has one of the lowest rates of gastric cancer (GC) in China. While intestinal metaplasia (IM) and dysplasia (DYS) are less common in Cangshan than in areas of Shandong at high risk of GC, these precursor lesions nevertheless affect about 20% of adults age >=55. Subjects and Setting In order to evaluate determinants of IM and DYS in Cangshan County, a low risk area of GC a survey was conducted among 214 adults who participated in a gastroscopic screening survey in Cangshan County in 1994. Method A dietary interview and measurement of serum Helicobacter pylori antibodies were performed. Results The prevalence of H. pylori was lowest (19%) among those with normal gastric mucosa, rising steadily to 35% for superficial gastritis (SG), 56% for chronic atrophic gastritis (CAG), 80% for IM, and 100% for DYS. The prevalence odds of precancerous lesions were compared with the odds of normal histology or SG. The odds ratio (OR) or CAG associated with H. pylori positivity was 4.2 (95% confidence interval [CI]: 1.7-10.0, while the OR of IM/DYS associated with H. pylori positivity was 31.5 (95% CI: 5.2-187). After adjusting for H. pylori infection, drinking alcohol was a risk factor for CAG (OR = 3.2, 95% CI: 1.1-9.2) and IM/DYS (OR = 7.8, 95% CI: 1.3-47.7). On the other hand, consumption of garlic showed non-significant protective effects and in inverse association with H. pylori infection. Conclusions The findings of this study suggest that infection with H. pylori is a risk factor and garlic may be protective, in the development and progression of advanced precancerous gastric lesions in an area of China at relatively low risk of GC. JF - International Journal of Epidemiology AU - You, W-C AU - Zhang, L AU - Gail, M H AU - Ma, J-L AU - Chang, Y-S AU - Blot, W J AU - Li, J-Y AU - Zhao, C-L AU - Liu, W-D AU - Li, H-Q AU - Hu, Y-R AU - Bravo, J C AU - Correa, P AU - Xu, G-W AU - Fraumeni, JF Jr AD - National Cancer Institute, EPN Room 431, Bethesda, MD 20892, USA Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 941 EP - 944 VL - 27 IS - 6 SN - 0300-5771, 0300-5771 KW - infection KW - man KW - Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Cancer patients KW - China, People's Rep. KW - Stomach KW - Carcinoma KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17342168?accountid=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=International+Journal+of+Epidemiology&rft.atitle=Helicobacter+pylori+infection%2C+garlic+intake+and+precancerous+lesions+in+a+Chinese+population+at+low+risk+of+gastric+cancer&rft.au=You%2C+W-C%3BZhang%2C+L%3BGail%2C+M+H%3BMa%2C+J-L%3BChang%2C+Y-S%3BBlot%2C+W+J%3BLi%2C+J-Y%3BZhao%2C+C-L%3BLiu%2C+W-D%3BLi%2C+H-Q%3BHu%2C+Y-R%3BBravo%2C+J+C%3BCorrea%2C+P%3BXu%2C+G-W%3BFraumeni%2C+JF+Jr&rft.aulast=You&rft.aufirst=W-C&rft.date=1998-12-01&rft.volume=27&rft.issue=6&rft.spage=941&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 - Helicobacter pylori; China, People's Rep.; Cancer patients; Carcinoma; Stomach ER - TY - JOUR T1 - Identification of free radical formation and F sub(2)-isoprostanes in vivo by acute Cr(VI) poisoning AN - 17257919; 4518227 AB - We previously reported the detection of a carbon-centered radical adduct of alpha -(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN) in the bile of rats acutely poisoned with Cr(VI) utilizing an electron spin resonance spin-trapping technique. These former studies suggested that the free radical metabolite was derived from a polyunsaturated fatty acid. The present studies were undertaken to further characterize this radical adduct and to determine whether its formation is associated with enhanced lipid peroxidation in vivo. This report demonstrates that electron spin resonance (ESR) spectra with hyperfine coupling constants a super(N) of 15.71 G and a super(H) sub( beta ) of 2.90 G were present in bile from Cr(VI)-poisoned rats. We found out that virtually identical ESR spectra were obtained when authentic POBN-pentyl radical adducts generated from the reaction of POBN with either pentylhydrazine or linoleic or arachidonic acid with lipoxygenase were added to bile. The hyperfine coupling constants for the POBN-pentyl radical adducts added to bile were as follows: a super(N) = 15.85 G and a super(H) sub( beta ) = 2.60 G for the reaction between pentylhydrazine and POBN; a super(N) = 15.72 G and a super(H) sub( beta ) = 2.61 G for the reaction between arachidonic acid, lipoxygenase, and POBN; and a super(N) = 15.85 G and a super(H) sub( beta ) = 2.85 G for the reaction between linoleic acid, lipoxygenase, and POBN. In addition, the formation of this radical adduct was associated with lipid peroxidation as quantified by increases in F sub(2)-isoprostane levels in bile. These studies, therefore, provide additional evidence that acute Cr(VI) poisoning is associated with enhanced generation of F sub(2)-isoprostanes in vivo and tentatively identify the radical species that is produced as the POBN-pentyl radical adduct. JF - Chemical Research in Toxicology AU - Kadiiska, M B AU - Morrow, J D AU - Awad, JA AU - Roberts, LJ II AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 1516 EP - 1520 VL - 11 IS - 12 SN - 0893-228X, 0893-228X KW - isoprostanes KW - rats KW - Toxicology Abstracts KW - Chromium KW - Heavy metals KW - Free radicals KW - Lipid peroxidation KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17257919?accountid=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=Identification+of+free+radical+formation+and+F+sub%282%29-isoprostanes+in+vivo+by+acute+Cr%28VI%29+poisoning&rft.au=Kadiiska%2C+M+B%3BMorrow%2C+J+D%3BAwad%2C+JA%3BRoberts%2C+LJ+II%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=1998-12-01&rft.volume=11&rft.issue=12&rft.spage=1516&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 - Lipid peroxidation; Free radicals; Heavy metals; Chromium ER - TY - JOUR T1 - U-shaped dose-response curves for carcinogens AN - 17244957; 4518279 JF - Human & Experimental Toxicology AU - Portier, C J AU - Ye, F AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 705 EP - 707 VL - 17 IS - 12 SN - 0960-3721, 0960-3721 KW - Toxicology Abstracts KW - Dose-response effects KW - Carcinogens KW - Toxicity testing KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17244957?accountid=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=Human+%26+Experimental+Toxicology&rft.atitle=U-shaped+dose-response+curves+for+carcinogens&rft.au=Portier%2C+C+J%3BYe%2C+F&rft.aulast=Portier&rft.aufirst=C&rft.date=1998-12-01&rft.volume=17&rft.issue=12&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=09603721&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 - Dose-response effects; Carcinogens; Toxicity testing ER - TY - JOUR T1 - An Improved Method for Construction of Directionally Cloned cDNA Libraries from Microdissected Cells AN - 17201640; 4494139 AB - Here, we developed an improved method for constructing microdissected cDNA libraries, based on strand-switching properties of reverse transcriptase, followed by PCR amplification with primers to mediate unidirectional insert cloning. Using RNA from microdissected ovarian carcinoma cells, we constructed a cDNA library consisting of 1.3 x 10 super(6) unidirectional recombinants with an average insert size of 500 bp. Singlepass sequencing of 100 clones with the T7 primer revealed 89 inserts derived from known genes, anonymous expressed sequence tags (ESTs), or novel sequences. Among these clones were known genes and ESTs previously found in cDNA libraries from bulk ovarian tissue RNA, sequences seen for the first time in an ovarian-derived library, and novel sequences not previously seen in any cDNA library. These results demonstrate a methodology for constructing quality cDNA libraries that are cloned in a unidirectional fashion, are complex and diverse, and reflect the tissue of origin. JF - Cancer Research AU - Peterson, LA AU - Brown, M R AU - Carlisle, A J AU - Kohn, E C AU - Liotta, LA AU - Emmert-Buck, M R AU - Krizman, D B AD - Laboratory of Pathology, National Cancer Institute, Advanced Technology Center, 134F, 8717 Grovemont Circle, Bethesda, MD 20892, USA, dkrizman@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 5326 EP - 5328 VL - 58 IS - 23 SN - 0008-5472, 0008-5472 KW - cDNA KW - microdissection KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene libraries KW - Polymerase chain reaction KW - Ovaries KW - Carcinoma KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17201640?accountid=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=An+Improved+Method+for+Construction+of+Directionally+Cloned+cDNA+Libraries+from+Microdissected+Cells&rft.au=Peterson%2C+LA%3BBrown%2C+M+R%3BCarlisle%2C+A+J%3BKohn%2C+E+C%3BLiotta%2C+LA%3BEmmert-Buck%2C+M+R%3BKrizman%2C+D+B&rft.aulast=Peterson&rft.aufirst=LA&rft.date=1998-12-01&rft.volume=58&rft.issue=23&rft.spage=5326&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 - Carcinoma; Ovaries; Polymerase chain reaction; Gene libraries ER - TY - JOUR T1 - Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities AN - 17175776; 4476302 AB - Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species. JF - Environmental Health Perspectives AU - Burkhart, J G AU - Helgen, J C AU - Fort, D J AU - Gallagher, K AU - Bowers, D AU - Propst, T L AU - Gernes, M AU - Magner, J AU - Shelby, MD AU - Lucier, G AD - National Institute of Environmental Health Sciences, MD C4-07, PO Box 12233, Research Triangle Park, NC 27709 USA Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 841 EP - 848 VL - 106 IS - 12 SN - 0091-6765, 0091-6765 KW - Clawed frogs KW - FETAX KW - USA, Minnesota KW - Xenopus laevis KW - Toxicology Abstracts; Pollution Abstracts KW - Ponds KW - Malformations KW - Xenopus KW - Embryos KW - Freshwater pollution KW - Assays KW - Toxicity testing KW - Water sampling KW - Teratogenesis KW - Mortality KW - Water pollution KW - Amphibia KW - Freshwater organisms KW - X 24240:Miscellaneous KW - P 2000:FRESHWATER POLLUTION KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17175776?accountid=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=Induction+of+mortality+and+malformation+in+Xenopus+laevis+embryos+by+water+sources+associated+with+field+frog+deformities&rft.au=Burkhart%2C+J+G%3BHelgen%2C+J+C%3BFort%2C+D+J%3BGallagher%2C+K%3BBowers%2C+D%3BPropst%2C+T+L%3BGernes%2C+M%3BMagner%2C+J%3BShelby%2C+MD%3BLucier%2C+G&rft.aulast=Burkhart&rft.aufirst=J&rft.date=1998-12-01&rft.volume=106&rft.issue=12&rft.spage=841&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 - Xenopus; Mortality; Water sampling; Embryos; Teratogenesis; Freshwater pollution; Assays; Amphibia; Toxicity testing; Freshwater organisms; Water pollution; Ponds; Malformations ER - TY - JOUR T1 - Evolution of antiviral activity in the ribonuclease A gene superfamily: evidence for a specific interaction between eosinophil-derived neurotoxin (EDN/RNase 2) and respiratory syncytial virus AN - 17158174; 4452437 AB - We have demonstrated that the human eosinophil-derived neurotoxin (EDN, RNase 2), a rapidly evolving secretory protein derived from eosinophilic leukocytes, mediates the ribonucleolytic destruction of extracellular virions of the single-stranded RNA virus respiratory syncytial virus (RSV). While RNase activity is crucial to antiviral activity, it is clearly not sufficient, as our results suggest that EDN has unique structural features apart from RNase activity that are necessary to promote antiviral activity. We demonstrate here that the interaction between EDN and extracellular virions of RSV is both saturatable and specific. Increasing concentrations of the antivirally inactivated, ribonucleolytically inactivated point mutant form of recombinant human EDN, rhEDNdK super(38), inhibits rhEDN's antiviral activity, while increasing concentrations of the related RNase, recombinant human RNase k6, have no effect whatsoever. Interestingly, acquisition of antiviral activity parallels the evolutionary development of the primate EDN lineage, having emerged some time after the divergence of the Old World from the New World monkeys. Using this information, we created ribonucleolytically active chimeras of human and New World monkey orthologs of EDN and, by evaluating their antiviral activity, we have identified an N-terminal segment of human EDN that contains one or more of the sequence elements that mediate its specific interaction with RSV. JF - Nucleic Acids Research AU - Domachowske, J B AU - Bonville, CA AU - Dyer, K D AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA, hr2k@nih.gov Y1 - 1998/12/01/ PY - 1998 DA - 1998 Dec 01 SP - 5327 EP - 5332 VL - 26 IS - 23 SN - 0305-1048, 0305-1048 KW - N-terminus KW - RNase 2 KW - eosinophil-derived neurotoxin KW - man KW - ribonuclease 2 KW - ribonuclease A KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - respiratory syncytial virus KW - RNA viruses KW - Leukocytes (eosinophilic) KW - Antiviral agents KW - Human respiratory syncytial virus KW - Respiratory syncytial virus KW - Neurotoxins KW - Evolution KW - N 14711:RNases KW - V 22100:Antiviral agents KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17158174?accountid=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=Nucleic+Acids+Research&rft.atitle=Evolution+of+antiviral+activity+in+the+ribonuclease+A+gene+superfamily%3A+evidence+for+a+specific+interaction+between+eosinophil-derived+neurotoxin+%28EDN%2FRNase+2%29+and+respiratory+syncytial+virus&rft.au=Domachowske%2C+J+B%3BBonville%2C+CA%3BDyer%2C+K+D%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-12-01&rft.volume=26&rft.issue=23&rft.spage=5327&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 - Human respiratory syncytial virus; Respiratory syncytial virus; respiratory syncytial virus; RNA viruses; Antiviral agents; Neurotoxins; Leukocytes (eosinophilic); Evolution ER - TY - JOUR T1 - Recombinant, Replication-Defective Adenovirus Gene Transfer Vectors Induce Cell Cycle Dysregulation and Inappropriate Expression of Cyclin Proteins AN - 17140608; 4443517 AB - First-generation adenovirus (Ad) vectors that had been rendered replication defective by removal of the E1 region of the viral genome ( Delta E1) or lacking the Ad E3 region in addition to E1 sequences ( Delta E1 Delta E3) induced G sub(2) cell cycle arrest and inhibited traverse across G sub(1)/S in primary and immortalized human bronchial epithelial cells. Cell cycle arrest was independent of the cDNA contained in the expression cassette and was associated with the inappropriate expression and increase in cyclin A, cyclin B1, cyclin D and cyclin-dependent kinase p34cdc2 protein levels. In some instances, infection with Delta E1 or Delta E1 Delta E3 Ad vectors produced aneuploid DNA histogram patterns and induced polyploidization as a result of successive rounds of cell division without mitosis. Cell cycle arrest was absent in cells infected with a second-generation Delta E1Ad vector in which all of the early region E4 except the sixth open reading frame was also deleted. Consequently, E4 viral gene products present in Delta E1 or Delta E1 Delta E3 Ad vectors induce G sub(2) growth arrest, which may pose new and unintended consequences for human gene transfer and gene therapy. JF - Journal of Virology AU - Wersto, R P AU - Rosenthal, E R AU - Seth, P K AU - Eissa, N T AU - Donahue, R E AD - Hematology Branch, NHLBI, Room 1B-05, 5 Research Court, Rockville, MD 20850 USA, werstor@gwgate.nhlbi.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 9491 EP - 9502 VL - 72 IS - 12 SN - 0022-538X, 0022-538X KW - Adenovirus KW - Immortalization KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Virology & AIDS Abstracts KW - Cell cycle KW - Expression vectors KW - Bronchus KW - Epithelium KW - Cloning vectors KW - Gene transfer KW - DNA KW - W3 33181:Gene therapy vectors KW - V 22050:Viral genetics including virus reactivation KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17140608?accountid=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=Recombinant%2C+Replication-Defective+Adenovirus+Gene+Transfer+Vectors+Induce+Cell+Cycle+Dysregulation+and+Inappropriate+Expression+of+Cyclin+Proteins&rft.au=Wersto%2C+R+P%3BRosenthal%2C+E+R%3BSeth%2C+P+K%3BEissa%2C+N+T%3BDonahue%2C+R+E&rft.aulast=Wersto&rft.aufirst=R&rft.date=1998-12-01&rft.volume=72&rft.issue=12&rft.spage=9491&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 - Adenovirus; Cloning vectors; Epithelium; Gene transfer; Bronchus; Cell cycle; Expression vectors; DNA; Immortalization ER - TY - JOUR T1 - Vaccine Protection against a Heterologous Non-Syncytium-Inducing, Primary Human Immunodeficiency Virus AN - 17140054; 4443556 AB - Vaccine-induced protection of chimpanzees against laboratory-adapted and syncytium-inducing, multiply passaged primary human immunodeficiency virus type 1 (HIV-1) isolates, but not against non-syncytium-inducing, minimally passaged ones, has been demonstrated. Following challenge with such an isolate HIV-1 sub(5016), we obtained complete protection in one of three chimpanzees previously protected against low- and high-dose HIV-1 sub(SF2) exposures after immunization with an adenovirus-HIV-1 sub(MN) gp160 priming-HIV-1 sub(SF2) gp120 boosting regimen. At challenge, the protected chimpanzee exhibited broad humoral immunity, including neutralizing antibody activity. These results demonstrate the potential of this combination vaccine strategy and suggest that vaccine protection against an HIV isolate relevant to infection of people is feasible. JF - Journal of Virology AU - Guroff, M R AU - Kaur, H AU - Patterson, L J AU - Leno, M AU - Conley, A J AU - McKenna, P M AU - Markham, P D AU - Richardson, E AU - Aldrich, K AU - Arora, K AU - Murty, L AU - Carter, L AU - Pazner, S Z AU - Sinangil, F AD - Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Building 37, Room 6B03, Bethesda, MD 20892-4255 USA, guroffm@dc37a.nci.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 10275 EP - 10280 VL - 72 IS - 12 SN - 0022-538X, 0022-538X KW - HIV-1 KW - Human immunodeficiency virus 1 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Syncytia KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06807:Active 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/17140054?accountid=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=Vaccine+Protection+against+a+Heterologous+Non-Syncytium-Inducing%2C+Primary+Human+Immunodeficiency+Virus&rft.au=Guroff%2C+M+R%3BKaur%2C+H%3BPatterson%2C+L+J%3BLeno%2C+M%3BConley%2C+A+J%3BMcKenna%2C+P+M%3BMarkham%2C+P+D%3BRichardson%2C+E%3BAldrich%2C+K%3BArora%2C+K%3BMurty%2C+L%3BCarter%2C+L%3BPazner%2C+S+Z%3BSinangil%2C+F&rft.aulast=Guroff&rft.aufirst=M&rft.date=1998-12-01&rft.volume=72&rft.issue=12&rft.spage=10275&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; Syncytia; Vaccines ER - TY - JOUR T1 - Actinomyces serovar WVA963 coaggregation-defective mutant strain PK2407 secretes lactose-sensitive adhesin that binds to coaggregation partner Streptococcus oralis 34 AN - 17140037; 4439358 AB - Actinomyces serovar WVA963 strain PK1259 mediates intergeneric coaggregation with several oral streptococci. These lactose-inhibitable coaggregations appear to involve a 95-kDa putative actinomyces adhesin in complex with type 2 fimbriae. A coaggregation-defective strain PK2407 lacking type 2 fimbriae synthesizes the putative adhesin but appears unable to present it properly on its surface. Antiserum was raised against surface sonicates of PK2407 and was absorbed with a different coaggregation-defective mutant PK3092 that synthesizes type 2 fimbriae but no adhesin. This absorbed antiserum specifically blocked lactose-inhibitable coaggregation of wild-type strain PK1259 and Streptococcus oralis 34 and identified a 95-kDa protein in ammonium sulfate precipitates of culture supernatant of the coaggregation-defective mutant PK2407. The 95-kDa secreted protein was bound to the streptococcal partner cells and to lactose-agarose affinity beads and was released by lactose from both the affinity beads and partner, indicating that the secreted and precipitated protein is biochemically active and may mediate coaggregation with streptococci. JF - Oral Microbiology and Immunology AU - Klier, C M AU - Roble, A G AU - Kolenbrander, P E AD - National Institute of Dental Research, National Institutes of Health, Building 30, Room 310, 30 Convent Drive MSC 4350, Bethesda, MD 20892-4350, USA Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 337 EP - 340 VL - 13 IS - 6 SN - 0902-0055, 0902-0055 KW - coaggregation KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Adhesins KW - Cell aggregation KW - Pili KW - Actinomyces KW - Mutants KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17140037?accountid=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=Oral+Microbiology+and+Immunology&rft.atitle=Actinomyces+serovar+WVA963+coaggregation-defective+mutant+strain+PK2407+secretes+lactose-sensitive+adhesin+that+binds+to+coaggregation+partner+Streptococcus+oralis+34&rft.au=Klier%2C+C+M%3BRoble%2C+A+G%3BKolenbrander%2C+P+E&rft.aulast=Klier&rft.aufirst=C&rft.date=1998-12-01&rft.volume=13&rft.issue=6&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Oral+Microbiology+and+Immunology&rft.issn=09020055&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 - Actinomyces; Streptococcus; Pili; Mutants; Adhesins; Cell aggregation ER - TY - JOUR T1 - Intranasal Immunization with Cytotoxic T-Lymphocyte Epitope Peptide and Mucosal Adjuvant Cholera Toxin: Selective Augmentation of Peptide-Presenting Dendritic Cells in Nasal Mucosa-Associated Lymphoid Tissue AN - 17138690; 4439452 AB - We previously reported that cholera toxin (CT) was required as a mucosal adjuvant for the induction of peptide-specific cytotoxic T lymphocytes (CTL) following intranasal immunization with CTL epitope peptides. The present study was performed to identify the site and the antigen-presenting cell (APC) population responsible for the presentation of intranasally administered CTL epitope peptide immunogens and to determine whether CT directly affects antigen presentation by these APCs. For these experiments, C57BL/6 mice were intranasally immunized with the ovalbumin H-2K super(b)-restricted CTL epitope SIINFEKL with or without CT. Cells were then isolated from the cervical lymph nodes (CLN) and the nasal mucosa-associated lymphoid tissue (NALT) and tested for the ability to stimulate the B3Z T-cell hybridoma, which recognizes SIINFEKL in association with H-2K super(b). Dendritic cell (DC)-enriched CLN cells from mice immunized with peptide and CT or peptide only could stimulate B3Z cells, while DC-depleted CLN cells from either group were unable to stimulate B3Z cells. NALT cells of mice immunized with peptide and CT, but not with peptide alone, were able to efficiently stimulate B3Z hybridomas. Depletion of N418-positive DC from these NALT cells resulted in significant reduction of B3Z activation. Our results indicate that DC are the APC responsible for the presentation of CTL epitope peptides following intranasal immunization and that CT augments the ability of dendritic cells in the NALT, but not in the draining CLN, to present CLT epitope peptides. This finding suggests that CT acts locally as a mucosal adjuvant and that NALT DC are the predominant APC involved with the induction of immunity after intranasal immunization with peptide immunogens and CT. JF - Infection and Immunity AU - Porgador, A AU - Staats, H F AU - Itoh, Y AU - Kelsall, B L AD - Immune Cell Interaction Unit, LCI, NIAID, NIH, 10/11N238, 10 Center Dr., Bethesda, MD 20892-1890, USA, Kelsall@nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 5876 EP - 5881 VL - 66 IS - 12 SN - 0019-9567, 0019-9567 KW - C57BL/6 mice KW - histocompatibility antigen H-2 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Adjuvants KW - Antigen presentation KW - Dendritic cells KW - Lymphocytes T KW - Cholera KW - Antigen-presenting cells KW - Mucosal immunity KW - Lymph nodes KW - Toxins KW - Lymphoid tissue KW - Nose KW - J 02834:Vaccination and immunization KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17138690?accountid=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=Intranasal+Immunization+with+Cytotoxic+T-Lymphocyte+Epitope+Peptide+and+Mucosal+Adjuvant+Cholera+Toxin%3A+Selective+Augmentation+of+Peptide-Presenting+Dendritic+Cells+in+Nasal+Mucosa-Associated+Lymphoid+Tissue&rft.au=Porgador%2C+A%3BStaats%2C+H+F%3BItoh%2C+Y%3BKelsall%2C+B+L&rft.aulast=Porgador&rft.aufirst=A&rft.date=1998-12-01&rft.volume=66&rft.issue=12&rft.spage=5876&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 - Mucosal immunity; Lymphoid tissue; Toxins; Adjuvants; Dendritic cells; Antigen presentation; Antigen-presenting cells; Lymph nodes; Cholera; Lymphocytes T; Nose ER - TY - JOUR T1 - Estimation of Group B Streptococcus Type III Polysaccharide-Specific Antibody Concentrations in Human Sera Is Antigen Dependent AN - 17137733; 4439429 AB - The presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toxoid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure less than or equal to 0.05 mu g of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS. JF - Infection and Immunity AU - Bhushan, R AU - Anthony, B F AU - Frasch, CE AD - Laboratory of Bacterial Polysaccharides, Division of Bacterial Products, Center for Biologics Evaluation and Research, 29 Lincoln Dr., Bethesda, MD 20892, USA, vaccine@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 5848 EP - 5853 VL - 66 IS - 12 SN - 0019-9567, 0019-9567 KW - Streptococcus agalactiae KW - biotin KW - human serum albumin KW - man KW - sialic acid KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Enzyme-linked immunosorbent assay KW - Antibody response KW - Serum KW - Immunoglobulin G KW - Vaccines KW - J 02831:Techniques and reagents KW - F 06801:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17137733?accountid=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=Estimation+of+Group+B+Streptococcus+Type+III+Polysaccharide-Specific+Antibody+Concentrations+in+Human+Sera+Is+Antigen+Dependent&rft.au=Bhushan%2C+R%3BAnthony%2C+B+F%3BFrasch%2C+CE&rft.aulast=Bhushan&rft.aufirst=R&rft.date=1998-12-01&rft.volume=66&rft.issue=12&rft.spage=5848&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 - Streptococcus agalactiae; Immunoglobulin G; Enzyme-linked immunosorbent assay; Vaccines; Antibody response; Serum ER - TY - JOUR T1 - Bulgarian emergency response models-validation against ETEX first release AN - 17135148; 4438962 AB - In the paper, the performance of two Bulgarian dispersion models is tested against European Tracer Experiment (ETEX) first release data base. The first one is the LED puff model which was the core of the Bulgarian Emergency Response System during all releases of ETEX. The second one is the newly created Eulerian dispersion model EMAP. These models have two important features: they are PC-oriented and they use quite a limited amount of input meteorological information. First, a number of runs with various source configurations are made on meteorological data produced by ECMWF. The aim of these runs is to verify the models' ability to simulate reliably ETEX first release. To this end, a set of statistical criteria selected in ATMES (Atmospheric Transport Models Evaluation Study, see Klug et al., 1992) are used. The best runs for both models are obtained when the source is presented as a column towering from the ground to heights of 400-700 m. These runs took part in the second phase of ETEX (ETEX-II), the so called ATMES-type exercise where EMAP ranked ninth and LED - fourteenth among 34 models. Here, additional sets of EMAP are presented where in the first run the value of the horizontal diffusion coefficient is varied and in the other runs different meteorological data sets are tested. The results obtained from the first run show that the values of K sub(h) = 4-6 x 10 super(4)m super(2)s super(-1) produce fields which fit experimental data best. The other sets of runs show that the higher the frequency of the meteorological data, the better the simulation. The results can be improved by linear interpolation of the meteorological parameters with time, the best fitting obtained with interpolation at each time step. JF - Atmospheric Environment AU - Syrakov, D AU - Prodanova, M AD - National Institute of Meteorology and Hydrology (NIMH), Sofia 1784, Bulgaria Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 4367 EP - 4375 VL - 32 IS - 24 SN - 1352-2310, 1352-2310 KW - Bulgaria KW - Pollution Abstracts KW - Air pollution KW - Mathematical models KW - Pollution dispersion KW - Meteorology KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17135148?accountid=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=Atmospheric+Environment&rft.atitle=Bulgarian+emergency+response+models-validation+against+ETEX+first+release&rft.au=Syrakov%2C+D%3BProdanova%2C+M&rft.aulast=Syrakov&rft.aufirst=D&rft.date=1998-12-01&rft.volume=32&rft.issue=24&rft.spage=4367&rft.isbn=&rft.btitle=&rft.title=Atmospheric+Environment&rft.issn=13522310&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: ETEX, A European Tracer Experiment. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pollution dispersion; Air pollution; Meteorology; Mathematical models ER - TY - JOUR T1 - Tick-borne relapsing fever in British Columbia, Canada: first isolation of Borrelia hermsii AN - 17134161; 4436540 AB - The spirochete that causes tick-borne relapsing fever, Borrelia hermsii, was isolated in pure culture during 1995 and 1996 from three acutely ill human patients infected in southern British Columbia, Canada. The geographic area of exposure is a known focus of this disease dating back to 1930 when the first case was recognized in a human. Analyses of plasmid DNA, protein profiles, and reactivity with a species-specific monoclonal antibody identified the new isolates of spirochetes as B. hermsii, all of which were most similar to an isolate of this spirochete from northern California described previously. These are the first reported isolates of B. hermsii from Canada. JF - Journal of Clinical Microbiology AU - Banerjee, S N AU - Banerjee, M AU - Fernando, K AU - Burgdorfer, W AU - Schwan, T G AD - Rocky Mountain Laboratories, 903 South 4th St., Hamilton, MT 59840, USA, tom_schwan@nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 3505 EP - 3508 VL - 36 IS - 12 SN - 0095-1137, 0095-1137 KW - Canada KW - Microbiology Abstracts B: Bacteriology KW - Culture KW - Etiology KW - Borrelia hermsii KW - Relapsing fever KW - Immunoreactivity KW - Protein composition KW - Taxonomy KW - Plasmids KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17134161?accountid=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=Tick-borne+relapsing+fever+in+British+Columbia%2C+Canada%3A+first+isolation+of+Borrelia+hermsii&rft.au=Banerjee%2C+S+N%3BBanerjee%2C+M%3BFernando%2C+K%3BBurgdorfer%2C+W%3BSchwan%2C+T+G&rft.aulast=Banerjee&rft.aufirst=S&rft.date=1998-12-01&rft.volume=36&rft.issue=12&rft.spage=3505&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 - Borrelia hermsii; Etiology; Plasmids; Culture; Taxonomy; Protein composition; Relapsing fever; Immunoreactivity ER - TY - JOUR T1 - Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes AN - 17133981; 4438858 AB - Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumors in rats (Wistar strain) but not in mice (NMRI strain). The protein metallothionein (MT) plays an important role in Cd detoxification, and it has been suggested that differential inducibility of pulmonary MT may lead to interspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been examined in rats or mice. We compared pulmonary MT expression in Wistar Furth (WF) rats with that in DBA and C57 mice, following a single 3-h exposure to CdO fumes containing 1 mg Cd/m super(3). Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/argon furnace gases. We observed differential intra- and interspecies inducibility of the MT gene in the lung following Cd inhalation. DBA mice exhibited greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein content, and number of MT positive cells relative to C57 mice. WF rats showed lower transcription and translation responses of the MT gene upon Cd stimuli than C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, predict greater susceptibility of C57 to the carcinogenic effects of inhaled Cd. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of this rat strain to develop malignant lung tumors after chronic exposure to Cd via inhalation. Parallel to our findings in mice, differences in the responsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rats or mice to lung carcinogenesis induced by inhalation of Cd compounds. JF - Toxicology and Applied Pharmacology AU - Mckenna, I M AU - Gordon, T AU - Chen, L C AU - Anver, M R AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, 21702, Maryland, mckenna.ilda@epa.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 169 EP - 178 PB - Academic Press VL - 153 IS - 2 SN - 0041-008X, 0041-008X KW - cadmium oxide KW - chronic exposure KW - metallothionein KW - mice KW - rats KW - Toxicology Abstracts; Pollution Abstracts KW - Inhalation KW - Metallothionein KW - Rats KW - Genetics KW - Carcinogenicity KW - Cadmium KW - Fumes KW - Mice KW - Cadmium compounds KW - Lung KW - Carcinogenesis KW - Proteins KW - Toxicity testing KW - X 24162:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17133981?accountid=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=Expression+of+metallothionein+protein+in+the+lungs+of+Wistar+rats+and+C57+and+DBA+mice+exposed+to+cadmium+oxide+fumes&rft.au=Mckenna%2C+I+M%3BGordon%2C+T%3BChen%2C+L+C%3BAnver%2C+M+R%3BWaalkes%2C+M+P&rft.aulast=Mckenna&rft.aufirst=I&rft.date=1998-12-01&rft.volume=153&rft.issue=2&rft.spage=169&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 - Carcinogenicity; Carcinogenesis; Proteins; Cadmium compounds; Rats; Inhalation; Cadmium; Toxicity testing; Mice; Fumes; Lung; Genetics; Metallothionein ER - TY - JOUR T1 - Recombinant Fv immunotoxins and Fv fragments as novel agents for cancer therapy and diagnosis AN - 17126135; 4433142 AB - Recombinant immunotoxins are new agents being developed for cancer therapy. They are composed of Fv fragments of antibodies that bind to cancer cells fused to a truncated form of a very potent bacterial toxin. The antibody moiety directs the toxin to cancer cells, which are killed, while normal cells are not recognized and thus survive. The excellent preclinical results in vitro and in vivo have led to the initiation of several clinical trials. JF - Trends in Biotechnology AU - Reiter, Y AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, 37 Convent Drive, Bethesda, MD 20892-4255, USA, pasta@helix.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 513 EP - 520 VL - 16 IS - 12 SN - 0167-7799, 0167-7799 KW - Fv KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Bacteria KW - Immunotherapy KW - Immunotoxins KW - Toxins KW - Carcinoma KW - Antibodies KW - Reviews KW - W3 33375:Antibodies 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/17126135?accountid=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=Trends+in+Biotechnology&rft.atitle=Recombinant+Fv+immunotoxins+and+Fv+fragments+as+novel+agents+for+cancer+therapy+and+diagnosis&rft.au=Reiter%2C+Y%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1998-12-01&rft.volume=16&rft.issue=12&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&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; Toxins; Reviews; Antibodies; Immunotoxins; Immunotherapy; Bacteria ER - TY - JOUR T1 - Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin AN - 17120540; 4427228 AB - The biophysical properties of T-type voltage-gated calcium channels are well suited to pacemaking and to supporting calcium flux near the resting membrane potential in both excitable and non-excitable cells. We have identified a new scorpion toxin (kurtoxin) that binds to the alpha sub(1G) T-type calcium channel with high affinity and inhibits the channel by modifying voltage-dependent gating. This toxin distinguishes between alpha sub(1G) T-type calcium channels and other types of voltage-gated calcium channels, including alpha sub(1A), alpha sub(1B), alpha sub(1C) and alpha sub(1E). Like the other alpha -scorpion toxins to which it is related, kurtoxin also interacts with voltage-gated sodium channels and slows their inactivation. Kurtoxin will facilitate characterization of the subunit composition of T-type calcium channels and help determine their involvement in electrical and biochemical signaiing. JF - Nature Neuroscience AU - Chuang, RS-I AU - Jaffe, H AU - Cribbs, L AU - Perez-Reyes, E AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, NINDS, NIH, Bldg. 36, Rm. 2C19, 36 Convent Drivex, MSC 4066, Bethesda, Maryland 20892, USA, kjswartz@codon.nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 668 EP - 674 VL - 1 IS - 8 SN - 1097-6256, 1097-6256 KW - Scorpiones KW - Scorpionidae KW - Scorpions KW - kurtoxin KW - Toxicology Abstracts; Calcium & Calcified Tissue Abstracts; Entomology Abstracts; CSA Neurosciences Abstracts KW - Toxins KW - Calcium channels (T-type) KW - Venom KW - Membrane potential KW - N3 11102:Invertebrates KW - Z 05173:Biochemistry & metabolism (incl. fat body) KW - X 24173:Animals KW - T 20019:Cellular calcium, channels and currents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17120540?accountid=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=Nature+Neuroscience&rft.atitle=Inhibition+of+T-type+voltage-gated+calcium+channels+by+a+new+scorpion+toxin&rft.au=Chuang%2C+RS-I%3BJaffe%2C+H%3BCribbs%2C+L%3BPerez-Reyes%2C+E%3BSwartz%2C+K+J&rft.aulast=Chuang&rft.aufirst=RS-I&rft.date=1998-12-01&rft.volume=1&rft.issue=8&rft.spage=668&rft.isbn=&rft.btitle=&rft.title=Nature+Neuroscience&rft.issn=10976256&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 - Scorpiones; Membrane potential; Toxins; Venom; Calcium channels (T-type) ER - TY - JOUR T1 - Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection AN - 17118348; 4424901 AB - The humoral immunity induced by many viral and bacterial vaccines mediates protection that is maintained over a long period of time. In contrast, for other intracellular infections (such as with Leishmania major or Mycobacterium tuberculosis) for which cell-mediated immunity is required for protection, the mechanisms for developing durable responses after vaccination have not been well defined. Here we demonstrate that vaccination with plasmid DNA encoding a specific leishmanial antigen is more effective than leishmanial protein plus recombinant IL-12 in eliciting long-term immunity capable of controlling L. major infection. We also show that leishmanial protein plus IL-12 DNA produces an immunity that lasts much longer than does immunity elicited by leishmanial protein plus IL-12 protein, indicating that the persistence of IL-12 may be the essential determinant in maintaining durable cell-mediated immune responses for an intracellular parasitic infection. JF - Nature Medicine AU - Gurunathan, S AU - Prussin, C AU - Sacks, D L AU - Seder, R A AD - National Institutes of Health, Bethesda, MD 20892, USA, rseder@nih.gov Y1 - 1998/12// PY - 1998 DA - Dec 1998 SP - 1409 EP - 1415 VL - 4 IS - 12 SN - 1078-8956, 1078-8956 KW - DNA vaccines KW - Leishmania major KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Plasmids KW - Interleukin 12 KW - Immune response (cell-mediated) KW - Vaccines KW - K 03086:Immunology & vaccination 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/17118348?accountid=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=Vaccine+requirements+for+sustained+cellular+immunity+to+an+intracellular+parasitic+infection&rft.au=Gurunathan%2C+S%3BPrussin%2C+C%3BSacks%2C+D+L%3BSeder%2C+R+A&rft.aulast=Gurunathan&rft.aufirst=S&rft.date=1998-12-01&rft.volume=4&rft.issue=12&rft.spage=1409&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 - Leishmania major; Plasmids; Immune response (cell-mediated); Interleukin 12; Vaccines ER - TY - JOUR T1 - Probing cellular protein targets of H2O2 with fluorescein-conjugated iodoacetamide and antibodies to fluorescein. AN - 69095522; 9862437 AB - Recent studies suggest that H2O2, at subtoxic concentrations generated in response to the activation of a variety of cell surface receptors, functions as an intracellular messenger. However, the intracellular targets of H2O2 action have not been identified. A procedure to detect proteins with reactive cysteine residues susceptible to oxidation by intracellularly generated H2O2 is now described. This approach is based on the labeling of proteinaceous cysteine with 5-iodoacetamidofluorescein at pH 5.5 and immunoblot analysis of the labeled proteins with antibodies specific to fluorescein. With this procedure, many proteins in human A431 cells were shown to contain reactive cysteines and to be readily oxidized by H2O2 generated in response to cellular stimulation with epidermal growth factor. One of these H2O2-sensitive proteins was identified as protein tyrosine phosphatase 1B. JF - FEBS letters AU - Wu, Y AU - Kwon, K S AU - Rhee, S G AD - Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/11/27/ PY - 1998 DA - 1998 Nov 27 SP - 111 EP - 115 VL - 440 IS - 1-2 SN - 0014-5793, 0014-5793 KW - Antibodies KW - 0 KW - Catecholamines KW - Fluoresceins KW - Imidazolines KW - Oxidants KW - Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Epidermal Growth Factor KW - 62229-50-9 KW - 5-iodoacetamidofluorescein KW - 63368-54-7 KW - Hydrogen Peroxide KW - BBX060AN9V KW - (3,4-dihydroxyphenylamino)-2-imidazoline KW - DEA5VW1N6R KW - Protein Tyrosine Phosphatases KW - EC 3.1.3.48 KW - Papain KW - EC 3.4.22.2 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Catecholamines -- pharmacology KW - Humans KW - Hydrogen-Ion Concentration KW - Phosphotyrosine -- metabolism KW - Epidermal Growth Factor -- pharmacology KW - Precipitin Tests KW - Molecular Weight KW - Phosphorylation -- drug effects KW - Oxidation-Reduction KW - Blotting, Western KW - Tumor Cells, Cultured KW - Papain -- metabolism KW - Substrate Specificity KW - Cysteine -- metabolism KW - Oxidants -- pharmacology KW - Protein Tyrosine Phosphatases -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Hydrogen Peroxide -- antagonists & inhibitors KW - Proteins -- metabolism KW - Proteins -- chemistry KW - Oxidants -- antagonists & inhibitors KW - Oxidants -- metabolism KW - Protein Tyrosine Phosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69095522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Probing+cellular+protein+targets+of+H2O2+with+fluorescein-conjugated+iodoacetamide+and+antibodies+to+fluorescein.&rft.au=Wu%2C+Y%3BKwon%2C+K+S%3BRhee%2C+S+G&rft.aulast=Wu&rft.aufirst=Y&rft.date=1998-11-27&rft.volume=440&rft.issue=1-2&rft.spage=111&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 - 1999-01-11 N1 - Date created - 1999-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signaling requirements for oncogenic forms of the Met tyrosine kinase receptor. AN - 70091480; 9840933 AB - The Met tyrosine kinase receptor has been implicated in human cancer. Here we have examined the signaling requirements of three oncogenic forms of this molecule: wild type Met in response to ligand/autocrine stimulation, Met which has been mutationally activated, and Tpr-Met (a constitutively active truncated Met fusion protein). Previous studies have demonstrated the importance of a Grb2 binding site, and of specific tyrosine residues (i.e. Y8,9 and Y14,15) for Met function, and we have now explored the relevance of these and other sites for oncogenic Met signaling. Following substitution of various intracellular tyrosines for phenylalanine, we find that the transforming activity of each Met oncogene is dependent upon tyrosines Y8,9 and Y14,15, in addition to two novel tyrosines (Y6 and Y10) not previously implicated in Met signaling. Tyrosines Y6 and Y10 influence a variety of Met-mediated responses both in vitro (transformation, mitogenicity and invasion), and in vivo (tumorigenicity and metastasis). We also show that Tpr-Met is much more dependent on its Grb2 binding site for biological activity than are the other oncogenic forms of the Met receptor. Thus, although the three Met oncogenes examined are similar in their dependency on a number of specific tyrosines for activity, the signaling strategy employed by Tpr-Met can be differentiated from that of the other two. JF - Oncogene AU - Jeffers, M AU - Koochekpour, S AU - Fiscella, M AU - Sathyanarayana, B K AU - Vande Woude, G F AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/11/26/ PY - 1998 DA - 1998 Nov 26 SP - 2691 EP - 2700 VL - 17 IS - 21 SN - 0950-9232, 0950-9232 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Proteins KW - Recombinant Fusion Proteins KW - Tyrosine KW - 42HK56048U KW - Phenylalanine KW - 47E5O17Y3R KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Models, Molecular KW - Mice KW - Mice, Nude KW - Proteins -- metabolism KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- physiology KW - Binding Sites KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Phenylalanine -- chemistry KW - Neoplasm Metastasis KW - Point Mutation KW - Female KW - Sequence Deletion KW - Proto-Oncogene Proteins c-met -- genetics KW - Proto-Oncogene Proteins c-met -- chemistry KW - Oncogenes KW - Proto-Oncogene Proteins c-met -- physiology KW - Signal Transduction KW - Cell Transformation, Neoplastic -- genetics KW - Amino Acid Substitution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70091480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Signaling+requirements+for+oncogenic+forms+of+the+Met+tyrosine+kinase+receptor.&rft.au=Jeffers%2C+M%3BKoochekpour%2C+S%3BFiscella%2C+M%3BSathyanarayana%2C+B+K%3BVande+Woude%2C+G+F&rft.aulast=Jeffers&rft.aufirst=M&rft.date=1998-11-26&rft.volume=17&rft.issue=21&rft.spage=2691&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-22 N1 - Date created - 1998-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GalR-mediated repression and activation of hybrid lacUV5 promoter: differential contacts with RNA polymerase AN - 17137987; 4440345 AB - The GalR repressor regulates expression of genes of the gal regulon in Escherichia coli. We studied the regulatory effect of GalR in vitro on a heterologous promoter, lacUV5, by placing the GalR-binding site, O sub(E), at different locations upstream of this promoter. Despite the fact that the lacUV5 promoter is transcribed efficiently by RNA polymerase (RNP) alone, GalR modulated transcription from many of the PlacUV5 variants. Depending on the location of O sub(E) and the neighboring DNA sequence, GalR repressed, activated or had no effect on the promoter. Both repression and activation involved formation of GalR-RNP-DNA ternary complexes and required an intact c-domain of the alpha subunit of the holoenzyme. These results support the differential contact model of a regulator action, in which a regulator differentially binds to, and lowers the energy of, intermediates of transcription initiation either to hinder or to facilitate a step of initiation. The nature of the contacts depends upon the context, i.e. the geometry of the ternary complex. The observed repression and activation effect of GalR on a heterologous promoter also underscores the point that a regulator is not a dedicated protein for repression or for activation. JF - Gene AU - Ryu, S AU - Fujita, N AU - Ishihama, A AU - Adhya, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bldg. 37/2E16, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/11/26/ PY - 1998 DA - 1998 Nov 26 SP - 235 EP - 245 PB - Elsevier Science B.V. VL - 223 IS - 1-2 SN - 0378-1119, 0378-1119 KW - GalR protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Promoters KW - DNA-directed RNA polymerase KW - Gene regulation KW - Escherichia coli KW - Transcription KW - J 02726:RNA and ribosomes KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17137987?accountid=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=Gene&rft.atitle=GalR-mediated+repression+and+activation+of+hybrid+lacUV5+promoter%3A+differential+contacts+with+RNA+polymerase&rft.au=Ryu%2C+S%3BFujita%2C+N%3BIshihama%2C+A%3BAdhya%2C+S&rft.aulast=Ryu&rft.aufirst=S&rft.date=1998-11-26&rft.volume=223&rft.issue=1-2&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&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; Promoters; Gene regulation; Transcription ER - TY - JOUR T1 - A new system to place single copies of genes, sites and lacZ fusions on the Escherichia coli chromosome AN - 17137874; 4440328 AB - To place a single-copy lacZ fusion on the E. coli chromosome, a method was developed based on in vivo homologous DNA recombination through P1 transduction. The fusions, initially constructed on plasmids, are crossed to lambda lacZ fusion vectors which are then lysogenized at the chromosomal lambda att site. The features of the new system are: (1) lambda lysogens carrying the fusion are made without regard for copy number; (2) P1 transduction from the lysogenic strain into an appropriate recipient generates the single-copy fusion; (3) The lacZ fusion has no prophage associated with it; (4) the lacZ fusion can be transferred by P1 transduction to other strains, simply by selecting for an antibiotic marker; (5) the system can be widely applied to construct single copies of any gene or site placed between bla and lacZ on the standard lacZ fusion plasmid vectors; and (6) the single-copy construct flanked by prophage att sites can be excised by site-specific recombination to generate non-replicating circular DNA of the clone or a cell cured of the construct. JF - Gene AU - Yu, D AU - Court, D L AD - Molecular Control and Genetics Section, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center Frederick, MD 21702-1201 USA Y1 - 1998/11/26/ PY - 1998 DA - 1998 Nov 26 SP - 77 EP - 81 PB - Elsevier Science B.V. VL - 223 IS - 1-2 SN - 0378-1119, 0378-1119 KW - chromosome 1 KW - lacZ gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Escherichia coli KW - Phage P1 KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17137874?accountid=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=Gene&rft.atitle=A+new+system+to+place+single+copies+of+genes%2C+sites+and+lacZ+fusions+on+the+Escherichia+coli+chromosome&rft.au=Yu%2C+D%3BCourt%2C+D+L&rft.aulast=Yu&rft.aufirst=D&rft.date=1998-11-26&rft.volume=223&rft.issue=1-2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&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; Phage P1 ER - TY - JOUR T1 - Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress. AN - 70082421; 9826655 AB - The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2'-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain. Substitution of methionine with methionine sulfoxide in a medium lacking hydrogen peroxide had little effect on the growth pattern, which suggests that the oxidation of free methionine in the growth medium was not the main cause of growth inhibition of the msrA mutant. Ultraviolet A radiation did not result in obvious differences in survival rates among the three strains. An enhanced resistance to hydrogen peroxide treatment was shown in human T lymphocyte cells (Molt-4) that were stably transfected with the bovine msrA and exposed to hydrogen peroxide. The survival rate of the transfected strain was much better than its parent strain when grown in the presence of hydrogen peroxide. These results support the proposition that the msrA gene is involved in the resistance of yeast and mammalian cells to oxidative stress. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Moskovitz, J AU - Flescher, E AU - Berlett, B S AU - Azare, J AU - Poston, J M AU - Stadtman, E R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20982-0342, USA. jmosko@helix.nih.gov Y1 - 1998/11/24/ PY - 1998 DA - 1998 Nov 24 SP - 14071 EP - 14075 VL - 95 IS - 24 SN - 0027-8424, 0027-8424 KW - Amidines KW - 0 KW - Oxidants KW - Recombinant Proteins KW - 2,2'-azobis(2-amidinopropane) KW - 7381JDR72F 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 - Paraquat KW - PLG39H7695 KW - Index Medicus KW - Paraquat -- pharmacology KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Oxidants -- pharmacology KW - Humans KW - Hydrogen Peroxide -- pharmacology KW - Cloning, Molecular KW - Amidines -- pharmacology KW - Polymerase Chain Reaction KW - Cattle KW - Transfection KW - Recombinant Proteins -- metabolism KW - Escherichia coli KW - Cell Line KW - T-Lymphocytes KW - Oxidative Stress -- physiology KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Saccharomyces cerevisiae -- growth & development KW - Saccharomyces cerevisiae -- enzymology KW - Saccharomyces cerevisiae -- drug effects KW - Oxidoreductases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70082421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overexpression+of+peptide-methionine+sulfoxide+reductase+in+Saccharomyces+cerevisiae+and+human+T+cells+provides+them+with+high+resistance+to+oxidative+stress.&rft.au=Moskovitz%2C+J%3BFlescher%2C+E%3BBerlett%2C+B+S%3BAzare%2C+J%3BPoston%2C+J+M%3BStadtman%2C+E+R&rft.aulast=Moskovitz&rft.aufirst=J&rft.date=1998-11-24&rft.volume=95&rft.issue=24&rft.spage=14071&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 - 1998-12-28 N1 - Date created - 1998-12-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1982 May 15;122(2):291-4 [7114447] Clin Exp Immunol. 1998 May;112(2):242-7 [9649186] Arch Biochem Biophys. 1983 May;223(1):271-81 [6859861] Proc Natl Acad Sci U S A. 1983 Dec;80(23):7160-4 [6580633] Methods Enzymol. 1984;107:352-60 [6390092] J Leukoc Biol. 1988 Apr;43(4):365-79 [2450941] J Immunol. 1989 Feb 1;142(3):907-12 [2783603] J Biol Chem. 1992 Aug 5;267(22):15549-51 [1386361] J Biol Chem. 1994 Feb 11;269(6):4683-91 [7508448] J Immunol. 1994 Dec 1;153(11):4880-9 [7963551] J Bacteriol. 1995 Feb;177(3):502-7 [7836279] Free Radic Biol Med. 1995 Jan;18(1):93-105 [7896176] Biochemistry. 1996 Feb 27;35(8):2767-87 [8611584] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3205-8 [8622914] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2095-9 [8700890] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7985-90 [8755589] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15036-40 [8986759] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9585-9 [9275166] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9932-7 [9275229] Cell Mol Life Sci. 1997 Dec;53(11-12):864-70 [9447238] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mutationally activated Met receptor mediates motility and metastasis. AN - 70075809; 9826715 AB - Mutations in Met have been identified in human papillary renal carcinomas. We have shown previously that these mutations deregulate the enzymatic activity of Met and that NIH 3T3 cells expressing mutationally activated Met are transformed in vitro and are tumorigenic in vivo. In the present investigation, we find that mutant Met induces the motility of Madin-Darby canine kidney cells in vitro and experimental metastasis of NIH 3T3 cells in vivo, and that the Ras-Raf-MEK-ERK signaling pathway, which has been implicated previously in cellular motility and metastasis, is constitutively activated by the Met mutants. We also report that transgenic mice harboring mutationally activated Met develop metastatic mammary carcinoma. These data confirm the tumorigenic activity of mutant Met molecules and demonstrate their ability to induce the metastatic phenotype. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Jeffers, M AU - Fiscella, M AU - Webb, C P AU - Anver, M AU - Koochekpour, S AU - Vande Woude, G F AD - Advanced BioScience Laboratories-Basic Research Program, Division of Basic Sciences, Frederick Cancer Research and Development Center, National Cancer Institute, P.O. Box B, Frederick, MD 21702, USA. Y1 - 1998/11/24/ PY - 1998 DA - 1998 Nov 24 SP - 14417 EP - 14422 VL - 95 IS - 24 SN - 0027-8424, 0027-8424 KW - Recombinant Fusion Proteins KW - 0 KW - Metallothionein KW - 9038-94-2 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - 3T3 Cells KW - Animals KW - Metallothionein -- biosynthesis KW - Humans KW - Metallothionein -- genetics KW - Mice KW - Mice, Transgenic KW - Mutagenesis, Site-Directed KW - Transfection KW - Cell Movement -- physiology KW - Point Mutation KW - Neoplasm Metastasis KW - Mice, Inbred C57BL KW - Dogs KW - Kidney KW - Mice, Inbred C3H KW - Cell Line KW - Female KW - Proto-Oncogene Proteins c-met -- biosynthesis KW - Proto-Oncogene Proteins c-met -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70075809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mutationally+activated+Met+receptor+mediates+motility+and+metastasis.&rft.au=Jeffers%2C+M%3BFiscella%2C+M%3BWebb%2C+C+P%3BAnver%2C+M%3BKoochekpour%2C+S%3BVande+Woude%2C+G+F&rft.aulast=Jeffers&rft.aufirst=M&rft.date=1998-11-24&rft.volume=95&rft.issue=24&rft.spage=14417&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 - 1998-12-28 N1 - Date created - 1998-12-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11445-50 [9326629] EMBO J. 1997 May 15;16(10):2634-45 [9184210] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8773-8 [9671754] Adv Cancer Res. 1998;75:163-201 [9709810] Cell. 1977 May;11(1):223-32 [194704] J Mol Appl Genet. 1982;1(4):327-41 [6286831] Am J Surg Pathol. 1982 Oct;6(7):655-63 [7180965] Cancer Metastasis Rev. 1983;2(2):183-200 [6352014] Nature. 1984 Sep 6-11;311(5981):29-33 [6590967] Nature. 1986 Feb 27-Mar 5;319(6056):743-8 [2869410] Nature. 1987 May 21-27;327(6119):239-42 [2952888] Acta Cytol. 1987 May-Jun;31(3):325-9 [3473868] Science. 1987 Oct 9;238(4824):202-5 [3659911] Science. 1991 Feb 15;251(4995):802-4 [1846706] Cell Growth Differ. 1990 Feb;1(2):87-95 [2085463] Cell. 1991 Jul 12;66(1):173-83 [1649007] EMBO J. 1991 Oct;10(10):2867-78 [1655405] Mol Cell Biol. 1992 Nov;12(11):5152-8 [1406687] Oncogene. 1992 Nov;7(11):2195-206 [1331934] J Cell Biol. 1993 Apr;121(1):145-54 [8384622] Mol Cell Biol. 1993 Sep;13(9):5266-75 [8355681] J Cell Biol. 1993 Oct;123(1):223-35 [8408200] Mol Cell Biol. 1993 Nov;13(11):6711-22 [8413267] Biochim Biophys Acta. 1993 Dec 23;1155(3):357-71 [8268192] Annu Rev Cell Biol. 1993;9:541-73 [8280471] Cancer Res. 1994 Apr 1;54(7):1630-3 [8137271] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4731-5 [8197126] Nature. 1995 Feb 23;373(6516):699-702 [7854452] Nature. 1995 Feb 23;373(6516):702-5 [7854453] Nature. 1995 Aug 31;376(6543):768-71 [7651534] Am J Pathol. 1996 Jan;148(1):225-32 [8546209] Mol Cell Biol. 1996 Mar;16(3):1115-25 [8622656] J Clin Invest. 1996 Jun 15;97(12):2872-7 [8675700] Oncogene. 1996 Aug 15;13(4):853-6 [8761307] J Mol Med (Berl). 1996 Sep;74(9):505-13 [8892055] Cancer Res. 1996 Dec 1;56(23):5369-74 [8968087] Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):701-6 [9012848] Cell. 1997 Feb 7;88(3):333-46 [9039260] J Cell Biol. 1997 Apr 21;137(2):481-92 [9128257] Nat Genet. 1997 May;16(1):68-73 [9140397] Toxicol Pathol. 1998 May-Jun;26(3):428-41 [9608650] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly. AN - 70064140; 9826658 AB - The bovine papillomavirus type 1 (BPV-1) exonic splicing suppressor (ESS) is juxtaposed immediately downstream of BPV-1 splicing enhancer 1 and negatively modulates selection of a suboptimal 3' splice site at nucleotide 3225. The present study demonstrates that this pyrimidine-rich ESS inhibits utilization of upstream 3' splice sites by blocking early steps in spliceosome assembly. Analysis of the proteins that bind to the ESS showed that the U-rich 5' region binds U2AF65 and polypyrimidine tract binding protein, the C-rich central part binds 35- and 54-55-kDa serine/arginine-rich (SR) proteins, and the AG-rich 3' end binds alternative splicing factor/splicing factor 2. Mutational and functional studies indicated that the most critical region of the ESS maps to the central C-rich core (GGCUCCCCC). This core sequence, along with additional nonspecific downstream nucleotides, is sufficient for partial suppression of spliceosome assembly and splicing of BPV-1 pre-mRNAs. The inhibition of splicing by the ESS can be partially relieved by excess purified HeLa SR proteins, suggesting that the ESS suppresses pre-mRNA splicing by interfering with normal bridging and recruitment activities of SR proteins. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Zheng, Z M AU - Huynen, M AU - Baker, C C AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 41, Room D305, Bethesda, MD 20892-5055, USA. zheng@dce41.nci.nih.gov Y1 - 1998/11/24/ PY - 1998 DA - 1998 Nov 24 SP - 14088 EP - 14093 VL - 95 IS - 24 SN - 0027-8424, 0027-8424 KW - Nuclear Proteins KW - 0 KW - RNA Precursors KW - RNA, Viral KW - RNA-Binding Proteins KW - Serine-Arginine Splicing Factors KW - 170974-22-8 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - HIV-1 -- genetics KW - HeLa Cells KW - Humans KW - Transcription, Genetic KW - Nucleic Acid Conformation KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Cattle KW - Spliceosomes -- metabolism KW - Enhancer Elements, Genetic KW - RNA, Viral -- chemistry KW - Molecular Sequence Data KW - Spliceosomes -- genetics KW - RNA Precursors -- chemistry KW - Templates, Genetic KW - RNA, Viral -- genetics KW - Nuclear Proteins -- metabolism KW - RNA Precursors -- genetics KW - Sequence Deletion KW - Bovine papillomavirus 1 -- metabolism KW - Exons KW - Alternative Splicing KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70064140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pyrimidine-rich+exonic+splicing+suppressor+binds+multiple+RNA+splicing+factors+and+inhibits+spliceosome+assembly.&rft.au=Zheng%2C+Z+M%3BHuynen%2C+M%3BBaker%2C+C+C&rft.aulast=Zheng&rft.aufirst=Z&rft.date=1998-11-24&rft.volume=95&rft.issue=24&rft.spage=14088&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 - 1998-12-28 N1 - Date created - 1998-12-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1987 Nov 11;15(21):8783-98 [3684574] Cell. 1986 Sep 12;46(6):845-55 [2944598] Cell. 1990 Jul 13;62(1):25-34 [2163768] Cell. 1990 Jul 13;62(1):35-42 [2364434] Genes Dev. 1991 Jul;5(7):1237-51 [1906036] Cell. 1991 Jul 26;66(2):373-82 [1855257] Cell. 1991 Jul 26;66(2):383-94 [1830244] Genes Dev. 1992 May;6(5):837-47 [1577277] Nucleic Acids Res. 1992 Jul 25;20(14):3671-8 [1641332] Mol Cell Biol. 1992 Oct;12(10):4279-87 [1383687] Genes Dev. 1993 Mar;7(3):407-18 [8449402] Mol Cell Biol. 1993 Jun;13(6):3660-74 [8388541] Mol Cell Biol. 1993 Oct;13(10):5999-6011 [8413203] Genes Dev. 1993 Dec;7(12A):2405-17 [8253386] Genes Dev. 1993 Dec;7(12B):2598-608 [8276242] Mol Cell Biol. 1994 Feb;14(2):1347-54 [8289812] J Biol Chem. 1994 Mar 4;269(9):6431-6 [8119993] Nucleic Acids Res. 1994 Mar 25;22(6):1018-22 [8152907] Mol Cell Biol. 1994 Jun;14(6):3960-70 [8196635] Cell. 1994 Jun 17;77(6):805-15 [7516265] Mol Cell Biol. 1994 Nov;14(11):7670-82 [7935481] Genes Dev. 1995 Feb 1;9(3):284-93 [7867927] Gene. 1995 Mar 10;154(2):187-92 [7890163] J Cell Biol. 1995 May;129(4):899-908 [7538140] Science. 1995 May 26;268(5214):1173-6 [7761834] Eur J Biochem. 1995 Jun 1;230(2):447-53 [7607214] Mol Cell Biol. 1995 Aug;15(8):4597-605 [7623851] Mol Cell Biol. 1995 Aug;15(8):4606-15 [7623852] EMBO J. 1995 Jul 17;14(14):3540-51 [7543047] Mol Cell Biol. 1995 Sep;15(9):4825-34 [7651400] RNA. 1995 May;1(3):335-46 [7489505] Mol Cell Biol. 1996 May;16(5):2325-31 [8628299] Genes Dev. 1996 Jun 1;10(11):1356-68 [8647433] Nucleic Acids Res. 1996 Jun 1;24(11):2017-21 [8668531] J Virol. 1996 Jul;70(7):4691-9 [8676495] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7582-7 [8755518] Science. 1996 Sep 20;273(5282):1706-9 [8781232] Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):163-8 [8990179] Mol Cell Biol. 1997 Apr;17(4):2143-50 [9121463] RNA. 1997 Jul;3(7):764-78 [9214659] RNA. 1997 Sep;3(9):996-1015 [9292499] J Virol. 1997 Nov;71(11):8542-51 [9343212] J Virol. 1997 Dec;71(12):9096-107 [9371566] J Biol Chem. 1997 Dec 26;272(52):33394-401 [9407134] Genes Dev. 1998 Jul 15;12(14):2222-33 [9679066] Mol Cell Biol. 1995 Sep;15(9):4898-907 [7651409] RNA. 1995 May;1(3):234-45 [7489496] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9243-7 [2531895] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Distinct structural requirements for the direct and indirect actions of the anaesthetic etomidate at GABA sub(A) receptors AN - 17264319; 4557543 AB - 1. The intravenous anaesthetic etomidate augments GABA-gated chloride currents (indirect action) and, at higher concentrations, evokes chloride currents in the absence of GABA (direct action). 2. In order to identify amino acid residues essential for these actions, site directed mutagenesis was performed on the beta 3 subunit. 3. Mutation of an asparagine to a serine residue at position 290 dramatically reduced both etomidate-induced chloride currents and its ability to enhance [ super(3)H]flunitrazepam binding in HEK293 cells expressing alpha 1 beta 3 gamma 2 recombinant GABA sub(A) receptors. 4. In contrast, the indirect effect of etomidate was retained, though its potency was reduced. 5. These findings indicate that there are distinct requirements for these dual actions of etomidate at GABA sub(A) receptors. JF - Toxicology Letters AU - Moody, E J AU - Knauer, C S AU - Granja, R AU - Strakhovaua, M AU - Skolnick, P Y1 - 1998/11/23/ PY - 1998 DA - 1998 Nov 23 SP - 209 EP - 215 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 100-101 IS - 1-3 KW - gamma -Aminobutyric acid A receptors KW - etomidate KW - Toxicology Abstracts KW - Site-directed mutagenesis KW - Chloride channels KW - Anesthetics KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17264319?accountid=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+Letters&rft.atitle=Distinct+structural+requirements+for+the+direct+and+indirect+actions+of+the+anaesthetic+etomidate+at+GABA+sub%28A%29+receptors&rft.au=Moody%2C+E+J%3BKnauer%2C+C+S%3BGranja%2C+R%3BStrakhovaua%2C+M%3BSkolnick%2C+P&rft.aulast=Moody&rft.aufirst=E&rft.date=1998-11-23&rft.volume=100-101&rft.issue=1-3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - Transforming growth factor-beta inhibits apoptosis induced by beta-amyloid peptide fragment 25-35 in cultured neuronal cells. AN - 70069544; 9813276 AB - Previously, we demonstrated that transforming growth factor-beta (TGF-beta) pretreatment protects neuroblastoma cell lines, human hNT neurons, and primary rat embryo hippocampal neurons (REHIPs) from degeneration caused by incubation with beta-amyloid peptide (Abeta). Here we present evidence suggesting that TGF-beta interferes with an apoptotic pathway induced by Abeta. TGF-beta preteatment decreases the amount of DNA laddering seen following Abeta treatment in neuroblastoma cells, while in REHIPs, TGF-beta decreases the number of positive cells detected in situ by Klenow labelling following Abeta treatment. RT-PCR shows that in REHIPs, Abeta decreases mRNA expression of Bcl-2, as well as the ratio of Bcl-xL/Bcl-xS, with little effect on Bax expression. These changes are expected to promote apoptosis. When REHIPs are incubated with TGF-beta before addition of Abeta, the Bcl-xL/Bcl-xS ratio and Bcl-2 levels are increased compared to cells treated with Abeta alone. Again there is little effect on Bax expression. Western blotting and immunohistochemistry experiments also show that TGF-beta maintains increased levels of Bcl-2 and Bcl-xL protein in REHIPs even in the presence of Abeta. This pattern of gene expression should function to decrease apoptosis. Similarly, RT-PCR analysis of mRNA prepared from hNT cells shows that TGF-beta pretreatment before addition of Abeta maintains a higher level of Bcl-2 expression and an increased Bcl-xL/Bcl-xS ratio as compared to cells treated with Abeta alone. In neuronal cell types treated with Abeta, TGF-beta appears to regulate expression of genes in the Bcl-2 family to favor an anti-apoptotic pathway. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Kim, E S AU - Kim, R S AU - Ren, R F AU - Hawver, D B AU - Flanders, K C AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Building 41/Room C-629, 41 Library Dr MSC 5055, Bethesda, MD 20892, USA. flanderk@dce41.nci.nih.gov Y1 - 1998/11/20/ PY - 1998 DA - 1998 Nov 20 SP - 122 EP - 130 VL - 62 IS - 2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Peptides KW - 0 KW - BAX protein, human KW - BCL2L1 protein, human KW - Bax protein, mouse KW - Bax protein, rat KW - Bcl2l1 protein, mouse KW - Bcl2l1 protein, rat KW - Peptide Fragments KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Transforming Growth Factor beta KW - amyloid beta-protein (25-35) KW - bcl-2-Associated X Protein KW - bcl-X Protein KW - Index Medicus KW - Neuroblastoma -- pathology KW - Proto-Oncogene Proteins c-bcl-2 -- biosynthesis KW - Animals KW - Humans KW - Mice KW - Rats KW - Genes, bcl-2 KW - Proto-Oncogene Proteins -- biosynthesis KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Hippocampus -- cytology KW - Proto-Oncogene Proteins -- genetics KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Transforming Growth Factor beta -- pharmacology KW - Neurons -- drug effects KW - Peptide Fragments -- pharmacology KW - Apoptosis -- drug effects KW - Amyloid beta-Peptides -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70069544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+growth+factor-beta+inhibits+apoptosis+induced+by+beta-amyloid+peptide+fragment+25-35+in+cultured+neuronal+cells.&rft.au=Kim%2C+E+S%3BKim%2C+R+S%3BRen%2C+R+F%3BHawver%2C+D+B%3BFlanders%2C+K+C&rft.aulast=Kim&rft.aufirst=E&rft.date=1998-11-20&rft.volume=62&rft.issue=2&rft.spage=122&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 - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New viral vectors for HIV vaccine delivery AN - 17116300; 4426129 AB - In the following sections, we (1) identify fundamental and minimal criteria of viral delivery vectors intended for global vaccine use, (2) discuss the candidate vectors and their unique features and properties, and (3) discuss current prospects and suggest a provisional platform for developing viral vectors for HIV vaccine delivery. JF - AIDS Research and Human Retroviruses AU - Cairns, J S AU - Sarver, N AD - Division of AIDS, NIAID/NIH, 2C01 Solar Building, 6003 Executive Boulevard, Bethesda, MD 20892, USA, ns18p@nih.gov Y1 - 1998/11/20/ PY - 1998 DA - 1998 Nov 20 SP - 1501 EP - 1508 VL - 14 IS - 17 SN - 0889-2229, 0889-2229 KW - HIV KW - human immunodeficiency virus KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Viruses KW - Vectors KW - Human immunodeficiency virus KW - Vaccines KW - W3 33365:Vaccines (other) KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17116300?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=New+viral+vectors+for+HIV+vaccine+delivery&rft.au=Cairns%2C+J+S%3BSarver%2C+N&rft.aulast=Cairns&rft.aufirst=J&rft.date=1998-11-20&rft.volume=14&rft.issue=17&rft.spage=1501&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&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; Vaccines; Vectors; Viruses ER - TY - JOUR T1 - The NIFS Protein Can Function as a Selenide Delivery Protein in the Biosynthesis of Selenophosphate AN - 17113406; 4429615 AB - The NIFS protein from Azobacter vinelandii is a pyridoxal phosphate-containing homodimer that catalyzes the formation of equimolar amounts of elemental sulfur and L-alanine from the substrate L-cysteine (Zheng L., White, R. H., Cash, V. L., Jack, R. F., and Dean, D. R. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 2754-2758). A sulfur transfer role of NIFS in which the enzyme donates sulfur for iron sulfur center formation in nitrogenase was suggested. The fact that NIFS also can catalyze the decomposition of L-selenocysteine to elemental selenium and L-alanine suggested the possibility that this enzyme might serve as a selenide delivery protein for the in vitro biosynthesis of selenophosphate. In agreement with this hypothesis, we have shown that replacement of selenide with NIFS and L-selenocysteine in the in vitro selenophosphate synthetase assay results in an increased rate of formation of selenophosphate. These results thus support the view that a selenocysteine-specific enzyme similar to NIFS may be involved as an in vivo selenide delivery protein for selenophosphate biosynthesis. A kinetic characterization of the two NIFS catalyzed reactions carried out in the present study indicates that the enzyme favors L-cysteine as a substrate compared with its selenium analog. A specific activity for L-cysteine of 142 nmol/min/mg compared with 55 nmol/min/mg for L-selenocysteine was determined. This level of enzyme activity on the selenoamino acid substrate is adequate to deliver selenium to selenophosphate synthetase in the in vitro assay system described. JF - Journal of Biological Chemistry AU - Lacourciere, G M AU - Stadtman, T C AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 1998/11/20/ PY - 1998 DA - 1998 Nov 20 SP - 30921 EP - 30926 VL - 273 IS - 47 SN - 0021-9258, 0021-9258 KW - L-Selenocysteine KW - NifS protein KW - selenophosphate synthetase KW - selenophosphates KW - Microbiology Abstracts B: Bacteriology KW - Selenium KW - Kinetics KW - Assays KW - Azotobacter vinelandii KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17113406?accountid=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=The+NIFS+Protein+Can+Function+as+a+Selenide+Delivery+Protein+in+the+Biosynthesis+of+Selenophosphate&rft.au=Lacourciere%2C+G+M%3BStadtman%2C+T+C&rft.aulast=Lacourciere&rft.aufirst=G&rft.date=1998-11-20&rft.volume=273&rft.issue=47&rft.spage=30921&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 - Azotobacter vinelandii; Kinetics; Selenium; Assays ER - TY - JOUR T1 - Effects of aspirin on endothelial dysfunction in atherosclerosis. AN - 69093913; 9860354 JF - The American journal of cardiology AU - Quyyumi, A A AD - National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/11/19/ PY - 1998 DA - 1998 Nov 19 SP - 31S EP - 33S VL - 82 IS - 10A SN - 0002-9149, 0002-9149 KW - Platelet Aggregation Inhibitors KW - 0 KW - Vasodilator Agents KW - Nitroprusside KW - 169D1260KM KW - Substance P KW - 33507-63-0 KW - Acetylcholine KW - N9YNS0M02X KW - Aspirin KW - R16CO5Y76E KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Interactions KW - Substance P -- pharmacology KW - Humans KW - Vasodilator Agents -- therapeutic use KW - Vascular Resistance -- drug effects KW - Acetylcholine -- pharmacology KW - Nitroprusside -- pharmacology KW - Platelet Aggregation Inhibitors -- therapeutic use KW - Endothelium, Vascular -- drug effects KW - Aspirin -- therapeutic use KW - Arteriosclerosis -- drug therapy KW - Aspirin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69093913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cardiology&rft.atitle=Effects+of+aspirin+on+endothelial+dysfunction+in+atherosclerosis.&rft.au=Quyyumi%2C+A+A&rft.aulast=Quyyumi&rft.aufirst=A&rft.date=1998-11-19&rft.volume=82&rft.issue=10A&rft.spage=31S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+cardiology&rft.issn=00029149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: the role of nitric oxide. AN - 69092805; 9860347 JF - The American journal of cardiology AU - Cannon, R O AD - National Institutes of Health, Bethesda, Maryland 20892-1650, USA. Y1 - 1998/11/19/ PY - 1998 DA - 1998 Nov 19 SP - 8S EP - 10S VL - 82 IS - 10A SN - 0002-9149, 0002-9149 KW - Angiotensin-Converting Enzyme Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Acetylcholine KW - N9YNS0M02X KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Drug Interactions KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Acetylcholine -- pharmacology KW - Coronary Circulation -- drug effects KW - Vasodilator Agents -- pharmacology KW - Arginine -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- drug effects KW - Nitric Oxide -- physiology KW - Angiotensin-Converting Enzyme Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69092805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cardiology&rft.atitle=Potential+mechanisms+for+the+effect+of+angiotensin-converting+enzyme+inhibitors+on+endothelial+dysfunction%3A+the+role+of+nitric+oxide.&rft.au=Cannon%2C+R+O&rft.aulast=Cannon&rft.aufirst=R&rft.date=1998-11-19&rft.volume=82&rft.issue=10A&rft.spage=8S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+cardiology&rft.issn=00029149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - von Hippel-Lindau gene mutations in N-nitrosodimethylamine-induced rat renal epithelial tumors. AN - 70089571; 9827526 AB - Mutations in the von Hippel-Lindau (VHL) gene are common in human clear cell kidney cancers. Carcinogens in cigarette smoke, especially nitrosamines, are known to induce kidney tumors of a variety of histologic types in rodents--but with no evidence of VHL mutations; however, none of these tumors resembled human clear cell carcinomas. We examined N-nitrosodimethylamine-induced kidney tumors of the clear or mixed clear/granular cell type in Wistar rats to assess the presence of VHL mutations. Sections of eight clear or mixed clear/granular cell kidney tumors that had been formalin fixed and paraffin embedded were microdissected. DNA was extracted from the microdissected tissue, and exons 1-3 of the rat VHL gene were examined by use of polymerase chain reaction and cycle sequencing techniques. Four VHL gene mutations (three G:C to A:T and one A:T to G:C) were detected in three of the tumors in contrast to no mutations in 40 previously reported rat kidney tumors of other histologic types (three of eight tumors versus none of 40; two-sided Fisher's exact test; P=.003). Only tumors showing prominent swollen clear cell cytology with a signet-ring appearance had VHL mutations. To our knowledge, this is the first report of VHL mutations in kidney tumors after direct chemical exposure and provides a possible molecular pathway linking tobacco smoking to kidney cancer. JF - Journal of the National Cancer Institute AU - Shiao, Y H AU - Rice, J M AU - Anderson, L M AU - Diwan, B A AU - Hard, G C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Shiao@mail.ncifcrf.gov Y1 - 1998/11/18/ PY - 1998 DA - 1998 Nov 18 SP - 1720 EP - 1723 VL - 90 IS - 22 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - Nitroso Compounds KW - 4-nitrosodimethylaniline KW - 138-89-6 KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - DNA Mutational Analysis KW - Rats, Wistar KW - Smoking -- adverse effects KW - Female KW - Kidney Neoplasms -- genetics KW - Adenocarcinoma, Clear Cell -- genetics KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Adenocarcinoma, Clear Cell -- chemically induced KW - von Hippel-Lindau Disease -- genetics KW - DNA, Neoplasm -- genetics KW - Mutation KW - Adenocarcinoma, Clear Cell -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70089571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=von+Hippel-Lindau+gene+mutations+in+N-nitrosodimethylamine-induced+rat+renal+epithelial+tumors.&rft.au=Shiao%2C+Y+H%3BRice%2C+J+M%3BAnderson%2C+L+M%3BDiwan%2C+B+A%3BHard%2C+G+C&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1998-11-18&rft.volume=90&rft.issue=22&rft.spage=1720&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 - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1998 Nov 18;90(22):1685-7 [9827515] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. AN - 70087528; 9827525 AB - The relationship between diet and pancreatic cancer remains unclear. In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans. We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. Reliable dietary histories were obtained for 436 patients and 2003 general-population control subjects aged 30-79 years. Obesity was associated with a statistically significant 50%-60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks were obese than were whites (women: 38% versus 16%; men: 27% versus 22%). A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of caloric intake experiencing a 70% higher risk than those in the lowest quartile. A statistically significant interaction between body mass index (weight in kg/height in m2 for men and weight in kg/height in m1.5 for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest quartile. Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis. JF - Journal of the National Cancer Institute AU - Silverman, D T AU - Swanson, C A AU - Gridley, G AU - Wacholder, S AU - Greenberg, R S AU - Brown, L M AU - Hayes, R B AU - Swanson, G M AU - Schoenberg, J B AU - Pottern, L M AU - Schwartz, A G AU - Fraumeni, J F AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. silvermd@EPNDCE.NCI.NIH.GOV Y1 - 1998/11/18/ PY - 1998 DA - 1998 Nov 18 SP - 1710 EP - 1719 VL - 90 IS - 22 SN - 0027-8874, 0027-8874 KW - Coffee KW - 0 KW - Dietary Fats KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Energy Intake KW - Body Mass Index KW - Adult KW - Case-Control Studies KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Pancreatic Neoplasms -- ethnology KW - Food -- adverse effects KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - Nutritional Physiological Phenomena KW - Pancreatic Neoplasms -- etiology KW - Diet -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70087528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dietary+and+nutritional+factors+and+pancreatic+cancer%3A+a+case-control+study+based+on+direct+interviews.&rft.au=Silverman%2C+D+T%3BSwanson%2C+C+A%3BGridley%2C+G%3BWacholder%2C+S%3BGreenberg%2C+R+S%3BBrown%2C+L+M%3BHayes%2C+R+B%3BSwanson%2C+G+M%3BSchoenberg%2C+J+B%3BPottern%2C+L+M%3BSchwartz%2C+A+G%3BFraumeni%2C+J+F%3BHoover%2C+R+N&rft.aulast=Silverman&rft.aufirst=D&rft.date=1998-11-18&rft.volume=90&rft.issue=22&rft.spage=1710&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 - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of action of the nongenotoxic peroxisome proliferators: role of the peroxisome proliferator-activator receptor alpha. AN - 70080533; 9827524 AB - Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators. JF - Journal of the National Cancer Institute AU - Gonzalez, F J AU - Peters, J M AU - Cattley, R C AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 1998/11/18/ PY - 1998 DA - 1998 Nov 18 SP - 1702 EP - 1709 VL - 90 IS - 22 SN - 0027-8874, 0027-8874 KW - Receptors, Cytoplasmic and Nuclear KW - 0 KW - Transcription Factors KW - Index Medicus KW - Animals KW - Mitosis KW - Humans KW - Oxidative Stress KW - Mice KW - Species Specificity KW - Cell Cycle KW - Liver Neoplasms -- metabolism KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70080533?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+action+of+the+nongenotoxic+peroxisome+proliferators%3A+role+of+the+peroxisome+proliferator-activator+receptor+alpha.&rft.au=Gonzalez%2C+F+J%3BPeters%2C+J+M%3BCattley%2C+R+C&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1998-11-18&rft.volume=90&rft.issue=22&rft.spage=1702&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 - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution to substrate specificity and transport of nonconserved residues in transmembrane domain 12 of human P-glycoprotein. AN - 70062252; 9819232 AB - P-glycoprotein (Pgp), the product of the MDR1 gene, confers multidrug resistance on cancer cells by ATP-dependent extrusion of anticancer drugs. Biochemical and genetic studies with Pgp have identified the putative transmembrane (TM) region 12 (residues 974-994) as a major region involved in drug interactions with amino acid residues conserved among Pgp family members shown to be essential for transport. To determine whether nonconserved residues might be involved in substrate specificity, seven amino acid residues were identified within TM 12 that were not strictly conserved among the MDR1 and MDR2 family of proteins from different mammalian species. We replaced all seven of these amino acid residues with alanine, one at a time and in combinations, and used a vaccinia virus based transient expression system to analyze function. None of the single replacements caused any alteration in transport function. However, when residues L975, V981, and F983 were replaced collectively, drug transport, drug-stimulated ATP hydrolysis, and photoaffinity labeling with the drug analogue, [125I]iodoarylazidoprazosin (IAAP), were abrogated, with little effect on [alpha-32P]-8-azido-ATP labeling and basal ATPase activity. Pairwise alanine substitutuions showed variable effects on function. Substitutions including L975A in combination with any one of the other two replacements had the least effect on Pgp function. The V981A and F983A double mutant showed the most effect on transport of fluorescent substrates. In contrast, alanine substitutions of all four nonconserved residues M986, V988, Q990, and V991 at the putative carboxy-terminal half of TM 12 showed no effect on drug transport except for a partial reduction in bodipy-verapamil extrusion. These results suggest that nonconserved residues in the putative amino-proximal half of TM 12 of Pgp play a more direct role in determining specificity of drug transport function than those in the putative carboxy-terminal half of TM 12. JF - Biochemistry AU - Hafkemeyer, P AU - Dey, S AU - Ambudkar, S V AU - Hrycyna, C A AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/11/17/ PY - 1998 DA - 1998 Nov 17 SP - 16400 EP - 16409 VL - 37 IS - 46 SN - 0006-2960, 0006-2960 KW - Fluorescent Dyes KW - 0 KW - P-Glycoprotein KW - Peptide Fragments KW - Photoaffinity Labels KW - Vanadates KW - 3WHH0066W5 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Humans KW - Cell Membrane -- genetics KW - Biological Transport -- genetics KW - Genes, MDR KW - Mutagenesis, Site-Directed KW - Rats KW - Photoaffinity Labels -- metabolism KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Alanine -- metabolism KW - Molecular Sequence Data KW - Alanine -- genetics KW - Flow Cytometry KW - Binding Sites -- genetics KW - Vanadates -- metabolism KW - Fluorescent Dyes -- metabolism KW - Amino Acid Sequence KW - Mice KW - Substrate Specificity -- genetics KW - Genetic Vectors -- metabolism KW - Hydrolysis KW - Transfection KW - Adenosine Triphosphate -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - ATP-Binding Cassette Transporters -- chemistry KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Cricetinae KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- biosynthesis KW - Conserved Sequence -- genetics KW - Peptide Fragments -- genetics KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - P-Glycoprotein -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70062252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Contribution+to+substrate+specificity+and+transport+of+nonconserved+residues+in+transmembrane+domain+12+of+human+P-glycoprotein.&rft.au=Hafkemeyer%2C+P%3BDey%2C+S%3BAmbudkar%2C+S+V%3BHrycyna%2C+C+A%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Hafkemeyer&rft.aufirst=P&rft.date=1998-11-17&rft.volume=37&rft.issue=46&rft.spage=16400&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-17 N1 - Date created - 1998-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. AN - 70070458; 9815270 AB - In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T helper cell type 2 (Th2)-mediated process since stimulated T cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, anti-IL-4 administration leads to a striking amelioration of disease, whereas anti-IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-beta (TGF-beta) response which limits both the extent and duration of disease: lesional (distal) T cells manifest a 20-30-fold increase in TGF-beta production, whereas nonlesional (proximal) T cells manifest an even greater 40-50-fold increase. In addition, anti-TGF-beta administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC. JF - The Journal of experimental medicine AU - Boirivant, M AU - Fuss, I J AU - Chu, A AU - Strober, W AD - Mucosal Immunity Section, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/11/16/ PY - 1998 DA - 1998 Nov 16 SP - 1929 EP - 1939 VL - 188 IS - 10 SN - 0022-1007, 0022-1007 KW - Antibodies KW - 0 KW - Cytokines KW - Interleukins KW - Oxazolone KW - 15646-46-5 KW - Interleukin-4 KW - 207137-56-2 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Colon -- pathology KW - Humans KW - Interleukins -- metabolism KW - Disease Models, Animal KW - Administration, Rectal KW - Cytokines -- metabolism KW - Mice KW - Histocytochemistry KW - Mice, Inbred Strains KW - Colitis, Ulcerative -- pathology KW - Inflammation -- immunology KW - Colitis, Ulcerative -- immunology KW - Oxazolone -- immunology KW - Antibodies -- therapeutic use KW - Interleukin-4 -- immunology KW - Oxazolone -- pharmacology KW - Colitis -- chemically induced KW - Th2 Cells -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxazolone+colitis%3A+A+murine+model+of+T+helper+cell+type+2+colitis+treatable+with+antibodies+to+interleukin+4.&rft.au=Boirivant%2C+M%3BFuss%2C+I+J%3BChu%2C+A%3BStrober%2C+W&rft.aulast=Boirivant&rft.aufirst=M&rft.date=1998-11-16&rft.volume=188&rft.issue=10&rft.spage=1929&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 - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10762-5 [7971958] J Clin Immunol. 1998 Jan;18(1):1-30 [9475350] Immunity. 1994 Oct;1(7):553-62 [7600284] J Exp Med. 1995 Nov 1;182(5):1281-90 [7595199] Immunology. 1970 Jan;18(1):99-106 [4903986] Immunology. 1973 Sep;25(3):485-94 [4542648] Int Arch Allergy Appl Immunol. 1973;45(6):828-43 [4796935] Cell Immunol. 1974 Mar 30;11(1-3):198-204 [4455392] Cell Immunol. 1977 Sep;33(1):145-55 [302759] Immunology. 1979 Mar;36(3):449-59 [312260] Immunology. 1980 Dec;41(4):1005-13 [6450725] J Immunol. 1981 Dec;127(6):2366-71 [7299129] Immunobiology. 1987 May;174(3):326-38 [3497865] J Immunol Methods. 1987 Nov 5;103(2):161-7 [2889781] Gastroenterology. 1989 Mar;96(3):795-803 [2914642] Cell Immunol. 1990 Feb;125(2):437-48 [2137034] Int Arch Allergy Appl Immunol. 1991;95(2-3):142-8 [1937916] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):421-5 [1370356] Gastroenterology. 1992 May;102(5):1524-34 [1314749] J Exp Med. 1992 Nov 1;176(5):1355-64 [1383385] Immunology. 1993 Jan;78(1):127-31 [8436398] Cell. 1993 Oct 22;75(2):263-74 [8402911] Cell. 1993 Oct 22;75(2):274-82 [8104709] Gastroenterology. 1996 Apr;110(4):975-84 [8613031] J Exp Med. 1996 Mar 1;183(3):847-56 [8642289] J Exp Med. 1996 Jun 1;183(6):2605-16 [8676081] J Exp Med. 1996 Jun 1;183(6):2669-74 [8676088] J Immunol. 1996 Aug 1;157(3):1261-70 [8757634] J Exp Med. 1996 Aug 1;184(2):707-15 [8760824] J Immunol. 1996 Sep 1;157(5):2174-85 [8757344] J Immunol. 1997 Jan 15;158(2):566-73 [8992969] Immunol Today. 1997 Feb;18(2):61-4 [9057354] Am J Pathol. 1997 Mar;150(3):823-32 [9060820] Lab Invest. 1997 Mar;76(3):385-97 [9121121] Gastroenterology. 1997 Apr;112(4):1169-78 [9098000] Eur J Immunol. 1997 May;27(5):1213-20 [9174613] Gastroenterology. 1997 Jun;112(6):1876-86 [9178680] J Immunol. 1997 Oct 1;159(7):3622-8 [9317162] J Immunol. 1995 Apr 1;154(7):3156-61 [7897205] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase. AN - 70069539; 9822604 AB - Diphosphoinositol pentakisphosphate (PP-InsP5 or 'InsP7') and bisdiphosphoinositol tetrakisphosphate ([PP]2-InsP4 or 'InsP8') are the most highly phosphorylated members of the inositol-based cell signaling family. We have purified a rat hepatic diphosphoinositol polyphosphate phosphohydrolase (DIPP) that cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (Km = 340 nM) and [PP]2-InsP4 (Km = 34 nM). Inositol hexakisphophate (InsP6) was not a substrate, but it inhibited metabolism of both [PP]2-InsP4 and PP-InsP5 (IC50 = 0.2 and 3 microM, respectively). Microsequencing of DIPP revealed a 'MutT' domain, which in other contexts guards cellular integrity by dephosphorylating 8-oxo-dGTP, which causes AT to CG transversion mutations. The MutT domain also metabolizes some nucleoside phosphates that may play roles in signal transduction. The rat DIPP MutT domain is conserved in a novel recombinant human uterine DIPP. The nucleotide sequence of the human DIPP cDNA was aligned to chromosome 6; the candidate gene contains at least four exons. The dependence of DIPP's catalytic activity upon its MutT domain was confirmed by mutagenesis of a conserved glutamate residue. DIPP's low molecular size, Mg2+ dependency and catalytic preference for phosphoanhydride bonds are also features of other MutT-type proteins. Because overlapping substrate specificity is a feature of this class of proteins, our data provide new directions for future studies of higher inositol phosphates. JF - The EMBO journal AU - Safrany, S T AU - Caffrey, J J AU - Yang, X AU - Bembenek, M E AU - Moyer, M B AU - Burkhart, W A AU - Shears, S B AD - Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, PO Box 12233, NC 27709, USA. Y1 - 1998/11/16/ PY - 1998 DA - 1998 Nov 16 SP - 6599 EP - 6607 VL - 17 IS - 22 SN - 0261-4189, 0261-4189 KW - Bacterial Proteins KW - 0 KW - DNA, Complementary KW - Escherichia coli Proteins KW - Inositol Phosphates KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Pyrophosphatases KW - EC 3.6.1.- KW - diphosphoinositol polyphosphate phosphohydrolase KW - mutT protein, E coli KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Liver -- enzymology KW - Gene Expression Regulation, Enzymologic KW - Inositol Phosphates -- metabolism KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Cloning, Molecular KW - Bacterial Proteins -- metabolism KW - Acid Anhydride Hydrolases -- metabolism KW - Acid Anhydride Hydrolases -- genetics KW - Phosphoric Monoester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70069539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+novel+context+for+the+%27MutT%27+module%2C+a+guardian+of+cell+integrity%2C+in+a+diphosphoinositol+polyphosphate+phosphohydrolase.&rft.au=Safrany%2C+S+T%3BCaffrey%2C+J+J%3BYang%2C+X%3BBembenek%2C+M+E%3BMoyer%2C+M+B%3BBurkhart%2C+W+A%3BShears%2C+S+B&rft.aulast=Safrany&rft.aufirst=S&rft.date=1998-11-16&rft.volume=17&rft.issue=22&rft.spage=6599&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 - 1999-01-13 N1 - Date created - 1999-01-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF062530; GENBANK; AF062529 N1 - SuppNotes - Cited By: J Biol Chem. 1998 Feb 6;273(6):3192-7 [9452430] Biochem J. 1997 Nov 15;328 ( Pt 1):75-81 [9359836] EMBO J. 1998 Mar 16;17(6):1710-6 [9501092] FEBS Lett. 1998 May 8;427(2):157-63 [9607303] Anal Biochem. 1976 May 7;72:248-54 [942051] Biochem Biophys Res Commun. 1987 Dec 31;149(3):874-81 [3426614] J Biochem Biophys Methods. 1989 Aug-Sep;19(2-3):249-51 [2555407] Biochemistry. 1990 Jun 26;29(25):6065-71 [2166573] J Biol Chem. 1991 May 15;266(14):9050-4 [1851162] Cell Calcium. 1990 Nov-Dec;11(10):611-24 [1965707] Nucleic Acids Res. 1991 Jul 25;19(14):3795-8 [1713664] Proc Biol Sci. 1991 Sep 23;245(1314):193-201 [1684044] Adv Second Messenger Phosphoprotein Res. 1992;26:63-92 [1329895] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11021-5 [1332067] J Biol Chem. 1993 Feb 25;268(6):3850-6 [8382679] J Biol Chem. 1993 Feb 25;268(6):4009-15 [8440693] Eur J Biochem. 1993 Jun 15;214(3):711-8 [8319681] Biochem J. 1993 Jul 15;293 ( Pt 2):583-90 [8343137] J Biol Chem. 1994 Apr 22;269(16):12339-44 [8163538] J Biol Chem. 1995 May 5;270(18):10489-97 [7737983] Biochem J. 1995 Aug 15;310 ( Pt 1):279-84 [7646456] Biochem J. 1995 Nov 1;311 ( Pt 3):717-21 [7487923] Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4305-10 [8633060] Biochemistry. 1996 May 28;35(21):6715-26 [8639622] Biochem J. 1996 May 15;316 ( Pt 1):175-82 [8645202] Cell. 1996 Jul 12;86(1):147-57 [8689682] Mamm Genome. 1996 Aug;7(8):563-74 [8679005] Biochem J. 1996 Aug 15;318 ( Pt 1):279-86 [8761483] J Biol Chem. 1996 Oct 4;271(40):24649-54 [8798731] J Biol Chem. 1996 Oct 11;271(41):25059-62 [8810257] Biochemistry. 1997 Feb 11;36(6):1199-211 [9063868] Biochem J. 1997 Oct 15;327 ( Pt 2):553-60 [9359429] J Cell Sci. 1998 Mar;111 ( Pt 6):803-13 [9472008] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of NMDA-induced membrane potential oscillations and spontaneous rhythmic activity in the chick spinal cord. AN - 69159204; 9928341 JF - Annals of the New York Academy of Sciences AU - Chub, N AU - Moore, L E AU - O'Donovan, M J AD - Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. nchub@box-n.nih.gov Y1 - 1998/11/16/ PY - 1998 DA - 1998 Nov 16 SP - 467 EP - 469 VL - 860 SN - 0077-8923, 0077-8923 KW - Excitatory Amino Acid Agonists KW - 0 KW - GABA Antagonists KW - Isotonic Solutions KW - Tyrode's solution KW - Tetrodotoxin KW - 4368-28-9 KW - N-Methylaspartate KW - 6384-92-5 KW - Magnesium KW - I38ZP9992A KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Isotonic Solutions -- pharmacology KW - Neurons -- drug effects KW - Chick Embryo KW - Neurons -- physiology KW - Magnesium -- pharmacology KW - Action Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - GABA Antagonists -- pharmacology KW - N-Methylaspartate -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Periodicity KW - Spinal Cord -- physiology KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69159204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+NMDA-induced+membrane+potential+oscillations+and+spontaneous+rhythmic+activity+in+the+chick+spinal+cord.&rft.au=Chub%2C+N%3BMoore%2C+L+E%3BO%27Donovan%2C+M+J&rft.aulast=Chub&rft.aufirst=N&rft.date=1998-11-16&rft.volume=860&rft.issue=&rft.spage=467&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 - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. AN - 70063380; 9827707 AB - Incidence rates for esophageal adenocarcinoma previously were reported to be increasing rapidly, especially among white males. Rates for gastric cardia adenocarcinoma also were observed to be rising, although less rapidly. In this article, the authors update the incidence trends through 1994 and further consider the trends by age group. Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate age-adjusted incidence rates for esophageal carcinoma by histologic type and gastric adenocarcinoma by anatomic subsite. Among white males, the incidence of adenocarcinoma of the esophagus rose > 350% since the mid-1970s, surpassing squamous cell carcinoma around 1990. Rates also rose among black males, but remained at much lower levels. To a lesser extent, there were continuing increases in gastric cardia adenocarcinoma among white and black males, which nearly equaled the rates for noncardia tumors of the stomach in white men. The upward trend for both tumors was much greater among older than younger men. Although the incidence also rose among females, rates remained much lower than among males. Previously reported increases of esophageal adenocarcinoma are continuing, most notably among white males. Cigarette smoking may contribute to the trend through an early stage carcinogenic effect, along with obesity, which may increase intraabdominal pressure and predispose to gastroesophageal reflux disease. Further research into esophageal and gastric cardia adenocarcinoma is needed to clarify the risk factors and mechanisms responsible for the upward trends as well as the racial and gender disparities in incidence. JF - Cancer AU - Devesa, S S AU - Blot, W J AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7368, USA. Y1 - 1998/11/15/ PY - 1998 DA - 1998 Nov 15 SP - 2049 EP - 2053 VL - 83 IS - 10 SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - African Americans -- statistics & numerical data KW - Incidence KW - European Continental Ancestry Group -- statistics & numerical data KW - Aged KW - Middle Aged KW - Male KW - Age Distribution KW - Carcinoma, Squamous Cell -- ethnology KW - Adenocarcinoma -- epidemiology KW - Adenocarcinoma -- ethnology KW - Carcinoma, Squamous Cell -- epidemiology KW - Esophageal Neoplasms -- ethnology KW - Stomach Neoplasms -- epidemiology KW - Stomach Neoplasms -- ethnology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70063380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Changing+patterns+in+the+incidence+of+esophageal+and+gastric+carcinoma+in+the+United+States.&rft.au=Devesa%2C+S+S%3BBlot%2C+W+J%3BFraumeni%2C+J+F&rft.aulast=Devesa&rft.aufirst=S&rft.date=1998-11-15&rft.volume=83&rft.issue=10&rft.spage=2049&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-01 N1 - Date created - 1998-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukemia: a joint children's cancer group and pediatric oncology branch study. AN - 70035756; 9808549 AB - We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m2) and weekly oral methotrexate (20 mg/m2). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients. Plasma drug concentrations of both agents were highly variable. The area under the plasma concentration-time curve (AUC) of methotrexate ranged from 0.63 to 12 micromol*h/L, and the AUC of mercaptopurine ranged from 0.11 to 8 micromol*h/L. Drug dose, patient age, and duration of therapy did not account for the variability. Methotrexate AUC was significantly higher in girls than boys (P =.007). There was considerable intrapatient variability for both agents. Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUC. A Cox regression analysis showed that mercaptopurine AUC was a marginally significant (P =.043) predictor of outcome, but a direct comparison of mercaptopurine AUC in the remission and relapsed patient groups failed to show a significant difference. Methotrexate and mercaptopurine plasma concentrations and erythrocyte thioguanine nucleotide levels were highly variable, but measurement of these pharmacokinetic parameters at the start of maintenance will not distinguish patients who are more likely to relapse. JF - Blood AU - Balis, F M AU - Holcenberg, J S AU - Poplack, D G AU - Ge, J AU - Sather, H N AU - Murphy, R F AU - Ames, M M AU - Waskerwitz, M J AU - Tubergen, D G AU - Zimm, S AU - Gilchrist, G S AU - Bleyer, W A AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; and the Children's Cancer Group, Arcadia, CA, USA. balisf@nih.gov Y1 - 1998/11/15/ PY - 1998 DA - 1998 Nov 15 SP - 3569 EP - 3577 VL - 92 IS - 10 SN - 0006-4971, 0006-4971 KW - Antimetabolites, Antineoplastic KW - 0 KW - DNA Adducts KW - Thionucleotides KW - Vincristine KW - 5J49Q6B70F KW - Guanosine Triphosphate KW - 86-01-1 KW - 6-Mercaptopurine KW - E7WED276I5 KW - Asparaginase KW - EC 3.5.1.1 KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Area Under Curve KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Thionucleotides -- blood KW - Asparaginase -- administration & dosage KW - Child KW - Cranial Irradiation KW - Recurrence KW - Biological Availability KW - Child, Preschool KW - Infant KW - Guanosine Triphosphate -- analogs & derivatives KW - Erythrocytes -- chemistry KW - Injections, Spinal KW - Treatment Outcome KW - Guanosine Triphosphate -- blood KW - Adolescent KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Proportional Hazards Models KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Methotrexate -- pharmacology KW - Methotrexate -- blood KW - 6-Mercaptopurine -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- pharmacology KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- metabolism KW - Methotrexate -- pharmacokinetics KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- radiotherapy KW - Antimetabolites, Antineoplastic -- blood KW - 6-Mercaptopurine -- administration & dosage KW - 6-Mercaptopurine -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Methotrexate -- administration & dosage KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70035756?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacokinetics+and+pharmacodynamics+of+oral+methotrexate+and+mercaptopurine+in+children+with+lower+risk+acute+lymphoblastic+leukemia%3A+a+joint+children%27s+cancer+group+and+pediatric+oncology+branch+study.&rft.au=Balis%2C+F+M%3BHolcenberg%2C+J+S%3BPoplack%2C+D+G%3BGe%2C+J%3BSather%2C+H+N%3BMurphy%2C+R+F%3BAmes%2C+M+M%3BWaskerwitz%2C+M+J%3BTubergen%2C+D+G%3BZimm%2C+S%3BGilchrist%2C+G+S%3BBleyer%2C+W+A&rft.aulast=Balis&rft.aufirst=F&rft.date=1998-11-15&rft.volume=92&rft.issue=10&rft.spage=3569&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-21 N1 - Date created - 1998-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vertical-scanning mutagenesis of a critical tryptophan in the minor groove binding track of HIV-1 reverse transcriptase. Molecular nature of polymerase-nucleic acid interactions. AN - 70046725; 9804810 AB - While sequence-specific DNA-binding proteins interact predominantly in the DNA major groove, DNA polymerases bind DNA through interactions in the minor groove that are sequence nonspecific. Through functional analyses of alanine-substituted mutant enzymes that were guided by molecular dynamics modeling of the human immunodeficiency virus type 1-reverse transcriptase and DNA complex, we previously identified a structural element in reverse transcriptase, the minor groove binding track (MGBT). The MGBT is comprised of five residues (Ile94, Gln258, Gly262, Trp266, and Gln269) which interact 2-6 base pairs upstream from the polymerase active site in the DNA minor groove and are important in DNA binding, processivity, and frameshift fidelity. These residues do not contribute equally; functional analysis of alanine mutants suggests that Trp266 contributes the most to binding. To define the molecular interactions between Trp266 and the DNA minor groove, we have analyzed the properties of eight mutants, each with an alternate side chain at this position. A refined molecular dynamics model was used to calculate relative binding free energies based on apolar surface area buried upon complex formation. In general, there was a strong correlation between the relative calculated binding free energies for the alternate residue 266 side chains and the magnitude of the change in the properties which reflect template-primer interactions (template-primer dissociation rate constant, Ki,AZTTP, processivity, and frameshift fidelity). This correlation suggests that hydrophobic interactions make a major contribution to the stability of the polymerase-DNA complex. Additionally, tyrosine and arginine substitutions resulted in mutant enzymes with DNA binding properties better than predicted by buried surface area alone, suggesting that hydrogen bonding could also play a role in DNA binding at this position. JF - The Journal of biological chemistry AU - Beard, W A AU - Bebenek, K AU - Darden, T A AU - Li, L AU - Prasad, R AU - Kunkel, T A AU - Wilson, S H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/11/13/ PY - 1998 DA - 1998 Nov 13 SP - 30435 EP - 30442 VL - 273 IS - 46 SN - 0021-9258, 0021-9258 KW - Antiviral Agents KW - 0 KW - Dideoxynucleotides KW - Thymine Nucleotides KW - Zidovudine KW - 4B9XT59T7S KW - 3'-azido-3'-deoxythymidine 5'-triphosphate KW - 6RGF96R053 KW - Tryptophan KW - 8DUH1N11BX KW - DNA KW - 9007-49-2 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- analogs & derivatives KW - Models, Molecular KW - Humans KW - Zidovudine -- pharmacology KW - Catalytic Domain KW - Nucleic Acid Conformation KW - Frameshift Mutation KW - Antiviral Agents -- pharmacology KW - Kinetics KW - Thymine Nucleotides -- pharmacology KW - Crystallography, X-Ray KW - Hydrogen Bonding KW - Protein Conformation KW - HIV Reverse Transcriptase -- genetics KW - DNA -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - Tryptophan -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70046725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vertical-scanning+mutagenesis+of+a+critical+tryptophan+in+the+minor+groove+binding+track+of+HIV-1+reverse+transcriptase.+Molecular+nature+of+polymerase-nucleic+acid+interactions.&rft.au=Beard%2C+W+A%3BBebenek%2C+K%3BDarden%2C+T+A%3BLi%2C+L%3BPrasad%2C+R%3BKunkel%2C+T+A%3BWilson%2C+S+H&rft.aulast=Beard&rft.aufirst=W&rft.date=1998-11-13&rft.volume=273&rft.issue=46&rft.spage=30435&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 - 1998-12-08 N1 - Date created - 1998-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mouse Ms6-hm hypervariable microsatellite forms a hairpin and two unusual tetraplexes. AN - 70043507; 9804850 AB - The mouse Ms6-hm microsatellite consists of a tandem array of the pentamer d(CAGGG)n. This microsatellite is extremely hypervariable, showing a germ line mutation rate of 2.5%/gamete. The mechanism responsible for this instability is not known. The ability to form intrastrand structures is a conserved feature of many hypervariable sequences, and it has been suggested that the formation of such structures might account for instability by affecting DNA replication, repair, or recombination. Here we show that this microsatellite is able to form intrastrand structures as well. Under physiological conditions, the Ms6-hm microsatellite forms a hairpin as well as two different unusual intrastrand tetraplexes. The hairpin forms in the absence of monovalent cation and contains G.A, G.C, and G.G base pairs in a 1:1:1 ratio. In the presence of K+, a tetraplex is formed in which the adenines are unpaired and extrahelical, and the cytosines are involved in C.C pairs. In Na+, a tetraplex forms that contains C.C+ pairs, with the adenines being intrahelical and hydrogen-bonded to guanines. Tetraplex formation in the presence of Na+ requires both cytosines and adenines and might reflect the altered internal dimensions of this tetraplex, perhaps resulting from the ability of the C.C+ pairs to become intercalated in this sequence context. Our demonstration of the stabilization of tetraplexes by hydrogen bonding between adenines and guanines expands the hydrogen-bonding possibilities for tetraplexes and suggests that the category of sequences with tetraplex-forming potential may be larger than previously appreciated. JF - The Journal of biological chemistry AU - Weitzmann, M N AU - Woodford, K J AU - Usdin, K AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. Y1 - 1998/11/13/ PY - 1998 DA - 1998 Nov 13 SP - 30742 EP - 30749 VL - 273 IS - 46 SN - 0021-9258, 0021-9258 KW - Sulfuric Acid Esters KW - 0 KW - Sodium KW - 9NEZ333N27 KW - dimethyl sulfate KW - JW5CW40Z50 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Base Sequence KW - Sulfuric Acid Esters -- metabolism KW - Molecular Sequence Data KW - Mice KW - Chromosome Mapping KW - Potassium -- metabolism KW - Immunoglobulin Switch Region -- genetics KW - Sodium -- metabolism KW - Minisatellite Repeats KW - Microsatellite Repeats KW - Tandem Repeat Sequences KW - Nucleic Acid Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70043507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mouse+Ms6-hm+hypervariable+microsatellite+forms+a+hairpin+and+two+unusual+tetraplexes.&rft.au=Weitzmann%2C+M+N%3BWoodford%2C+K+J%3BUsdin%2C+K&rft.aulast=Weitzmann&rft.aufirst=M&rft.date=1998-11-13&rft.volume=273&rft.issue=46&rft.spage=30742&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 - 1998-12-08 N1 - Date created - 1998-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C delta (PKCdelta) inhibits the expression of glutamine synthetase in glial cells via the PKCdelta regulatory domain and its tyrosine phosphorylation. AN - 70041152; 9804846 AB - Protein kinase C (PKC) plays an important role in the proliferation and differentiation of glial cells. In a recent study we found that overexpression of PKCdelta reduced the expression of the astrocytic marker glutamine synthetase (GS). In this study we explored the mechanisms involved in the inhibitory effect of PKCdelta on the expression of glutamine synthetase. Using PKC chimeras we first examined the role of the catalytic and regulatory domains of PKCdelta on the expression of glutamine synthetase. We found that cells stably transfected with chimeras between the regulatory domain of PKCdelta and the catalytic domains of PKCalpha or epsilon inhibited the expression of GS, similar to the inhibition exerted by overexpression of PKCdelta itself. In contrast, no significant effects were observed in cells transfected with the reciprocal PKC chimeras between the regulatory domains of PKCalpha or epsilon and the catalytic domain of PKCdelta. PKCdelta has been shown to undergo tyrosine phosphorylation in response to various activators. Tyrosine phosphorylation of PKCdelta in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor occurred only in chimeras which contained the PKCdelta regulatory domain. Cells transfected with a PKCdelta mutant (PKCdelta5), in which the five putative tyrosine phosphorylation sites were mutated to phenylalanine, showed markedly diminished tyrosine phosphorylation in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor and normal levels of GS. Our results indicate that the regulatory domain of PKCdelta mediates the inhibitory effect of this isoform on the expression of GS. Phosphorylation of PKCdelta on tyrosine residues in the regulatory domain is implicated in this inhibitory effect. JF - The Journal of biological chemistry AU - Brodie, C AU - Bogi, K AU - Acs, P AU - Lorenzo, P S AU - Baskin, L 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 - 1998/11/13/ PY - 1998 DA - 1998 Nov 13 SP - 30713 EP - 30718 VL - 273 IS - 46 SN - 0021-9258, 0021-9258 KW - Bryostatins KW - 0 KW - Isoenzymes KW - Lactones KW - Macrolides KW - Recombinant Fusion Proteins KW - bryostatin 1 KW - 37O2X55Y9E KW - Tyrosine KW - 42HK56048U KW - PRKCD protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-delta KW - Glutamate-Ammonia Ligase KW - EC 6.3.1.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- biosynthesis KW - Phosphorylation KW - Enzyme Activation KW - Cells, Cultured KW - Humans KW - Catalytic Domain -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lactones -- pharmacology KW - Protein Kinase C -- metabolism KW - Glutamate-Ammonia Ligase -- genetics KW - Gene Expression Regulation, Enzymologic KW - Neuroglia -- enzymology KW - Protein Kinase C -- genetics KW - Tyrosine -- metabolism KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein+kinase+C+delta+%28PKCdelta%29+inhibits+the+expression+of+glutamine+synthetase+in+glial+cells+via+the+PKCdelta+regulatory+domain+and+its+tyrosine+phosphorylation.&rft.au=Brodie%2C+C%3BBogi%2C+K%3BAcs%2C+P%3BLorenzo%2C+P+S%3BBaskin%2C+L%3BBlumberg%2C+P+M&rft.aulast=Brodie&rft.aufirst=C&rft.date=1998-11-13&rft.volume=273&rft.issue=46&rft.spage=30713&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 - 1998-12-08 N1 - Date created - 1998-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal Structure and ATPase Activity of MutL: Implications for DNA Repair and Mutagenesis AN - 17113856; 4426151 AB - MutL and its homologs are essential for DNA mismatch repair. Mutations in genes encoding human homologs of MutL cause multiorgan cancer susceptibility. We have determined the crystal structure of a 40 kDa N-terminal fragment of E. coli MutL that retains all of the conserved residues in the MutL family. The structure of MutL is homologous to that of an ATPase-containing fragment of DNA gyrase. We have demonstrated that MutL binds and hydrolyzes ATP to ADP and Pi. Mutations in the MutL family that cause deficiencies in DNA mismatch repair and a predisposition to cancer mainly occur in the putative ATP-binding site. We provide evidence that the flexible, yet conserved, loops surrounding this ATP-binding site undergo conformational changes upon ATP hydrolysis thereby modulating interactions between MutL and other components of the repair machinery. JF - Cell AU - Ban, C 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 - 1998/11/13/ PY - 1998 DA - 1998 Nov 13 SP - 541 EP - 552 VL - 95 IS - 4 SN - 0092-8674, 0092-8674 KW - MutL protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Adenosinetriphosphatase KW - ATP KW - DNA repair KW - Escherichia coli KW - J 02725:DNA KW - J 02728:Enzymes KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17113856?accountid=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=Crystal+Structure+and+ATPase+Activity+of+MutL%3A+Implications+for+DNA+Repair+and+Mutagenesis&rft.au=Ban%2C+C%3BYang%2C+Wei&rft.aulast=Ban&rft.aufirst=C&rft.date=1998-11-13&rft.volume=95&rft.issue=4&rft.spage=541&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; Adenosinetriphosphatase; ATP ER - TY - JOUR T1 - Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. AN - 70102291; 9843382 AB - Accumulating evidence suggests that G protein-coupled receptors (GPCRs) can form dimeric or oligomeric arrays. Based on this concept, we have tested the hypothesis that truncated GPCRs can act as negative regulators of wild-type receptor function. Using the GS-coupled V2 vasopressin receptor as a model system, we systematically analyzed the ability of N- and C-terminal V2 receptor fragments to interfere with the activity of the wild-type V2 receptor coexpressed in COS-7 cells. Several N-terminal V2 receptor truncation mutants were identified that strongly inhibited the function (as determined in cAMP and radioligand binding assays) and cell surface trafficking of the coexpressed full-length V2 receptor. However, these truncation mutants did not interfere with the function of other GS-coupled receptors such as the D1 dopamine and the beta2-adrenergic receptors. Dominant negative effects were only observed with mutant receptors that contained at least three transmembrane domains. In addition, immunoblotting experiments showed that all V2 receptor truncation mutants displaying dominant negative activity (but not those mutant receptors lacking this activity) were able to form heterodimers with the full-length V2 receptor, suggesting that complex formation between mutant and wild-type V2 receptors underlies the observed inhibition of wild-type receptor function. Given the high degree of structural homology shared by all GPCRs, our findings should also be applicable to other members of this receptor superfamily. JF - Biochemistry AU - Zhu, X AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/11/10/ PY - 1998 DA - 1998 Nov 10 SP - 15773 EP - 15784 VL - 37 IS - 45 SN - 0006-2960, 0006-2960 KW - Antidiuretic Hormone Receptor Antagonists KW - 0 KW - Ligands KW - Peptide Fragments KW - Receptors, Vasopressin KW - Index Medicus KW - Animals KW - COS Cells KW - Dimerization KW - Humans KW - Cell Membrane -- genetics KW - Amino Acid Sequence KW - Blotting, Western KW - Transfection KW - Signal Transduction -- genetics KW - Molecular Sequence Data KW - Protein Binding -- genetics KW - Cell Membrane -- metabolism KW - Mutagenesis, Insertional KW - Receptors, Vasopressin -- metabolism KW - Peptide Fragments -- metabolism KW - Peptide Fragments -- biosynthesis KW - Receptors, Vasopressin -- biosynthesis KW - Peptide Fragments -- genetics KW - Down-Regulation -- genetics KW - Receptors, Vasopressin -- genetics KW - Peptide Fragments -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70102291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Truncated+V2+vasopressin+receptors+as+negative+regulators+of+wild-type+V2+receptor+function.&rft.au=Zhu%2C+X%3BWess%2C+J&rft.aulast=Zhu&rft.aufirst=X&rft.date=1998-11-10&rft.volume=37&rft.issue=45&rft.spage=15773&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-21 N1 - Date created - 1998-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBR3 human breast cancer cells. AN - 70010066; 9797142 AB - Previously, we have shown that phorbol ester (PMA) induces p21(WAF1/CIP1)-dependent growth arrest in SKBr3 breast cancer and LNCaP prostate cancer cells. Here, I demonstrate that inhibition of Raf-1 kinase by dominant-negative Raf-1 or pharmacological depletion of Raf-1 prevented PMA-mediated induction of p21(WAF1/CIP1). Similarly, PD98059, a specific inhibitor of MEK, abolished p21(WAF1/CIP1) induction and PMA-induced growth arrest. Like PMA, the H-ras oncogene, another activator of the Raf-1/MEK/MAPK pathway, transactivated p21(WAF1/CIP1) in SKBr3 cells. I further investigated PMA-induced growth arrest following infection of SKBr3 cells with 12S E1A-expressing adenovirus. Although high levels of E1A oncoprotein prevented both PMA-induced p21(WAF1/CIP1) and growth arrest, smaller amounts of E1A abrogated growth arrest without down-regulation of p21(WAF1/CIP1). Therefore, E1A can stimulate proliferation downstream of p21(WAF1/CIP1). Albeit less effective than full activity, either Rb- or p300-binding activity of E1A was sufficient for the abrogation of PMA-mediated growth arrest. E1A-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-1/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells. JF - International journal of cancer AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. mikhailb@box-m.nih.gov Y1 - 1998/11/09/ PY - 1998 DA - 1998 Nov 09 SP - 511 EP - 517 VL - 78 IS - 4 SN - 0020-7136, 0020-7136 KW - Adenovirus E1A Proteins KW - 0 KW - CDKN1A protein, human KW - Carcinogens KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Isoenzymes KW - Phorbol Esters KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - PRKCA protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Cyclins -- biosynthesis KW - Tumor Cells, Cultured KW - Enzyme Activation KW - Humans KW - ras Proteins -- metabolism KW - Isoenzymes -- metabolism KW - Cell Cycle -- drug effects KW - Phorbol Esters -- pharmacology KW - Carcinogens -- pharmacology KW - Apoptosis KW - Breast Neoplasms -- pathology KW - Adenovirus E1A Proteins -- pharmacology KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Breast Neoplasms -- enzymology KW - Proto-Oncogene Proteins c-raf -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70010066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+mitogen-activated+protein+kinase+pathway+mediates+growth+arrest+or+E1A-dependent+apoptosis+in+SKBR3+human+breast+cancer+cells.&rft.au=Blagosklonny%2C+M+V&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1998-11-09&rft.volume=78&rft.issue=4&rft.spage=511&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 - 1998-11-10 N1 - Date created - 1998-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice. AN - 70038053; 9811472 AB - We have previously documented that transgenic mice expressing SV40 Tag regulated by the rat prostatic steroid-binding protein C3(1) 5'-flanking region display multistage mammary tumorigenesis. To delineate genetic changes associated with mammary tumor progression, comparative genomic hybridization (CGH) was performed. CGH revealed a consistent gain of the telomeric region of chromosome 6. This region contains the Ki-ras proto-oncogene. Analyses of genomic DNA by Southern blot demonstrated up to 40-fold amplification of the Ki-ras gene. Ki-ras amplification was detected in 12, 46 and 68% of tumors from 4, 5 and 6 month old mice, respectively, whereas no amplifications were found in any preneoplastic mammary tissues. Tumors bearing Ki-ras gene amplification exhibited high levels of Ki-ras RNA and protein. The over-expressed Ki-Ras protein in these tumors appeared functionally active as indicated by the elevated MAP kinase activity. These data demonstrate that while Ki-ras amplification might not be an early event, there is a strong association between Ki-ras amplification and over-expression and mammary tumor progression in this model. This study also shows that CGH is a powerful and useful technique for identifying chromosomal copy number changes during tumor progression, and that this model may provide a predictable in vivo system for studying gene amplification. JF - Oncogene AU - Liu, M L AU - Von Lintig, F C AU - Liyanage, M AU - Shibata, M A AU - Jorcyk, C L AU - Ried, T AU - Boss, G R AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Science, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/11/05/ PY - 1998 DA - 1998 Nov 05 SP - 2403 EP - 2411 VL - 17 IS - 18 SN - 0950-9232, 0950-9232 KW - RNA, Messenger KW - 0 KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine Triphosphate KW - 86-01-1 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Receptor, ErbB-2 -- metabolism KW - Guanosine Diphosphate -- metabolism KW - In Situ Hybridization, Fluorescence KW - Disease Progression KW - Mice KW - ras Proteins -- metabolism KW - Mice, Transgenic KW - Mutation KW - Guanosine Triphosphate -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Genes, ras -- genetics KW - Mammary Neoplasms, Animal -- genetics KW - Gene Amplification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70038053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amplification+of+Ki-ras+and+elevation+of+MAP+kinase+activity+during+mammary+tumor+progression+in+C3%281%29%2FSV40+Tag+transgenic+mice.&rft.au=Liu%2C+M+L%3BVon+Lintig%2C+F+C%3BLiyanage%2C+M%3BShibata%2C+M+A%3BJorcyk%2C+C+L%3BRied%2C+T%3BBoss%2C+G+R%3BGreen%2C+J+E&rft.aulast=Liu&rft.aufirst=M&rft.date=1998-11-05&rft.volume=17&rft.issue=18&rft.spage=2403&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thyroid cancer rates and 131I doses from Nevada atmospheric nuclear bomb tests. AN - 70041400; 9811315 AB - We examined data on death from thyroid cancer across the continental United States and data on incidence from selected areas of the country for evidence of an association between this disease and exposure to radioactive iodine (131I) from nuclear tests in Nevada in the 1950s. Analyses involving 4602 thyroid cancer deaths (1957-1994) and 12 657 incident cases of thyroid cancer (1973-1994) were performed. Excess relative risks (ERRs) per Gray (Gy) of radiation were estimated by relating age-, calendar year-, sex-, and county-specific rates to estimates of dose to the thyroid that take age at exposure into account. Analyses of cumulative dose yielded negative ERRs that were not statistically significant. An association was suggested for dose received by children under 1 year of age for both mortality data (ERR per Gy = 10.6; 95% confidence interval [CI] = -1.1 to 29) and incidence data (ERR per Gy = 2.4; 95% CI = -0.5 to 5.6); no association was found for dose received at older ages. For mortality data, but not incidence data, there was an elevated ERR in the 1950-1959 birth cohort of 12.0 (95% CI = 2.8 to 31) per Gy. Risk of thyroid cancer from exposure to 131I from atmospheric nuclear tests did not increase with cumulative dose or dose received at ages 1-15 years, but associations were suggested for individuals exposed under 1 year of age and for those in the 1950-1959 birth cohort. The absence of increased risk from dose received at ages 1-15 years is not consistent with studies of children exposed to external radiation sources. This inconsistency may result from the limitations and biases inherent in ecologic studies, including the error introduced when studying a mobile population. These problems preclude making a quantitative estimate of risk due to exposure; however, given such limitations, it is perhaps remarkable that any evidence of the effects of 131I emerges from this study. JF - Journal of the National Cancer Institute AU - Gilbert, E S AU - Tarone, R AU - Bouville, A AU - Ron, E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/11/04/ PY - 1998 DA - 1998 Nov 04 SP - 1654 EP - 1660 VL - 90 IS - 21 SN - 0027-8874, 0027-8874 KW - Iodine Radioisotopes KW - 0 KW - Radioactive Fallout KW - Index Medicus KW - Radiation Dosage KW - Southeastern United States -- epidemiology KW - Humans KW - Dose-Response Relationship, Radiation KW - Age Distribution KW - Risk KW - Adult KW - Confounding Factors (Epidemiology) KW - Incidence KW - Middle Aged KW - Nevada -- epidemiology KW - Adolescent KW - Bias (Epidemiology) KW - Sex Distribution KW - Female KW - Male KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Iodine Radioisotopes -- adverse effects KW - Neoplasms, Radiation-Induced -- mortality KW - Thyroid Neoplasms -- etiology KW - Thyroid Neoplasms -- mortality KW - Radioactive Fallout -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thyroid+cancer+rates+and+131I+doses+from+Nevada+atmospheric+nuclear+bomb+tests.&rft.au=Gilbert%2C+E+S%3BTarone%2C+R%3BBouville%2C+A%3BRon%2C+E&rft.aulast=Gilbert&rft.aufirst=E&rft.date=1998-11-04&rft.volume=90&rft.issue=21&rft.spage=1654&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 - 1998-11-24 N1 - Date created - 1998-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1999 Aug 18;91(16):1423-5 [10451455] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Middle-Aged and Older People with AIDS. Trends in National Surveillance Rates, Transmission Routes, and Risk Factors AN - 877591249; 13600619 AB - This article explores the stability and changes in national trends related to AIDS rates, transmission routes, and risk factors from the mid-1980s to 1997. The authors show that while the numbers of AIDS cases have grown dramatically for all age groups, the proportion of cases for persons age 50 and older (at diagnosis) has remained a fairly stable 10% of the total case load, resulting in more than 60,000 cases in 1997. Contrary to popular belief, the most prevalent transmission route for middle-aged and older people has always been through sexual contact. While middle-aged and older people may be at reduced risk compared to younger age groups, these data also reveal a disturbing trend. People age 50 and older continue to be less knowledgeable about AIDS risks, perceive themselves to be at lower risk, and, for those with known AIDS-related risks, have made fewer behavioral accommodations to avoid such risksas compared to younger people. With recent data indicating a faster rise in new AIDScases among the 50-plus population, middle-aged and older people can no longer beignored in AIDS prevention or treatment efforts. JF - Research on Aging AU - Ory, Marcia G AU - Mack, Karin A AD - National Institute on Aging Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 653 EP - 664 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 20 IS - 6 SN - 0164-0275, 0164-0275 KW - Risk Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/877591249?accountid=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=Research+on+Aging&rft.atitle=Middle-Aged+and+Older+People+with+AIDS.+Trends+in+National+Surveillance+Rates%2C+Transmission+Routes%2C+and+Risk+Factors&rft.au=Ory%2C+Marcia+G%3BMack%2C+Karin+A&rft.aulast=Ory&rft.aufirst=Marcia&rft.date=1998-11-01&rft.volume=20&rft.issue=6&rft.spage=653&rft.isbn=&rft.btitle=&rft.title=Research+on+Aging&rft.issn=01640275&rft_id=info:doi/10.1177%2F0164027598206002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/0164027598206002 ER - TY - JOUR T1 - Is There a Self-Monitoring Speech Perception System? AN - 85607261; 9904085 AB - Findings of recent research on the role of feedback in speech production are reviewed with focus on evidence for an auditory transformation system affecting the audiophonatoric perceptual representation of a person's own speech, as formulated by K. T. Kalveram (1993). Studies of speech self-monitoring in foreign language learners & in young children are cited to show that discrimination of phonemic distinctions in the speech of others tends to precede the development of an audiophonatoric monitoring system. A regulatory role of auditory feedback in speech motor activity is sparsely but positively evidenced in three areas: compensation for production alterations, voice control, & the development of a perceptual representation for self-monitoring of speech. 21 References. J. Hitchcock JF - Journal of Communication Disorders AU - Ludlow, Christy L AU - Cikoja, Dragana Barac AD - National Instits Health National Instit Deafness & Other Communication Disorders Voice & Speech Section, Bldg 10 Room 5D38 Bethesda MD 20892 [tel: 301-480-0803; fax: 301-496-9365; mailto:ludlowc@nidcd.nih.gov] Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 505 EP - 510 VL - 31 IS - 6 SN - 0021-9924, 0021-9924 KW - Feedback (23950) KW - Auditory Perception (05800) KW - Speech Production (82780) KW - article KW - 6210: hearing and speech physiology; hearing and speech physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85607261?accountid=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=Journal+of+Communication+Disorders&rft.atitle=Is+There+a+Self-Monitoring+Speech+Perception+System%3F&rft.au=Ludlow%2C+Christy+L%3BCikoja%2C+Dragana+Barac&rft.aulast=Ludlow&rft.aufirst=Christy&rft.date=1998-11-01&rft.volume=31&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Journal+of+Communication+Disorders&rft.issn=00219924&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 - JCDIAI N1 - SubjectsTermNotLitGenreText - Feedback (23950); Speech Production (82780); Auditory Perception (05800) ER - TY - JOUR T1 - Estimation of component and parameter distributions in spectral analysis. AN - 85274923; pmid-9809510 AB - A method is presented for estimating the distributions of the components and parameters determined with spectral analysis when it is applied to a single data set. The method uses bootstrap resampling to simulate the effect of noise on the computed spectrum and to correct for possible bias in the estimates. A number of bootstrap procedures are reviewed, and one is selected for application to the kinetic analysis of positron emission tomography dynamic studies. The technique is shown to require minimal assumptions about noise in the measurements, and its small sample properties are established through Monte-Carlo simulations. The advantages and limitations of spectral analysis with bootstrap resampling for deriving inferences for tracer kinetic modeling are illustrated through sample analyses of time-activity curves for [18F]fluorodeoxyglucose and [15O]-labeled water. JF - Journal of Cerebral Blood Flow and Metabolism AU - Turkheimer, F AU - Sokoloff, L AU - Bertoldo, A AU - Lucignani, G AU - Reivich, M AU - Jaggi, J L AU - Schmidt, K AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 1211 EP - 1222 VL - 18 IS - 11 SN - 0271-678X, 0271-678X KW - Probability KW - Computer Simulation KW - Reproducibility of Results KW - Human KW - Algorithms KW - Brain KW - Monte Carlo Method KW - Water KW - Fludeoxyglucose F 18 KW - Kinetics KW - Oxygen Radioisotopes KW - Radiopharmaceuticals KW - Confidence Intervals KW - Support, Non-U.S. Gov't KW - Tomography, Emission-Computed KW - Male KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274923?accountid=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+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Estimation+of+component+and+parameter+distributions+in+spectral+analysis.&rft.au=Turkheimer%2C+F%3BSokoloff%2C+L%3BBertoldo%2C+A%3BLucignani%2C+G%3BReivich%2C+M%3BJaggi%2C+J+L%3BSchmidt%2C+K&rft.aulast=Turkheimer&rft.aufirst=F&rft.date=1998-11-01&rft.volume=18&rft.issue=11&rft.spage=1211&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Neuropsychiatric features of corticobasal degeneration. AN - 85265164; pmid-9810944 AB - OBJECTIVE: To characterise the neuropsychiatric symptoms of patients with corticobasal degeneration (CBD). METHODS: The neuropsychiatric inventory (NPI), a tool with established validity and reliability, was administered to 15 patients with CBD (mean (SEM), age 67.9 (2) years); 34 patients with progressive supranuclear palsy (PSP) (66.6 (1.2) years); and 25 controls (70 (0.8) years), matched for age and education. Both patient groups had similar duration of symptoms and mini mental state examination scores. Semantic fluency and motor impairment were also assessed. RESULTS: Patients with CBD exhibited depression (73%), apathy (40%), irritability (20%), and agitation (20%) but less often had anxiety, disinhibition, delusions, or aberrant motor behaviour (for example, pacing). The depression and irritability of patients with CBD were more frequent and severe than those of patients with PSP. Conversely, patients with PSP exhibited significantly more apathy than patients with CBD. The presence of high depression and irritability and low apathy scale scores correctly differentiated the patients with CBD 88% of the time. The irritability of patients with CBD was significantly associated with disinhibition (r=0.85) and apathy (r=0.72). In CBD, apathy was associated with disinhibition (r=0.67); disinhibition was associated with aberrant motor behaviour (r=0.68) and apathy (r=0.67); and aberrant motor behaviour with delusions (r=1.0). On the other hand, depression was not associated with any other behaviour, suggesting that it has a different pathophysiological mechanism. Symptom duration was associated with total motor scores (r=0.69). However, total motor score was not associated with any behaviour or cognitive scores. CONCLUSIONS: The findings indicate that frontosubcortical pathways mediating cognition, emotion, and motor function in CBD are not affected in parallel. Patients with CBD and PSP have overlapping neuropsychiatric manifestations, but they express distinctive symptom profiles. Evaluating the behavioural abnormalities of parkinsonian patients may help clarify the role of the basal ganglia in behaviour. JF - Journal of Neurology, Neurosurgery, and Psychiatry AU - Litvan, I AU - Cummings, J L AU - Mega, M AD - National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-9130, USA. PY - 1998 SP - 717 EP - 721 VL - 65 IS - 5 SN - 0022-3050, 0022-3050 KW - Cerebral Cortex KW - Severity of Illness Index KW - Nerve Degeneration KW - Comparative Study KW - Support, U.S. Gov't, P.H.S. KW - Mental Disorders KW - Human KW - Supranuclear Palsy, Progressive KW - Psychomotor Disorders KW - Aged KW - Support, Non-U.S. Gov't KW - Neuropsychological Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265164?accountid=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+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.atitle=Neuropsychiatric+features+of+corticobasal+degeneration.&rft.au=Litvan%2C+I%3BCummings%2C+J+L%3BMega%2C+M&rft.aulast=Litvan&rft.aufirst=I&rft.date=1998-11-01&rft.volume=65&rft.issue=5&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.issn=00223050&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. AN - 85227982; pmid-9819448 AB - BACKGROUND: Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. METHODS: We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle-ear immittance, and recording of otoacoustic emissions. RESULTS: Two frame-shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. CONCLUSIONS: The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin, whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations. JF - The New England Journal of Medicine AU - Morell, R J AU - Kim, H J AU - Hood, L J AU - Goforth, L AU - Friderici, K AU - Fisher, R AU - Van Camp G AU - Berlin, C I AU - Oddoux, C AU - Ostrer, H AU - Keats, B AU - Friedman, Thomas B AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 1500 EP - 1505 VL - 339 IS - 21 SN - 0028-4793, 0028-4793 KW - Linkage (Genetics) KW - Reference Values KW - Support, U.S. Gov't, P.H.S. KW - Gene Frequency KW - Human KW - Connexins KW - Jews KW - Deafness KW - Otoacoustic Emissions, Spontaneous KW - Heterozygote KW - Hearing Tests KW - Support, Non-U.S. Gov't KW - Male KW - Genes, Recessive KW - Female KW - Frameshift Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227982?accountid=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=Mutations+in+the+connexin+26+gene+%28GJB2%29+among+Ashkenazi+Jews+with+nonsyndromic+recessive+deafness.&rft.au=Morell%2C+R+J%3BKim%2C+H+J%3BHood%2C+L+J%3BGoforth%2C+L%3BFriderici%2C+K%3BFisher%2C+R%3BVan+Camp+G%3BBerlin%2C+C+I%3BOddoux%2C+C%3BOstrer%2C+H%3BKeats%2C+B%3BFriedman%2C+Thomas+B&rft.aulast=Morell&rft.aufirst=R&rft.date=1998-11-01&rft.volume=339&rft.issue=21&rft.spage=1500&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 - Resistance to 6-thioguanine in mismatch repair-deficient human cancer cell lines correlates with an increase in induced mutations at the HPRT locus. AN - 70125058; 9855005 AB - Although the resistance to the cytotoxic response of certain DNA damaging agents has been well characterized in cells deficient in mismatch repair, little is known about how such resistance affects mutagenesis. Using human cancer cell lines defective in mismatch repair (MMR) and complementary cell lines in which the MMR defects were corrected by chromosome transfer, we present the cytotoxic effect and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus following exposure to the chemotherapeutic agent, 6-thioguanine (6-TG). Upon exposure to 6-TG, there was a differential cytotoxic response. The MMR-deficient cells were resistant to 6-TG exposure up to 5 microM, whereas the MMR-proficient cell lines were significantly more sensitive at the same levels of exposure. Furthermore, the mutagenic response at HPRT induced by 6-TG was substantially increased in the MMR-deficient lines relative to the MMR-proficient cell lines. These findings support the notion that cytotoxicity to 6-TG is mediated through functional MMR and that resistance to the cytotoxic effects of 6-TG is directly associated with an increase in induced mutations in MMR-defective cells. These data suggest that the use of 6-TG as a chemotherapeutic agent may result in the selection of MMR-defective cells, thereby predisposing the patient to an increased risk for developing secondary tumors. JF - Carcinogenesis AU - Glaab, W E AU - Risinger, J I AU - Umar, A AU - Barrett, J C AU - Kunkel, T A AU - Tindall, K R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1931 EP - 1937 VL - 19 IS - 11 SN - 0143-3334, 0143-3334 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Antimetabolites, Antineoplastic KW - Carrier Proteins KW - DNA-Binding Proteins KW - Fungal Proteins KW - MLH1 protein, human KW - MSH6 protein, S cerevisiae KW - Neoplasm Proteins KW - Nuclear Proteins KW - Saccharomyces cerevisiae Proteins KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Humans KW - Neoplasm Proteins -- genetics KW - Drug Resistance, Neoplasm KW - Fungal Proteins -- genetics KW - Chromosome Mapping KW - DNA Repair KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Mutation KW - Thioguanine -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70125058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Resistance+to+6-thioguanine+in+mismatch+repair-deficient+human+cancer+cell+lines+correlates+with+an+increase+in+induced+mutations+at+the+HPRT+locus.&rft.au=Glaab%2C+W+E%3BRisinger%2C+J+I%3BUmar%2C+A%3BBarrett%2C+J+C%3BKunkel%2C+T+A%3BTindall%2C+K+R&rft.aulast=Glaab&rft.aufirst=W&rft.date=1998-11-01&rft.volume=19&rft.issue=11&rft.spage=1931&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Melatonin does not inhibit estradiol-stimulated proliferation in MCF-7 and BG-1 cells. AN - 70117647; 9854999 AB - Melatonin, an indolic pineal hormone, is produced primarily at night in mammals and is important in controlling biological rhythms. Previous research suggested that melatonin can attenuate proliferation in the estrogen-responsive MCF-7 breast cancer cell line. We tested whether these anti-proliferative effects may have physiological consequences upon two estrogen-responsive cell lines, MCF-7 (a breast cancer cell line) and BG-1 (an ovarian adenocarcinoma cell line). Melatonin (10(-9)-10(-5) M) attenuated proliferation of MCF-7 and BG-1 cells by >20% in the absence of estrogen. However, 17beta-estradiol exposure negated the ability of melatonin to inhibit proliferation. To substantiate this finding, cells were estrogen starved followed by multiple treatments with estradiol and melatonin. Melatonin did not inhibit estradiol-stimulated proliferation under this protocol. Estradiol increased MCF-7 and BG-1 cell cycle transition from G1 to S phase, however, melatonin did not inhibit this transition nor did it down-regulate estradiol-induced pS2 mRNA levels measured by northern blotting, further indicating that melatonin was unable to attenuate estradiol-induced proliferation and gene expression. We also examined the effects of melatonin on estradiol-induced proliferation in MCF-7 cell xenografts in athymic nude mice. Melatonin at a dose 28 times greater than 17beta-estradiol did not inhibit estradiol-induced proliferation in vivo. Furthermore, pinealectomy did not increase proliferation. Therefore, we conclude that melatonin does not directly inhibit estradiol-induced proliferation. JF - Carcinogenesis AU - Baldwin, W S AU - Travlos, G S AU - Risinger, J I AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1895 EP - 1900 VL - 19 IS - 11 SN - 0143-3334, 0143-3334 KW - Proteins KW - 0 KW - RNA, Messenger KW - TFF1 protein, human KW - Trefoil Factor-1 KW - Tumor Suppressor Proteins KW - Estradiol KW - 4TI98Z838E KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Breast Neoplasms -- pathology KW - Ovarian Neoplasms -- pathology KW - Humans KW - RNA, Messenger -- analysis KW - Mice, Nude KW - Mice KW - Proteins -- genetics KW - Female KW - Cell Cycle -- drug effects KW - Melatonin -- pharmacology KW - Estradiol -- pharmacology KW - Cell Division -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70117647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Melatonin+does+not+inhibit+estradiol-stimulated+proliferation+in+MCF-7+and+BG-1+cells.&rft.au=Baldwin%2C+W+S%3BTravlos%2C+G+S%3BRisinger%2C+J+I%3BBarrett%2C+J+C&rft.aulast=Baldwin&rft.aufirst=W&rft.date=1998-11-01&rft.volume=19&rft.issue=11&rft.spage=1895&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver. AN - 70116413; 9855014 AB - The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are unclear but are mediated by the peroxisome proliferator-activated receptor alpha (PPARalpha). To determine the role of PPARalpha in the mechanisms of hepatocarcinogenesis, the effect of Wy-14,643 on expression patterns of acyl CoA oxidase (ACO) and proteins involved in cell proliferation in the PPARalpha-null mouse were evaluated. ACO, CDK-1, CDK-2, CDK-4, PCNA and c-myc proteins were significantly increased in wild-type mice fed Wy-14,643 for 5 weeks or 11 months, as compared with controls. This effect was not observed in Wy-14,643-treated PPARalpha-null mice. Expression patterns of cyclin B1, cyclin D, cyclin E and p53 were not different in any of the groups. mRNAs encoding CDK-1, CDK-4, cyclin D1 and c-myc were also increased in wild-type mice fed Wy-14,643 but not in PPARalpha-null mice. These results indicate that the increase in CDK-1, CDK-4 and c-myc may be caused by an increase in transcription that is mediated directly or indirectly by PPARalpha. Thus PPARalpha-dependent alterations in cell cycle regulatory proteins induced by peroxisome proliferators are likely to contribute to the hepatocarcinogenicity of peroxisome proliferators. JF - Carcinogenesis AU - Peters, J M AU - Aoyama, T AU - Cattley, R C AU - Nobumitsu, U AU - Hashimoto, T AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jpeters@helix.nih.gov Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1989 EP - 1994 VL - 19 IS - 11 SN - 0143-3334, 0143-3334 KW - Peroxisome Proliferators KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Proto-Oncogene Proteins c-myc KW - Pyrimidines KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - pirinixic acid KW - 86C4MRT55A KW - Oxidoreductases KW - EC 1.- KW - Acyl-CoA Oxidase KW - EC 1.3.3.6 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - Oxidoreductases -- metabolism KW - Cyclin-Dependent Kinases -- analysis KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Proto-Oncogene Proteins c-myc -- analysis KW - Male KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- metabolism KW - Pyrimidines -- toxicity KW - Peroxisome Proliferators -- toxicity KW - Liver Neoplasms -- chemically induced KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70116413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+peroxisome+proliferator-activated+receptor+alpha+in+altered+cell+cycle+regulation+in+mouse+liver.&rft.au=Peters%2C+J+M%3BAoyama%2C+T%3BCattley%2C+R+C%3BNobumitsu%2C+U%3BHashimoto%2C+T%3BGonzalez%2C+F+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1998-11-01&rft.volume=19&rft.issue=11&rft.spage=1989&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occurrence of cocaine in urine of substance-abuse treatment patients. AN - 70112056; 9847008 AB - As part of ongoing research efforts to improve methods of monitoring drug use in treatment patients, the presence of cocaine in urine specimens was evaluated as a possible marker for recent illicit cocaine use. A total of 2327 urine specimens collected during a 17-week clinical trial of a cocaine-abuse treatment study were tested. Cocaine was measured by gas chromatography-mass spectrometry, and benzoylecgonine (BZE) equivalents were determined by fluorescence polarization immunoassay (FPIA). More than one-third of the specimens were positive (> 25 ng/mL) for cocaine (36.8%), and nearly two-thirds were positive (> 300 ng/mL) for cocaine metabolite by FPIA (62.7%). Median concentrations of cocaine and BZE equivalents were 235 and 14,900 ng/mL, respectively, and maximum concentrations were 112,025 and 1,101,190 ng/mL in cocaine- and BZE-positive specimens, respectively. There were 52 specimens that contained cocaine in equal or higher concentrations than BZE equivalents. No significant differences in cocaine or BZE concentrations between Caucasian and African-American or between male and female patients were found. Cocaine was present less frequently and at lower concentrations than BZE but more frequently than expected based on an average half-life of approximately 1 h, which suggests that cocaine may exhibit a longer terminal half-life and/or that accumulation of cocaine can occur in chronic, heavy users. JF - Journal of analytical toxicology AU - Preston, K L AU - Goldberger, B A AU - Cone, E J AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. PY - 1998 SP - 580 EP - 586 VL - 22 IS - 7 SN - 0146-4760, 0146-4760 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Fluorescence Polarization Immunoassay KW - Sex Factors KW - Humans KW - African Americans KW - Aged KW - Substance Abuse Treatment Centers KW - Substance Abuse Detection KW - European Continental Ancestry Group KW - Adult KW - Gas Chromatography-Mass Spectrometry KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Cocaine -- urine KW - Substance-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70112056?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=Occurrence+of+cocaine+in+urine+of+substance-abuse+treatment+patients.&rft.au=Preston%2C+K+L%3BGoldberger%2C+B+A%3BCone%2C+E+J&rft.aulast=Preston&rft.aufirst=K&rft.date=1998-11-01&rft.volume=22&rft.issue=7&rft.spage=580&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 completed - 1999-03-24 N1 - Date created - 1999-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - yTAFII61 has a general role in RNA polymerase II transcription and is required by Gcn4p to recruit the SAGA coactivator complex. AN - 70110550; 9844640 AB - We obtained a recessive insertion mutation in the gene encoding yeast TBP-associated factor yTAFII61/68 that impairs Gcn4p-independent and Gcn4p-activated HIS3 transcription. This mutation also reduces transcription of seven other class II genes, thus indicating a broad role for this yTAFII in RNA polymerase II transcription. The Gcn4p activation domain interacts with multiple components of the SAGA complex in cell extracts, including the yTAFII proteins associated with SAGA, but not with two yTAFIIs restricted to TFIID. The taf61-1 mutation impairs binding of Gcn4p to SAGA/yTAFII subunits but not to components of holoenzyme mediator. Our results provide strong evidence that recruitment of SAGA, in addition to holoenzyme, is crucial for activation by Gcn4p in vivo and that yTAFII61 plays a key role in this process. JF - Molecular cell AU - Natarajan, K AU - Jackson, B M AU - Rhee, E AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 683 EP - 692 VL - 2 IS - 5 SN - 1097-2765, 1097-2765 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Recombinant Fusion Proteins KW - Saccharomyces cerevisiae Proteins KW - TAF(II)61 protein, S cerevisiae KW - TATA-Binding Protein Associated Factors KW - Transcription Factor TFIID KW - Transcription Factors KW - Transcription Factors, TFII KW - Acetyltransferases KW - EC 2.3.1.- KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - Protein Kinases KW - EC 2.7.- KW - RNA Polymerase II KW - EC 2.7.7.- KW - Hydro-Lyases KW - EC 4.2.1.- KW - imidazoleglycerolphosphate dehydratase KW - EC 4.2.1.19 KW - Amitrole KW - ZF80H5GXUF KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Blotting, Northern KW - Cell Division -- drug effects KW - Precipitin Tests KW - Protein Binding KW - Recombinant Fusion Proteins -- metabolism KW - Phenotype KW - Genes, Fungal -- genetics KW - Models, Genetic KW - Hydro-Lyases -- genetics KW - Amitrole -- pharmacology KW - Mutagenesis, Insertional KW - Sequence Deletion KW - RNA Polymerase II -- metabolism KW - Transcription Factors, TFII -- metabolism KW - Transcription Factors -- metabolism KW - Acetyltransferases -- metabolism KW - DNA-Binding Proteins -- genetics KW - Transcription, Genetic KW - Transcription Factors -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Protein Kinases -- metabolism KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Saccharomyces cerevisiae -- drug effects KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70110550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=yTAFII61+has+a+general+role+in+RNA+polymerase+II+transcription+and+is+required+by+Gcn4p+to+recruit+the+SAGA+coactivator+complex.&rft.au=Natarajan%2C+K%3BJackson%2C+B+M%3BRhee%2C+E%3BHinnebusch%2C+A+G&rft.aulast=Natarajan&rft.aufirst=K&rft.date=1998-11-01&rft.volume=2&rft.issue=5&rft.spage=683&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 - 1998-12-24 N1 - Date created - 1998-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease. AN - 70101833; 9844789 AB - The contribution of dopamine D1 receptor stimulation to the motor effects of dopaminergic drugs in patients with Parkinson's disease remains undetermined. The authors of this article studied the clinical efficacy, pharmacokinetics, and tolerability of the full D1 receptor agonist dihydrexidine, (+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine hydrochloride in a double-blind, placebo-controlled trial in four patients with Parkinson's disease. Single intravenous doses were carefully titrated according to a fixed schedule ranging from 2 mg to the highest tolerated dose (or a maximum of 70 mg) infused over either 15 or 120 minutes. The only patient to achieve a plasma drug concentration greater than 100 ng/ml had a brief but definite motor improvement accompanied by choreic dyskinesias similar to the response to levodopa. Dose-limiting adverse effects, including flushing, hypotension, and tachycardia, were observed in all cases, especially with rapid infusions. No nausea or emesis occurred. Pharmacokinetic studies yielded a plasma half-life < 5 minutes. These preliminary data suggest that dihydrexidine has a marginal therapeutic window for providing an antiparkinsonian effect, although it remains uncertain how much of this effect is attributable to pure D1 receptor stimulation. JF - Clinical neuropharmacology AU - Blanchet, P J AU - Fang, J AU - Gillespie, M AU - Sabounjian, L AU - Locke, K W AU - Gammans, R AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. PY - 1998 SP - 339 EP - 343 VL - 21 IS - 6 SN - 0362-5664, 0362-5664 KW - Dopamine Agonists KW - 0 KW - Phenanthridines KW - Receptors, Dopamine D1 KW - dihydrexidine KW - 32D64VH037 KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Motor Activity -- drug effects KW - Middle Aged KW - Male KW - Phenanthridines -- pharmacokinetics KW - Dopamine Agonists -- therapeutic use KW - Receptors, Dopamine D1 -- agonists KW - Dopamine Agonists -- pharmacokinetics KW - Parkinson Disease -- metabolism KW - Phenanthridines -- therapeutic use KW - Dopamine Agonists -- adverse effects KW - Phenanthridines -- adverse effects KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70101833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropharmacology&rft.atitle=Effects+of+the+full+dopamine+D1+receptor+agonist+dihydrexidine+in+Parkinson%27s+disease.&rft.au=Blanchet%2C+P+J%3BFang%2C+J%3BGillespie%2C+M%3BSabounjian%2C+L%3BLocke%2C+K+W%3BGammans%2C+R%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1998-11-01&rft.volume=21&rft.issue=6&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropharmacology&rft.issn=03625664&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic and environmental influences on drug use and abuse/dependence in male and female twins. AN - 70099549; 9839149 AB - Twins were recruited through alcohol and drug treatment programs. With structural equation modeling, genetic and environmental estimates were obtained for use and DSM-III abuse/dependence of sedatives, opioids, cocaine, stimulants, and cannabis as well as any illicit drug. Analyses were conducted separately for males and females. Models included thresholds based on population prevalence of use or abuse/dependence and ever having been in treatment. Genetic influences were found for most measures. They were generally stronger for males than females and for clinical diagnoses of abuse/dependence compared to use. Common environmental influences played a greater role in use than abuse/dependence. JF - Drug and alcohol dependence AU - van den Bree, M B AU - Johnson, E O AU - Neale, M C AU - Pickens, R W AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. mvandenb@intra.nida.nih.gov Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 231 EP - 241 VL - 52 IS - 3 SN - 0376-8716, 0376-8716 KW - Psychotropic Drugs KW - 0 KW - Street Drugs KW - Index Medicus KW - Alcoholism -- rehabilitation KW - Minnesota KW - Humans KW - Alcoholism -- genetics KW - Genetic Predisposition to Disease -- psychology KW - Alcoholism -- psychology KW - Genetic Predisposition to Disease -- genetics KW - Risk Factors KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Diseases in Twins -- psychology KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology KW - Diseases in Twins -- genetics KW - Substance-Related Disorders -- genetics KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70099549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+and+environmental+influences+on+drug+use+and+abuse%2Fdependence+in+male+and+female+twins.&rft.au=van+den+Bree%2C+M+B%3BJohnson%2C+E+O%3BNeale%2C+M+C%3BPickens%2C+R+W&rft.aulast=van+den+Bree&rft.aufirst=M&rft.date=1998-11-01&rft.volume=52&rft.issue=3&rft.spage=231&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 - 1999-02-26 N1 - Date created - 1999-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of nitric oxide in cyclosporine A-induced hypertension. AN - 70081342; 9822443 AB - Cyclosporine A (CsA) is an immunosuppressive agent that also 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-1. d-1) in olive oil or vehicle by intraperitoneal injection for 7 days. CsA administration produced a 42% increase (P<0.001) in mean arterial pressure (MAP) that reached a plateau after 3 days. Conversely, the levels of both nitrate/nitrite, metabolites of nitric oxide (NO), and cGMP, which mediates NO action, decreased by 50% (P<0.001) and 35% (P<0.001), 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<0.001) in tension, whereas endothelium-dependent relaxation induced by acetylcholine (ACh, 10(-9) mol/L) was inhibited 65% (P<0.001) compared with that in untreated rats. This response was similar to that of endothelium-denuded aortic rings from untreated rats in which ACh-induced relaxation was completely abolished (P<0.001), but relaxation induced by S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) mol/L) was unaffected (P<0.001). ACh-induced formation of both nitrate/nitrite and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P<0.001) and 65% (P<0.001), respectively, compared with intact aortic rings. The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (10 mg. kg-1. d-1 IP), the precursor of NO. There were no changes in MAP and tension in rats treated with L-arginine alone. In summary, CsA inhibits endothelial NO activity, with resulting increases in MAP and tension, and this inhibition can be overcome by parenteral administration of L-arginine. JF - Hypertension (Dallas, Tex. : 1979) AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 849 EP - 855 VL - 32 IS - 5 SN - 0194-911X, 0194-911X KW - Endothelin Receptor Antagonists KW - 0 KW - Enzyme Inhibitors KW - Immunosuppressive Agents KW - Nitrates KW - Nitrites KW - Olive Oil KW - Peptides, Cyclic KW - Plant Oils KW - S-nitro-N-acetylpenicillamine KW - Sulfonamides KW - Cyclosporine KW - 83HN0GTJ6D KW - Arginine KW - 94ZLA3W45F KW - Penicillamine KW - GNN1DV99GX KW - Cyclic GMP KW - H2D2X058MU KW - bosentan KW - Q326023R30 KW - cyclo(Trp-Asp-Pro-Val-Leu) KW - S2A8YZM151 KW - Index Medicus KW - Animals KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Cyclic GMP -- urine KW - Nitrites -- urine KW - Arginine -- pharmacology KW - Rats KW - Nitrates -- urine KW - Rats, Sprague-Dawley KW - Aorta -- drug effects KW - Sulfonamides -- pharmacology KW - Plant Oils -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Male KW - Hypertension -- chemically induced KW - Hypertension -- physiopathology KW - Cyclosporine -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Vasoconstriction -- drug effects KW - Blood Pressure -- drug effects KW - Immunosuppressive Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70081342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Role+of+nitric+oxide+in+cyclosporine+A-induced+hypertension.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1998-11-01&rft.volume=32&rft.issue=5&rft.spage=849&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=0194911X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-07 N1 - Date created - 1998-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anxiety and depression among HIV-infected heterosexuals--a report from India. AN - 70078467; 9835233 AB - The aim of the study was to study factors related to anxiety, depression, and suicidal ideation among HIV-seropositive heterosexuals soon after being tested for their HIV status for the first time. Anxiety, depression, and suicidal ideation were assessed among 51 HIV-seropositive heterosexual men and women with various stages of HIV infection. All assessments were done between 4 and 6 weeks after revelation of positive serostatus. Psychosocial variables such as quality of family relationships and substance use and sociodemographic details such as gender, income, education, and residence were studied for their association with psychiatric morbidity. Illness details studied for their association with psychiatric morbidity included stage of HIV infection, spouse's HIV status, presence of physical illness, and pain. Depression was present in 40% and anxiety in 36% of the sample. Serious suicidal intent was seen in 14%. Multiple regression analysis indicated that presence of pain, concurrent alcohol abuse, poor family relations, and presence of AIDS in the spouse were significant factors associated with depression, anxiety, and suicidal ideation. JF - Journal of psychosomatic research AU - Chandra, P S AU - Ravi, V AU - Desai, A AU - Subbakrishna, D K AD - Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bangalore, India. chandra@nimhans.ren.nic.in Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 401 EP - 409 VL - 45 IS - 5 SN - 0022-3999, 0022-3999 KW - Index Medicus KW - AIDS/HIV KW - Socioeconomic Factors KW - Regression Analysis KW - India -- epidemiology KW - Suicide, Attempted -- psychology KW - Risk Factors KW - Humans KW - Interpersonal Relations KW - Adult KW - Pain Measurement KW - Substance-Related Disorders -- psychology KW - Male KW - Female KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Depressive Disorder -- epidemiology KW - HIV Seropositivity -- psychology KW - Depressive Disorder -- psychology KW - Anxiety Disorders -- psychology KW - Anxiety Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70078467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychosomatic+research&rft.atitle=Anxiety+and+depression+among+HIV-infected+heterosexuals--a+report+from+India.&rft.au=Chandra%2C+P+S%3BRavi%2C+V%3BDesai%2C+A%3BSubbakrishna%2C+D+K&rft.aulast=Chandra&rft.aufirst=P&rft.date=1998-11-01&rft.volume=45&rft.issue=5&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Journal+of+psychosomatic+research&rft.issn=00223999&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 - Gene-environment interactions in alcohol research: round table discussion of conceptual and methodological issues using animal models. AN - 70076510; 9835286 JF - Alcoholism, clinical and experimental research AU - Witt, E AU - Cunningham, C AU - Dudek, B AU - Finn, P AU - Henderson, N AU - Plomin, R AU - Samson, H AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1719 EP - 1723 VL - 22 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Genotype KW - Animals KW - Humans KW - Research KW - Gene Expression -- physiology KW - Disease Models, Animal KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70076510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene-environment+interactions+in+alcohol+research%3A+round+table+discussion+of+conceptual+and+methodological+issues+using+animal+models.&rft.au=Witt%2C+E%3BCunningham%2C+C%3BDudek%2C+B%3BFinn%2C+P%3BHenderson%2C+N%3BPlomin%2C+R%3BSamson%2C+H&rft.aulast=Witt&rft.aufirst=E&rft.date=1998-11-01&rft.volume=22&rft.issue=8&rft.spage=1719&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 - 1999-02-22 N1 - Date created - 1999-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of the pharmacokinetics of a radioimmunoconjugate, 90Y-T101, in patients with CD5-expressing leukemia and lymphoma. AN - 70075738; 9829731 AB - Ten patients with advanced or refractory CD5-expressing hematologic neoplasms [two with chronic lymphocytic leukemia and eight with cutaneous T-cell lymphoma (CTCL)] were treated in a Phase I study with the radioimmunoconjugate 90Y-T101, which targets CD5+ lymphocytes. Prior imaging studies using 111In-T101 demonstrated uptake in involved lymph nodes and skin in patients with CTCL, and Phase I studies with unmodified T101 demonstrated transient responses. In this study, patients were treated with 5 or 10 mCi of 90Y chelated to T101 via isothiocyanatobenzyl diethylenetriamine pentaacetic acid, along with tracer doses of 111In-T101 for imaging. The biodistribution of the radioimmunoconjugate was determined by measuring 90Y and 111In blood clearance, urine excretion, and accumulation in bone marrow and in involved skin lesions. The intravascular pharmacokinetics of 90Y were predicted by 111In-labeled T101. The greatest differences in biodistribution between 111In and 90Y were in the higher bone accumulation of 90Y and its lower urinary excretion. Imaging studies demonstrated targeting of skin lesions and involved lymph nodes in CTCL patients. The predominant toxicity was bone marrow suppression. Rapid antigenic modulation of CD5 on circulating T and B cells was observed. Recovery of T-cell populations occurred within 2-3 weeks; however, suppression of B-cell populations persisted after 5+ weeks. All CTCL patients developed human antimouse antibody after one cycle and thus were not retreated; one patient with chronic lymphocytic leukemia received a second cycle of therapy. Partial responses occurred in five patients, two with chronic lymphocytic leukemia and three with CTCL. The median response duration was 23 weeks. One CTCL patient who subsequently received electron beam irradiation to a residual lesion is disease-free after 6 years. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Foss, F M AU - Raubitscheck, A AU - Mulshine, J L AU - Fleisher, T A AU - Reynolds, J C AU - Paik, C H AU - Neumann, R D AU - Boland, C AU - Perentesis, P AU - Brown, M R AU - Frincke, J M AU - Lollo, C P AU - Larson, S M AU - Carrasquillo, J A AD - National Cancer Institute Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 2691 EP - 2700 VL - 4 IS - 11 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD5 KW - Immunoconjugates KW - Indium Radioisotopes KW - Yttrium Radioisotopes KW - Index Medicus KW - Radioimmunotherapy KW - Humans KW - Lymphocyte Subsets -- drug effects KW - Adult KW - Treatment Outcome KW - Indium Radioisotopes -- pharmacokinetics KW - Lymphocyte Subsets -- immunology KW - Middle Aged KW - Tissue Distribution KW - Yttrium Radioisotopes -- therapeutic use KW - Antigens, CD5 -- immunology KW - Lymphoma, T-Cell, Cutaneous -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- radiotherapy KW - Immunoconjugates -- therapeutic use KW - Lymphoma, T-Cell, Cutaneous -- therapy KW - Antibodies, Monoclonal -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- metabolism KW - Lymphoma, T-Cell, Cutaneous -- metabolism KW - Immunoconjugates -- immunology KW - Immunoconjugates -- pharmacokinetics KW - Antibodies, Monoclonal -- pharmacokinetics KW - Yttrium Radioisotopes -- pharmacokinetics KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - Lymphoma, T-Cell, Cutaneous -- radiotherapy KW - Immunoconjugates -- adverse effects KW - Yttrium Radioisotopes -- adverse effects KW - Antibodies, Monoclonal -- adverse effects KW - Leukemia, Lymphocytic, Chronic, B-Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70075738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+study+of+the+pharmacokinetics+of+a+radioimmunoconjugate%2C+90Y-T101%2C+in+patients+with+CD5-expressing+leukemia+and+lymphoma.&rft.au=Foss%2C+F+M%3BRaubitscheck%2C+A%3BMulshine%2C+J+L%3BFleisher%2C+T+A%3BReynolds%2C+J+C%3BPaik%2C+C+H%3BNeumann%2C+R+D%3BBoland%2C+C%3BPerentesis%2C+P%3BBrown%2C+M+R%3BFrincke%2C+J+M%3BLollo%2C+C+P%3BLarson%2C+S+M%3BCarrasquillo%2C+J+A&rft.aulast=Foss&rft.aufirst=F&rft.date=1998-11-01&rft.volume=4&rft.issue=11&rft.spage=2691&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 - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans. AN - 70073824; 9821993 AB - Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-pinprick hyperalgesia were studied after the injection of intradermal capsaicin. Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 microg capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick hyperalgesia, and side effects were determined every 5 min for 60 min. The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and neurological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states. JF - Anesthesiology AU - Sang, C N AU - Hostetter, M P AU - Gracely, R H AU - Chappell, A S AU - Schoepp, D D AU - Lee, G AU - Whitcup, S AU - Caruso, R AU - Max, M B AD - NIDR/NIH Pain Research Clinic, Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. sang@etherdome.mgh.harvard.edu Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1060 EP - 1067 VL - 89 IS - 5 SN - 0003-3022, 0003-3022 KW - Analgesics, Non-Narcotic KW - 0 KW - Isoquinolines KW - Receptors, AMPA KW - Receptors, Kainic Acid KW - Tetrazoles KW - tezampanel KW - 6XN50U405Y KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Hot Temperature KW - Skin -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Pain Threshold -- drug effects KW - Adult KW - Pain Measurement -- drug effects KW - Middle Aged KW - Physical Stimulation KW - Male KW - Nociceptors -- drug effects KW - Tetrazoles -- pharmacology KW - Isoquinolines -- pharmacology KW - Receptors, AMPA -- antagonists & inhibitors KW - Pain -- drug therapy KW - Analgesics, Non-Narcotic -- pharmacology KW - Pain -- chemically induced KW - Receptors, Kainic Acid -- antagonists & inhibitors KW - Hyperalgesia -- chemically induced KW - Hyperalgesia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70073824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=AMPA%2Fkainate+antagonist+LY293558+reduces+capsaicin-evoked+hyperalgesia+but+not+pain+in+normal+skin+in+humans.&rft.au=Sang%2C+C+N%3BHostetter%2C+M+P%3BGracely%2C+R+H%3BChappell%2C+A+S%3BSchoepp%2C+D+D%3BLee%2C+G%3BWhitcup%2C+S%3BCaruso%2C+R%3BMax%2C+M+B&rft.aulast=Sang&rft.aufirst=C&rft.date=1998-11-01&rft.volume=89&rft.issue=5&rft.spage=1060&rft.isbn=&rft.btitle=&rft.title=Anesthesiology&rft.issn=00033022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-30 N1 - Date created - 1998-11-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Anesthesiology. 1998 Nov;89(5):1049-51 [9821991] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sedation for pediatric procedures, using ketamine and midazolam, in a primarily adult intensive care unit: a retrospective evaluation. AN - 70072238; 9824086 AB - To evaluate the effectiveness and safety of pediatric procedures performed by adult critical care practitioners, using the combination of ketamine and midazolam for anesthesia and sedation. A retrospective case series. The intensive care unit (ICU) of a 325-bed tertiary research hospital. Individuals from 1 to 18 yrs of age who had intravenous midazolam sedation and ketamine anesthesia administered while undergoing lumbar puncture, bone biopsy, central venous catheter placement, liver biopsy, thoracentesis, or bone marrow aspirate/biopsy. None. A retrospective chart review was performed. The dosages of medications used were tabulated, and milligram per kilogram dosages were calculated. The procedures performed, their durations, and any complications of the anesthesia and sedation were noted. These complications included: oxygen desaturations <90%, vital sign alterations requiring intervention, rashes, subjective complaints of dizziness by the patient, and emergence reactions to ketamine. A total of 127 pediatric patients were admitted to the ICU sedation area for a total of 295 procedures. All patients received ketamine and midazolam intravenously in divided doses and titrated to effect. A total of nine complications were observed. These complications included oxygen desaturation <90% (n = 1), vital sign alterations requiring treatment (n = 3), rash (n = 2), dizziness (n = 1), wheezing (n = 1), and emergence reaction (n = 1). No patient required admission to the ICU because of a complication. There were no episodes of bradycardia or other cardiopulmonary compromise. Pediatric anesthesia and sedation, using ketamine and midazolam, can be performed in a designated monitored setting, outside of the operating room, by experienced personnel, including nonpediatricians. This therapeutic combination allows painful procedures to be performed with less anxiety and discomfort. In experienced hands, a limited number of side effects occur. JF - Critical care medicine AU - Slonim, A D AU - Ognibene, F P AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1662, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1900 EP - 1904 VL - 26 IS - 11 SN - 0090-3493, 0090-3493 KW - Anesthetics, Combined KW - 0 KW - Anesthetics, Dissociative KW - Anesthetics, Intravenous KW - Ketamine KW - 690G0D6V8H KW - Midazolam KW - R60L0SM5BC KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Humans KW - Retrospective Studies KW - Child KW - Child, Preschool KW - Infant KW - Drug Evaluation KW - Adult KW - National Institutes of Health (U.S.) KW - Intensive Care Units KW - Adolescent KW - Female KW - Male KW - Anesthetics, Combined -- administration & dosage KW - Conscious Sedation -- statistics & numerical data KW - Anesthetics, Dissociative -- administration & dosage KW - Anesthetics, Intravenous -- administration & dosage KW - Midazolam -- adverse effects KW - Conscious Sedation -- adverse effects KW - Anesthetics, Combined -- adverse effects KW - Ketamine -- administration & dosage KW - Conscious Sedation -- methods KW - Ketamine -- adverse effects KW - Pain -- prevention & control KW - Midazolam -- administration & dosage KW - Anesthetics, Dissociative -- adverse effects KW - Anesthetics, Intravenous -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70072238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+care+medicine&rft.atitle=Sedation+for+pediatric+procedures%2C+using+ketamine+and+midazolam%2C+in+a+primarily+adult+intensive+care+unit%3A+a+retrospective+evaluation.&rft.au=Slonim%2C+A+D%3BOgnibene%2C+F+P&rft.aulast=Slonim&rft.aufirst=A&rft.date=1998-11-01&rft.volume=26&rft.issue=11&rft.spage=1900&rft.isbn=&rft.btitle=&rft.title=Critical+care+medicine&rft.issn=00903493&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Crit Care Med. 2000 Mar;28(3):909-10 [10752865] Crit Care Med. 1998 Nov;26(11):1791-2 [9824068] Crit Care Med. 2000 Jun;28(6):2176-7 [10890706] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity and DNA fragmentation associated with sequential gemcitabine and 5-fluoro-2'-deoxyuridine in HT-29 colon cancer cells. AN - 70071653; 9829747 AB - The combined cytotoxic effects of the antimetabolites gemcitabine (dFdCyd) and 5-fluoro-2'-deoxyuridine (FdUrd) were studied. Cytotoxicity, biochemical perturbations, and DNA damage seen with dFdCyd and FdUrd alone and in combination were evaluated in HT-29 human colon cancer cells. A 4-h exposure to dFdCyd followed by FdUrd for 24 h produced more than additive cytotoxicity and marked S-phase accumulation. Cells progressed through the cell cycle, however, after a 22-h drug-free interval. [3H]dFdCyd was rapidly metabolized to the 5'-triphosphate and incorporated into DNA. [3H]FdUrd was anabolized exclusively to FdUrd monophosphate, and preexposure to dFdCyd did not affect FdUrd monophosphate formation. Thymidylate synthase catalytic activity was inhibited by 48% after a 4-h exposure to 10 nM FdUrd and by 80% after exposure to the combination. Sequential 4-h exposures to 15 nM dFdCyd and 10 nM FdUrd led to greater depletion of dTTP pools (29% of control) than with either drug alone. Greater effects on nascent DNA integrity were seen with sequential dFdCyd followed by FdUrd. Although parental DNA damage was not evident immediately after exposure to 15 nM dFdCyd for 4 h followed by 10 nM FdUrd for 24 h, high molecular mass DNA fragmentation was evident 72-96 h after drug removal. Sequential dFdCyd/FdUrd was associated with prominent disturbance of the cell cycle, dTTP pool depletion, dATP/dTTP imbalance, and nascent DNA damage. Induction of double-strand parental DNA damage and cell death was delayed, consistent with postmitotic apoptosis. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Ren, Q AU - Kao, V AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 2811 EP - 2818 VL - 4 IS - 11 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - DNA, Neoplasm KW - Floxuridine KW - 039LU44I5M KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Index Medicus KW - Thymidylate Synthase -- antagonists & inhibitors KW - DNA Damage KW - Humans KW - Colonic Neoplasms -- drug therapy KW - HT29 Cells KW - Colonic Neoplasms -- pathology KW - DNA Fragmentation KW - Cell Cycle -- drug effects KW - DNA, Neoplasm -- drug effects KW - Floxuridine -- pharmacology KW - Deoxycytidine -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Deoxycytidine -- pharmacology KW - DNA, Neoplasm -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70071653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxicity+and+DNA+fragmentation+associated+with+sequential+gemcitabine+and+5-fluoro-2%27-deoxyuridine+in+HT-29+colon+cancer+cells.&rft.au=Ren%2C+Q%3BKao%2C+V%3BGrem%2C+J+L&rft.aulast=Ren&rft.aufirst=Q&rft.date=1998-11-01&rft.volume=4&rft.issue=11&rft.spage=2811&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 - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. AN - 70069659; 9819067 AB - In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01). These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15. JF - Archives of general psychiatry AU - Lappalainen, J AU - Long, J C AU - Eggert, M AU - Ozaki, N AU - Robin, R W AU - Brown, G L AU - Naukkarinen, H AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Section of Population Genetics and Linkage, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20852, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 989 EP - 994 VL - 55 IS - 11 SN - 0003-990X, 0003-990X KW - HTR1B protein, human KW - 0 KW - Receptor, Serotonin, 5-HT1B KW - Receptors, Serotonin KW - Abridged Index Medicus KW - Index Medicus KW - Pedigree KW - Southwestern United States -- epidemiology KW - Animals KW - Polymorphism, Genetic KW - Humans KW - Mice KW - Tandem Repeat Sequences -- genetics KW - Comorbidity KW - Indians, North American -- genetics KW - Finland -- ethnology KW - Genotype KW - Base Sequence KW - Adult KW - Molecular Sequence Data KW - Adolescent KW - Finland -- epidemiology KW - Female KW - Male KW - Genetic Linkage KW - Disruptive, Impulse Control, and Conduct Disorders -- genetics KW - Disruptive, Impulse Control, and Conduct Disorders -- epidemiology KW - Antisocial Personality Disorder -- epidemiology KW - Alcoholism -- epidemiology KW - Antisocial Personality Disorder -- genetics KW - Alcoholism -- genetics KW - Receptors, Serotonin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70069659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Linkage+of+antisocial+alcoholism+to+the+serotonin+5-HT1B+receptor+gene+in+2+populations.&rft.au=Lappalainen%2C+J%3BLong%2C+J+C%3BEggert%2C+M%3BOzaki%2C+N%3BRobin%2C+R+W%3BBrown%2C+G+L%3BNaukkarinen%2C+H%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Lappalainen&rft.aufirst=J&rft.date=1998-11-01&rft.volume=55&rft.issue=11&rft.spage=989&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 - 1998-11-24 N1 - Date created - 1998-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine. AN - 70066450; 9827817 AB - Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in long-term survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34+ progenitors or CD3+ cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series. JF - Bone marrow transplantation AU - Childs, R AU - Sanchez, C AU - Engler, H AU - Preuss, J AU - Rosenfeld, S AU - Dunbar, C AU - van Rhee, F AU - Plante, M AU - Phang, S AU - Barrett, A J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 889 EP - 893 VL - 22 IS - 9 SN - 0268-3369, 0268-3369 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Polyomavirus Infections -- complications KW - Humans KW - Adult KW - Middle Aged KW - Child KW - Transplantation, Homologous KW - Adenoviridae Infections -- complications KW - Adolescent KW - T-Lymphocytes -- immunology KW - Male KW - Female KW - Tumor Virus Infections -- complications KW - Hematologic Neoplasms -- therapy KW - Cyclosporine -- administration & dosage KW - Cystitis -- etiology KW - Cyclosporine -- adverse effects KW - Bone Marrow Transplantation -- immunology KW - Lymphocyte Depletion -- adverse effects KW - Bone Marrow Transplantation -- adverse effects KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage KW - Hemorrhage -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70066450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bone+marrow+transplantation&rft.atitle=High+incidence+of+adeno-+and+polyomavirus-induced+hemorrhagic+cystitis+in+bone+marrow+allotransplantation+for+hematological+malignancy+following+T+cell+depletion+and+cyclosporine.&rft.au=Childs%2C+R%3BSanchez%2C+C%3BEngler%2C+H%3BPreuss%2C+J%3BRosenfeld%2C+S%3BDunbar%2C+C%3Bvan+Rhee%2C+F%3BPlante%2C+M%3BPhang%2C+S%3BBarrett%2C+A+J&rft.aulast=Childs&rft.aufirst=R&rft.date=1998-11-01&rft.volume=22&rft.issue=9&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Bone+marrow+transplantation&rft.issn=02683369&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 - Comparison of recombinant immunotoxins against LeY antigen expressing tumor cells: influence of affinity, size, and stability. AN - 70060449; 9815167 AB - Monoclonal antibody B3 (MAb B3) reacts with many epithelial cancers. It recognizes a carbohydrate antigen (Ley) which is expressed in a variety of solid tumors including breast and colon. We have used the Fab portion of MAb B3 and a portion of the constant domain of human IgG1 to make recombinant immunotoxins of different compositions. The toxin component employed is a truncated form of Pseudomonas exotoxin (PE38). The light chain or Fd of the antibody was cloned from hybridoma RNA and fused to PE38. Immunotoxin (IT) was then expressed in Escherichia coli as a fusion protein and refolded with either the Fd or the light chain. We have also made B3(Fab) immunotoxins of different sizes ranging 85-140 kDa, by introducing different portions of the constant domain of human IgG1 at the junction of Fd and PE38 fusion site. We compared the properties of the resulting immunotoxins with existing anti-Ley immunotoxins side by side. All recombinant Fab-immunotoxins made in this study were cytotoxic to antigen-positive cancer cell lines. However, in contrast to the B3(scFv) immunotoxin, the B3(Fab) immunotoxins are very stable, retaining 90% of their activity after 24 h of incubation in human serum albumin at 37 degreesC. A pharmacokinetics study with these immunotoxin molecules showed a longer survival in the circulation of mice compared to the smaller Fv immunotoxins. The smaller size of the Fab immunotoxins compared to B3Lys-PE38 and the increased T1/2 value compared to B3(scFv)-PE38 and B3(dsFv)-PE38 make these recombinant immunotoxins alternative therapeutic agents to treat Ley antigen positive cancers. JF - Bioconjugate chemistry AU - Bera, T K AU - Pastan, I AD - Laboratory of Molecular Biology, DBS, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, Maryland 20892-4255, USA. PY - 1998 SP - 736 EP - 743 VL - 9 IS - 6 SN - 1043-1802, 1043-1802 KW - Antigens, Neoplasm KW - 0 KW - Immunotoxins KW - Lewis Blood-Group System KW - Lewis Y antigen KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Spleen -- metabolism KW - Humans KW - Escherichia coli -- genetics KW - Mice KW - Plasmids KW - Mice, Inbred BALB C KW - Molecular Weight KW - Cloning, Molecular KW - Chromatography, Affinity KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Genetic Vectors KW - Protein Folding KW - Female KW - Immunotoxins -- chemistry KW - Antigens, Neoplasm -- chemistry KW - Lewis Blood-Group System -- chemistry KW - Antigens, Neoplasm -- immunology KW - Lewis Blood-Group System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70060449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Comparison+of+recombinant+immunotoxins+against+LeY+antigen+expressing+tumor+cells%3A+influence+of+affinity%2C+size%2C+and+stability.&rft.au=Bera%2C+T+K%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-11-01&rft.volume=9&rft.issue=6&rft.spage=736&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-19 N1 - Date created - 1999-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclosporine therapy for severe sight-threatening uveitis in children and adolescents. AN - 70054631; 9818601 AB - To review the safety and efficacy of cyclosporine in the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis. A retrospective chart review was performed on all children younger than 18 years of age with chronic bilateral sight-threatening uveitis who were treated with cyclosporine. Assessment of the therapeutic efficacy and development of adverse effects of cyclosporine after 6 months, 2 years, and 4 years of therapy was performed. Between 1983 and 1992, 15 children and adolescents were treated with cyclosporine. After 6 months, visual acuity improved or stabilized in 82.1% of eyes, while median vitreous inflammation decreased from 2.0 to 0.5. After 2 and 4 years, visual acuity improved or stabilized in 64% and 75% of eyes, respectively. Median vitreous inflammation remained 0.5 after 2 and 4 years of therapy. Mean creatinine clearance and hemoglobin values decreased and serum creatinine increased after 6 months. After 2 years, only mean hemoglobin values remained decreased. After 4 years, no significant differences were noted in any of the laboratory studies. The most frequently noted side effects included transient increases in serum creatinine in 53%, gingival hyperplasia in 40%, and hirsutism in 20% of patients. The authors' results suggest that cyclosporine is a safe and effective therapy for the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis. JF - Ophthalmology AU - Walton, R C AU - Nussenblatt, R B AU - Whitcup, S M AD - Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 2028 EP - 2034 VL - 105 IS - 11 SN - 0161-6420, 0161-6420 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Vision Disorders -- etiology KW - Humans KW - Safety KW - Treatment Outcome KW - Retrospective Studies KW - Vision Disorders -- blood KW - Child KW - Adolescent KW - Creatinine -- blood KW - Visual Acuity KW - Male KW - Female KW - Panuveitis -- blood KW - Uveitis, Intermediate -- drug therapy KW - Cyclosporine -- adverse effects KW - Panuveitis -- drug therapy KW - Cyclosporine -- therapeutic use KW - Uveitis, Intermediate -- blood KW - Panuveitis -- complications KW - Immunosuppressive Agents -- therapeutic use KW - Uveitis, Intermediate -- complications KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70054631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=Cyclosporine+therapy+for+severe+sight-threatening+uveitis+in+children+and+adolescents.&rft.au=Walton%2C+R+C%3BNussenblatt%2C+R+B%3BWhitcup%2C+S+M&rft.aulast=Walton&rft.aufirst=R&rft.date=1998-11-01&rft.volume=105&rft.issue=11&rft.spage=2028&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Botulinum toxin type F for treatment of dystonia: long-term experience. AN - 70051936; 9818895 AB - The authors analyzed retrospectively the results of open-labeled botulinum toxin type F (BTXF) treatment for 1 year or longer in 18 BTXA-resistant patients. All patients except one primary nonresponder to BTXA improved initially with BTXF. Most patients continued to respond to BTXF for 1 year or longer, but four patients became resistant to BTXF. BTXF-resistant patients received a higher dose per treatment and a higher cumulative dose than BTXF-responsive patients. BTXF can be used for long-term treatment of dystonia. It seems prudent to limit BTX doses of all serotypes to the lowest necessary for clinical efficacy. JF - Neurology AU - Chen, R AU - Karp, B I AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1428, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1494 EP - 1496 VL - 51 IS - 5 SN - 0028-3878, 0028-3878 KW - Anti-Dyskinesia Agents KW - 0 KW - botulinum toxin type F KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Abridged Index Medicus KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Blepharospasm -- drug therapy KW - Injections KW - Torticollis -- drug therapy KW - Time Factors KW - Male KW - Female KW - Botulinum Toxins -- administration & dosage KW - Anti-Dyskinesia Agents -- administration & dosage KW - Botulinum Toxins -- therapeutic use KW - Anti-Dyskinesia Agents -- therapeutic use KW - Dystonia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70051936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Botulinum+toxin+type+F+for+treatment+of+dystonia%3A+long-term+experience.&rft.au=Chen%2C+R%3BKarp%2C+B+I%3BHallett%2C+M&rft.aulast=Chen&rft.aufirst=R&rft.date=1998-11-01&rft.volume=51&rft.issue=5&rft.spage=1494&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - General and specific inheritance of substance abuse and alcoholism. AN - 70051366; 9819063 JF - Archives of general psychiatry AU - Goldman, D AU - Bergen, A AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 964 EP - 965 VL - 55 IS - 11 SN - 0003-990X, 0003-990X KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Abridged Index Medicus KW - Index Medicus KW - Genotype KW - Aldehyde Dehydrogenase -- genetics KW - Risk Factors KW - Humans KW - Family KW - Diseases in Twins -- epidemiology KW - Diseases in Twins -- genetics KW - Male KW - Female KW - Comorbidity KW - Alcoholism -- epidemiology KW - Alcoholism -- genetics KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70051366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=General+and+specific+inheritance+of+substance+abuse+and+alcoholism.&rft.au=Goldman%2C+D%3BBergen%2C+A&rft.aulast=Goldman&rft.aufirst=D&rft.date=1998-11-01&rft.volume=55&rft.issue=11&rft.spage=964&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 - 1998-11-24 N1 - Date created - 1998-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Arch Gen Psychiatry. 1998 Nov;55(11):967-72 [9819064] Arch Gen Psychiatry. 1998 Nov;55(11):982-8 [9819066] Arch Gen Psychiatry. 1998 Nov;55(11):973-9 [9819065] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced central serotonin transporters in alcoholism. AN - 70040089; 9812115 AB - Dysfunction of monoamine uptake mechanisms has been implicated in the pathogenesis of alcohol dependence. The authors explored whether serotonergic dysfunction is associated with anxiety and depression, which increase the risk of relapse in alcoholics. The availability of serotonin and dopamine transporters in 22 male alcoholics and 13 healthy male volunteers was measured with the use of [123I] beta-CIT and single photon emission computed tomography, and psychopathological correlates were assessed. A significant reduction (a mean of about 30%) in the availability of brainstem serotonin transporters was found in the alcoholics, which was significantly correlated with lifetime alcohol consumption and with ratings of depression and anxiety during withdrawal. The findings support the hypothesis of serotonergic dysfunction in alcoholism and in withdrawal-emergent depressive symptoms. JF - The American journal of psychiatry AU - Heinz, A AU - Ragan, P AU - Jones, D W AU - Hommer, D AU - Williams, W AU - Knable, M B AU - Gorey, J G AU - Doty, L AU - Geyer, C AU - Lee, K S AU - Coppola, R AU - Weinberger, D R AU - Linnoila, M AD - Clinical Brain Disorders Branch, NIMH, Washington, D.C., USA. jonesjeinz@aol.com Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1544 EP - 1549 VL - 155 IS - 11 SN - 0002-953X, 0002-953X KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Iodine Radioisotopes KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Serotonin KW - 333DO1RDJY KW - Ethanol KW - 3K9958V90M KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Alcohol Drinking -- metabolism KW - Humans KW - Dopamine -- physiology KW - Ethanol -- adverse effects KW - Brain Stem -- diagnostic imaging KW - Substance Withdrawal Syndrome -- etiology KW - Adult KW - Alcohol Drinking -- physiopathology KW - Anxiety Disorders -- chemically induced KW - Male KW - Tomography, Emission-Computed, Single-Photon KW - Brain Stem -- metabolism KW - Substance Withdrawal Syndrome -- physiopathology KW - Depressive Disorder -- chemically induced KW - Brain Stem -- chemistry KW - Dopamine -- metabolism KW - Anxiety Disorders -- physiopathology KW - Recurrence KW - Cocaine -- analogs & derivatives KW - Risk Factors KW - Depressive Disorder -- physiopathology KW - Middle Aged KW - Carrier Proteins -- metabolism KW - Serotonin -- analysis KW - Serotonin -- physiology KW - Membrane Glycoproteins -- physiology KW - Alcoholism -- metabolism KW - Membrane Glycoproteins -- analysis KW - Carrier Proteins -- physiology KW - Carrier Proteins -- analysis KW - Alcoholism -- physiopathology KW - Serotonin -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70040089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+central+serotonin+transporters+in+alcoholism.&rft.au=Heinz%2C+A%3BRagan%2C+P%3BJones%2C+D+W%3BHommer%2C+D%3BWilliams%2C+W%3BKnable%2C+M+B%3BGorey%2C+J+G%3BDoty%2C+L%3BGeyer%2C+C%3BLee%2C+K+S%3BCoppola%2C+R%3BWeinberger%2C+D+R%3BLinnoila%2C+M&rft.aulast=Heinz&rft.aufirst=A&rft.date=1998-11-01&rft.volume=155&rft.issue=11&rft.spage=1544&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose intensive combination platinum and cyclophosphamide in the treatment of patients with advanced untreated epithelial ovarian cancer. AN - 70039660; 9806657 AB - The authors combined cisplatin and carboplatin together with cyclophosphamide to maximize platinum dose intensity in patients with advanced epithelial ovarian cancer (AOC). The authors treated 26 consecutive, newly diagnosed patients with International Federation of Gynecology and Obstetrics (FIGO) Stage III/IV AOC with carboplatin, 600 mg/m2, on Day 1; cyclophosphamide, 250 mg/m2, on Day 1; and cisplatin, 100 mg/m2, on Day 8 every 4 weeks with or without pretreatment with amifostine (range, 740-1140 mg/m2). Platinum dose intensity was estimated using a 4:1 conversion for equipotent doses of cisplatin and carboplatin for expression as cisplatin dose equivalents (CDE). The mean administered CDE was 49.4 mg/m2/week, which was 79% of the planned dose. Hematologic toxicity was severe, with FIGO Grade 3-4 anemia in 81% of patients, Grade 3-4 neutropenia in 92% of patients, and Grade 4 thrombocytopenia in 96% of patients. Eleven patients (42%) were admitted to the hospital for febrile neutropenia and there was 1 toxic death. Sensory neuropathy > or = Grade 2 occurred in 10 patients (38%), ototoxicity > or = Grade 2 occurred in 18 patients (69%), and 6 patients (23%) required long term hearing aids. Elevations in serum creatinine > or = Grade 2 occurred in 7 patients (27%) and > or = Grade 2 hypomagnesemia was noted in 23 patients (88%). Other Grade 3 toxicities were nausea (42%), emesis (38%), fatigue (15%), mucositis (4%), and respiratory toxicities (4%). Twenty-two of 26 patients (85%) had a clinical response (19 with a complete response [CR] and 3 with a partial response). Pathologic CR was demonstrated in 10 of 26 patients (38%) and residual microscopic disease in 4 of 26 patients (15%) for a total pathologic response rate of 53%. The median progression free survival was 13.5 months and the median overall survival was 37.2 months at a median potential follow-up of 79.3 months. Three of 26 patients remained free of disease at 66, 71, and 103 months, respectively. Although dose intensive combination platinum treatment combined with cyclophosphamide in patients with AOC is active, it also is associated with substantial toxicity. JF - Cancer AU - Shapiro, J D AU - Rothenberg, M L AU - Sarosy, G A AU - Steinberg, S M AU - Adamo, D O AU - Reed, E AU - Ozols, R F AU - Kohn, E C AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 1980 EP - 1988 VL - 83 IS - 9 SN - 0008-543X, 0008-543X KW - Cyclophosphamide KW - 8N3DW7272P KW - Amifostine KW - M487QF2F4V KW - Cisplatin KW - Q20Q21Q62J KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Aged KW - Remission Induction -- methods KW - Middle Aged KW - Amifostine -- administration & dosage KW - Female KW - Cisplatin -- administration & dosage KW - Ovarian Neoplasms -- mortality KW - Carcinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Carcinoma -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70039660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Dose+intensive+combination+platinum+and+cyclophosphamide+in+the+treatment+of+patients+with+advanced+untreated+epithelial+ovarian+cancer.&rft.au=Shapiro%2C+J+D%3BRothenberg%2C+M+L%3BSarosy%2C+G+A%3BSteinberg%2C+S+M%3BAdamo%2C+D+O%3BReed%2C+E%3BOzols%2C+R+F%3BKohn%2C+E+C&rft.aulast=Shapiro&rft.aufirst=J&rft.date=1998-11-01&rft.volume=83&rft.issue=9&rft.spage=1980&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-17 N1 - Date created - 1998-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ionizing radiation and cancer risk: evidence from epidemiology. AN - 70038755; 9806607 AB - Epidemiological studies provide the primary data on the carcinogenic effects of radiation in humans. Much of what is known has come from studies of the atomic bomb survivors, and to a lesser extent from patients receiving radiotherapy. These studies demonstrate that exposure to moderate to high doses of radiation increases the risk of cancer in most organs. For all solid cancers combined, cancers of the thyroid, breast and lung, and leukemia, risk estimates are fairly precise, and associations have been found at relatively low doses (<0.2 Gy). Associations between radiation and cancers of the salivary glands, stomach, colon, bladder, ovary, central nervous system and skin have also been reported, but the relationships are not as well quantified. Associations between radiation and cancers of the liver and esophagus, and to a lesser extent multiple myeloma and non-Hodgkin's lymphoma, have been reported in a few studies, but results are inconsistent. Chronic lymphocytic leukemia, Hodgkin's disease, and cancers of the pancreas, prostate, testis and cervix have rarely been linked to radiation exposure. A linear no-threshold model adequately describes the dose-response relationship for solid cancers, although at extremely high doses the risk appears to flatten out. Because few populations have been followed until the end of life, the temporal patterns of risk are not completely known. An increased risk, however, does continue for several decades. In contrast, radiation-related leukemias begin to occur shortly (2-3 years) after exposure and, at least in the A-bomb survivors, a linear-quadratic dose response seems to fit the data better than a pure linear model. Radiation does not act entirely in isolation. It can interact with other carcinogens, e.g. tobacco or chemotherapeutic agents, and with host factors such as age at exposure, gender or reproductive history. Interactions with medical interventions or with certain heritable mutations have also been suggested. While the studies of high-dose exposures are essential for understanding the overall biological consequences of radiation exposure, the public is more concerned about the long-term health effects from protracted exposures at low doses. Unfortunately, the inherent limitations of epidemiology make it extremely difficult to directly quantify health risks from these exposures. While most epidemiological data are compatible with linear extrapolations from exposures at high doses or high dose rates, they cannot entirely exclude other possibilities. As the field of epidemiology advances, understanding more about the health effects of prolonged and low-dose exposures will be the next challenge. JF - Radiation research AU - Ron, E AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - S30 EP - S41 VL - 150 IS - 5 Suppl SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Occupational Exposure KW - Nuclear Warfare KW - Humans KW - Cohort Studies KW - Environmental Exposure KW - Case-Control Studies KW - Incidence KW - Dose-Response Relationship, Radiation KW - Nuclear Reactors KW - Radiotherapy -- adverse effects KW - Radiation, Ionizing KW - Neoplasms, Radiation-Induced -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70038755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ionizing+radiation+and+cancer+risk%3A+evidence+from+epidemiology.&rft.au=Ron%2C+E&rft.aulast=Ron&rft.aufirst=E&rft.date=1998-11-01&rft.volume=150&rft.issue=5+Suppl&rft.spage=S30&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentially reactive cyclic carbamate metabolite of the antiepileptic drug felbamate produced by human liver tissue in vitro. AN - 70035580; 9806951 AB - Felbamate (FBM) is a novel antiepileptic drug that was approved in 1993 for treatment of several forms of epilepsy. After its introduction, toxic reactions (aplastic anemia and hepatotoxicity) associated with its use were reported. It is unknown whether FBM or one of its metabolites is responsible for these idiosyncratic adverse reactions. Although the metabolism of FBM has not been fully characterized, three primary metabolites of FBM have been identified, i.e. 2-hydroxy, p-hydroxy, and monocarbamate metabolites. In addition, the monocarbamate metabolite leads to a carboxylic acid, which is the major metabolite of FBM in humans. Formation of the hydroxylated products of FBM involves cytochrome P450 enzymes, but the enzymes involved in the formation and further metabolism of the monocarbamate have not yet been elucidated. Recently, mercapturate metabolites of FBM have been identified in human urine, and a metabolic scheme involving reactive aldehyde metabolite formation from the monocarbamate metabolite has been proposed. The present study confirmed the formation of the proposed metabolites using human liver tissue in vitro. The aldehyde intermediates were trapped as oxime derivatives, and the cyclic equilibrium product (proposed as a storage and transport form for the aldehydes) was monitored directly by HPLC or GC/MS. Formation of putative toxic aldehyde intermediates and the major carboxylic acid metabolite of FBM was differentially effected with the cofactors NADP+ and NAD+. It is possible that the cofactors may influence the relative metabolism via activation and inactivation pathways. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Kapetanovic, I M AU - Torchin, C D AU - Thompson, C D AU - Miller, T A AU - McNeilly, P J AU - Macdonald, T L AU - Kupferberg, H J AU - Perhach, J L AU - Sofia, R D AU - Strong, J M AD - Epilepsy Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 1089 EP - 1095 VL - 26 IS - 11 SN - 0090-9556, 0090-9556 KW - Anticonvulsants KW - 0 KW - Carbamates KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Phenylcarbamates KW - Propylene Glycols KW - NAD KW - 0U46U6E8UK KW - NADP KW - 53-59-8 KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - NAD -- metabolism KW - Spectrometry, Mass, Secondary Ion KW - Biotransformation KW - Humans KW - In Vitro Techniques KW - NADP -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Chromatography, High Pressure Liquid KW - Liver -- enzymology KW - Carbamates -- metabolism KW - Anticonvulsants -- pharmacokinetics KW - Propylene Glycols -- pharmacokinetics KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70035580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Potentially+reactive+cyclic+carbamate+metabolite+of+the+antiepileptic+drug+felbamate+produced+by+human+liver+tissue+in+vitro.&rft.au=Kapetanovic%2C+I+M%3BTorchin%2C+C+D%3BThompson%2C+C+D%3BMiller%2C+T+A%3BMcNeilly%2C+P+J%3BMacdonald%2C+T+L%3BKupferberg%2C+H+J%3BPerhach%2C+J+L%3BSofia%2C+R+D%3BStrong%2C+J+M&rft.aulast=Kapetanovic&rft.aufirst=I&rft.date=1998-11-01&rft.volume=26&rft.issue=11&rft.spage=1089&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a. AN - 70033656; 9809471 AB - 1. The nicotinic agonist (+)anatoxin-a was studied in acute preparations of adrenal chromaffin cells and was compared with other known stimulants in this system. 2. (+)Anatoxin-a was found to be a potent stimulant of catecholamine secretion with EC50=545.7 nM, which was 5.8 times as strong as nicotine (EC50=3,165 nM). (+)Anatoxin-a action was time dependent and saturable. 3. The pharmacological characteristics of (+)anatoxin-a were tested by using nicotinic and muscarinic antagonists (mecamylamine and atropine, respectively). Mecamylamine (1 microM) and atropine (100 microM) inhibited the secretion induced by (+)anatoxin-a (1 microM), as well as that induced by nicotine (10 microM), acetylcholine (10 microM and 100 microM) and oxotremorine-M (100 microM). 4. The calcium requirement for (+)anatoxin-a action was tested in comparison with the aforementioned stimulants. Addition of the calcium antagonist verapamil (10 microM) or the calcium chelator EGTA (3 mM) reduced all stimulants' action. 5. These results show that the (+)enantiomer of anatoxin-a is both dose and time dependent. Its action is mediated through the classical operation of the nicotinic acetylcholine receptor, by using calcium influx. JF - General pharmacology AU - Dar, D E AU - Zinder, O AD - Department of Clinical Biochemistry, Rambam Medical Center, Haifa, Israel. ddar@irp.nida.nih.gov Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 737 EP - 740 VL - 31 IS - 5 SN - 0306-3623, 0306-3623 KW - Bacterial Toxins KW - 0 KW - Calcium Channel Blockers KW - Catecholamines KW - Chelating Agents KW - Marine Toxins KW - Microcystins KW - Muscarinic Antagonists KW - Neurotoxins KW - Nicotinic Agonists KW - Nicotinic Antagonists KW - Tropanes KW - cyanobacterial toxin KW - Egtazic Acid KW - 526U7A2651 KW - anatoxin a KW - 80023A73NK KW - Verapamil KW - CJ0O37KU29 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Dose-Response Relationship, Drug KW - Verapamil -- pharmacology KW - Calcium -- metabolism KW - Chelating Agents -- pharmacology KW - Cattle KW - Calcium Channel Blockers -- pharmacology KW - Muscarinic Antagonists -- pharmacology KW - In Vitro Techniques KW - Nicotinic Antagonists -- pharmacology KW - Time Factors KW - Egtazic Acid -- pharmacology KW - Marine Toxins -- pharmacology KW - Catecholamines -- metabolism KW - Adrenal Medulla -- cytology KW - Neurotoxins -- pharmacology KW - Chromaffin Cells -- metabolism KW - Bacterial Toxins -- chemistry KW - Adrenal Medulla -- metabolism KW - Bacterial Toxins -- pharmacology KW - Nicotinic Agonists -- pharmacology KW - Nicotinic Agonists -- chemistry KW - Neurotoxins -- chemistry KW - Marine Toxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70033656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=General+pharmacology&rft.atitle=Catecholamine+secretion+from+bovine+adrenal+chromaffin+cells+induced+by+the+dextrorotatory+isomer+of+anatoxin-a.&rft.au=Dar%2C+D+E%3BZinder%2C+O&rft.aulast=Dar&rft.aufirst=D&rft.date=1998-11-01&rft.volume=31&rft.issue=5&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=General+pharmacology&rft.issn=03063623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia. AN - 70030605; 9804340 AB - A 4 y old boy of Korean ancestry had xeroderma pigmentosum (XP) with sun sensitivity, multiple cutaneous neoplasms, and inability to speak. Neurologic examination revealed hyperactivity and autistic features without typical XP neurologic abnormalities. Cultured skin fibroblasts (XP22BE) showed decreased post-UV survival, reduced post-UV plasmid host cell reactivation and defective DNA repair (16% of normal unscheduled DNA synthesis in intact cells and undetectable excision repair in a cell free extract). In vitro and in vivo complementation assigned XP22BE to XP group C (XPC) and a markedly reduced level of XPC mRNA was found. Two XPC cDNA bands were identified. One band had a deletion of 161 bases comprising the entire exon 9, which resulted in premature termination of the mutant XPC mRNA. The larger band also had the same deletion of exon 9 but, in addition, had an insertion of 155 bases in its place (exon 9a), resulting in an in-frame XPC mRNA. Genomic DNA analysis revealed a T-->G mutation at the splice donor site of XPC exon 9, which markedly reduced its information content. The 155 base pair XPC exon 9a insertion was located in intron 9 and was flanked by strong splice donor and acceptor sequences. Analysis of the patient's blood showed persistently low levels of glycine (68 microM; NL, 125-318 microM). Normal glycine levels were maintained with oral glycine supplements and his hyperactivity diminished. These data provide evidence of an association of an XPC splice site mutation with autistic neurologic features and hypoglycinemia. JF - The Journal of investigative dermatology AU - Khan, S G AU - Levy, H L AU - Legerski, R AU - Quackenbush, E AU - Reardon, J T AU - Emmert, S AU - Sancar, A AU - Li, L AU - Schneider, T D AU - Cleaver, J E AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 791 EP - 796 VL - 111 IS - 5 SN - 0022-202X, 0022-202X KW - DNA-Binding Proteins KW - 0 KW - Genetic Markers KW - XPC protein, human KW - 156533-34-5 KW - DNA KW - 9007-49-2 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Ultraviolet Rays KW - Microsatellite Repeats -- genetics KW - Blotting, Northern KW - DNA Repair KW - Humans KW - Transcription, Genetic KW - Child, Preschool KW - Chromosomes, Human, Pair 3 KW - Genetic Markers -- genetics KW - Survival Rate KW - Alternative Splicing KW - DNA -- genetics KW - Fibroblasts -- radiation effects KW - Mutation KW - Male KW - Autistic Disorder -- complications KW - DNA-Binding Proteins -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Xeroderma Pigmentosum -- complications KW - Glycine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70030605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Xeroderma+pigmentosum+group+C+splice+mutation+associated+with+autism+and+hypoglycinemia.&rft.au=Khan%2C+S+G%3BLevy%2C+H+L%3BLegerski%2C+R%3BQuackenbush%2C+E%3BReardon%2C+J+T%3BEmmert%2C+S%3BSancar%2C+A%3BLi%2C+L%3BSchneider%2C+T+D%3BCleaver%2C+J+E%3BKraemer%2C+K+H&rft.aulast=Khan&rft.aufirst=S&rft.date=1998-11-01&rft.volume=111&rft.issue=5&rft.spage=791&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-18 N1 - Date created - 1998-11-18 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF076952; GENBANK N1 - SuppNotes - Erratum In: J Invest Dermatol 1999 Mar;112(3):402 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiation of cultured human epidermal keratinocytes at high cell densities is mediated by endogenous activation of the protein kinase C signaling pathway. AN - 70027667; 9804335 AB - Normal human epidermal keratinocytes (NHEK) grown in serum-free medium on a plastic substrate spontaneously differentiate at high cell densities in vitro. Because protein kinase C (PKC) regulates murine keratinocyte differentiation triggered by a variety of stimuli, we examined the role of this signaling pathway in density-dependent activation of NHEK differentiation. Relative to subconfluent cultures, confluent NHEK expressed markedly higher levels of multiple differentiation markers assayed by immunoblotting, including keratin 1, loricrin, filaggrin, involucrin, TGK, and SPR-1. Expression of several of these markers continued to increase for several days after cells reached confluency. The total level of several PKC isoforms was not substantially altered in NHEK harvested at different cell densities, based on immunoblotting; however, subcellular fractionation revealed that PKCalpha underwent a redistribution to the particulate fraction in confluent and postconfluent NHEK cultures, suggesting that this isozyme was activated under these conditions and may be involved in triggering the terminal differentiation program. Supporting this concept, inhibition of PKC function using bryostatin 1 or GF 109203X blocked the induction of keratinocyte differentiation markers at high cell densities. These data suggest that endogenous activation of PKC is responsible for cell density-mediated stimulation of NHEK differentiation, establishing a critical role for this pathway in regulating human as well as murine keratinocyte differentiation. JF - The Journal of investigative dermatology AU - Lee, Y S AU - Yuspa, S H AU - Dlugosz, A A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 762 EP - 766 VL - 111 IS - 5 SN - 0022-202X, 0022-202X KW - Antigens, Differentiation KW - 0 KW - Isoenzymes KW - PRKCA protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Index Medicus KW - Cell Count -- drug effects KW - Humans KW - Enzyme Activation -- physiology KW - Antigens, Differentiation -- physiology KW - Up-Regulation KW - Cell Differentiation -- drug effects KW - Isoenzymes -- genetics KW - Translocation, Genetic KW - Signal Transduction KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Protein Kinase C -- genetics KW - Keratinocytes -- cytology KW - Keratinocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70027667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Differentiation+of+cultured+human+epidermal+keratinocytes+at+high+cell+densities+is+mediated+by+endogenous+activation+of+the+protein+kinase+C+signaling+pathway.&rft.au=Lee%2C+Y+S%3BYuspa%2C+S+H%3BDlugosz%2C+A+A&rft.aulast=Lee&rft.aufirst=Y&rft.date=1998-11-01&rft.volume=111&rft.issue=5&rft.spage=762&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-18 N1 - Date created - 1998-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of pesticides and other compounds in carpet dust samples collected from used vacuum cleaner bags and from a high-volume surface sampler. AN - 70022912; 9799187 AB - Epidemiologic studies of the association between residential pesticide use and cancer risk require an assessment of past pesticide exposures. Pesticide levels in carpet dust are believed to reflect long-term pesticide use. Recent epidemiologic studies have found collection of dust samples using the high-volume surface sampler (HVS3) to be expensive and cumbersome. We compared the levels of pesticides and other compounds in dust obtained from subjects' personal used vacuum cleaner bags to that collected by the HVS3 to see if this simpler method could replace the HVS3 in epidemiologic research. We visited the homes of 15 subjects, took the used bags from their vacuums, and collected carpet dust samples with the HVS3. The samples were analyzed for 42 target compounds: 26 pesticides, 10 polycyclic aromatic hydrocarbons (PAHs), and six polychlorinated biphenyl (PCB) congeners using GC/MS in selected ion monitoring mode. The two methods agreed in detecting the presence of the target compounds between 80% and 100% of the time. Neither sampling method was consistently more sensitive. The median target compound concentrations were similar, and a paired t-test showed no significant differences. For many compounds, the concentrations of compounds in the HVS3 samples were higher than those in the used bag samples at the upper end of the concentration ranges. However, the Spearman rank correlation coefficients were 0.85 or higher for most compounds, indicating that homes would be ranked similarly using both methods. Overall, there appears to be no clear difference in the quality of the pesticide, PAH, or PCB concentration data for the two dust collection methods. JF - Environmental health perspectives AU - Colt, J S AD - Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7364 USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 721 EP - 724 VL - 106 IS - 11 SN - 0091-6765, 0091-6765 KW - Dust KW - 0 KW - Pesticides KW - Soil Pollutants KW - Index Medicus KW - Humans KW - Maryland KW - Pesticides -- analysis KW - Floors and Floorcoverings KW - Air Pollution, Indoor -- analysis KW - Dust -- analysis KW - Environmental Monitoring -- methods KW - Soil Pollutants -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70022912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+pesticides+and+other+compounds+in+carpet+dust+samples+collected+from+used+vacuum+cleaner+bags+and+from+a+high-volume+surface+sampler.&rft.au=Colt%2C+J+S&rft.aulast=Colt&rft.aufirst=J&rft.date=1998-11-01&rft.volume=106&rft.issue=11&rft.spage=721&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Occup Med. 1997 Apr-Jun;12(2):269-89 [9220486] Arch Environ Contam Toxicol. 1994 Jan;26(1):37-46 [8110022] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - The first international conference on the environmental health and safety of jet fuel. AN - 70017007; 9799193 JF - Environmental health perspectives AU - Zeiger, E AU - Smith, L Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 763 EP - 764 VL - 106 IS - 11 KW - Air Pollutants KW - 0 KW - Hydrocarbons KW - JP8 aviation fuel KW - Kerosene KW - JP5 jet fuel KW - 8008-20-6 KW - Index Medicus KW - United States KW - Occupational Health KW - Animals KW - Humans KW - Environmental Health KW - Kerosene -- adverse effects KW - Hydrocarbons -- adverse effects KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70017007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=The+first+international+conference+on+the+environmental+health+and+safety+of+jet+fuel.&rft.au=Zeiger%2C+E%3BSmith%2C+L&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1998-11-01&rft.volume=106&rft.issue=11&rft.spage=763&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hexachlorobenzene as a possible major contributor to the dioxin activity of human milk. AN - 70016912; 9799183 AB - A dioxinlike compound is a compound that binds to the aryl hydrocarbon (Ah) receptor, results in dioxinlike effects, and bioaccumulates. These are the three factors for including dioxinlike chemicals in the toxic equivalency factor (TEF) concept. Risk assessment of dioxinlike compounds is based on using these TEFs. Hexachlorobenzene (HCB) has all three features and should therefore be included in this TEF concept. Relative potency values express the potency of a specific compound in comparison to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxinlike compound, with a relative potency value of 1. For the estimation of the total dioxin activity in an environmental biological sample, the TEF value of a compound is multiplied by the concentration in the specific matrix. This results in a certain amount of toxic equivalents (TEQs) for this compound. The summation of all TEQs in a certain mixture gives the total dioxin activity of this mixture. HCB binds to the Ah receptor about 10,000 times less than TCDD. HCB is also about 10,000 times less potent than TCDD based on in vitro cytochrome P4501A induction and porphyrin accumulation. Using a relative potency value of 0.0001, HCB could add 10-60% to the total TEQ in human milk samples in most countries. In a few countries such as Spain, Slovakia, and the Czech Republic, HCB levels in human milk expressed as TEQ could contribute up to a factor of six to the total TEQ in comparison to the contribution of polychlorinated dioxins, dibenzofurans, and biphenyls together, i.e., up to a daily intake of about 1 ng TEQ/kg for a breast-fed infant. The HCB levels in human milk in these countries are about the same as in India. Biochemical, immunological, and neurological alterations have been observed in infants fed breast milk in countries with relatively low TEQ levels in human milk. Based on the above information, it is clear that HCB should be classified as a dioxinlike compound, that more studies are needed to reduce the uncertainty in the estimation of a relative potency value for HCB, and that epidemiological studies should be undertaken in infants fed breast milk in countries with high HCB exposure levels. Furthermore, measurements of HCB levels in human and environmental samples in conjunction with other dioxinlike compounds is a prerequisite to estimate the total dioxin activity in these samples. JF - Environmental health perspectives AU - van Birgelen, A P AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 683 EP - 688 VL - 106 IS - 11 SN - 0091-6765, 0091-6765 KW - Dioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Hexachlorobenzene KW - 4Z87H0LKUY KW - Index Medicus KW - Humans KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Female KW - Structure-Activity Relationship KW - Dioxins -- metabolism KW - Milk, Human -- chemistry KW - Hexachlorobenzene -- analysis KW - Dioxins -- chemistry KW - Dioxins -- analysis KW - Environmental Exposure -- analysis KW - Hexachlorobenzene -- metabolism KW - Hexachlorobenzene -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70016912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hexachlorobenzene+as+a+possible+major+contributor+to+the+dioxin+activity+of+human+milk.&rft.au=van+Birgelen%2C+A+P&rft.aulast=van+Birgelen&rft.aufirst=A&rft.date=1998-11-01&rft.volume=106&rft.issue=11&rft.spage=683&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Pharmacol. 1992 Dec 1;228(4):179-99 [1335882] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] Carcinogenesis. 1993 Jul;14(7):1381-7 [8330354] Food Addit Contam. 1993 Jul-Aug;10(4):429-41 [8405582] Carcinogenesis. 1993 Oct;14(10):2063-71 [8222055] Biochem Pharmacol. 1993 Oct 19;46(8):1385-91 [8240387] Bull Environ Contam Toxicol. 1993 Dec;51(6):827-31 [8257808] Sci Total Environ. 1993 Nov 1;139-140:347-55 [8272839] Int J Cancer. 1994 Jan 15;56(2):200-3 [8314301] Environ Health Perspect. 1993 Dec;101(7):618-20 [8143594] Crit Rev Toxicol. 1994;24(1):1-74 [8172651] Environ Health Perspect. 1994 Jan;102 Suppl 1:187-93 [8187707] J Toxicol Environ Health. 1994 Jun;42(2):157-71 [8207752] Hum Exp Toxicol. 1994 May;13(5):299-302 [8043308] Ecotoxicol Environ Saf. 1994 Jun;28(1):1-13 [7523063] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] Toxicol Appl Pharmacol. 1996 May;138(1):98-109 [8658519] Environ Health Perspect. 1996 May;104(5):550-7 [8743444] Arch Environ Contam Toxicol. 1996 Oct;31(3):354-67 [8854829] Environ Health Perspect. 1997 Jan;105(1):78-83 [9074885] J Nutr. 1997 Apr;127(4):648-54 [9109618] Bull Environ Contam Toxicol. 1997 May;58(5):769-75 [9115141] Toxicol Appl Pharmacol. 1997 Dec;147(2):171-9 [9439713] Nature. 1961 Jul 22;191:363-6 [13720711] J Toxicol Environ Health. 1984;14(2-3):353-62 [6502739] Toxicol Appl Pharmacol. 1993 Apr;119(2):181-94 [8480328] Pediatr Res. 1995 Sep;38(3):404-10 [7494667] Med J Aust. 1973 Oct 27;2(17):815-8 [4128216] Pathol Biol (Paris). 1975 Jan;23(1):45-9 [53804] Toxicol Appl Pharmacol. 1976 Feb;35(2):239-56 [1265744] Wien Klin Wochenschr. 1975 Nov 14;87(21):732-6 [818822] Toxicology. 1994 Nov-Dec;94(1-3):197-208 [7801323] Zentralbl Hyg Umweltmed. 1994 Aug;196(2):95-103 [7528509] Pediatr Res. 1994 Oct;36(4):468-73 [7816522] Food Chem Toxicol. 1995 Jan;33(1):49-56 [7821877] Fundam Appl Toxicol. 1995 Jan;24(1):145-8 [7713338] Nature. 1977 Oct 6;269(5628):510-11 [198674] Ecotoxicol Environ Saf. 1978 Sep;2(2):161-72 [103705] Int J Cancer. 1979 Jan 15;23(1):47-51 [759379] Ann N Y Acad Sci. 1979 May 31;320:535-50 [378061] Arch Toxicol. 1979 Apr 23;42(1):19-31 [454182] Virchows Arch A Pathol Anat Histol. 1979 May 31;382(2):127-37 [157602] Chem Biol Interact. 1979 Oct;27(2-3):353-63 [498361] Toxicol Appl Pharmacol. 1981 Feb;57(2):156-63 [7222031] Bull Environ Contam Toxicol. 1983 Sep;31(3):251-6 [6414557] Biochem Pharmacol. 1983 Dec 15;32(24):3797-801 [6661253] Carcinogenesis. 1985 Apr;6(4):631-6 [3986965] Food Chem Toxicol. 1985 Sep;23(9):779-93 [4043882] Arch Environ Contam Toxicol. 1985 Sep;14(5):517-21 [3931568] Toxicol Lett. 1986 Jan;30(1):71-8 [3952775] Biochem J. 1988 Aug 15;254(1):245-54 [2845946] Arch Biochem Biophys. 1989 Apr;270(1):344-55 [2539049] Carcinogenesis. 1989 Jul;10(7):1225-30 [2736716] Bull Environ Contam Toxicol. 1989 May;42(5):682-6 [2742998] J Biochem Toxicol. 1986 Jun;1(2):95-107 [2856071] J Assoc Off Anal Chem. 1991 Jan-Feb;74(1):89-91 [1902831] Arch Environ Contam Toxicol. 1992 Aug;23(2):235-9 [1514844] J Toxicol Environ Health. 1995 Oct;46(2):133-48 [7563213] Comment In: Environ Health Perspect. 1999 Apr;107(4):A183-4 [10383245] Environ Health Perspect. 2000 Feb;108(2):A58 [10656862] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits. AN - 70014923; 9797223 AB - LY303366 is a novel semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1,3)-beta-D-glucan synthase. The antifungal efficacy and safety of LY303366 were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Treatment study groups were either not treated (controls) or treated with amphotericin B (AmB) at 1 mg/kg of body weight per day or with LY303366 at 1, 5, 10, and 20 mg/kg/day. In rabbits treated with LY303366, there was a significant improvement in survival and a reduction in organism-mediated pulmonary injury measured by the number of infarcts, total lung weight, and ultrafast computerized tomography scan pulmonary lesion score. Rabbits receiving prophylactic LY303366 also demonstrated significant improvement in survival and reduction in organism-mediated pulmonary injury. AmB and LY303366 had comparable therapeutic efficacies by all parameters with the exception of reduction in tissue burden of A. fumigatus, where AmB was superior to LY303366. LY303366 demonstrated a dose-dependent effect on hyphal injury with progressive truncation, swelling, and vacuolization. LY303366 administered in single doses of 1, 5, 10, and 20 mg/kg demonstrated dose-proportional increases in the maximum concentration of drug in plasma and the area under the concentration-time curve from 0 to 72 h with no changes in plasma drug clearance. The 1-mg/kg dosage maintained plasma drug levels above the MIC for 18 h, and dosages of >/=5 mg/kg maintained plasma drug levels above the MIC for the entire 24-h dosing interval. There was no significant elevation of the concentrations of hepatic transaminases or creatinine in serum in LY303366-treated rabbits. In summary, LY303366 improved survival and decreased pulmonary injury with no apparent toxicity in the treatment and prevention of invasive pulmonary aspergillosis in persistently neutropenic rabbits. JF - Antimicrobial agents and chemotherapy AU - Petraitis, V AU - Petraitiene, R AU - Groll, A H AU - Bell, A AU - Callender, D P AU - Sein, T AU - Schaufele, R L AU - McMillian, C L AU - Bacher, J AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 2898 EP - 2905 VL - 42 IS - 11 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Echinocandins KW - Peptides, Cyclic KW - Amphotericin B KW - 7XU7A7DROE KW - anidulafungin KW - 9HLM53094I KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Amphotericin B -- administration & dosage KW - Rabbits KW - Aspergillus fumigatus -- drug effects KW - Female KW - Lung Diseases, Fungal -- prevention & control KW - Peptides, Cyclic -- therapeutic use KW - Peptides, Cyclic -- adverse effects KW - Lung Diseases, Fungal -- drug therapy KW - Aspergillosis -- prevention & control KW - Neutropenia -- complications KW - Aspergillosis -- drug therapy KW - Neutropenia -- prevention & control KW - Peptides, Cyclic -- pharmacokinetics KW - Neutropenia -- drug therapy KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70014923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antifungal+efficacy%2C+safety%2C+and+single-dose+pharmacokinetics+of+LY303366%2C+a+novel+echinocandin+B%2C+in+experimental+pulmonary+aspergillosis+in+persistently+neutropenic+rabbits.&rft.au=Petraitis%2C+V%3BPetraitiene%2C+R%3BGroll%2C+A+H%3BBell%2C+A%3BCallender%2C+D+P%3BSein%2C+T%3BSchaufele%2C+R+L%3BMcMillian%2C+C+L%3BBacher%2C+J%3BWalsh%2C+T+J&rft.aulast=Petraitis&rft.aufirst=V&rft.date=1998-11-01&rft.volume=42&rft.issue=11&rft.spage=2898&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 - 1998-12-04 N1 - Date created - 1998-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Antibiot (Tokyo). 1984 Sep;37(9):1054-65 [6389460] Diagn Microbiol Infect Dis. 1998 Apr;30(4):251-5 [9582584] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Ann N Y Acad Sci. 1988;544:294-309 [3063174] Eur J Clin Microbiol Infect Dis. 1990 Sep;9(9):697-9 [2226501] Antimicrob Agents Chemother. 1991 Jul;35(7):1321-8 [1929288] Antimicrob Agents Chemother. 1991 Jul;35(7):1329-33 [1929289] Cancer. 1992 Jun 1;69(11):2653-62 [1315207] J Infect Dis. 1994 Feb;169(2):356-68 [8106769] Antimicrob Agents Chemother. 1994 Mar;38(3):518-22 [8203848] Antimicrob Agents Chemother. 1994 Apr;38(4):713-8 [8031034] Antimicrob Agents Chemother. 1994 Jul;38(7):1480-9 [7979276] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] J Med Chem. 1995 Aug 18;38(17):3271-81 [7650681] Am J Respir Crit Care Med. 1995 Sep;152(3):1079-86 [7663787] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] J Clin Microbiol. 1997 Jan;35(1):139-43 [8968895] Diagn Microbiol Infect Dis. 1996 Nov-Dec;26(3-4):125-31 [9078447] Antimicrob Agents Chemother. 1997 Apr;41(4):763-6 [9087485] Antimicrob Agents Chemother. 1997 Apr;41(4):863-5 [9087508] Antimicrob Agents Chemother. 1997 May;41(5):1156-7 [9145888] J Med Vet Mycol. 1997 Mar-Apr;35(2):79-86 [9147267] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational risk factors for breast cancer among women in Shanghai. AN - 69995263; 9787852 AB - Although female breast cancer rates are lower in China than in Western countries, rates have been rising rapidly in China. This increase may be due to changes in established breast cancer risk factors, but it is possible that exposure to occupational and environmental carcinogens in Shanghai also have contributed to the rise in incidence. We used data collected by the Shanghai Cancer Registry and the Chinese Third National Census to study the risk of breast cancer by occupation and by occupational exposures. Standardized incidence ratios (SIRs) were used to compare observed cases to expected numbers of cases, based on the incidence rates for Shanghai and the number of women in each occupation according to the 1982 census. Statistically elevated SIRs for breast cancer were seen for a number of professional occupational categories, with the greatest risk seen among scientific research workers (SIR = 3.3). Administrative clerks, political and security personnel, and makers of rubber and plastics products also had significant excesses. Significant deficits of risk were seen for the categories of production and related workers, construction workers, and transportation equipment operators. For specific occupations, the highest SIRs were observed among doctors of Chinese-Western medicine (SIR = 14.7, 95% CI = 5.9-30.3) and doctors of Chinese medicine (SIR = 7.2, 95% CI = 4.4-11.4). We also found excesses among teachers at each level of education, librarians, clerical workers, electrical and electronic engineers, nurses, lab technicians, accountants and bookkeepers, rubber manufacturing products makers, weavers, and knitters. SIRs were significantly elevated for high probability of exposure to organic solvents (SIR = 1.4). For benzene exposure, we found significant excesses for overall exposure (SIR = 1.1) and for medium level of exposure (SIR = 1.3). There was no evidence of an association between risk and electromagnetic fields (EMF) exposure. Based on a small number of exposed, SIRs were elevated for both medium probability and high level of exposure to pesticides. The elevations in occupations reported here support some previous reports. Our finding of an increased risk associated with benzene also has been reported previously; the finding for organic solvents is new. However, the literature on the risk of breast cancer related to occupational exposures is limited and there is no consistent body of literature for any of the exposures studied here. Further, many comparisons were made and the problem of multiple hypothesis testing cannot be ignored in a survey such as ours. JF - American journal of industrial medicine AU - Petralia, S A AU - Chow, W H AU - McLaughlin, J AU - Jin, F AU - Gao, Y T AU - Dosemeci, M AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. sp126i@nih.gov Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 477 EP - 483 VL - 34 IS - 5 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Incidence KW - Female KW - Occupational Exposure KW - Occupational Diseases -- epidemiology KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69995263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+risk+factors+for+breast+cancer+among+women+in+Shanghai.&rft.au=Petralia%2C+S+A%3BChow%2C+W+H%3BMcLaughlin%2C+J%3BJin%2C+F%3BGao%2C+Y+T%3BDosemeci%2C+M&rft.aulast=Petralia&rft.aufirst=S&rft.date=1998-11-01&rft.volume=34&rft.issue=5&rft.spage=477&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 - 1998-12-17 N1 - Date created - 1998-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. AN - 69982618; 9778499 AB - S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in the generation of severely aneuploid cells and, in the case of aurora, monopolar spindles arising from a failure in centrosome separation. Here we show that a related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to mitotic centrosomes. Disruption of AIR-1 protein expression in C. elegans embryos results in severe aneuploidy and embryonic lethality. Unlike aurora mutants, this aneuploidy does not arise from a failure in centrosome separation. Bipolar spindles are formed in the absence of AIR-1, but they appear to be disorganized and are nucleated by abnormal-looking centrosomes. In addition to its requirement during mitosis, AIR-1 may regulate microtubule-based developmental processes as well. Our data suggests AIR-1 plays a role in P-granule segregation and the association of the germline factor PIE-1 with centrosomes. JF - Development (Cambridge, England) AU - Schumacher, J M AU - Ashcroft, N AU - Donovan, P J AU - Golden, A AD - Cell Biology of Development and Differentiation Group, Developmental Signal Transduction Group, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, PO Box B, Frederick, MD 21702, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 4391 EP - 4402 VL - 125 IS - 22 SN - 0950-1991, 0950-1991 KW - Caenorhabditis elegans Proteins KW - 0 KW - Chromatin KW - Nuclear Proteins KW - pie-1 protein, C elegans KW - Aurora Kinase A KW - EC 2.7.11.1 KW - Aurora Kinases KW - Protein-Serine-Threonine Kinases KW - air-1 protein, C elegans KW - Index Medicus KW - Animals KW - Aneuploidy KW - Amino Acid Sequence KW - Mutagenesis KW - Cell Polarity KW - Conserved Sequence KW - Spindle Apparatus -- pathology KW - Chromatin -- pathology KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Cell Cycle KW - Fluorescent Antibody Technique KW - Caenorhabditis elegans -- embryology KW - Protein-Serine-Threonine Kinases -- isolation & purification KW - Chromosome Segregation KW - Protein-Serine-Threonine Kinases -- genetics KW - Centrosome -- enzymology KW - Caenorhabditis elegans -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69982618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+highly+conserved+centrosomal+kinase%2C+AIR-1%2C+is+required+for+accurate+cell+cycle+progression+and+segregation+of+developmental+factors+in+Caenorhabditis+elegans+embryos.&rft.au=Schumacher%2C+J+M%3BAshcroft%2C+N%3BDonovan%2C+P+J%3BGolden%2C+A&rft.aulast=Schumacher&rft.aufirst=J&rft.date=1998-11-01&rft.volume=125&rft.issue=22&rft.spage=4391&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 - 1999-01-19 N1 - Date created - 1999-01-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF071207; GENBANK; AF071206 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reverse transcription of a self-primed retrotransposon requires an RNA structure similar to the U5-IR stem-loop of retroviruses. AN - 69973410; 9774699 AB - An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV. The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop. Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of Tf1 does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak U5-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the U5-IR structure. However, all of the mutations in the U5-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5' end of Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer. Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. JF - Molecular and cellular biology AU - Lin, J H 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 - 1998/11// PY - 1998 DA - November 1998 SP - 6859 EP - 6869 VL - 18 IS - 11 SN - 0270-7306, 0270-7306 KW - DNA, Fungal KW - 0 KW - RNA, Messenger KW - RNA, Viral KW - Retroelements KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Base Sequence KW - Mutagenesis, Site-Directed -- genetics KW - RNA, Viral -- chemistry KW - Molecular Sequence Data KW - DNA, Fungal -- genetics KW - Retroviridae -- genetics KW - Avian Sarcoma Viruses -- genetics KW - Ribonucleases -- metabolism KW - Nucleic Acid Conformation KW - Cell Division -- genetics KW - Retroelements -- genetics KW - Schizosaccharomyces -- metabolism KW - RNA, Messenger -- chemistry KW - Transcription, Genetic -- genetics KW - Repetitive Sequences, Nucleic Acid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69973410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reverse+transcription+of+a+self-primed+retrotransposon+requires+an+RNA+structure+similar+to+the+U5-IR+stem-loop+of+retroviruses.&rft.au=Lin%2C+J+H%3BLevin%2C+H+L&rft.aulast=Lin&rft.aufirst=J&rft.date=1998-11-01&rft.volume=18&rft.issue=11&rft.spage=6859&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] J Virol. 1997 Oct;71(10):7648-56 [9311847] Methods Enzymol. 1987;154:164-75 [3323810] J Virol. 1989 Jan;63(1):319-27 [2908924] Methods Enzymol. 1991;194:795-823 [2005825] J Virol. 1991 Jul;65(7):3864-72 [1710292] EMBO J. 1992 Mar;11(3):1145-53 [1312461] J Virol. 1992 Apr;66(4):2464-72 [1548772] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3236-40 [1314382] J Mol Biol. 1993 Jan 20;229(2):382-97 [8429553] EMBO J. 1993 Dec;12(12):4885-95 [8223497] Mol Cell Biol. 1994 Sep;14(9):5731-40 [7520525] J Mol Biol. 1995 Mar 24;247(2):236-50 [7707372] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] J Virol. 1995 Aug;69(8):4683-92 [7609033] Mol Cell Biol. 1996 Jan;16(1):338-46 [8524313] J Virol. 1996 Feb;70(2):966-75 [8551637] Mol Cell Biol. 1996 Oct;16(10):5645-54 [8816477] Science. 1996 Nov 1;274(5288):765-8 [8864112] Genes Dev. 1997 Jan 15;11(2):270-85 [9009208] Biochemistry. 1997 Apr 22;36(16):4844-51 [9125504] RNA. 1997 Sep;3(9):952-3 [9292494] J Bacteriol. 1984 May;158(2):636-43 [6233260] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The apolipoprotein E epsilon 4 allele is associated with blunting of ketamine-induced psychosis in schizophrenia. A preliminary report. AN - 69971340; 9778666 AB - Interindividual differences in the psychotomimetic response to the N-methyl-d-aspartate receptor antagonist ketamine are commonly observed. The apolipoprotein E (APOE) epsilon 4 allele has been associated with reduced severity of positive psychotic symptoms in schizophrenia. In this study, we sought to determine if the APOE epsilon 4 allele influences the psychotomimetic response to ketamine in schizophrenics. Eighteen patients genotyped at the APOE locus underwent a double-blind infusion of ketamine and of placebo. Ketamine-induced alterations in the brief psychiatric rating scale factors were compared between schizophrenics with and without the APOE epsilon 4 allele. APOE epsilon 4+ schizophrenics displayed significantly reduced ketamine-induced psychosis, as compared to epsilon 4-patients. These preliminary data indicate that the psychotomimetic response to ketamine may be genetically influenced and may provide additional evidence that APOE may modify expression of the positive symptoms in schizophrenia. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Malhotra, A K AU - Breier, A AU - Goldman, D AU - Picken, L AU - Pickar, D AD - Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 445 EP - 448 VL - 19 IS - 5 SN - 0893-133X, 0893-133X KW - Apolipoprotein E4 KW - 0 KW - Apolipoproteins E KW - Ketamine KW - 690G0D6V8H KW - Index Medicus KW - Affect -- drug effects KW - Double-Blind Method KW - Humans KW - Adult KW - Brief Psychiatric Rating Scale KW - Male KW - Female KW - Apolipoproteins E -- physiology KW - Psychoses, Substance-Induced -- physiopathology KW - Psychoses, Substance-Induced -- genetics KW - Schizophrenia -- genetics KW - Schizophrenia -- physiopathology KW - Ketamine -- pharmacology KW - Apolipoproteins E -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69971340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=The+apolipoprotein+E+epsilon+4+allele+is+associated+with+blunting+of+ketamine-induced+psychosis+in+schizophrenia.+A+preliminary+report.&rft.au=Malhotra%2C+A+K%3BBreier%2C+A%3BGoldman%2C+D%3BPicken%2C+L%3BPickar%2C+D&rft.aulast=Malhotra&rft.aufirst=A&rft.date=1998-11-01&rft.volume=19&rft.issue=5&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-23 N1 - Date created - 1998-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to cocaine following repeated administration of a selective kappa-opioid receptor agonist. AN - 69968870; 9776129 AB - Previous data have shown that the repeated administration of kappa-opioid receptor agonists attenuates the acute behavioral effects of cocaine. The site and mechanism by which kappa-agonists interact with this psychostimulant, however, are unknown. Accordingly, the present microdialysis study characterized the effects of prior, repeated administration of the selective kappa-opioid receptor agonist U69593 on basal and cocaine-evoked DA levels within the nucleus accumbens (NAC) and caudate putamen (CPU). The influence of U69593 treatment on the locomotor-activating effects of an acute cocaine challenge was also assessed. Rats received once daily injections of U69593 (0.16-0.32 mg/kg/day) or vehicle (1.0 ml/kg/day) for 3 days. The behavioral and neurochemical effects produced by an acute cocaine challenge (20 mg/kg i.p.) were assessed 2 days following treatment cessation. Administration of cocaine to control animals increased locomotor activity. This effect was attenuated in animals which had previously received U69593 (0.32 mg/kg/day x 3 days). Prior administration of U69593 failed to modify basal DA levels in either the NAC or CPU. Thus, 2 days following the cessation of U69593 treatment, dialysate DA levels did not differ from that of controls. Administration of cocaine to vehicle-treated animals increased dialysate levels of DA in both brain regions. However, in animals previously exposed to U69593 (0.32 mg/kg/day x 3 days), a significant enhancement in the response of DA neurons to cocaine was seen. These data demonstrate that prior, repeated administration of a selective kappa-opioid receptor agonist attenuates the locomotor-activating effects of cocaine and increases cocaine-evoked DA overflow in terminal projection areas of mesostriatal and mesolimbic DA neurons. These findings indicate that the behavioral interactions of kappa-agonists with cocaine observed in this and previous studies cannot be attributed to a presynaptic inhibition of DA release. Rather, they suggest that postsynaptic or non-DA mechanisms mediate the interaction of these agents with cocaine. JF - Synapse (New York, N.Y.) AU - Heidbreder, C A AU - Schenk, S AU - Partridge, B AU - Shippenberg, T S AD - Integrative Neuroscience Unit, Behavioral Neuroscience Branch, National Institute of Health, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 255 EP - 262 VL - 30 IS - 3 SN - 0887-4476, 0887-4476 KW - Analgesics KW - 0 KW - Benzeneacetamides KW - Pyrrolidines KW - Receptors, Opioid, kappa KW - Cocaine KW - I5Y540LHVR KW - U 69593 KW - J5S4K6TKTG KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Analysis of Variance KW - Kinetics KW - Analgesics -- pharmacology KW - Motor Activity -- drug effects KW - Time Factors KW - Male KW - Caudate Nucleus -- metabolism KW - Neurons -- metabolism KW - Limbic System -- metabolism KW - Nucleus Accumbens -- drug effects KW - Neurons -- drug effects KW - Caudate Nucleus -- drug effects KW - Dopamine -- metabolism KW - Limbic System -- drug effects KW - Receptors, Opioid, kappa -- agonists KW - Putamen -- metabolism KW - Pyrrolidines -- pharmacology KW - Nucleus Accumbens -- metabolism KW - Cocaine -- pharmacology KW - Putamen -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+responsiveness+of+mesolimbic+and+mesostriatal+dopamine+neurons+to+cocaine+following+repeated+administration+of+a+selective+kappa-opioid+receptor+agonist.&rft.au=Heidbreder%2C+C+A%3BSchenk%2C+S%3BPartridge%2C+B%3BShippenberg%2C+T+S&rft.aulast=Heidbreder&rft.aufirst=C&rft.date=1998-11-01&rft.volume=30&rft.issue=3&rft.spage=255&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 - 1998-12-28 N1 - Date created - 1998-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells. AN - 69964326; 9772291 AB - Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage. JF - International journal of oncology AU - Li, Q AU - Ding, L AU - Yu, J J AU - Mu, C 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, Bethesda, MD 20892, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 987 EP - 992 VL - 13 IS - 5 SN - 1019-6439, 1019-6439 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Proteins KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Neoplasm Proteins -- biosynthesis KW - Carcinogens -- pharmacology KW - Blotting, Western KW - Tumor Cells, Cultured KW - Humans KW - Proteins -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Female KW - Protein Biosynthesis KW - Ovarian Neoplasms -- metabolism KW - Ovarian Neoplasms -- genetics KW - Cisplatin -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69964326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Cisplatin+and+phorbol+ester+independently+induce+ERCC-1+protein+in+human+ovarian+carcinoma+cells.&rft.au=Li%2C+Q%3BDing%2C+L%3BYu%2C+J+J%3BMu%2C+C%3BTsang%2C+B%3BBostick-Bruton%2C+F%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=1998-11-01&rft.volume=13&rft.issue=5&rft.spage=987&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-09 N1 - Date created - 1998-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Acute dimethylformamide (DMF) poisoning: a case report]. TT - Intossicazione acuta da dimetilformamide (DMF): descrizione di un caso. AN - 69200909; 10217941 AB - This paper describes a case of acute occupational intoxication by dimethylformamide in a worker assigned to polyurethanic resin preparation in a simulated leather factory. The peculiarity of this case is constituted by the association of a dimethylformamide classic clinical syndrome, frequently described in the scientific literature (alcohol intolerance, gastroenteric manifestations with liver injury), with coagulation alterations and thrombocytopenia. Measurement of environmental concentrations of the solvents and biological monitoring revealed high levels of exposure to dimethylformamide at the workplace. Our observations confirm the effects of dimethylformamide on hemostasis reported by other authors in previous studies. It is possible to speculate that the effects of dimethylformamide on coagulation and platelets strictly depend on the amount of solvent accumulated in the body. JF - La Medicina del lavoro AU - Amatimaggio, F AU - Calistri, S AU - Ventura, F AU - Margheri, M AU - Niglio, F AU - Perico, A AU - Perissi, S AD - Unità Operativa Igiene e Salute nei Luoghi di Lavoro, Azienda USL 4 di Prato. PY - 1998 SP - 533 EP - 537 VL - 89 IS - 6 SN - 0025-7818, 0025-7818 KW - Solvents KW - 0 KW - Dimethylformamide KW - 8696NH0Y2X KW - Index Medicus KW - Chemical and Drug Induced Liver Injury -- blood KW - Acute Disease KW - Gloves, Protective KW - Chemical and Drug Induced Liver Injury -- etiology KW - Chemical and Drug Induced Liver Injury -- diagnosis KW - Humans KW - Hemostasis -- drug effects KW - Adult KW - Poisoning -- diagnosis KW - Poisoning -- etiology KW - Male KW - Poisoning -- blood KW - Occupational Diseases -- diagnosis KW - Occupational Diseases -- blood KW - Solvents -- poisoning KW - Dimethylformamide -- poisoning KW - Occupational Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69200909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BAcute+dimethylformamide+%28DMF%29+poisoning%3A+a+case+report%5D.&rft.au=Amatimaggio%2C+F%3BCalistri%2C+S%3BVentura%2C+F%3BMargheri%2C+M%3BNiglio%2C+F%3BPerico%2C+A%3BPerissi%2C+S&rft.aulast=Amatimaggio&rft.aufirst=F&rft.date=1998-11-01&rft.volume=89&rft.issue=6&rft.spage=533&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 - 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 - More ethical challenges: commentary on Fischman and Johanson's ethical and practical issues involved in behavioral pharmacology research that administers drug of abuse to human volunteers. AN - 69188735; 10094591 JF - Behavioural pharmacology AU - Ernst, M AU - London, E D AD - Brain Imaging Center, NIDA NIH, Baltimore, Maryland, Usa. mersnt@irp.nida.nih.gov Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 499 EP - 501 VL - 9 IS - 7 SN - 0955-8810, 0955-8810 KW - Index Medicus KW - Volunteers KW - Humans KW - Research Design KW - Risk Assessment KW - Behavior -- drug effects KW - Ethics, Medical KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69188735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=More+ethical+challenges%3A+commentary+on+Fischman+and+Johanson%27s+ethical+and+practical+issues+involved+in+behavioral+pharmacology+research+that+administers+drug+of+abuse+to+human+volunteers.&rft.au=Ernst%2C+M%3BLondon%2C+E+D&rft.aulast=Ernst&rft.aufirst=M&rft.date=1998-11-01&rft.volume=9&rft.issue=7&rft.spage=499&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 - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Behav Pharmacol. 1998 Nov;9(7):479-98 [9862072] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ALARA study of teaching effectiveness on reducing radiation exposure. AN - 69184823; 10095504 AB - The purpose of this study was to measure the effectiveness of radiation safety instruction and the impact on radiation film badge levels. A convenience sample of 144 endoscopy nurses and technicians was pretested for radiation safety knowledge, given a course in radiation safety, and then posttested immediately after the course and then 6 months later. Radiation badges were analyzed for radiation exposure at preinstruction, 1 month postinstruction, and 6 months postinstruction. Results showed that the instruction was effective. There was only a slight decrease in radiation badge readings; the decrease, however, was not statistically significant. JF - Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates AU - Feigenbaum, K AU - Ellett, M L AU - Miller, R AU - Hyland, L AD - National Institutes of Health, Bethesda, MD, USA. PY - 1998 SP - 234 EP - 238 VL - 21 IS - 6 SN - 1042-895X, 1042-895X KW - Nursing KW - Maximum Allowable Concentration KW - Humans KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Program Evaluation KW - Middle Aged KW - Male KW - Female KW - Nursing Staff, Hospital -- psychology KW - Nursing Staff, Hospital -- education KW - Radiation Protection KW - Cholangiopancreatography, Endoscopic Retrograde -- nursing KW - Education, Nursing, Continuing -- organization & administration KW - Staff Development -- organization & administration KW - Radiation Monitoring KW - Specialties, Nursing -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69184823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing+%3A+the+official+journal+of+the+Society+of+Gastroenterology+Nurses+and+Associates&rft.atitle=ALARA+study+of+teaching+effectiveness+on+reducing+radiation+exposure.&rft.au=Feigenbaum%2C+K%3BEllett%2C+M+L%3BMiller%2C+R%3BHyland%2C+L&rft.aulast=Feigenbaum&rft.aufirst=K&rft.date=1998-11-01&rft.volume=21&rft.issue=6&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Gastroenterology+nursing+%3A+the+official+journal+of+the+Society+of+Gastroenterology+Nurses+and+Associates&rft.issn=1042895X&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 - Tumor angiogenesis: biology and therapeutic prospects. AN - 69144070; 9891218 AB - Angiogenesis is now recognized as a critical process in tumor progression and is required for solid tumors to grow beyond a few millimeters in size. The transition from a non angiogenic to an angiogenic phenotype and subsequent tumor vascularization is not well understood but is likely to involve angiogenic stimulators and inhibitors. Regulation of vascular growth also involves complex interactions of extracellular matrix molecules, proteolytic enzymes and cell adhesion molecules. Each step in the angiogenic process represents a potential target for therapeutic anticancer strategies. Antiangiogenic compounds have proven very successful as cancer treatments in murine animal models and demonstrated utility in treating humans cancers in clinical trials. These agents exhibit reduced toxicity and a decreased likelihood for the development of drug resistance compared to conventional chemotherapies. This review summarizes current knowledge of tumor angiogenesis and the factors involved, and, in addition, presents an overview of current and future antiangiogenic therapies. JF - In vivo (Athens, Greece) AU - Harris, S R AU - Thorgeirsson, U P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892, USA. PY - 1998 SP - 563 EP - 570 VL - 12 IS - 6 SN - 0258-851X, 0258-851X KW - Angiogenesis Inhibitors KW - 0 KW - Biomarkers KW - Growth Substances KW - Proteins KW - Index Medicus KW - Neoplasms, Experimental -- blood supply KW - Animals KW - Endothelium, Vascular -- cytology KW - Basement Membrane -- metabolism KW - Neoplasms, Experimental -- therapy KW - Humans KW - Biomarkers -- analysis KW - Proteins -- therapeutic use KW - Neoplasms, Experimental -- chemistry KW - Cell Movement -- drug effects KW - Growth Substances -- physiology KW - Neovascularization, Pathologic -- physiopathology KW - Neoplasms -- chemistry KW - Neoplasms -- blood supply KW - Neoplasms -- therapy KW - Neovascularization, Pathologic -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69144070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Tumor+angiogenesis%3A+biology+and+therapeutic+prospects.&rft.au=Harris%2C+S+R%3BThorgeirsson%2C+U+P&rft.aulast=Harris&rft.aufirst=S&rft.date=1998-11-01&rft.volume=12&rft.issue=6&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&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 - Theophylline-induced mesenteric periarteritis in F344/N rats. AN - 69123747; 9879811 AB - The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall. JF - Archives of toxicology AU - Nyska, A AU - Herbert, R A AU - Chan, P C AU - Haseman, J K AU - Hailey, J R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 731 EP - 737 VL - 72 IS - 11 SN - 0340-5761, 0340-5761 KW - Carcinogens KW - 0 KW - Vasodilator Agents KW - Theophylline KW - C137DTR5RG KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Time Factors KW - Male KW - Female KW - Carcinogens -- toxicity KW - Theophylline -- toxicity KW - Arteritis -- chemically induced KW - Vasodilator Agents -- toxicity KW - Mesenteric Arteries -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69123747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+toxicology&rft.atitle=Theophylline-induced+mesenteric+periarteritis+in+F344%2FN+rats.&rft.au=Nyska%2C+A%3BHerbert%2C+R+A%3BChan%2C+P+C%3BHaseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Nyska&rft.aufirst=A&rft.date=1998-11-01&rft.volume=72&rft.issue=11&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-29 N1 - Date created - 1999-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Different populations of progesterone receptor-steroid complexes in binding to specific DNA sequences: effects of salts on kinetics and specificity. AN - 69119669; 9879984 AB - We previously reported evidence for two subpopulations of several classes of steroid receptors that could be distinguished by their requirement of a low molecular weight factor (Mr=700-3000 Da) for binding to nonspecific, calf thymus DNA-cellulose [Cavanaugh, A. H. and Simons Jr., S. S., Journal of Steroid Biochemistry and Molecular Biology, 48, 433-446 (1994)]. This factor appeared to be enriched in (NH4)2SO4 precipitates of nuclear extracts. Using human progesterone receptors (PRs) and biologically active DNA sequences in a modified avidin/biotin-coupled DNA (ABCD) binding assay, we now report a factor-mediated increase in PR binding to specific DNA sites that was indistinguishable from that seen with nonspecific sites. The main advantages of this modified assay are that both kinetic and equilibrium binding of receptor-steroid complexes to DNA can be directly monitored in solution. The ability of either Sephadex G-50 chromatography or sodium arsenite to prevent that binding which is increased by added factor supported the existence of PR subpopulations that are independent of the acceptor DNA sequence. The factor was found, surprisingly, to be low concentrations (> or = 5 mM) of (NH4)2SO4, which anomalously is partially excluded from Sephadex G-10 columns, and can be mimicked by some salts but not sodium arsenite. Kinetic analyses demonstrated that the mechanism of action of salt was to accelerate the rate of binding of PR. Salt also had a much greater effect on the nonspecific binding of PR, such that the ratio of specific to nonspecific DNA binding was greatest at elevated salt concentrations (approximately 75 mM) that afforded submaximal levels of PR binding to specific DNA sites. Further analysis of the DNA-bound receptors revealed that the smaller, A-form of PR is preferentially bound to specific DNA sequences both in the presence and in the absence of various salt concentrations. Thus, the differences in DNA binding of PR +/- salt do not correlate with the preferential binding of A or B isoform. The unequal behavior of PR subpopulations and/or isoforms for binding to specific DNA sequences offers added mechanisms for selective transcriptional regulation of genes in intact cells. JF - The Journal of steroid biochemistry and molecular biology AU - Plisov, S Y AU - Poirot, M E AU - Modarress, K J AU - Cavanaugh, A H AU - Edwards, D P AU - Simons, S S AD - Steroid Hormones Section, NIDDK/LMCB, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 251 EP - 266 VL - 67 IS - 3 SN - 0960-0760, 0960-0760 KW - Arsenites KW - 0 KW - Oligodeoxyribonucleotides KW - Receptors, Progesterone KW - Salts KW - Steroids KW - methyl methanethiosulfonate KW - 2949-92-0 KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - arsenite KW - N5509X556J KW - Ammonium Sulfate KW - SU46BAM238 KW - Index Medicus KW - Animals KW - Drug Stability KW - Arsenites -- pharmacology KW - Humans KW - Oligodeoxyribonucleotides -- genetics KW - Methyl Methanesulfonate -- analogs & derivatives KW - Methyl Methanesulfonate -- pharmacology KW - Rats KW - Base Sequence KW - Cattle KW - Kinetics KW - In Vitro Techniques KW - Salts -- pharmacology KW - Oligodeoxyribonucleotides -- metabolism KW - Binding Sites -- genetics KW - Ammonium Sulfate -- pharmacology KW - Cell Line KW - Receptors, Progesterone -- genetics KW - Receptors, Progesterone -- metabolism KW - DNA -- metabolism KW - DNA -- genetics KW - Receptors, Progesterone -- classification KW - Steroids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69119669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Different+populations+of+progesterone+receptor-steroid+complexes+in+binding+to+specific+DNA+sequences%3A+effects+of+salts+on+kinetics+and+specificity.&rft.au=Plisov%2C+S+Y%3BPoirot%2C+M+E%3BModarress%2C+K+J%3BCavanaugh%2C+A+H%3BEdwards%2C+D+P%3BSimons%2C+S+S&rft.aulast=Plisov&rft.aufirst=S&rft.date=1998-11-01&rft.volume=67&rft.issue=3&rft.spage=251&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 - 1999-01-21 N1 - Date created - 1999-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic characterization of the transgenic Big Blue Rat2 and Big Blue mouse embryonic fibroblast cell lines. AN - 69091715; 9862199 AB - The transgenic Big Blue Rat2 and Big Blue mouse embryonic fibroblast cell lines have been used to complement the transgenic Big Blue rat and mouse in vivo mutagenesis assays. However, limited information is available regarding the karyology of these cell lines. Therefore, we have characterized the ploidy, mitotic index, spontaneous frequencies of chromosome and chromatid aberrations and rate of micronucleus (MN) formation in both cell lines. We have also characterized the frequency of sister chromatid exchange (SCE) in transgenic Big Blue mouse cells. Big Blue Rat2 cells are hyperploid and have extremely high baseline frequencies of cytogenetic damage. In addition, Big Blue Rat2 cells are BrdU-resistant, therefore, SCE frequencies cannot be assessed in these cells. We conclude that Big Blue Rat2 cells are not useful for routine cytogenetic toxicology studies. The transgenic Big Blue mouse cell line is polyploid and consistently yields a low mitotic index (approximately 1%) in untreated cells. These mouse cells also exhibited moderately high baseline frequencies of chromosome and chromatid aberrations, however, baseline frequencies of SCE and of MN were not elevated. Transgenic Big Blue mouse embryonic fibroblasts were further studied for MN induction following treatment with N-ethyl-N-nitrosourea (ENU) for 0.5 h at concentrations of 0.425, 0.85 and 1.7 mM. Concentration-dependent increases in MN were observed in these cells. Thus, while an ENU-induced cytogenetic response using transgenic Big Blue mouse cells demonstrates that this cellular model could be used to cytogenetically complement the mutagenesis assays, the low mitotic index and the high spontaneous frequency of chromosome damage confounds its use for routine genetic toxicology studies. JF - Mutagenesis AU - Erexson, G L AU - Cunningham, M L AU - Tindall, K R AD - Molecular Mutagenesis Group, Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/11// PY - 1998 DA - November 1998 SP - 649 EP - 653 VL - 13 IS - 6 SN - 0267-8357, 0267-8357 KW - Mutagens KW - 0 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Rats KW - Fibroblasts -- drug effects KW - Animals KW - Micronucleus Tests KW - Ethylnitrosourea -- toxicity KW - Sister Chromatid Exchange KW - Chromosome Aberrations KW - Mutagens -- toxicity KW - Mice KW - Mice, Transgenic KW - Cell Line KW - Mutagenicity Tests -- methods KW - Animals, Genetically Modified -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69091715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Cytogenetic+characterization+of+the+transgenic+Big+Blue+Rat2+and+Big+Blue+mouse+embryonic+fibroblast+cell+lines.&rft.au=Erexson%2C+G+L%3BCunningham%2C+M+L%3BTindall%2C+K+R&rft.aulast=Erexson&rft.aufirst=G&rft.date=1998-11-01&rft.volume=13&rft.issue=6&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&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 - Partitioning of dioxins, dibenzofurans, and coplanar PCBs in blood, milk, adipose tissue, placenta and cord blood from five American women AN - 17591026; 4664886 AB - Partitioning of dioxins, dibenzofurans and the dioxin-like coplanar PCBs was determined by congener-specific high resolution gc-ms analysis of compounds in 6 tissue samples each from 5 women. Samples were whole blood obtained prior to delivery; maternal adipose tissue, cord blood and placenta obtained during cesarean section delivery; and whole blood and milk taken at the time of first obstetrical follow-up examination, one to two months following delivery. All women lived in upstate New York. Specimens were collected in late 1995 and early 1996. Mean measured levels of total PCDDs, PCDFs and coplanar PCBs were 352 pg/g for adipose tissue, 526 pg/g for predelivery blood, 182 pg/g for placenta, 165 pg/g for cord blood, 352 pg/g for postpartum blood and 220 pg/g for milk. Mean total TEQ levels were 11.6 pg/g TEQ for adipose tissue, 12.1 pg/g TEQ for predelivery blood, 10.5 pg/g TEQ for placenta, 5.8 pg/g TEQ for cord blood, 10.0 pg/g TEQ for postpartum blood and 10.2 pg/g TEQ for milk. JF - Chemosphere AU - Schecter, A AU - Kassis, I AU - Paepke, O AD - National Institute of Environmental Health Sciences, MD A3-02, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 1817 EP - 1823 VL - 37 IS - 9-12 SN - 0045-6535, 0045-6535 KW - man KW - Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - Breast milk KW - Cord blood KW - Placenta KW - PCDF KW - PCB compounds KW - PCB KW - PCDD KW - Polychlorinated dibenzo(p)dioxins KW - Polychlorinated dibenzofurans KW - Pregnancy KW - USA 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/17591026?accountid=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=Chemosphere&rft.atitle=Partitioning+of+dioxins%2C+dibenzofurans%2C+and+coplanar+PCBs+in+blood%2C+milk%2C+adipose+tissue%2C+placenta+and+cord+blood+from+five+American+women&rft.au=Schecter%2C+A%3BKassis%2C+I%3BPaepke%2C+O&rft.aulast=Schecter&rft.aufirst=A&rft.date=1998-11-01&rft.volume=37&rft.issue=9-12&rft.spage=1817&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Chlorinated Dioxins and related Compounds 1996. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Breast milk; Pregnancy; PCDD; PCDF; PCB compounds; PCB; Polychlorinated dibenzofurans; Polychlorinated dibenzo(p)dioxins; Cord blood; Placenta ER - TY - JOUR T1 - Decrease in levels and body burden of dioxins, dibenzofurans, PCBs, DDE, and HCB in blood and milk in a mother nursing twins over a thirty-eight month period AN - 17588226; 4664885 AB - This paper presents measured dioxin, dibenzofuran, PCB, DDE and HCB blood and milk levels and estimated body burdens in a mother who nursed twins for thirty-eight months. A total of thirteen milk samples and three blood samples were collected and analyzed. Measured PCDD and PCDF levels in milk decreased from 309 and 21 ng/kg (ppt) to 173 and 9 ng/kg, respectively, between March 1993 and September 1995. Based on the decrease in breast milk dioxin levels, we estimate that the nursing mother reduced her dioxin body burden from 310 to 96 ng dioxin toxic equivalents (TEQs), or approximately 69%. In two and one half years the level of HCB in the mother's milk decreased from 10.7 to less than 1.8 ng/g (ppb), the level of DDE decreased from 246 to 46 ng/g and the total level of non-coplanar PCBs decreased from 285 to 63 ng/g, on a lipid basis. We estimate that the twin's consumption of dioxins, dibenzofurans, and coplanar PCBs from breast feeding was approximately 115 ng TEQ per twin. JF - Chemosphere AU - Schecter, A AU - Ryan, J J AU - Paepke, O AD - National Institute of Environmental Health Sciences, MD A3-02, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 1807 EP - 1816 VL - 37 IS - 9-12 SN - 0045-6535, 0045-6535 KW - man KW - Health & Safety Science Abstracts; Toxicology Abstracts; Pollution Abstracts KW - Breast milk KW - PCDF KW - PCB compounds KW - PCB KW - PCDD KW - Polychlorinated dibenzo(p)dioxins KW - DDE KW - Polychlorinated dibenzofurans KW - Blood KW - Infants 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/17588226?accountid=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=Chemosphere&rft.atitle=Decrease+in+levels+and+body+burden+of+dioxins%2C+dibenzofurans%2C+PCBs%2C+DDE%2C+and+HCB+in+blood+and+milk+in+a+mother+nursing+twins+over+a+thirty-eight+month+period&rft.au=Schecter%2C+A%3BRyan%2C+J+J%3BPaepke%2C+O&rft.aulast=Schecter&rft.aufirst=A&rft.date=1998-11-01&rft.volume=37&rft.issue=9-12&rft.spage=1807&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Chlorinated Dioxins and related Compounds 1996. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast milk; DDE; PCB compounds; PCDD; Infants; PCDF; PCB; Polychlorinated dibenzofurans; Polychlorinated dibenzo(p)dioxins; Blood ER - TY - JOUR T1 - A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon AN - 17453716; 4664876 AB - The primary source of dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar PCBs for the general population is food, especially meat, fish, and dairy products. However, most data on the levels of these chemicals is from food in the raw or uncooked state. We report here the effect of one type of cooking (broiling) on the levels of PCDDs, PCDFs, and coplanar PCBs in ground beef (hamburger), bacon and catfish. Samples of hamburger, bacon, and catfish were broiled and compared to uncooked samples in order to measure changes in the amounts of dioxins in cooked food. The total amount of PCDD, PCDF, and coplanar PCB TEQ decreased by approximately 50% on average for each portion as a result of broiling the hamburger, bacon and catfish specimens. The mean concentration (pg TEQ/kg, wet weight) of PCDDs, PCDFs, and coplanar PCBs, however, remained the same in the hamburger, increased by 83% in the bacon, and decreased by 34% in the catfish. On average, the total measured concentration (pg/kg) of the congeners of PCDDs, PCDFs, and coplanar PCBs increased 14% in the hamburger, increased 29% in the bacon, and decreased 33% in the catfish. JF - Chemosphere AU - Schecter, A AU - Dellarco, M AU - Paepke, O AU - Olson, J AD - National Institute of Environmental Health Sciences, MD A3-02, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 1723 EP - 1730 VL - 37 IS - 9-12 SN - 0045-6535, 0045-6535 KW - bacon KW - beef KW - cooking KW - meat KW - polychlorinated dibenzo(p)dioxins KW - polychlorinated dibenzofurans KW - Toxicology Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; Health & Safety Science Abstracts KW - Food KW - Ictalurus KW - Human food KW - Freshwater KW - Public health KW - Minced meat KW - Cooking KW - PCDF KW - Seafood KW - PCB compounds KW - PCDD KW - PCB KW - Marine KW - Chemical composition KW - Brackish KW - Food contamination KW - Bacon KW - Food fish KW - Bioaccumulation KW - Beef KW - Pesticides KW - Fishery products KW - X 24120:Food, additives & contaminants KW - Q5 08524:Public health, medicines, dangerous organisms KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17453716?accountid=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=Chemosphere&rft.atitle=A+comparison+of+dioxins%2C+dibenzofurans+and+coplanar+PCBs+in+uncooked+and+broiled+ground+beef%2C+catfish+and+bacon&rft.au=Schecter%2C+A%3BDellarco%2C+M%3BPaepke%2C+O%3BOlson%2C+J&rft.aulast=Schecter&rft.aufirst=A&rft.date=1998-11-01&rft.volume=37&rft.issue=9-12&rft.spage=1723&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Special Issue: Chlorinated Dioxins and related Compounds 1996. N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Bioaccumulation; Chemical composition; Human food; Pesticides; PCB; Food fish; Public health; Fishery products; Minced meat; Beef; Food; Cooking; Bacon; PCDF; Seafood; Food contamination; PCB compounds; PCDD; Ictalurus; Freshwater; Brackish; Marine ER - TY - JOUR T1 - Immunization with a Peptide Epitope (p369-377) from HER-2/neu Leads to Peptide-specific Cytotoxic T Lymphocytes That Fail to Recognize HER-2/neu+ Tumors AN - 17215886; 4498421 AB - The oncogene HER-2/neu is genetically amplified and overexpressed in a large number of human adenocarcinomas and has been implicated in the tumorigenic phenotype. Although it is a nonmutated self-protein, it is barely detectable in adult tissues, and immune responses toward it have been described in a number of patients. It is, thus, an attractive candidate antigen for the immunotherapy of cancer patients. HLA-A2 super(+) patients with metastatic breast, ovarian, or colorectal adenocarcinomas that over-expressed HER-2/neu were immunized with the HLA-A2-binding epitope p369-377 (p369). Patients were treated by repeated immunization with 1 mg of p369 in Freund's incomplete adjuvant every 3 weeks. Peripheral blood mononuclear cells were collected prior to immunization and following two and four immunizations and were stimulated in vitro with peptide and assayed for peptide and tumor recognition. In three of four patients, peptide-specific CTLs were detected in post- but not preimmunization blood. These CTLs recognized peptide-pulsed target cells at peptide concentrations of greater than or equal to 1 ng/ml yet failed to react with a panel of HLA-A2 super(+) HER-2/neu super(+) tumor lines. In addition, infecting HLA-A2 super(+) cells with recombinant vaccinia virus encoding HER-2/neu or up-regulating HLA-A2 with IFN- gamma in HER-2/neu super(+) cells also failed to confer reactivity by p369-reactive T-cells. A T-cell response to the HLA-A2 binding epitope p369 can be easily generated by immunizing patients with peptide in Freund's incomplete adjuvant. However, the CTLs failed to react with HER-2/neu super(+) tumor cells. Further studies are needed to determine whether and how HER-2 might serve as an antigen for tumor immunotherapy. JF - Cancer Research AU - Zaks, T Z AU - Rosenberg, SA AD - Surgery Branch, National Cancer Institute, Building 10, Room 2B-46, NIH, Bethesda, MD 20892-1502, USA, zakst@nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 4902 EP - 4908 VL - 58 IS - 21 SN - 0008-5472, 0008-5472 KW - A2 determinant KW - HER2 gene KW - cancer patients KW - histocompatibility antigen HLA KW - man KW - neu gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Immunotherapy KW - Tumors KW - Killer cells KW - Lymphocytes T KW - Vaccines KW - B 26020:EGF & EGF receptor family/TGF alpha /Her/ErbB-2 (Neu)/ErbB-3/ErbB-4/amphiregulin KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17215886?accountid=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=Immunization+with+a+Peptide+Epitope+%28p369-377%29+from+HER-2%2Fneu+Leads+to+Peptide-specific+Cytotoxic+T+Lymphocytes+That+Fail+to+Recognize+HER-2%2Fneu%2B+Tumors&rft.au=Zaks%2C+T+Z%3BRosenberg%2C+SA&rft.aulast=Zaks&rft.aufirst=T&rft.date=1998-11-01&rft.volume=58&rft.issue=21&rft.spage=4902&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 - Killer cells; Vaccines; Immunotherapy; Tumors; Lymphocytes T ER - TY - JOUR T1 - Identification of HIV-1 integrase inhibitors based on a four-point pharmacophore AN - 17209639; 4489873 AB - The rapid emergence of human immunodeficiency virus (HIV) strains resistant to available drugs implies that effective treatment modalities will require the use of a combination of drugs targeting different sites of the HIV life cycle. Because the virus cannot replicate without integration into a host chromosome, HIV-1 integrase (IN) is an attractive therapeutic target. Thus, an effective IN inhibitor should provide additional benefit in combination chemotherapy. A four-point pharmacophore has been identified based on the structures of quinalizarin and purpurin, which were found to be potent IN inhibitors using both a preintegration complex assay and a purified enzyme assay in vitro. Searching with this four-point pharmacophore in the `open' part of the National Cancer Institute three-dimensional structure database produced 234 compounds containing the pharmacophore. Sixty of these compounds were tested for their inhibitory activity against IN using the purified enzyme; 19 were found to be active against IN with IC sub(50) values of less than 100 mu M, among which 10 had IC sub(50) values of less than 10 mu M. These inhibitors can further serve as leads, and studies are in progress to design novel inhibitors based on the results presented in this study. JF - Antiviral Chemistry & Chemotherapy AU - Hong, H AU - Neamati, N AU - Winslow, HE AU - Christensen, J L AU - Orr, A AU - Pommier, Y AU - Milne, GWA AD - Laboratory of Medicinal Chemistry, and Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, 5B29, MD 20892, USA, bill@phm.com Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 461 EP - 472 VL - 9 IS - 6 SN - 0956-3202, 0956-3202 KW - HIV-1 KW - human immunodeficiency virus 1 KW - integrase inhibitors KW - pharmacophore KW - pharmacophores KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Drug resistance KW - Life cycle KW - Chromosomes KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Integrase KW - A 01068:Antiviral & viricidal 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/17209639?accountid=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+Chemistry+%26+Chemotherapy&rft.atitle=Identification+of+HIV-1+integrase+inhibitors+based+on+a+four-point+pharmacophore&rft.au=Hong%2C+H%3BNeamati%2C+N%3BWinslow%2C+HE%3BChristensen%2C+J+L%3BOrr%2C+A%3BPommier%2C+Y%3BMilne%2C+GWA&rft.aulast=Hong&rft.aufirst=H&rft.date=1998-11-01&rft.volume=9&rft.issue=6&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Antiviral+Chemistry+%26+Chemotherapy&rft.issn=09563202&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; Life cycle; Drug resistance; Antiviral agents; Integrase; Chromosomes ER - TY - JOUR T1 - Membrane Fusion Mediated by Baculovirus gp64 Involves Assembly of Stable gp64 Trimers into Multiprotein Aggregates AN - 17197329; 4486478 AB - The baculovirus fusogenic activity depends on the low pH conformation of virally-encoded trimeric glycoprotein, gp64. We used two experimental approaches to investigate whether monomers, trimers, and/or higher order oligomers are functionally involved in gp64 fusion machine. First, dithiothreitol (DTT)-based reduction of intersubunit disulfides was found to reversibly inhibit fusion, as assayed by fluorescent probe redistribution between gp64-expressing and target cells (i.e., erythrocytes or Sf9 cells). This inhibition correlates with disappearance of gp64 trimers and appearance of dimers and monomers in SDS-PAGE. Thus, stable (i.e., with intact intersubunit disulfides) gp64 trimers, rather than independent monomers, drive fusion. Second, we established that merger of membranes is preceded by formation of large (greater than 2 MDa), short-lived gp64 complexes. These complexes were stabilized by cell-surface cross-linking and characterized by glycerol density gradient ultracentrifugation. The basic structural unit of the complexes is stable gp64 trimer. Although DTT-destabilized trimers were still capable of assuming the low pH conformation, they failed to form multimeric complexes. The fact that formation of these complexes correlated with fusion in timing, and was dependent on (a) low pH application, (b) stable gp64 trimers, and (c) cell-cell contacts, suggests that such multimeric complexes represent a fusion machine. JF - Journal of Cell Biology AU - Markovic, I AU - Pulyaeva, H AU - Sokoloff, A AU - Chernomordik, LV AD - Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Building 10, Room 10D04, 10 Center Dr., Bethesda, MD 20892-1855, USA, lchern@helix.nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 1155 EP - 1166 VL - 143 IS - 5 SN - 0021-9525, 0021-9525 KW - glycoprotein gp64 KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Membrane fusion KW - Probes KW - Assembly KW - Gel electrophoresis KW - Reduction KW - Trimers KW - Baculovirus KW - pH effects KW - V 22023:Virus behavior in cell culture KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17197329?accountid=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+Cell+Biology&rft.atitle=Membrane+Fusion+Mediated+by+Baculovirus+gp64+Involves+Assembly+of+Stable+gp64+Trimers+into+Multiprotein+Aggregates&rft.au=Markovic%2C+I%3BPulyaeva%2C+H%3BSokoloff%2C+A%3BChernomordik%2C+LV&rft.aulast=Markovic&rft.aufirst=I&rft.date=1998-11-01&rft.volume=143&rft.issue=5&rft.spage=1155&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Biology&rft.issn=00219525&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 - Baculovirus; pH effects; Assembly; Reduction; Gel electrophoresis; Trimers; Membrane fusion; Probes ER - TY - JOUR T1 - Characterization of circular plasmid dimers in Borrelia burgdorferi AN - 17144861; 4436655 AB - We have inactivated the ospC, oppAIV, and guaB genes on the 26-kb circular plasmid of Borrelia burgdorferi (cp26) by allelic exchange. On several occasions following such transformations, the cp26 of transformants had an aberrant mobility through agarose gels. Characterization of these cp26 molecules showed that the plasmid had dimerized. These dimers were quite stable during either selective or nonselective passage. Subsequent transformations with dimer DNA supported the hypothesis that in B. burgdorferi, transforming cp26 DNA most likely does not displace the resident homologous plasmid but rather must recombine in order to donate sequences that it carries. These serendipitous findings provide a mechanism for obtaining heterozygous complemented control strains when mutant phenotypes are characterized. JF - Journal of Bacteriology AU - Tilly, K AU - Lubke, L AU - Rosa, P AD - Rocky Mountain Laboratories, NIAID, NIH, 903 S. 4th St., Hamilton, MT 59840, USA, ktilly@nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 5676 EP - 5681 VL - 180 IS - 21 SN - 0021-9193, 0021-9193 KW - alleles KW - guaB gene KW - oppAIV gene KW - ospC gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Transformation KW - Borrelia burgdorferi KW - Dimerization KW - Plasmids KW - Passage KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17144861?accountid=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=Characterization+of+circular+plasmid+dimers+in+Borrelia+burgdorferi&rft.au=Tilly%2C+K%3BLubke%2C+L%3BRosa%2C+P&rft.aulast=Tilly&rft.aufirst=K&rft.date=1998-11-01&rft.volume=180&rft.issue=21&rft.spage=5676&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 - Borrelia burgdorferi; Passage; Plasmids; Transformation; Dimerization ER - TY - JOUR T1 - Risk for prostate cancer by occupation and industry: A 24-state death certificate study AN - 17139237; 4439910 AB - Current knowledge of the etiology of prostate cancer is limited. Numerous studies have suggested that certain occupations and industries may be associated with the occurrence of prostate cancer. Information on occupation and industry on death certificates from 24 states gathered from 1984 to 1993 was used in case control study on prostate cancer. A total of 60,878 men with prostate cancer as underlying cause of death was selected and matched with controls who died of all other causes except cancer. Similar to the findings of our parallel large case control study of prostate cancer, we observed excess risks in some white-collar occupations, such as administrators, managers, teachers, engineers, and sales occupations. However, some blue-collar occupations, such as power plant operators and stationary engineers, brickmasons, machinery maintenance workers, airplane pilots, longshoreman, railroad industry workers, and other occupations with potential exposure to PAH also showed risk of excess prostate cancer. Risk was significantly decreased for blue-collar occupations, including farm workers, commercial fishermen, mechanics and repairers, structural metal workers, mining, printing, winding, dry cleaning, textile machine operators, cooks, bakers, and bartenders. Although we observed excess risks of prostate cancer among some low socioeconomic status (SES) occupations, the overall results suggest that the effects of higher SES cannot be ruled out in associations between occupational factors and the risk of prostate cancer. JF - American Journal of Industrial Medicine AU - Krstev, S AU - Baris, D AU - Stewart, P A AU - Hayes, R B AU - Blair, A AU - Dosemeci, M AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bldg. EPN, Room 418, Rockville, MD 20892, USA, dosemecm@epndce.nci.nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 413 EP - 420 VL - 34 IS - 5 SN - 0271-3586, 0271-3586 KW - man KW - prostate KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Socioeconomics KW - Prostate KW - Risk assessment KW - Occupational exposure KW - Mortality KW - Polycyclic aromatic hydrocarbons KW - Cancer KW - Occupational health KW - R2 23080:Industrial and labor KW - X 24190:Polycyclic hydrocarbons KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17139237?accountid=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=Risk+for+prostate+cancer+by+occupation+and+industry%3A+A+24-state+death+certificate+study&rft.au=Krstev%2C+S%3BBaris%2C+D%3BStewart%2C+P+A%3BHayes%2C+R+B%3BBlair%2C+A%3BDosemeci%2C+M&rft.aulast=Krstev&rft.aufirst=S&rft.date=1998-11-01&rft.volume=34&rft.issue=5&rft.spage=413&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Socioeconomics; Mortality; Occupational exposure; Cancer; Risk assessment; Occupational health; Polycyclic aromatic hydrocarbons; Prostate ER - TY - JOUR T1 - Occupational risk factors and prostate cancer in U.S. blacks and whites AN - 17138663; 4439911 AB - Although prostate cancer is a major disease, causal factors are only partially understood. We examined occupational risk factors for this disease in a large case control study among U.S. blacks and whites. The study included 981 new pathologically confirmed prostate cancer cases (479 blacks and 502 whites) diagnosed between 1986 and 1989, and 1,315 population controls (594 blacks and 721 whites) who resided in Atlanta, Detroit, and 10 counties in New Jersey, covered by population-based cancer registries. Information on occupation, including a lifetime work history, was collected by in-person interview. No clear patterns of risk were found for U.S. whites versus blacks, nor for white-collar versus blue-collar jobs. Farming was related to prostate cancer (OR = 2.17; 95% CI = 1.18-3.98). Risk was restricted, however, to short-term workers and workers in crop production. Risk was not limited to those farming after 1950, when widespread use of pesticides started. Risks increased with increasing years of employment in firefighting ( chi super(2) sub(trend), p = 0.02) and power plant operations ( chi super(2) sub(trend), p = 0.03), and were elevated among long-term railroad line-haulers (OR = 5.85; 95% CI = 1.25-27.4); jobs with potential polycyclic aromatic hydrocarbon (PAH) exposures. Risk was elevated among athletes (OR = 5.38; 95% CI = 1.48-19.6). However, most of the cases were athletes before 1960, so the potential use of anabolic steroids was excluded. Although some clues about potential occupational associations were found, the overall results show that occupation is not a major determinant of prostate cancer risk. JF - American Journal of Industrial Medicine AU - Krstev, S AU - Baris, D AU - Stewart, P AU - Dosemeci, M AU - Swanson, G M AU - Greenberg, R S AU - Schoenberg, J B AU - Schwartz, A G AU - Liff, J M AU - Hayes, R B AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer institute, Executive Plaza North, Room 418, Rockville, MD 20892, USA Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 421 EP - 430 VL - 34 IS - 5 SN - 0271-3586, 0271-3586 KW - USA KW - man KW - prostate KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Diseases KW - Ethnic groups KW - Prostate KW - Risk assessment KW - Statistical analysis KW - Occupational exposure KW - Polycyclic aromatic hydrocarbons KW - Steroid hormones KW - Cancer KW - Occupational health KW - R2 23080:Industrial and labor KW - X 24190:Polycyclic hydrocarbons KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17138663?accountid=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=Occupational+risk+factors+and+prostate+cancer+in+U.S.+blacks+and+whites&rft.au=Krstev%2C+S%3BBaris%2C+D%3BStewart%2C+P%3BDosemeci%2C+M%3BSwanson%2C+G+M%3BGreenberg%2C+R+S%3BSchoenberg%2C+J+B%3BSchwartz%2C+A+G%3BLiff%2C+J+M%3BHayes%2C+R+B&rft.aulast=Krstev&rft.aufirst=S&rft.date=1998-11-01&rft.volume=34&rft.issue=5&rft.spage=421&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Cancer; Risk assessment; Ethnic groups; Steroid hormones; Occupational health; Statistical analysis; Diseases; Polycyclic aromatic hydrocarbons; Prostate ER - TY - JOUR T1 - Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12-and gamma interferon-dependent mechanism AN - 17124863; 4433369 AB - Mice rendered deficient in interleukin-10 (IL-10) by gene targeting (IL-10 super(-/-) mice) develop chronic enterocolitis resembling human inflammatory bowel disease (IBD) when maintained in conventional animal facilities. However, they display a minimal and delayed intestinal inflammatory response when reared under specific-pathogen-free (SPF) conditions, suggesting the involvement of a microbial component in pathogenesis. We show here that experimental infection with a single bacterial agent, Helicobacter hepaticus, induces chronic colitis in SPF-reared IL-10 super(-/-) mice and that the disease is accompanied by a type 1 cytokine response (gamma interferon [IFN- gamma ], tumor necrosis factor alpha, and nitric oxide) detected by restimulation of spleen and mesenteric lymph node cells with a soluble H. hepaticus antigen (Ag) preparation. In contrast, wild-type (WT) animals infected with the same bacteria did not develop disease and produced IL-10 as the dominant cytokine in response to Helicobacter Ag. Strong H. hepaticus-reactive antibody responses as measured by Ag-specific total immunoglobulin G (IgG), IgG1, IgG2a, IgG2b, IgG3, and IgA were observed in both WT and IL-10 super(-/-) mice. In vivo neutralization of IFN- gamma or IL-12 resulted in a significant reduction of intestinal inflammation in H. hepaticus-infected IL-10 super(-/-) mice, suggesting an important role for these cytokines in the development of colitis in the model. Taken together, these microbial reconstitution experiments formally establish that a defined bacterial agent can serve as the immunological target in the development of large bowel inflammation in IL-10 super(-/-) mice and argue that in nonimmunocompromised hosts IL-10 stimulated in response to intestinal flora is important in preventing IBD. JF - Infection and Immunity AU - Kullberg, M C AU - Ward, J M AU - Gorelick, P L AU - Caspar, P AU - Hieny, S AU - Cheever, A AU - Jankovic, D AU - Sher, A AD - Immunobiol. Sect., Lab. Parasitic Dis., Natl. Inst. of Allergy and Infect. Dis., Natl. Inst. Health, Bldg 4, Rm 126, 4 Center Dr. MSC 0425, Bethesda, MD 20892-0425, USA, MKULLBERG@atlas.niaid.nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 5157 EP - 5166 VL - 66 IS - 11 SN - 0019-9567, 0019-9567 KW - Helicobacter hepaticus KW - Interleukin 10 KW - Interleukin 12 KW - gamma -Interferon KW - immunoglobulin G1 KW - immunoglobulin G2 KW - immunoglobulin G3 KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Tumor necrosis factor KW - Gnotobiotics KW - Antibody response KW - Inflammation KW - Immunoglobulin G KW - Nitric oxide KW - Colitis KW - F 067735:Interleukins 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/17124863?accountid=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=Helicobacter+hepaticus+triggers+colitis+in+specific-pathogen-free+interleukin-10+%28IL-10%29-deficient+mice+through+an+IL-12-and+gamma+interferon-dependent+mechanism&rft.au=Kullberg%2C+M+C%3BWard%2C+J+M%3BGorelick%2C+P+L%3BCaspar%2C+P%3BHieny%2C+S%3BCheever%2C+A%3BJankovic%2C+D%3BSher%2C+A&rft.aulast=Kullberg&rft.aufirst=M&rft.date=1998-11-01&rft.volume=66&rft.issue=11&rft.spage=5157&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 hepaticus; Immunoglobulin G; Colitis; Interleukin 10; Gnotobiotics; Nitric oxide; Inflammation; Tumor necrosis factor; Interleukin 12; Antibody response ER - TY - JOUR T1 - Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue AN - 17121310; 4427173 AB - Type 2 diabetes is a complex metabolic disorder characterized by peripheral insulin resistance and impaired beta cell function. Insulin resistance is inherited as a non-mendelian trait. In genetically predisposed individuals, resistance of skeletal muscle and adipose tissue to insulin action precedes the onset of clinical diabetes, and is thought to contribute to hyperglycaemia by leading to impaired beta cell function and increased hepatic glucose production. It is not clear whether beta cell and liver defects are also genetically determined. To test the hypothesis that insulin resistance in muscle and fat is sufficient to cause type 2 diabetes in the absence of intrinsic beta cell and liver abnormality, we generated transgenic mice that were insulin-resistant in skeletal muscle and adipose tissue. These mice developed all the prodromal features of type 2 diabetes but, despite the compounded effect of peripheral insulin resistance and a mild impairment of beta cell function, failed to become diabetic. These findings indicate the need for a critical re-examination of the primary site(s) of insulin resistance in diabetes. JF - Nature Genetics AU - Lauro, D AU - Kido, Y AU - Castle, AL AU - Zarnowski, M-J AU - Hayashi, H AU - Ebina, Y AU - Accili, D AD - Dev. Endocrinol. Branch, Nat. Inst. of Child Health and Human Development, Diabetes Branch, Nat. Inst. of Diabetes and Digestive and Kidney Diseases, Nat. Inst. of Health, Bethesda, Maryland 20892, USA, accilid@mail.nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 294 EP - 298 VL - 20 IS - 3 SN - 1061-4036, 1061-4036 KW - diabetes KW - insulin KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Transgenic mice KW - Glucose tolerance KW - Adipose tissue KW - Skeletal muscle KW - G 07397:Rodentia (mice) 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/17121310?accountid=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+Genetics&rft.atitle=Impaired+glucose+tolerance+in+mice+with+a+targeted+impairment+of+insulin+action+in+muscle+and+adipose+tissue&rft.au=Lauro%2C+D%3BKido%2C+Y%3BCastle%2C+AL%3BZarnowski%2C+M-J%3BHayashi%2C+H%3BEbina%2C+Y%3BAccili%2C+D&rft.aulast=Lauro&rft.aufirst=D&rft.date=1998-11-01&rft.volume=20&rft.issue=3&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&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; Adipose tissue; Skeletal muscle; Glucose tolerance ER - TY - JOUR T1 - Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats AN - 17114212; 4420001 AB - Limited experimental access to the central nervous system (CNS) is a key problem in the study of human neural development, disease, and regeneration. We have addressed this problem by generating neural chimeras composed of human and rodent cells. Fetal human brain cells implanted into the cerebral ventricles of embryonic rats incorporate individually into all major compartments of the brain, generating widespread CNS chimerism. The human cells differentiate into neurons, astrocytes, and oligodendrocytes, which populate the host fore-, mid-, and hindbrain. These chimeras provide a unique model to study human neural cell migration and differentiation in a functional nervous system. JF - Nature Biotechnology AU - Bruestle, O AU - Choudhary, K AU - Karram, K AU - Huettner, A AU - Murray, K AU - Dubois-Dalcq, M AU - McKay, RDG AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4092, USA, brustle@uni-bonn.de Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 1040 EP - 1044 VL - 16 IS - 11 SN - 1087-0156, 1087-0156 KW - brain KW - central nervous system KW - fetuses KW - man KW - rats KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Central nervous system KW - Transplantation KW - Brain KW - Transplants KW - Chimeras KW - Cell migration KW - Xenografts KW - W3 33235:New cell lines KW - N3 11057:Neural transplantation and regeneration KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17114212?accountid=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=Chimeric+brains+generated+by+intraventricular+transplantation+of+fetal+human+brain+cells+into+embryonic+rats&rft.au=Bruestle%2C+O%3BChoudhary%2C+K%3BKarram%2C+K%3BHuettner%2C+A%3BMurray%2C+K%3BDubois-Dalcq%2C+M%3BMcKay%2C+RDG&rft.aulast=Bruestle&rft.aufirst=O&rft.date=1998-11-01&rft.volume=16&rft.issue=11&rft.spage=1040&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 - Xenografts; Transplants; Cell migration; Brain; Transplantation; Chimeras; Central nervous system ER - TY - JOUR T1 - Characterization of Diverse Viral Vector Preparations, Using a Simple and Rapid Whole-Virion Dot-Blot Method AN - 17112607; 4421737 AB - A number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (AAVs), herpes simplex virus, SV40 viruses, and alphaviruses (both Semliki Forest and Sindbis viruses). One of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers. In addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility of viral vector preparations. We demonstrate here that supernatant from diverse classes of viral victors, with either RNA or DNA genomes, can be rapidly evaluated by a simple virus dot-blot hybridization without prior extraction of nucleic acids. This system can provide a reliable screen for physical titer of viral vector supernatants in 1 day. JF - Human Gene Therapy AU - Nelson, D M AU - Wahlfors, J J AU - Chen, Lin AU - Onodera, M AU - Morgan, R A AD - Gene Transfer Technology Section, 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 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 2401 EP - 2405 VL - 9 IS - 16 SN - 1043-0342, 1043-0342 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17112607?accountid=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=Characterization+of+Diverse+Viral+Vector+Preparations%2C+Using+a+Simple+and+Rapid+Whole-Virion+Dot-Blot+Method&rft.au=Nelson%2C+D+M%3BWahlfors%2C+J+J%3BChen%2C+Lin%3BOnodera%2C+M%3BMorgan%2C+R+A&rft.aulast=Nelson&rft.aufirst=D&rft.date=1998-11-01&rft.volume=9&rft.issue=16&rft.spage=2401&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 therapy; Expression vectors ER - TY - JOUR T1 - Electronic PCR: bridging the gap between genome mapping and genome sequencing AN - 17112535; 4420017 AB - A crucial event in the history of the Human Genome Project was the decision to use sequence-tagged sites (STSs) as common landmarks for genomic mapping. Following several years of constructing STS-based maps of ever-increasing detail, the emphasis has recently shifted towards large-scale genomic sequencing. A computational procedure called `electronic PCR' allows STS landmarks to be revealed as data emerge from the sequencing pipeline, thereby bridging the gap between mapping and sequencing activities. JF - Trends in Biotechnology AU - Schuler, G D AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, schuler@ncbi.nlm.nih.gov Y1 - 1998/11// PY - 1998 DA - Nov 1998 SP - 456 EP - 459 VL - 16 IS - 11 SN - 0167-7799, 0167-7799 KW - Human Genome Project KW - sequence-tagged sites KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Computer applications KW - Reviews KW - Polymerase chain reaction KW - Gene mapping KW - N 14610:Occurrence, isolation & assay KW - W3 33243:Molecular methods 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/17112535?accountid=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=Trends+in+Biotechnology&rft.atitle=Electronic+PCR%3A+bridging+the+gap+between+genome+mapping+and+genome+sequencing&rft.au=Schuler%2C+G+D&rft.aulast=Schuler&rft.aufirst=G&rft.date=1998-11-01&rft.volume=16&rft.issue=11&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&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 - Polymerase chain reaction; Reviews; Gene mapping; Computer applications ER - TY - JOUR T1 - Ex Vivo Fibroblast Transduction in Rabbits Results in Long-Term (>600 Days) Factor IX Expression in a Small Percentage of Animals AN - 17112416; 4421731 AB - Delivery of human factor IX to the circulation was analyzed in rabbits by ex vivo fibroblast transduction followed by subcutaneous implantation. Kinetic studies of human factor IX in rabbits demonstrated a half-life of approximately 16 hr and a volume distribution of 22%, where intraperitoneal and subcutaneous bioavailability was three- to sevenfold lower than by intravenous administration. Ex vivo retroviral transduction of autologous fibroblasts was performed on 15 animals. After subcutaneous injection of fibroblast-collagen mixtures, the expression of human factor IX in rabbit plasma was followed by ELISA. Of 15 rabbits injected, expression of human factor IX was detected in 2 animals, and expression was long term (>600 days). One animal had stable levels of human factor IX, at 20 ng/ml, while the second animal had lower and gradually decreasing levels of human factor IX. There were no gross differences in pathology at the injection sites, when comparing animals with human factor IX in plasma and those without. Immunological studies demonstrated antibody formation in response to injection mixture components (including human factor IX), but again there was no correlation with immune response and long-term factor IX production in animals. Tissues at the implantation sites were positive for factor IX DNA by PCR analysis, regardless of whether there was detectable plasma factor IX or not. Small numbers of PCR-positive cells were detected in the internal organs of the long term-expressing rabbits while similar tissues were negative in nonexpressing animals. JF - Human Gene Therapy AU - Chen, Lin AU - Nelson, D M AU - Zheng, Zhili AU - Morgan, R A AD - Gene Transfer Technology Section, Clinical Gene Therapy Branch, National Human Genome Research Institute, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 2341 EP - 2351 VL - 9 IS - 16 SN - 1043-0342, 1043-0342 KW - fibroblasts KW - rabbits KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Coagulation factor IX KW - Fibroblasts KW - Collagen KW - Transduction KW - G 07443:Gene therapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17112416?accountid=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=Ex+Vivo+Fibroblast+Transduction+in+Rabbits+Results+in+Long-Term+%28%26gt%3B600+Days%29+Factor+IX+Expression+in+a+Small+Percentage+of+Animals&rft.au=Chen%2C+Lin%3BNelson%2C+D+M%3BZheng%2C+Zhili%3BMorgan%2C+R+A&rft.aulast=Chen&rft.aufirst=Lin&rft.date=1998-11-01&rft.volume=9&rft.issue=16&rft.spage=2341&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 therapy; Coagulation factor IX; Collagen; Transduction; Fibroblasts ER - TY - JOUR T1 - Cloning, Expression, and Mapping of Ribonucleases H of Human and Mouse Related to Bacterial RNase HI AN - 17112102; 4418204 AB - We identified two human sequences and one mouse sequence in the database of expressed sequence tags that are highly homologous to the N-terminal sequence of eukaryotic RNases H1. The cDNAs for human RNASEH1 and mouse Rnaseh1 were obtained, their nucleotide sequences determined, and the proteins expressed in Escherichia coli and partially purified. Both proteins have RNase H activity in vitro and they bind to dsRNA and RNA-DNA hybrids through the N-terminal conserved motif present in eukaryotic RNases H1. The RNASEH1 gene is expressed in all human tissues at similar levels, indicating that RNase H1 may be a housekeeping protein. The human RNASEH1 and mouse Rnaseh1 cDNAs were used to isolate BAC genomic clones that were used as probes for fluorescence in situ hybridization. The human gene was localized to chromosome 17p11.2 and the mouse gene to a nonsyntenic region on chromosome 12A3. The chromosomal location and possible disease association of the human RNASEH1 gene are discussed. JF - Genomics AU - Cerritelli, S M AU - Crouch, R J AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, 20892, Maryland, robert_crouch@nih.gov Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 300 EP - 307 PB - Academic Press VL - 53 IS - 3 SN - 0888-7543, 0888-7543 KW - RNASEH1 gene KW - amino acid sequence prediction KW - cDNA KW - chromosome 12 KW - chromosome 17 KW - man KW - mice KW - nucleotide sequence KW - ribonuclease H KW - ribonuclease HI KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07430:Chromosome studies/nucleotide sequence KW - J 02728:Enzymes KW - G 07397:Rodentia (mice) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17112102?accountid=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=Genomics&rft.atitle=Cloning%2C+Expression%2C+and+Mapping+of+Ribonucleases+H+of+Human+and+Mouse+Related+to+Bacterial+RNase+HI&rft.au=Cerritelli%2C+S+M%3BCrouch%2C+R+J&rft.aulast=Cerritelli&rft.aufirst=S&rft.date=1998-11-01&rft.volume=53&rft.issue=3&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&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 - CD40 Ligand/Trimer DNA Enhances Both Humoral and Cellular Immune Responses and Induces Protective Immunity to Infectious and Tumor Challenge AN - 17102590; 4417037 AB - CD40/CD40 ligand interactions have a central role in the induction of both humoral and cellular immunity. In this study, we examined whether a plasmid expressing CD40 ligand/trimer (CD40LT) could enhance immune responses in vivo. BALB/c mice were injected with plasmid expressing beta -galactosidase DNA with or without CD40LT DNA or IL-12 DNA, and immune responses were assessed. Mice vaccinated with beta -gal DNA plus CD40LT DNA or IL-12 DNA had a striking increase in Ag-specific production of IFN- gamma , cytolytic T cell activity, and IgG2a Ab. The mechanism by which CD40LT DNA enhanced these responses was further assessed by treating vaccinated mice with anti-IL-12 mAb or CTLA-4 Ig (CTLA4Ig). Production of IFN- gamma and CTL activity was abrogated by these treatments, suggesting that CD40LT DNA was mediating its effects on IFN- gamma and CTL activity through induction of IL-12 and enhancement of B7 expression, respectively. Physiologic relevance for the ability of CD40LT DNA to enhance immune responses by the aforementioned pathways was shown in two in vivo models. First, with regard to CTL activity, mice vaccinated with CD40LT DNA did not develop metastatic tumor following challenge with lethal dose of tumor. Moreover, in a mouse model requiring IL-12-dependent production of IFN- gamma , mice vaccinated with soluble Leishmania Ag and CD40LT DNA were able to control infection with Leishmania major. These data suggest that CD40LT DNA could be a useful vaccine adjuvant for diseases requiring cellular and/or humoral immunity. JF - Journal of Immunology AU - Gurunathan, S AU - Irvine, K R AU - Wu, Chang-You AU - Cohen, JI AU - Thomas, E AU - Prussin, C AU - Restifo, N P AU - Seder, R A AD - Clinical Immunology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Building 10, Room 11C215, National Institutes of Health, Bethesda, MD 20892, USA, rseder@nih.gov Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 4563 EP - 4571 VL - 161 IS - 9 SN - 0022-1767, 0022-1767 KW - CD40L protein KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antibody response KW - Tumors KW - Adjuvants KW - Plasmids KW - Interleukin 12 KW - Immune response (cell-mediated) KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews KW - W3 33360:Adjuvants and carriers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17102590?accountid=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=CD40+Ligand%2FTrimer+DNA+Enhances+Both+Humoral+and+Cellular+Immune+Responses+and+Induces+Protective+Immunity+to+Infectious+and+Tumor+Challenge&rft.au=Gurunathan%2C+S%3BIrvine%2C+K+R%3BWu%2C+Chang-You%3BCohen%2C+JI%3BThomas%2C+E%3BPrussin%2C+C%3BRestifo%2C+N+P%3BSeder%2C+R+A&rft.aulast=Gurunathan&rft.aufirst=S&rft.date=1998-11-01&rft.volume=161&rft.issue=9&rft.spage=4563&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 - Immune response (cell-mediated); Plasmids; Interleukin 12; Adjuvants; Tumors; Antibody response ER - TY - JOUR T1 - Chemokines and their role in tumor growth and metastasis AN - 16510718; 4412687 AB - Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that selectively attract and activate different cell types. Many patho-physiological conditions require the participation of chemokines, including inflammation, infection, tissue injury, allergy, cardiovascular diseases, as well as malignant tumors. Chemokines activate cells through their binding to shared or unique cell surface receptors which belong to the seven-transmembrane, G-protein-coupled Rhodopsin superfamily. The role of chemokines in malignant tumors is complex: while some chemokines may enhance innate or specific host immunity against tumor implantation, others may favor tumor growth and metastasis by promoting tumor cell proliferation, migration or neovascularization in tumor tissue. In this review, the authors summarize some of the recent advances in chemokine research and emphasis is made on the effect of chemokines in tumor growth and metastasis. JF - Journal of Immunological Methods AU - Wang, J M AU - Deng, X AU - Gong, W AU - Su, S AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Building 560, Room 31-40, Frederick, MD 21702, USA Y1 - 1998/11/01/ PY - 1998 DA - 1998 Nov 01 SP - 1 EP - 17 PB - Elsevier Science B.V. VL - 220 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06775:Chemokines 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/16510718?accountid=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=Chemokines+and+their+role+in+tumor+growth+and+metastasis&rft.au=Wang%2C+J+M%3BDeng%2C+X%3BGong%2C+W%3BSu%2C+S&rft.aulast=Wang&rft.aufirst=J&rft.date=1998-11-01&rft.volume=220&rft.issue=1-2&rft.spage=1&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 ER - TY - JOUR T1 - Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings. AN - 70028108; 9807990 AB - (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular recreational drug that selectively damages brain serotonin (5-HT) neurons in animals at doses that closely approach those used by humans. We investigated the status of brain 5-HT neurons in MDMA users. We enrolled 14 previous users of MDMA who were currently abstaining from use and 15 controls who had never used MDMA. We used positron emission tomography (PET) with the radioligand carbon-11-labelled McN-5652, which selectively labels the 5-HT transporter. We analysed whether there were differences in 5-HT transporter binding between abstinent MDMA users and participants in the control group. Blood and urine samples were taken and tested to check for abstinence. MDMA users showed decreased global and regional brain 5-HT transporter binding compared with controls. Decreases in 5-HT transporter binding positively correlated with the extent of previous MDMA use. Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users. JF - Lancet (London, England) AU - McCann, U D AU - Szabo, Z AU - Scheffel, U AU - Dannals, R F AU - Ricaurte, G A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA. Y1 - 1998/10/31/ PY - 1998 DA - 1998 Oct 31 SP - 1433 EP - 1437 VL - 352 IS - 9138 SN - 0140-6736, 0140-6736 KW - Serotonin Agents KW - 0 KW - Serotonin KW - 333DO1RDJY KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Tomography, Emission-Computed KW - Male KW - Female KW - Neurons -- metabolism KW - N-Methyl-3,4-methylenedioxyamphetamine -- adverse effects KW - Neurons -- drug effects KW - Brain -- drug effects KW - Serotonin -- metabolism KW - Serotonin Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70028108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Positron+emission+tomographic+evidence+of+toxic+effect+of+MDMA+%28%22Ecstasy%22%29+on+brain+serotonin+neurons+in+human+beings.&rft.au=McCann%2C+U+D%3BSzabo%2C+Z%3BScheffel%2C+U%3BDannals%2C+R+F%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1998-10-31&rft.volume=352&rft.issue=9138&rft.spage=1433&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1999 Apr 10;353(9160):1268-9; author reply 1270-1 [10217102] Lancet. 1999 Apr 10;353(9160):1268; author reply 1270-1 [10217101] Lancet. 1999 Apr 10;353(9160):1269; author reply 1270-1 [10217103] Lancet. 1999 Apr 10;353(9160):1269-70; author reply 1270-1 [10217104] Lancet. 1999 Apr 10;353(9160):1270-1 [10217105] Lancet. 1999 Feb 13;353(9152):592-3 [10029009] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myc suppresses induction of the growth arrest genes gadd34, gadd45, and gadd153 by DNA-damaging agents. AN - 70038841; 9811446 AB - The growth arrest and DNA damage inducible (gadd) genes are induced by various genotoxic and non-genotoxic stresses such as serum starvation, ultraviolet irradiation and treatment with alkylating agents. Their coordinate induction is a growth arrest signal which may play an important role in the response of cells to DNA damage. Conversely, c-myc is a strong proliferative signal, and overexpression of Myc is frequently observed in cancer cells. We have found that ectopic expression of v-myc in RAT-1 cells results in an attenuated induction of the three major gadd transcripts by methyl methanesulfonate (MMS), and almost completely blocks the response to ultraviolet (UV) radiation. Myc acts in part by reducing the stress-responsiveness of the gadd45 promoter, as a c-myc expression vector strongly suppressed activation of gadd45-reporter constructs. This activity of Myc localizes to a recently described GC-rich binding site within the gadd45 promoter. These results indicate that a coordinate down-regulation of the gadd gene response is one mechanism by which Myc can circumvent growth arrest and contribute to the neoplastic phenotype. JF - Oncogene AU - Amundson, S A AU - Zhan, Q AU - Penn, L Z AU - Fornace, A J AD - NCI, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/10/29/ PY - 1998 DA - 1998 Oct 29 SP - 2149 EP - 2154 VL - 17 IS - 17 SN - 0950-9232, 0950-9232 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Ddit3 protein, rat KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Mutagens KW - Proteins KW - Proto-Oncogene Proteins c-myc KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Tumor Cells, Cultured -- drug effects KW - DNA Damage KW - Mutagens -- toxicity KW - Proteins -- genetics KW - Tumor Cells, Cultured -- radiation effects KW - Proteins -- drug effects KW - Rats KW - Base Sequence KW - Methyl Methanesulfonate -- toxicity KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Up-Regulation KW - Proteins -- radiation effects KW - Protein Biosynthesis KW - Transcription Factors -- drug effects KW - Transcription Factors -- radiation effects KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- drug effects KW - DNA-Binding Proteins -- biosynthesis KW - Proto-Oncogene Proteins c-myc -- metabolism KW - DNA-Binding Proteins -- radiation effects KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Genes, myc -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70038841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Myc+suppresses+induction+of+the+growth+arrest+genes+gadd34%2C+gadd45%2C+and+gadd153+by+DNA-damaging+agents.&rft.au=Amundson%2C+S+A%3BZhan%2C+Q%3BPenn%2C+L+Z%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=1998-10-29&rft.volume=17&rft.issue=17&rft.spage=2149&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of human beta2-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant. Implications for peptide-based vaccines. AN - 69966957; 9774416 AB - The ability to directly load cell surface major histocompatibility complex (MHC) class I molecules with peptides provides a potentially powerful approach toward the development of vaccines to generate cell-mediated immunity. We demonstrate that exogenous beta2-microglobulin (beta2m) stabilizes human cell surface MHC I molecules and facilitates their loading with exogenous peptides. Additionally, using three-dimensional crystal structures and known interaction sites between MHC I heavy chains and beta2m, we engineered variants of human beta2m (hbeta2m) with a single serine substitution at residue 55. This alteration was predicted to promote hydrophobic interactions at the MHC I heavy chain/beta2m interface and displace an ordered water molecule. Compared with hbeta2m, the serine to valine substitution at residue 55 had improved ability to bind to cell surface HLA-A1, HLA-A2, and HLA-A3 molecules, facilitate exogenous peptide loading, and promote recognition by peptide-specific T cells. The inclusion of hbeta2m or higher affinity variants when pulsing cells with MHC-restricted peptides increases the efficiency of peptide loading 50-80-fold. Therefore, the inclusion of hbeta2m in peptide-based vaccines may increase cell surface antigen densities above thresholds that allow recognition of peptide antigens by the immune system, particularly for cryptic, subdominant, or marginally antigenic peptides. JF - The Journal of biological chemistry AU - Shields, M J AU - Kubota, R AU - Hodgson, W AU - Jacobson, S AU - Biddison, W E AU - Ribaudo, R K AD - Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1152, USA. Y1 - 1998/10/23/ PY - 1998 DA - 1998 Oct 23 SP - 28010 EP - 28018 VL - 273 IS - 43 SN - 0021-9258, 0021-9258 KW - HLA-A Antigens KW - 0 KW - Peptides KW - Vaccines KW - beta 2-Microglobulin KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Vaccines -- immunology KW - Genetic Variation KW - Protein Engineering KW - Humans KW - T-Lymphocytes, Cytotoxic KW - Protein Binding KW - Drug Design KW - Antigen Presentation KW - beta 2-Microglobulin -- metabolism KW - Peptides -- metabolism KW - HLA-A Antigens -- metabolism KW - beta 2-Microglobulin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69966957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+effect+of+human+beta2-microglobulin+on+major+histocompatibility+complex+I+peptide+loading+and+the+engineering+of+a+high+affinity+variant.+Implications+for+peptide-based+vaccines.&rft.au=Shields%2C+M+J%3BKubota%2C+R%3BHodgson%2C+W%3BJacobson%2C+S%3BBiddison%2C+W+E%3BRibaudo%2C+R+K&rft.aulast=Shields&rft.aufirst=M&rft.date=1998-10-23&rft.volume=273&rft.issue=43&rft.spage=28010&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and evaluation of N-[11C]methylated analogues of epibatidine as tracers for positron emission tomographic studies of nicotinic acetylcholine receptors. AN - 69984501; 9784094 AB - Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They were (+/-)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7-azabicyclo[2. 2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl analogues 1, 2, 3, and 4 inhibited the in vitro binding of [3H]epibatidine to nAChRs to a similar degree, with affinities in the 27-50 pM range. The binding affinity of N-ethylepibatidine (2b), however, was substantially lower. The N-[11C]methyl derivatives of 1, 2, and 3 were synthesized from high-specific radioactivity [11C]methyl iodide using a high-temperature/high-pressure technique. The corresponding radiolabeled compounds [11C]1a, [11C]2a, and [11C]3a were administrated to mice intravenously. The pattern of regional distribution of the three tracers in the mouse brain following intravenous administration matched those of [3H]epibatidine, [3H]norchloroepibatidine, and (+/-)-exo-2-(2-[18F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([18F]FPH), which are highly specific nAChR probes. The initial brain uptake of the 11C analogues and the acute toxicity of the corresponding authentic nonlabeled compounds appeared to be related to their lipophilicity. JF - Journal of medicinal chemistry AU - Horti, A G AU - Scheffel, U AU - Kimes, A S AU - Musachio, J L AU - Ravert, H T AU - Mathews, W B AU - Zhan, Y AU - Finley, P A AU - London, E D AU - Dannals, R F AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.ahorti@intra.nida.nih.gov Y1 - 1998/10/22/ PY - 1998 DA - 1998 Oct 22 SP - 4199 EP - 4206 VL - 41 IS - 22 SN - 0022-2623, 0022-2623 KW - Bridged Bicyclo Compounds, Heterocyclic KW - 0 KW - Carbon Radioisotopes KW - Pyridines KW - Radiopharmaceuticals KW - Receptors, Nicotinic KW - epibatidine KW - M6K314F1XX KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Lethal Dose 50 KW - Tomography, Emission-Computed KW - Mice KW - Brain -- metabolism KW - Tissue Distribution KW - Brain -- diagnostic imaging KW - Male KW - Radiopharmaceuticals -- pharmacokinetics KW - Pyridines -- chemical synthesis KW - Bridged Bicyclo Compounds, Heterocyclic -- toxicity KW - Radiopharmaceuticals -- toxicity KW - Bridged Bicyclo Compounds, Heterocyclic -- chemical synthesis KW - Receptors, Nicotinic -- metabolism KW - Radiopharmaceuticals -- chemical synthesis KW - Bridged Bicyclo Compounds, Heterocyclic -- pharmacokinetics KW - Pyridines -- toxicity KW - Pyridines -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69984501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synthesis+and+evaluation+of+N-%5B11C%5Dmethylated+analogues+of+epibatidine+as+tracers+for+positron+emission+tomographic+studies+of+nicotinic+acetylcholine+receptors.&rft.au=Horti%2C+A+G%3BScheffel%2C+U%3BKimes%2C+A+S%3BMusachio%2C+J+L%3BRavert%2C+H+T%3BMathews%2C+W+B%3BZhan%2C+Y%3BFinley%2C+P+A%3BLondon%2C+E+D%3BDannals%2C+R+F&rft.aulast=Horti&rft.aufirst=A&rft.date=1998-10-22&rft.volume=41&rft.issue=22&rft.spage=4199&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Limitations of differential display. AN - 70013616; 9792829 AB - Since its original description, differential display PCR (DD-PCR) has been extensively used in attempts to identify novel genes under a variety of circumstances. Despite its widespread use, however, few novel genes of interest have been identified. In the present study we describe a set of experiments examining reasons for failure of differential display. Evidence is presented that aberrant priming at both the 5' and 3' ends results in competition in the PCR, precluding detection of messages other than those which are abundantly expressed. Appropriate calculations are discussed which indicate this was predictable and unlikely to be overcome. While DD may be successfully applied in some settings, the evidence indicates that only abundantly expressed messages can be detected. This limitation is emphasized. Copyright 1998 Academic Press. JF - Biochemical and biophysical research communications AU - Ledakis, P AU - Tanimura, H AU - Fojo, T AD - Medicine Branch, National Cancer Institute, Bldg. 10, Rm. 12N226, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA. Y1 - 1998/10/20/ PY - 1998 DA - 1998 Oct 20 SP - 653 EP - 656 VL - 251 IS - 2 SN - 0006-291X, 0006-291X KW - DNA Primers KW - 0 KW - P-Glycoprotein KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Clone Cells KW - Base Sequence KW - Ovarian Neoplasms KW - Tumor Cells, Cultured KW - P-Glycoprotein -- genetics KW - Humans KW - Cisplatin -- toxicity KW - Drug Resistance, Neoplasm KW - Colonic Neoplasms KW - Female KW - Polymerase Chain Reaction -- methods KW - Gene Expression KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70013616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Limitations+of+differential+display.&rft.au=Ledakis%2C+P%3BTanimura%2C+H%3BFojo%2C+T&rft.aulast=Ledakis&rft.aufirst=P&rft.date=1998-10-20&rft.volume=251&rft.issue=2&rft.spage=653&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct 1,N6-ethenoadenine. AN - 69949468; 9765247 AB - We used purified mammalian topoisomerases I (top1) and oligonucleotides to study top1-mediated cleavage and religation in the presence of a potent carcinogenic adduct, 1,N6-ethenoadenosine (epsilonA) incorporated immediately downstream of a unique top1 cleavage site. We found tha epsilonA markedly enhanced top1 cleavage complexes when it was incorporated at the +1 position of the top1 cleavage. This enhancement was due to a reduction of the religation step of the top1 reaction. In addition, epsilonA reduced the top1-mediated cleavage and decreased binding of the enzyme to DNA. We also studied the effects of the epsilonA adduct on top1 trapping by camptothecin (CPT), a well known top1 inhibitor. CPT was inactive when epsilonA was present at the +1 position. Alkylation of the top1 cleavage complex by 7-chloromethyl-10,11-methylenedioxycamptothecin (7-ClMe-MDO-CPT) was also blocked by the epsilonA adduct. Altogether, these results demonstrate that the epsilonA carcinogenic adduct can efficiently trap human top1 and mimic CPT effects. Normal hydrogen bonding of the base pairs immediately downstream from the top1 cleavage site is probably essential for efficient DNA religation and binding of camptothecins in the top1 cleavage complex. JF - The Journal of biological chemistry AU - Pourquier, P AU - Bjornsti, M A AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/10/16/ PY - 1998 DA - 1998 Oct 16 SP - 27245 EP - 27249 VL - 273 IS - 42 SN - 0021-9258, 0021-9258 KW - Carcinogens KW - 0 KW - DNA Adducts KW - 1,N(6)-ethenoadenine KW - 13875-63-3 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Adenine KW - JAC85A2161 KW - Vinyl Chloride KW - WD06X94M2D KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Base Pairing KW - Humans KW - Molecular Mimicry KW - Carcinogens -- metabolism KW - Adenine -- metabolism KW - Vinyl Chloride -- metabolism KW - Adenine -- analogs & derivatives KW - DNA Topoisomerases, Type I -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69949468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+topoisomerase+I+cleavage+complexes+by+the+vinyl+chloride+adduct+1%2CN6-ethenoadenine.&rft.au=Pourquier%2C+P%3BBjornsti%2C+M+A%3BPommier%2C+Y&rft.aulast=Pourquier&rft.aufirst=P&rft.date=1998-10-16&rft.volume=273&rft.issue=42&rft.spage=27245&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 - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The gene glvA of Bacillus subtilis 168 encodes a metal-requiring, NAD(H)-dependent 6-phospho-alpha-glucosidase. Assignment to family 4 of the glycosylhydrolase superfamily. AN - 69948774; 9765262 AB - The gene glvA (formerly glv-1) from Bacillus subtilis has been cloned and expressed in Escherichia coli. The purified protein GlvA (449 residues, Mr = 50,513) is a unique 6-phosphoryl-O-alpha-D-glucopyranosyl:phosphoglucohydrolase (6-phospho-alpha-glucosidase) that requires both NAD(H) and divalent metal (Mn2+, Fe2+, Co2+, or Ni2+) for activity. 6-Phospho-alpha-glucosidase (EC 3.2.1.122) from B. subtilis cross-reacts with polyclonal antibody to maltose 6-phosphate hydrolase from Fusobacterium mortiferum, and the two proteins exhibit amino acid sequence identity of 73%. Estimates for the Mr of GlvA determined by SDS-polyacrylamide gel electrophoresis (51,000) and electrospray-mass spectroscopy (50,510) were in excellent agreement with the molecular weight of 50,513 deduced from the amino acid sequence. The sequence of the first 37 residues from the N terminus determined by automated analysis agreed precisely with that predicted by translation of glvA. The chromogenic and fluorogenic substrates, p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate and 4-methylumbelliferyl-alpha-D-glucopyranoside 6-phosphate were used for the discontinuous assay and in situ detection of enzyme activity, respectively. Site-directed mutagenesis shows that three acidic residues, Asp41, Glu111, and Glu359, are required for GlvA activity. Asp41 is located at the C terminus of a betaalphabeta fold that may constitute the dinucleotide binding domain of the protein. Glu111 and Glu359 may function as the catalytic acid (proton donor) and nucleophile (base), respectively, during hydrolysis of 6-phospho-alpha-glucoside substrates including maltose 6-phosphate and trehalose 6-phosphate. In metal-free buffer, GlvA exists as an inactive dimer, but in the presence of Mn2+ ion, these species associate to form the NAD(H)-dependent catalytically active tetramer. By comparative sequence alignment with its homologs, the novel 6-phospho-alpha-glucosidase from B. subtilis can be assigned to the nine-member family 4 of the glycosylhydrolase superfamily. JF - The Journal of biological chemistry AU - Thompson, J AU - Pikis, A AU - Ruvinov, S B AU - Henrissat, B AU - Yamamoto, H AU - Sekiguchi, J AD - Microbial Biochemistry and Genetics Unit, Oral Infection and Immunity Branch, NIDR, National Institutes of Health, Bethesda, Maryland 20892, USA. jthompson@yoda.nidr.nih.gov Y1 - 1998/10/16/ PY - 1998 DA - 1998 Oct 16 SP - 27347 EP - 27356 VL - 273 IS - 42 SN - 0021-9258, 0021-9258 KW - Cations, Divalent KW - 0 KW - Chromogenic Compounds KW - Recombinant Proteins KW - Sugar Phosphates KW - maltose 6-phosphate KW - NAD KW - 0U46U6E8UK KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - alpha-Glucosidases KW - EC 3.2.1.20 KW - Index Medicus KW - Mass Spectrometry KW - Multigene Family KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Ultracentrifugation KW - Hydrolysis KW - Molecular Weight KW - Cross Reactions KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - NAD -- metabolism KW - Glycoside Hydrolases -- chemistry KW - Sugar Phosphates -- metabolism KW - Base Sequence KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Sugar Phosphates -- chemistry KW - Sequence Homology, Amino Acid KW - Bacillus subtilis -- enzymology KW - Bacillus subtilis -- genetics KW - Genes, Bacterial KW - alpha-Glucosidases -- metabolism KW - alpha-Glucosidases -- immunology KW - alpha-Glucosidases -- genetics KW - alpha-Glucosidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69948774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gene+glvA+of+Bacillus+subtilis+168+encodes+a+metal-requiring%2C+NAD%28H%29-dependent+6-phospho-alpha-glucosidase.+Assignment+to+family+4+of+the+glycosylhydrolase+superfamily.&rft.au=Thompson%2C+J%3BPikis%2C+A%3BRuvinov%2C+S+B%3BHenrissat%2C+B%3BYamamoto%2C+H%3BSekiguchi%2C+J&rft.aulast=Thompson&rft.aufirst=J&rft.date=1998-10-16&rft.volume=273&rft.issue=42&rft.spage=27347&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 - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - D50543; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis. AN - 69947039; 9765259 AB - Estrogen sulfotransferase (EST) catalyzes transfer of the 5'-sulfuryl group of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to the 3alpha-phenol group of estrogenic steroids such as estradiol (E2). The recent crystal structure of EST-adenosine 3', 5'-diphosphate (PAP)- E2 complex has revealed that residues Lys48, Thr45, Thr51, Thr52, Lys106, His108, and Try240 are in position to play a catalytic role in the sulfuryl transfer reaction of EST (Kakuta Y., Pedersen, L. G., Carter, C. W., Negishi, M., and Pedersen, L. C. (1997) Nat. Struct. Biol. 4, 904-908). Mutation of Lys48, Lys106, or His108 nearly abolishes EST activity, indicating that they play a critical role in catalysis. A present 2.2-A resolution structure of EST-PAP-vanadate complex indicates that the vanadate molecule adopts a trigonal bipyramidal geometry with its equatorial oxygens coordinated to these three residues. The apical positions of the vanadate molecule are occupied by a terminal oxygen of the 5'-phosphate of PAP (2.1 A) and a possible water molecule (2. 3 A). This water molecule superimposes well to the 3alpha-phenol group of E2 in the crystal structure of the EST.PAP.E2 complex. These structures are characteristic of the transition state for an in-line sulfuryl transfer reaction from PAPS to E2. Moreover, residues Lys48, Lys106, and His108 are found to be coordinated with the vanadate molecule at the transition state of EST. JF - The Journal of biological chemistry AU - Kakuta, Y AU - Petrotchenko, E V 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 - 1998/10/16/ PY - 1998 DA - 1998 Oct 16 SP - 27325 EP - 27330 VL - 273 IS - 42 SN - 0021-9258, 0021-9258 KW - adenosine 3'-phosphate-5'-phosphate KW - 1053-73-2 KW - Vanadates KW - 3WHH0066W5 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Synchrotrons KW - Models, Molecular KW - DNA Mutational Analysis KW - Crystallography KW - Mice KW - Sulfotransferases -- genetics KW - Vanadates -- chemistry KW - Sulfotransferases -- chemistry KW - Adenosine Diphosphate -- chemistry KW - Catalytic Domain -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69947039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+sulfuryl+transfer+mechanism.+Crystal+structure+of+a+vanadate+complex+of+estrogen+sulfotransferase+and+mutational+analysis.&rft.au=Kakuta%2C+Y%3BPetrotchenko%2C+E+V%3BPedersen%2C+L+C%3BNegishi%2C+M&rft.aulast=Kakuta&rft.aufirst=Y&rft.date=1998-10-16&rft.volume=273&rft.issue=42&rft.spage=27325&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 - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1BO2; PDB; 1BO3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormone-induced Translocation of Thyroid Hormone Receptors in Living Cells Visualized Using a Receptor Green Fluorescent Protein Chimera AN - 16516362; 4404611 AB - Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors that regulate growth, differentiation, and development. To understand the role of the hormone, 3,3',5-triiodo-L-thyronine (T sub(3)) in the nuclear translocation and targeting of TRs to the regulatory sites in chromatin, we appended green fluorescent protein (GFP) to the human TR subtype beta 1 (TR beta 1). The fusion of GFP to the amino terminus of TR beta 1 protein did not alter T sub(3) binding or transcriptional activities of the receptor. The subcellular localization of GFP-TR beta 1 in living cells was visualized by laser-scanning confocal microscopy. In the presence of T sub(3) the expressed GFP-TR beta 1 was predominately localized in the nucleus exhibiting a nuclear/cytoplasmic ratio of ~5.5. No GFP-TR beta 1 was detected in the nucleolus. In the absence of T sub(3), more GFP-TR beta 1 was present in the cytoplasm, exhibiting a nuclear/cytoplasmic ratio of ~1.5. In these cells, cytoplasmic GFP-TR beta 1 could be induced to enter the nucleus by T sub(3). The T sub(3)-induced translocation was blocked when Lys super(184)-Arg super(185) in domain D of TR beta 1 was mutated to Ala super(184)-Ala super(185). Furthermore, the inability of the mutant TR to translocate to the nucleus correlated with the loss of most of its transcriptional activity. These results suggest that TR functions may, in part, be regulated by T sub(3)- induced nuclear entry. JF - Journal of Biological Chemistry AU - Zhu, X AU - Hanover, JA AU - Hager, G L AU - Cheng, S AD - Laboratory of Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 1998/10/16/ PY - 1998 DA - 1998 Oct 16 SP - 27058 EP - 27063 VL - 273 IS - 42 SN - 0021-9258, 0021-9258 KW - green fluorescent protein KW - thyroid hormone receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16516362?accountid=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=Hormone-induced+Translocation+of+Thyroid+Hormone+Receptors+in+Living+Cells+Visualized+Using+a+Receptor+Green+Fluorescent+Protein+Chimera&rft.au=Zhu%2C+X%3BHanover%2C+JA%3BHager%2C+G+L%3BCheng%2C+S&rft.aulast=Zhu&rft.aufirst=X&rft.date=1998-10-16&rft.volume=273&rft.issue=42&rft.spage=27058&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 ER - TY - JOUR T1 - The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding. AN - 69969485; 9774350 AB - OxyS is a small untranslated RNA which is induced in response to oxidative stress in Escherichia coli. This novel RNA acts as a global regulator to activate or repress the expression of as many as 40 genes, including the fhlA-encoded transcriptional activator and the rpoS-encoded sigma(s) subunit of RNA polymerase. Deletion analysis of OxyS showed that different domains of the small RNA are required for the regulation of fhlA and rpoS. We examined the mechanism of OxyS repression of fhlA and found that the OxyS RNA inhibits fhlA translation by pairing with a short sequence overlapping the Shine-Dalgarno sequence, thereby blocking ribosome binding/translation. JF - The EMBO journal AU - Altuvia, S AU - Zhang, A AU - Argaman, L AU - Tiwari, A AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/10/15/ PY - 1998 DA - 1998 Oct 15 SP - 6069 EP - 6075 VL - 17 IS - 20 SN - 0261-4189, 0261-4189 KW - Escherichia coli Proteins KW - 0 KW - Nucleic Acid Heteroduplexes KW - RNA, Bacterial KW - Trans-Activators KW - Untranslated Regions KW - fhlA protein, E coli KW - 131689-36-6 KW - Index Medicus KW - Ribosomes -- metabolism KW - Base Sequence KW - Nucleic Acid Heteroduplexes -- metabolism KW - Ribosomes -- genetics KW - Dimerization KW - Molecular Sequence Data KW - Escherichia coli KW - Untranslated Regions -- physiology KW - Oxidative Stress -- genetics KW - Nucleic Acid Conformation KW - Mutagenesis KW - Trans-Activators -- biosynthesis KW - RNA, Bacterial -- pharmacology KW - Trans-Activators -- genetics KW - Regulatory Sequences, Nucleic Acid -- physiology KW - RNA, Bacterial -- chemistry KW - RNA, Bacterial -- physiology KW - Trans-Activators -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69969485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Escherichia+coli+OxyS+regulatory+RNA+represses+fhlA+translation+by+blocking+ribosome+binding.&rft.au=Altuvia%2C+S%3BZhang%2C+A%3BArgaman%2C+L%3BTiwari%2C+A%3BStorz%2C+G&rft.aulast=Altuvia&rft.aufirst=S&rft.date=1998-10-15&rft.volume=17&rft.issue=20&rft.spage=6069&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 - 1998-12-10 N1 - Date created - 1998-12-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene. 1987;53(1):85-96 [3596251] Mol Gen Genet. 1976 Apr 23;145(1):101-8 [775304] J Bacteriol. 1989 May;171(5):2563-72 [2523380] J Biol Chem. 1989 Oct 25;264(30):17961-70 [2478539] J Mol Biol. 1989 Nov 20;210(2):265-80 [2532257] EMBO J. 1990 Apr;9(4):1267-74 [1691097] J Mol Biol. 1990 Apr 20;212(4):695-708 [1691791] J Bacteriol. 1990 Sep;172(9):4798-806 [2118503] Biochemistry. 1990 Oct 2;29(39):9249-56 [1702997] Mol Microbiol. 1990 Aug;4(8):1319-27 [2280686] EMBO J. 1992 Jul;11(7):2675-83 [1378398] J Bacteriol. 1994 May;176(9):2677-88 [7513326] Genes Dev. 1994 Jul 1;8(13):1600-12 [7525405] Annu Rev Microbiol. 1994;48:713-42 [7826024] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2003-7 [7534408] Mol Microbiol. 1995 Feb;15(3):411-4 [7540245] EMBO J. 1996 Aug 1;15(15):3993-4000 [8670904] RNA. 1996 Oct;2(10):1022-32 [8849778] J Biol Chem. 1997 May 9;272(19):12508-12 [9139701] Cell. 1997 Jul 11;90(1):43-53 [9230301] Nat Biotechnol. 1997 Aug;15(8):751-3 [9255788] EMBO J. 1998 Oct 15;17(20):6061-8 [9774349] Methods Enzymol. 1988;164:419-25 [2468068] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428. AN - 69952647; 9763484 AB - Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has recently been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [11C]WIN-35,428, a DA transporter (DAT) ligand. The present studies determined whether living humans with a history of methamphetamine or methcathinone abuse showed evidence of lasting decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson's disease (PD). On average, subjects had abstained from amphetamine use for approximately 3 years. Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%, respectively). Larger decreases in DAT density were evident in patients with PD (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor methcathinone users showed clinical signs of parkinsonism. Persistent reductions of DAT density in methamphetamine and methcathinone users are suggestive of loss of DAT or loss of DA terminals and raise the possibility that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in which brain DA neurons have been implicated. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - McCann, U D AU - Wong, D F AU - Yokoi, F AU - Villemagne, V AU - Dannals, R F AU - Ricaurte, G A AD - Unit on Anxiety Disorders, Biological Psychiatry Branch, National Institute of Mental Health, Intramural Research Program, Bethesda, Maryland 20892, USA. Y1 - 1998/10/15/ PY - 1998 DA - 1998 Oct 15 SP - 8417 EP - 8422 VL - 18 IS - 20 SN - 0270-6474, 0270-6474 KW - Carbon Radioisotopes KW - 0 KW - Carrier Proteins KW - Central Nervous System Stimulants KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Propiophenones KW - SLC6A3 protein, human KW - monomethylpropion KW - 386QA522QG KW - Methamphetamine KW - 44RAL3456C KW - (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester KW - 50370-56-4 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Nerve Tissue Proteins -- analysis KW - Parkinson Disease, Secondary -- chemically induced KW - Amphetamine-Related Disorders -- metabolism KW - Brain Chemistry -- drug effects KW - Humans KW - Cocaine -- analogs & derivatives KW - Adult KW - Tomography, Emission-Computed KW - Nerve Tissue Proteins -- metabolism KW - Amphetamine-Related Disorders -- diagnosis KW - Middle Aged KW - Female KW - Male KW - Propiophenones -- administration & dosage KW - Neostriatum -- metabolism KW - Methamphetamine -- administration & dosage KW - Carrier Proteins -- metabolism KW - Neostriatum -- chemistry KW - Carrier Proteins -- analysis KW - Central Nervous System Stimulants -- administration & dosage KW - Neostriatum -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69952647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+striatal+dopamine+transporter+density+in+abstinent+methamphetamine+and+methcathinone+users%3A+evidence+from+positron+emission+tomography+studies+with+%5B11C%5DWIN-35%2C428.&rft.au=McCann%2C+U+D%3BWong%2C+D+F%3BYokoi%2C+F%3BVillemagne%2C+V%3BDannals%2C+R+F%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1998-10-15&rft.volume=18&rft.issue=20&rft.spage=8417&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 - 1998-10-23 N1 - Date created - 1998-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein AN - 17101666; 4412034 AB - The OxyS regulatory RNA integrates the adaptive response to hydrogen peroxide with other cellular stress responses and protects against DNA damage. Among the OxyS targets is the rpoS- encoded sigma super(s) subunit of RNA polymerase. sigma super(s) is a central regulator of genes induced by osmotic stress, starvation and entry into stationary phase. We examined the mechanism whereby OxyS represses rpoS expression and found that the OxyS RNA inhibits translation of the rpoS message. This repression is dependent on the hfq-encoded RNA-binding protein (also denoted host factor I, HF-I). Co-immunoprecipitation and gel mobility shift experiments revealed that the OxyS RNA binds Hfq, suggesting that OxyS represses rpoS translation by altering Hfq activity. JF - EMBO Journal AU - Zhang, A AU - Altuvia, S AU - Tiwari, A AU - Argaman, L AU - Hengge-Aronis, R AU - Storz, G 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 - 1998/10/15/ PY - 1998 DA - 1998 Oct 15 SP - 6061 EP - 6068 VL - 17 IS - 20 SN - 0261-4189, 0261-4189 KW - HF-I protein KW - hfq gene KW - host factor I KW - oxyS gene KW - rpoS gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Translation KW - DNA-directed RNA polymerase KW - Gene regulation KW - Stress KW - J 02726:RNA and ribosomes KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17101666?accountid=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=The+OxyS+regulatory+RNA+represses+rpoS+translation+and+binds+the+Hfq+%28HF-I%29+protein&rft.au=Zhang%2C+A%3BAltuvia%2C+S%3BTiwari%2C+A%3BArgaman%2C+L%3BHengge-Aronis%2C+R%3BStorz%2C+G&rft.aulast=Zhang&rft.aufirst=A&rft.date=1998-10-15&rft.volume=17&rft.issue=20&rft.spage=6061&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 - DNA-directed RNA polymerase; Translation; Stress; Gene regulation ER - TY - JOUR T1 - Probing the structure of complex macromolecular interactions by homolog specificity scanning: the P1 and P7 plasmid partition systems AN - 17100901; 4412036 AB - The P1 plasmid partition locus, P1 par, actively distributes plasmid copies to Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA and ParB. Plasmid P7 uses a similar system, but the key macromolecular interactions are species specific. Homolog specificity scanning (HSS) exploits such specificities to map critical contact points between component macromolecules. The ParA protein contacts the par operon operator for operon autoregulation, and the ParB contacts the parS partition site during partition. Here, we refine the mapping of these contacts and extend the use of HSS to map protein-protein contacts. We found that ParB participates in autoregulation at the operator site by making a specific contact with ParA. Similarly, ParA acts in partition by making a specific contact with ParB bound at parS. Both these interactions involve contacts between a C-terminal region of ParA and the extreme N- terminus of ParB. As a single type of ParA-ParB complex appears to be involved in recognizing both DNA sites, the operator and the parS sites may both be occupied by a single protein complex during partition. The general HSS strategy may aid in solving the three-dimensional structures of large complexes of macromolecules. JF - EMBO Journal AU - Radnedge, L AU - Youngren, B AU - Davis, M AU - Austin, S AD - Laboratory of Gene Regulation and Chromosome Biology ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA, austin@ncifcrf.gov Y1 - 1998/10/15/ PY - 1998 DA - 1998 Oct 15 SP - 6076 EP - 6085 VL - 17 IS - 20 SN - 0261-4189, 0261-4189 KW - ParA protein KW - ParB protein KW - plasmid P1 KW - plasmid P7 KW - Microbiology Abstracts B: Bacteriology KW - Copy number control KW - Escherichia coli KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17100901?accountid=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=Probing+the+structure+of+complex+macromolecular+interactions+by+homolog+specificity+scanning%3A+the+P1+and+P7+plasmid+partition+systems&rft.au=Radnedge%2C+L%3BYoungren%2C+B%3BDavis%2C+M%3BAustin%2C+S&rft.aulast=Radnedge&rft.aufirst=L&rft.date=1998-10-15&rft.volume=17&rft.issue=20&rft.spage=6076&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; Copy number control ER - TY - JOUR T1 - Functional Dissociation Between Local and Systemic Immune Response During Anti-Melanoma Peptide Vaccination AN - 16504183; 4411600 AB - Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted. To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100 sub(209-217). G209/g209-2M-reactive CTL were identified in post- but not pre-vaccination PBL. Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR V beta 6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1-35. Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic lesion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone. JF - Journal of Immunology AU - Lee, KH AU - Panelli, M C AU - Kim, C J AU - Riker, AI AU - Bettinotti, M P AU - Roden, M M AU - Fetsch, P AU - Abati, A AU - Rosenberg, SA AU - Marincola, F M AD - Surgery Branch, National Cancer Institute, Building 10, Room 2B42, 10 Center Drive MSC 1502, Bethesda, MD 20892-1502, USA, marincola@nih.gov Y1 - 1998/10/15/ PY - 1998 DA - 1998 Oct 15 SP - 4183 EP - 4194 VL - 161 IS - 8 SN - 0022-1767, 0022-1767 KW - cancer vaccines KW - man KW - peptide vaccines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts 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/16504183?accountid=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=Functional+Dissociation+Between+Local+and+Systemic+Immune+Response+During+Anti-Melanoma+Peptide+Vaccination&rft.au=Lee%2C+KH%3BPanelli%2C+M+C%3BKim%2C+C+J%3BRiker%2C+AI%3BBettinotti%2C+M+P%3BRoden%2C+M+M%3BFetsch%2C+P%3BAbati%2C+A%3BRosenberg%2C+SA%3BMarincola%2C+F+M&rft.aulast=Lee&rft.aufirst=KH&rft.date=1998-10-15&rft.volume=161&rft.issue=8&rft.spage=4183&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 ER - TY - JOUR T1 - Glycosylation and NH2-terminal domain mutants of the tissue inhibitor of metalloproteinases-1 (TIMP-1). AN - 69968104; 9774703 AB - Mutants in the tissue inhibitor of metalloproteinases-1 (TIMP-1) protein have been created by site-directed mutagenesis and expressed in HeLa cells, using a recombinant vaccinia virus system. Removal of either or both glycosylation sites yielded proteins which retained wild-type inhibitory activity against both human fibroblast-type collagenase (FIB-CL) and Mr 72000 gelatinase (GL). However, the double glycosylation mutant protein was expressed at a level that was 2-4-fold lower than that of the wild-type or the single site glycosylation mutants. The 'tiny-TIMP' COOH-terminal deletion mutant that lacks the last 57 residues was also inhibitory, but the dose-response curve suggested that the interaction with the Mr 72000 gelatinase had been altered. A number of replacement mutants in the highly conserved NH2-terminal domain, including replacement of P5A and P8A or a double mutation in the VIRAK sequence which is absolutely conserved in all TIMPs in all species (VIRAK to VIAAA), also yielded functional proteins capable of inhibiting FIB-CL and Mr 72000 GL and of forming SDS-resistant complexes with FIB-CL. None of the above manipulations abolished inhibitory function suggesting that binding of the inhibitor by the enzyme involves multiple interactions. JF - Biochimica et biophysica acta AU - Caterina, N C AU - Windsor, L J AU - Bodden, M K AU - Yermovsky, A E AU - Taylor, K B AU - Birkedal-Hansen, H AU - Engler, J A AD - National Institute of Dental Research, National Institutes of Health, Bldg. 30, Room 132, Bethesda, MD 20892, USA. Y1 - 1998/10/14/ PY - 1998 DA - 1998 Oct 14 SP - 21 EP - 34 VL - 1388 IS - 1 SN - 0006-3002, 0006-3002 KW - Recombinant Proteins KW - 0 KW - Tissue Inhibitor of Metalloproteinase-1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Vaccinia virus -- genetics KW - Recombinant Proteins -- biosynthesis KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Glycosylation KW - Recombinant Proteins -- genetics KW - Molecular Weight KW - Sequence Deletion KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Mutation KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Tissue Inhibitor of Metalloproteinase-1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glycosylation+and+NH2-terminal+domain+mutants+of+the+tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29.&rft.au=Caterina%2C+N+C%3BWindsor%2C+L+J%3BBodden%2C+M+K%3BYermovsky%2C+A+E%3BTaylor%2C+K+B%3BBirkedal-Hansen%2C+H%3BEngler%2C+J+A&rft.aulast=Caterina&rft.aufirst=N&rft.date=1998-10-14&rft.volume=1388&rft.issue=1&rft.spage=21&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 - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tryptophan synthase mutations that alter cofactor chemistry lead to mechanism-based inactivation. AN - 69968441; 9772188 AB - Mutations in the pyridoxal phosphate binding site of the tryptophan synthase beta subunit (S377D and S377E) alter cofactor chemistry [Jhee, K.-H., et al. (1998) J. Biol. Chem. 273, 11417-11422]. We now report that the S377D, S377E, and S377A beta2 subunits form alpha2 beta2 complexes with the alpha subunit and activate the alpha subunit-catalyzed cleavage of indole 3-glycerol phosphate. The apparent Kd for dissociation of the alpha and beta subunits is unaffected by the S377A mutation but is increased up to 500-fold by the S377D and S377E mutations. Although the three mutant alpha2 beta2 complexes exhibit very low activities in beta elimination and beta replacement reactions catalyzed at the beta site in the presence of Na+, the activities and spectroscopic properties of the S377A alpha2 beta2 complex are partially repaired by addition of Cs+. The S377D and S377E alpha2 beta2 complexes, unlike the wild-type and S377A alpha2 beta2 complexes and the mutant beta2 subunits, undergo irreversible substrate-induced inactivation by L-serine or by beta-chloro-L-alanine. The rates of inactivation (kinact) are similar to the rates of catalysis (kcat). The partition ratios are very low (kcat/kinact = 0.25-3) and are affected by alpha subunit ligands and monovalent cations. The inactivation product released by alkali was shown by HPLC and by fluorescence, absorption, and mass spectroscopy to be identical to a compound previously synthesized from pyridoxal phosphate and pyruvate. We suggest that alterations in the cofactor chemistry that result from the engineered Asp377 in the active site of the beta subunit may promote the mechanism-based inactivation. JF - Biochemistry AU - Jhee, K H AU - McPhie, P AU - Ro, H S AU - Miles, E W AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-0830, USA. Y1 - 1998/10/13/ PY - 1998 DA - 1998 Oct 13 SP - 14591 EP - 14604 VL - 37 IS - 41 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Multienzyme Complexes KW - Peptide Fragments KW - Aspartic Acid KW - 30KYC7MIAI KW - Serine KW - 452VLY9402 KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Aspartic Acid -- genetics KW - Bacterial Proteins -- genetics KW - Spectrometry, Fluorescence KW - Peptide Fragments -- genetics KW - Circular Dichroism KW - Substrate Specificity -- genetics KW - Serine -- metabolism KW - Multienzyme Complexes -- genetics KW - Serine -- genetics KW - Enzyme Activation -- genetics KW - Multienzyme Complexes -- chemistry KW - Bacterial Proteins -- antagonists & inhibitors KW - Bacterial Proteins -- chemistry KW - Alanine -- genetics KW - Catalysis KW - Mutagenesis, Site-Directed KW - Tryptophan Synthase -- chemistry KW - Pyridoxal Phosphate -- chemistry KW - Tryptophan Synthase -- antagonists & inhibitors KW - Tryptophan Synthase -- genetics KW - Pyridoxal Phosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tryptophan+synthase+mutations+that+alter+cofactor+chemistry+lead+to+mechanism-based+inactivation.&rft.au=Jhee%2C+K+H%3BMcPhie%2C+P%3BRo%2C+H+S%3BMiles%2C+E+W&rft.aulast=Jhee&rft.aufirst=K&rft.date=1998-10-13&rft.volume=37&rft.issue=41&rft.spage=14591&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-03 N1 - Date created - 1998-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription AN - 17104147; 4402061 AB - DsrA RNA regulates both transcription, by overcoming transcriptional silencing by the nucleoid- associated H-NS protein, and translation, by promoting efficient translation of the stress sigma factor, RpoS. These two activities of DsrA can be separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is necessary for RpoS translation but not for anti-H- NS action, while the second stem-loop is essential for antisilencing and less critical for RpoS translation. The third stem-loop, which behaves as a transcription terminator, can be substituted by the trp transcription terminator without loss of either DsrA function. The sequence of the first stem-loop of DsrA is complementary with the upstream leader portion of rpoS messenger RNA, suggesting that pairing of DsrA with the rpoS message might be important for translational regulation. Mutations in the Rpos leader and compensating mutations in DsrA confirm that this predicted pairing is necessary for DsrA stimulation of RpoS translation. We propose that DsrA pairing stimulates RpoS translation by acting as an anti- antisense RNA, freeing the translation initiation region from the cis- acting antisense RNA and allowing increased translation. JF - Proceedings of the National Academy of Sciences, USA AU - Majdalani, N AU - Cunning, C AU - Sledjeski, D AU - Elliott, T AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute National Institutes of Health, Bethesda, MD 20892, susang@helix.nih.gov Y1 - 1998/10/13/ PY - 1998 DA - 1998 Oct 13 SP - 12462 EP - 12467 VL - 95 IS - 21 SN - 0027-8424, 0027-8424 KW - DsrA protein KW - H-NS protein KW - RpoS protein KW - rpoS gene KW - translation KW - trp gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Gene silencing KW - J 02726:RNA and ribosomes KW - N 14560:Antisense research UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17104147?accountid=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=DsrA+RNA+regulates+translation+of+RpoS+message+by+an+anti-antisense+mechanism%2C+independent+of+its+action+as+an+antisilencer+of+transcription&rft.au=Majdalani%2C+N%3BCunning%2C+C%3BSledjeski%2C+D%3BElliott%2C+T%3BGottesman%2C+S&rft.aulast=Majdalani&rft.aufirst=N&rft.date=1998-10-13&rft.volume=95&rft.issue=21&rft.spage=12462&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 - Gene silencing ER - TY - JOUR T1 - Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression AN - 16495728; 4402080 AB - Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of viral replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor alpha (TNF alpha ) and HIV-1 coreceptors monitored. MAC enhanced TNF alpha production in vitro, consistent with its expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5 coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5 expression was increased at both the mRNA level and on the cell surface. Up-regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic coreceptor, CXCR4. Increases in NF- Kappa B, TNF alpha , and CCR5 were consistent with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected lymph nodes as compared with tissues with only HIV-1. The increased production of TNF alpha , together with elevated expression of CCR5, provide potential mechanisms for enhanced infection and replication of HIV-1 by macrophages in OI- infected cells and tissues. Consequently, treating OI may inhibit not only the OI-induced pathology, but also limit the viral burden. JF - Proceedings of the National Academy of Sciences, USA AU - Wahl, S M AU - Wild, T G AU - Peng, G AU - Donze, H H AU - Doherty, T M AU - Mizel, D AU - Orenstein, J M AD - Oral Infection and Immunity Branch, Nat. Inst. Dental Res., 30 Convent Dr., MSC 4352, National Institutes of Health, Bethesda, MD 20892 USA, smwahl@yoda.nidr.nih.gov Y1 - 1998/10/13/ PY - 1998 DA - 1998 Oct 13 SP - 12574 EP - 12579 VL - 95 IS - 21 SN - 0027-8424, 0027-8424 KW - CCR5 protein KW - HIV-1 KW - Mycobacterium avium KW - Opportunist infection KW - human immunodeficiency virus 1 KW - man KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06775:Chemokines KW - J 02833:Immune response and immune mechanisms KW - V 22003:AIDS: Immunological aspects KW - F 06800:Viruses KW - F 06764:Function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16495728?accountid=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=Mycobacterium+avium+complex+augments+macrophage+HIV-1+production+and+increases+CCR5+expression&rft.au=Wahl%2C+S+M%3BWild%2C+T+G%3BPeng%2C+G%3BDonze%2C+H+H%3BDoherty%2C+T+M%3BMizel%2C+D%3BOrenstein%2C+J+M&rft.aulast=Wahl&rft.aufirst=S&rft.date=1998-10-13&rft.volume=95&rft.issue=21&rft.spage=12574&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 ER - TY - JOUR T1 - Characterization of distinct human endometrial carcinoma cell lines deficient in mismatch repair that originated from a single tumor. AN - 73989759; 9756907 AB - The role of specific mismatch repair (MMR) gene products was examined by observing several phenotypic end points in two MMR-deficient human endometrial carcinoma cell lines that were originally isolated from the same tumor. The first cell line, HEC-1-A, contains a nonsense mutation in the hPMS2 gene, which results in premature termination and a truncated hPMS2 protein. In addition, HEC-1-A cells carry a splice mutation in the hMSH6 gene and lack wild-type hMSH6 protein. The second cell line, HEC-1-B, possesses the same defective hMSH6 locus. However, HEC-1-B cells are heterozygous at the hPMS2 locus; that is, along with carrying the same nonsense mutation in hPMS2 as in HEC-1-A, HEC-1-B cells also contain a wild-type hPMS2 gene. Initial recognition of mismatches in DNA requires either the hMSH2/hMSH6 or hMSH2/hMSH3 heterodimer, with hPMS2 functioning downstream of damage recognition. Therefore, cells defective in hPMS2 should completely lack MMR (HEC-1-A), whereas cells mutant in hMSH6 only (HEC-1-B) can potentially repair damage via the hMSH2/hMSH3 heterodimer. The data presented here in HEC-1-B cells illustrate (i) the reduction of instability at microsatellite sequences, (ii) a significant decrease in frameshift mutation rate at HPRT, and (iii) the in vitro repair of looped substrates, relative to HEC-1-A cells, illustrating the repair of frameshift intermediates by hMSH2/hMSH3 heterodimer. Furthermore, the role of hMSH2/hMSH3 heterodimer in the repair of base:base mismatches is supported by observing the reduction in base substitution mutation rate at HPRT in HEC-1-B cells (hMSH6-defective but possessing wild-type hPMS2), as compared with HEC-1-A (hMSH6/hPMS2-defective) cells. These data support a critical role for hPMS2 in human MMR, while further defining the role of the hMSH2/hMSH3 heterodimer in maintaining genomic stability in the absence of a wild-type hMSH2/hMSH6 heterodimer. JF - The Journal of biological chemistry AU - Glaab, W E AU - Risinger, J I AU - Umar, A AU - Kunkel, T A AU - Barrett, J C AU - Tindall, K R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. warren_glaab@merck.com Y1 - 1998/10/09/ PY - 1998 DA - 1998 Oct 09 SP - 26662 EP - 26669 VL - 273 IS - 41 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Neoplasm Proteins KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Microsatellite Repeats KW - Base Sequence KW - Tumor Cells, Cultured KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Humans KW - Dimerization KW - Neoplasm Proteins -- genetics KW - Female KW - DNA Repair KW - Base Pair Mismatch KW - Endometrial Neoplasms -- pathology KW - Endometrial Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73989759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+distinct+human+endometrial+carcinoma+cell+lines+deficient+in+mismatch+repair+that+originated+from+a+single+tumor.&rft.au=Glaab%2C+W+E%3BRisinger%2C+J+I%3BUmar%2C+A%3BKunkel%2C+T+A%3BBarrett%2C+J+C%3BTindall%2C+K+R&rft.aulast=Glaab&rft.aufirst=W&rft.date=1998-10-09&rft.volume=273&rft.issue=41&rft.spage=26662&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 - 1998-11-02 N1 - Date created - 1998-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: effects on cell surface expression, dimerization and signal transduction. AN - 70013423; 9801147 AB - Mammalian calcium receptors (CaRs) share with the metabotropic glutamate receptors (mGluRs) the relative positions of 16 cysteine residues in the amino-terminal extracellular domain. To investigate the role of these cysteines, a series of mutants in the extracellular domain of the human CaR was prepared in which each of these 16 cysteine residues and three others not conserved in the mGluRs were replaced by serines. Wild-type and mutant CaR cDNAs were expressed in HEK-293 cells, and evaluated for expression and response to extracellular calcium. Mutation of three non-conserved cysteines and of two conserved cysteines produced proteins with near wild-type phenotype. In contrast, mutation of the other conserved cysteines gave proteins that showed drastic reduction in cell surface expression and/or failed to respond to calcium. We identified 14 cysteines essential for proper trafficking and function of the receptor, two of which may be involved in formation of a disulfide-linked dimer. JF - FEBS letters AU - Fan, G F AU - Ray, K AU - Zhao, X M AU - Goldsmith, P K AU - Spiegel, A M AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/10/09/ PY - 1998 DA - 1998 Oct 09 SP - 353 EP - 356 VL - 436 IS - 3 SN - 0014-5793, 0014-5793 KW - Phosphatidylinositols KW - 0 KW - Receptors, Calcium-Sensing KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Phosphatidylinositols -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Transfection KW - Kinetics KW - Humans KW - Dimerization KW - Recombinant Proteins -- chemistry KW - Signal Transduction KW - Cell Line KW - Amino Acid Substitution KW - Calcium -- metabolism KW - Calcium -- pharmacology KW - Receptors, Cell Surface -- physiology KW - Receptors, Cell Surface -- biosynthesis KW - Receptors, Cell Surface -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70013423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+the+cysteines+in+the+extracellular+domain+of+the+human+Ca2%2B+receptor%3A+effects+on+cell+surface+expression%2C+dimerization+and+signal+transduction.&rft.au=Fan%2C+G+F%3BRay%2C+K%3BZhao%2C+X+M%3BGoldsmith%2C+P+K%3BSpiegel%2C+A+M&rft.aulast=Fan&rft.aufirst=G&rft.date=1998-10-09&rft.volume=436&rft.issue=3&rft.spage=353&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the generic promoter III of the rat prolactin receptor gene by C/EBPbeta and Sp1. AN - 73936651; 9748306 AB - Three promoters are operative in the rat prolactin receptor gene as follows: promoter I (PI) and II (PII) are specific for the gonads and liver, respectively, and promoter III (PIII) is common to several tissues. To investigate the mechanisms controlling the activity of promoter III, its regulatory elements and transcription factors were characterized in gonadal and non-gonadal cells. The TATA-less PIII domain was localized to the region -437 to -179 (ATG +1) containing the 5'-flanking region and part of the non-coding first exon. Within the promoter domain, a functional CAAT-box/enhancer binding protein (C/EBP) (-398) and an Sp1 element (-386), which bind C/EBPbeta and Sp1/Sp3, respectively, contribute individually to promoter activation in gonadal and non-gonadal cells. However, significant redundancy was demonstrated between these elements in non-gonadal cells. Additionally, an element within the non-coding exon 1 (-338) is also required for promoter activity. Activation of PIII by the widely expressed Sp1 and C/EBPbeta factors explains its common utilization in multiple tissues. Moreover, whereas the rat and mouse PIII share similar structure and function, the mouse PI lacks the functional SF-1 element and hence is inactive. These findings indicate that promoter III is of central importance in prolactin receptor gene transcription across species. JF - The Journal of biological chemistry AU - Hu, Z Z AU - Zhuang, L AU - Meng, J AU - Dufau, M L AD - Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10/02/ PY - 1998 DA - 1998 Oct 02 SP - 26225 EP - 26235 VL - 273 IS - 40 SN - 0021-9258, 0021-9258 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Receptors, Prolactin KW - Sp1 Transcription Factor KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Mutagenesis, Site-Directed -- genetics KW - Mice KW - Sequence Analysis, DNA KW - Cloning, Molecular KW - Rats, Inbred Strains KW - Rats KW - Base Sequence KW - Genes, Reporter -- genetics KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Transcriptional Activation -- genetics KW - Binding Sites -- genetics KW - Gonads -- metabolism KW - Female KW - Nuclear Proteins -- analysis KW - Sp1 Transcription Factor -- metabolism KW - Promoter Regions, Genetic -- genetics KW - Nuclear Proteins -- metabolism KW - Receptors, Prolactin -- genetics KW - Gene Expression Regulation -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73936651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+regulation+of+the+generic+promoter+III+of+the+rat+prolactin+receptor+gene+by+C%2FEBPbeta+and+Sp1.&rft.au=Hu%2C+Z+Z%3BZhuang%2C+L%3BMeng%2C+J%3BDufau%2C+M+L&rft.aulast=Hu&rft.aufirst=Z&rft.date=1998-10-02&rft.volume=273&rft.issue=40&rft.spage=26225&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF064034; GENBANK; AF064033 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor. AN - 73934676; 9748222 AB - The gonadotropin-releasing hormone (GnRH) receptor, which is a unique G protein-coupled receptor without a C-terminal cytoplasmic domain, activates both inositol phosphate (InsP) and cAMP signaling responses. The function of the highly basic first intracellular (1i) loop of the GnRH receptor in signal transduction was evaluated by mutating selected residues located in its N and C termini. Replacements of Leu58, Lys59, Gln61, and Lys62 at the N terminus, and Leu73, Ser74, and Leu80 at the C terminus, caused no change in binding affinity. The agonist-induced InsP and cAMP responses of the Q61E and K59Q,K62Q receptors were also unaffected, but the L58A receptor showed a normal InsP response and an 80% decrease in cAMP production. At the C terminus, the InsP response of the L73R receptor was normal, but cAMP production was reduced by 80%. The EC50 for GnRH-induced InsP responses of the S74E and L80A receptors was increased by about one order of magnitude, and the cAMP responses were essentially abolished. These findings indicate that cAMP signaling from the GnRH receptor is dependent on specific residues in the 1i loop that are not essential for activation of the phosphoinositide signaling pathway. JF - The Journal of biological chemistry AU - Arora, K K AU - Krsmanovic, L Z AU - Mores, N AU - O'Farrell, H AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10/02/ PY - 1998 DA - 1998 Oct 02 SP - 25581 EP - 25586 VL - 273 IS - 40 SN - 0021-9258, 0021-9258 KW - Inositol Phosphates KW - 0 KW - Receptors, LHRH KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Animals KW - COS Cells KW - Inositol Phosphates -- metabolism KW - Mutagenesis, Site-Directed -- genetics KW - Transfection -- genetics KW - Molecular Sequence Data KW - Protein Binding -- genetics KW - Mice KW - Amino Acid Sequence KW - Gonadotropin-Releasing Hormone -- pharmacology KW - Receptors, LHRH -- chemistry KW - Signal Transduction -- physiology KW - Cyclic AMP -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73934676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mediation+of+cyclic+AMP+signaling+by+the+first+intracellular+loop+of+the+gonadotropin-releasing+hormone+receptor.&rft.au=Arora%2C+K+K%3BKrsmanovic%2C+L+Z%3BMores%2C+N%3BO%27Farrell%2C+H%3BCatt%2C+K+J&rft.aulast=Arora&rft.aufirst=K&rft.date=1998-10-02&rft.volume=273&rft.issue=40&rft.spage=25581&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of UmuD cleavage: Role of the amino-terminal tail AN - 16560052; 4398278 AB - An essential step in SOS mutagenesis is the RecA-mediated posttranslational processing of UmuD-like proteins to the shorter, but mutagenically active, UmuD'-like proteins. Interestingly, the UmuD-like proteins undergo posttranslational processing at different rates. For example, although the Escherichia coli UmuD (UmuD sub(Ec)) and the Salmonella typhimurium UmuD (UmuD sub(St)) proteins are 73% identical, UmuD sub(St) is processed in vivo at a significantly faster rate than the UmuD sub(Ec) protein. Here, we report experiments aimed at investigating the molecular basis of these phenotypic differences. The faster rate of UmuD sub(St) cleavage probably does not result solely from a better interaction with RecA, since we observed that, in vitro, UmuD sub(St) undergoes RecA-independent autocatalytic processing about four-times faster than UmuD sub(Ec). By constructing chimeric UmuD proteins, we determined that the amino-terminal tail of the UmuD proteins proximal to the Cys24-Gly25 cleavage site is mainly responsible for the difference in UmuD sub(St) and UmuD sub(Ec) cleavage rates. Site-directed mutagenesis of the UmuD sub(Ec) protein suggests that most of the enhanced cleavage observed with the UmuD sub(St) protein can be attributed to the presence of a Pro23 residue, juxtaposed to the cleavage site in UmuD sub(St). Furthermore, this proline residue appears to result in a UmuD protein that is a much better substrate for intermolecular cleavage. These findings clearly implicate the N-terminal tail of the UmuD-like proteins as playing an important and unexpected regulatory function in the maturation of the mutagenically active UmuD'-like mutagenesis proteins. JF - Journal of Molecular Biology AU - McDonald, J P AU - Maury, EE AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, 20892-2725, MD, USA Y1 - 1998/10/02/ PY - 1998 DA - 1998 Oct 02 SP - 721 EP - 730 PB - Academic Press VL - 282 IS - 4 SN - 0022-2836, 0022-2836 KW - UmuD protein KW - cleavage KW - Microbiology Abstracts B: Bacteriology KW - Site-directed mutagenesis KW - Post-translation KW - Escherichia coli KW - Salmonella typhimurium KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16560052?accountid=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=Regulation+of+UmuD+cleavage%3A+Role+of+the+amino-terminal+tail&rft.au=McDonald%2C+J+P%3BMaury%2C+EE%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1998-10-02&rft.volume=282&rft.issue=4&rft.spage=721&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 - Escherichia coli; Salmonella typhimurium; Site-directed mutagenesis; Post-translation ER - TY - JOUR T1 - In Acta Neurol Scand 1998: 97: 131-137, the name of the 3rd author, A. Waziri, was misspelled as A. Warzeri. We regret this error. The corrected version is shown below. AN - 923210800; 14397810 AB - Objective- To explore the role of the motor cortex during implicit and explicit learning. Materials and methods- EEG signals were recorded from 30 channels by measuring task-related desynchronization (TRD) when 10 right-handed naive volunteers performed a variation of the serial reaction task. Stimuli, consisting of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented binaurally through a pair of tubephones at 60 dB with a 2-s constant interstimulus interval. A series of 10 repetitive tones represented the test sequence; the random sequence was the control. Results- All subjects developed implicit and explicit knowledge reflected by decreased response time, increased accuracy, and the ability to generate the sequence. Six of 10 subjects demonstrated implicit learning without explicit learning during the first 3 blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a peak amplitude, declining thereafter. Conclusions- Properties of the sensorimotor cortex change during learning and these changes are independent of stimulus modality. JF - Acta Neurologica Scandinavica AU - Zhuang, P AU - Dang, N AU - Waziri, A AU - Gerloff, C AU - Cohen, L G AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 295 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 98 IS - 4 SN - 0001-6314, 0001-6314 KW - Ecology Abstracts KW - Cortex (motor) KW - Learning KW - D 04040:Ecosystem and Ecology Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/923210800?accountid=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=Acta+Neurologica+Scandinavica&rft.atitle=In+Acta+Neurol+Scand+1998%3A+97%3A+131-137%2C+the+name+of+the+3rd+author%2C+A.+Waziri%2C+was+misspelled+as+A.+Warzeri.+We+regret+this+error.+The+corrected+version+is+shown+below.&rft.au=Zhuang%2C+P%3BDang%2C+N%3BWaziri%2C+A%3BGerloff%2C+C%3BCohen%2C+L+G%3BHallett%2C+M&rft.aulast=Zhuang&rft.aufirst=P&rft.date=1998-10-01&rft.volume=98&rft.issue=4&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Acta+Neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/10.1111%2Fj.1600-0404.1998.tb07314.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-02-01 N1 - Last updated - 2014-02-11 N1 - SubjectsTermNotLitGenreText - Learning DO - http://dx.doi.org/10.1111/j.1600-0404.1998.tb07314.x ER - TY - JOUR T1 - Working Memory Capacity and Suppression AN - 85662656; 9900125 AB - Reported are the results of two paired-associate task experiments designed to determine if a relationship exists between a person's working memory capacity & (1) the number of covert intrusions experienced & (2) their ability to suppress intrusions. For both experiments, subjects (N = 120 each) learned lists in tasks with interference & non-interference conditions. For Experiment 1, speed of response was emphasized, & it was found that high span subjects (ie, those who scored high on a measure of working memory capacity) produced fewer first-list intrusions during second-list learning than low span subjects. In Experiment 2, accuracy was emphasized; here it was found that the high span subjects in the interference condition were slower than the control group, whereas the low span subjects were faster than their control group. The overall findings support the idea that there is a definite relationship between working memory capacity & an individual's ability to suppress intrusions. 2 Tables, 2 Figures, 50 References. R. Meyer JF - Journal of Memory and Language AU - Rosen, Virginia M AU - Engle, Randall W AD - National Instit Mental Health, Federal Bldg Room B1A-14 7550 Wisconsin Ave Bethesda MD 20892-9005 rosenv@intra.nimh.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 418 EP - 436 VL - 39 IS - 3 SN - 0749-596X, 0749-596X KW - Associative Processes (05300) KW - Paired Associate Learning (62100) KW - Interference (Learning) (37150) KW - Short Term Memory (78150) KW - article KW - 4016: psycholinguistics; verbal learning: paired associate, serial learning, memory, recognition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85662656?accountid=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=Journal+of+Memory+and+Language&rft.atitle=Working+Memory+Capacity+and+Suppression&rft.au=Rosen%2C+Virginia+M%3BEngle%2C+Randall+W&rft.aulast=Rosen&rft.aufirst=Virginia&rft.date=1998-10-01&rft.volume=39&rft.issue=3&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Journal+of+Memory+and+Language&rft.issn=0749596X&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 - JMLAE6 N1 - SubjectsTermNotLitGenreText - Paired Associate Learning (62100); Short Term Memory (78150); Associative Processes (05300); Interference (Learning) (37150) ER - TY - JOUR T1 - Differential expression of the murine Ly-6A/E antigen homolog of human squamous cell carcinoma antigen E48 during malignant transformation and tumor progression of squamous cell carcinoma line Pam 212. AN - 85414406; pmid-9782003 AB - The mRNA differential display method detected increased expression of the mRNA of an immune recognition antigen known as Ly-6A/E after malignant transformation of the murine squamous cell carcinoma line Pam 212. Subsequent loss of expression of Ly-6A/E occurred with metastatic tumor progression of Pam in vivo. Ly-6 molecules have been implicated in immune cell recognition and signal transduction and are homologous to the human E48 SCC antigen that has been shown to be involved in cell-cell recognition. These observations suggest that loss of Ly-6A/E antigen may contribute to tumor progression and metastasis of squamous cell carcinoma through decreased tumor-lymphocyte or tumor-tumor recognition. JF - Otolaryngology and head and neck surgery AU - Kato, T AU - Dong, G AU - Loukinova, E AU - Chen, Z 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, Maryland 20892-1419, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 408 EP - 411 VL - 119 IS - 4 SN - 0194-5998, 0194-5998 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Cell Adhesion Molecules -- genetics KW - Glycoproteins -- analysis KW - Tumor Markers, Biological -- analysis KW - Humans KW - Antigens, Ly -- analysis KW - Disease Progression KW - Serpins -- analysis KW - Cell Adhesion Molecules -- analysis KW - Membrane Proteins -- genetics KW - Membrane Proteins -- analysis KW - Cell Communication -- genetics KW - Mice, Inbred BALB C KW - RNA, Messenger -- genetics KW - Carcinoma, Squamous Cell -- immunology KW - Lymphocytes -- immunology KW - Carcinoma, Squamous Cell -- secondary KW - Tumor Cells, Cultured KW - Carcinoma, Squamous Cell -- genetics KW - Keratinocytes KW - Cell Line, Transformed KW - Serpins -- genetics KW - Antigens, Neoplasm -- analysis KW - RNA, Messenger -- analysis KW - Mice KW - Glycoproteins -- genetics KW - Neoplasm Transplantation KW - Antigens, Ly -- genetics KW - Tumor Markers, Biological -- genetics KW - Signal Transduction -- genetics KW - Antigens, Neoplasm -- genetics KW - Gene Expression Regulation, Neoplastic KW - Hematopoietic Stem Cells -- immunology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85414406?accountid=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=Otolaryngology+and+head+and+neck+surgery&rft.atitle=Differential+expression+of+the+murine+Ly-6A%2FE+antigen+homolog+of+human+squamous+cell+carcinoma+antigen+E48+during+malignant+transformation+and+tumor+progression+of+squamous+cell+carcinoma+line+Pam+212.&rft.au=Kato%2C+T%3BDong%2C+G%3BLoukinova%2C+E%3BChen%2C+Z%3BVan+Waes%2C+C&rft.aulast=Kato&rft.aufirst=T&rft.date=1998-10-01&rft.volume=119&rft.issue=4&rft.spage=408&rft.isbn=&rft.btitle=&rft.title=Otolaryngology+and+head+and+neck+surgery&rft.issn=01945998&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Early-response cytokine expression in adult middle ear effusions. AN - 85412952; pmid-9781987 AB - Various cytokines are presently known to be associated with the regulation of inflammatory responses. In pediatric otitis media, cytokines that correlate with various degrees of inflammation are present in middle ear effusions as inflammatory mediators. The present study was undertaken to examine the potential role of the early-response cytokines, interleukin-1beta and tumor necrosis factor-alpha, in adult otitis media. Fifty-nine adults with otitis media underwent tympanocentesis, and the effusion specimens were analyzed for the presence of both cytokines by enzyme-linked immunosorbent assay methods. Eighty-eight percent of the effusions were serous in nature. Sixty-seven percent of the patients had a known history of head and neck malignancy and radiation to the temporal bone. Twelve percent of the effusions were positive for interleukin-1beta expression, compared with 85% of effusions in children with otitis media. Eight percent of the effusions contained tumor necrosis factor-alpha, compared with 85% of those collected in pediatric otitis media. All of the specimens that contained tumor necrosis factor-alpha also contained interleukin-1beta. In the present study, there was no correlation with head and neck malignancy/radiation or the clinical degree of inflammation with the presence of either cytokine. We conclude that adult otitis media is associated with lower expression of an acute inflammatory response, as judged by the levels of interleukin-1beta and tumor necrosis factor-alpha in the effusions. Additionally, adult otitis probably represents a less severe and more chronic inflammatory state in comparison with pediatric otitis media. Further analysis of inflammatory mediators in adult otitis media is necessary to evaluate the contribution of cytokines in relation to various etiologic factors. JF - Otolaryngology and head and neck surgery AU - Ondrey, F G AU - Juhn, S K AU - Adams, G L AD - Tumor Cell Biology Division/Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 342 EP - 345 VL - 119 IS - 4 SN - 0194-5998, 0194-5998 KW - Index Medicus KW - National Library of Medicine KW - Temporal Bone -- radiation effects KW - Humans KW - Head and Neck Neoplasms -- complications KW - Aged KW - Child KW - Inflammation Mediators -- analysis KW - Aged, 80 and over KW - Adult KW - Head and Neck Neoplasms -- radiotherapy KW - Enzyme-Linked Immunosorbent Assay KW - Middle Aged KW - Chronic Disease KW - Gene Expression Regulation KW - Male KW - Female KW - Paracentesis KW - Tumor Necrosis Factor-alpha -- analysis KW - Otitis Media with Effusion -- metabolism KW - Interleukin-1 -- genetics KW - Interleukin-1 -- analysis KW - Tumor Necrosis Factor-alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85412952?accountid=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=Otolaryngology+and+head+and+neck+surgery&rft.atitle=Early-response+cytokine+expression+in+adult+middle+ear+effusions.&rft.au=Ondrey%2C+F+G%3BJuhn%2C+S+K%3BAdams%2C+G+L&rft.aulast=Ondrey&rft.aufirst=F&rft.date=1998-10-01&rft.volume=119&rft.issue=4&rft.spage=342&rft.isbn=&rft.btitle=&rft.title=Otolaryngology+and+head+and+neck+surgery&rft.issn=01945998&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Muscarinic cholinergic receptor measurements with [18F]FP-TZTP: control and competition studies. AN - 85270091; pmid-9778190 AB - [18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 microg x kg(-1) x h(-1)) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL x min(-1) x mL(-1) in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution (V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower (P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller (P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography. JF - Journal of Cerebral Blood Flow and Metabolism AU - Carson, R E AU - Kiesewetter, D O AU - Jagoda, E AU - Der, M G AU - Herscovitch, P AU - Eckelman, W C AD - Positron Emission Tomography Department, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. PY - 1998 SP - 1130 EP - 1142 VL - 18 IS - 10 SN - 0271-678X, 0271-678X KW - Blood Proteins KW - Thiazoles KW - Animal KW - Brain KW - Pyridines KW - Anesthetics, Inhalation KW - Cholinesterase Inhibitors KW - Anesthesia KW - Receptors, Muscarinic KW - Kinetics KW - Binding, Competitive KW - Fluorine Radioisotopes KW - Isoflurane KW - Tomography, Emission-Computed KW - Macaca mulatta KW - Chromatography, Thin Layer KW - Acetylcholine KW - Physostigmine KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270091?accountid=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+Cerebral+Blood+Flow+and+Metabolism&rft.atitle=Muscarinic+cholinergic+receptor+measurements+with+%5B18F%5DFP-TZTP%3A+control+and+competition+studies.&rft.au=Carson%2C+R+E%3BKiesewetter%2C+D+O%3BJagoda%2C+E%3BDer%2C+M+G%3BHerscovitch%2C+P%3BEckelman%2C+W+C&rft.aulast=Carson&rft.aufirst=R&rft.date=1998-10-01&rft.volume=18&rft.issue=10&rft.spage=1130&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cerebral+Blood+Flow+and+Metabolism&rft.issn=0271678X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Human exposure assessment and the National Toxicology Program. AN - 85259621; pmid-9755136 AB - The National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP) is developing a new interagency initiative in exposure assessment. This initiative involves the NIEHS, the Centers for Disease Control and Prevention through its National Center for Environmental Health, the National Institute for Occupational Safety and Health, the EPA, and other participating institutes and agencies of the NTP. This initiative will benefit public health and priority setting in a number of ways. First, as discussed above, it will strengthen the scientific foundation for risk assessments by the development of more credible exposure/response relationships in people by improving cross-species extrapolation, the development of biologically based dose-response models, and the identification of sensitive subpopulations and for "margin of exposure" based estimates of risk. Second, it will provide the kind of information necessary for deciding which chemicals should be studied with the limited resources available for toxicological testing. For example, there are 85,000 chemicals in commerce today, and the NTP can only provide toxicological evaluations on 10-20 per year. Third, we would use the information obtained from the exposure initiative to focus our research on mixtures that are actually present in people's bodies. Fourth, we would obtain information on the kinds and amount of chemicals in children and other potentially sensitive subpopulations. Determinations of whether additional safety factors need to be applied to children must rest, in part, upon comparative exposure analyses between children and adults. Fifth, this initiative, taken together with the environmental genome initiative, will provide the science base essential for meaningful studies on gene/environment interactions, particularly for strengthening the evaluation of epidemiology studies. Sixth, efficacy of public health policies aimed at reducing human exposure to chemical agents could be evaluated in a more meaningful way if body burden data were available over time, including remediation around Superfund sites and efforts to achieve environmental justice. The exposure assessment initiative is needed to address public health needs. It is feasible because of recent advances in analytical technology and molecular biology, and it is an example of how different agencies can work together to better fulfill their respective missions. JF - Environmental Health Perspectives AU - Lucier, G W AU - Schecter, A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA. PY - 1998 SP - 623 EP - 627 VL - 106 IS - 10 SN - 0091-6765, 0091-6765 KW - United States KW - Human KW - National Institutes of Health (U.S.) KW - Environmental Exposure KW - Risk Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85259621?accountid=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=Environmental+Health+Perspectives&rft.atitle=Human+exposure+assessment+and+the+National+Toxicology+Program.&rft.au=Lucier%2C+G+W%3BSchecter%2C+A&rft.aulast=Lucier&rft.aufirst=G&rft.date=1998-10-01&rft.volume=106&rft.issue=10&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Clinical applications of the camptothecins. AN - 73941531; 9748525 AB - The camptothecin topoisomerase I-targeting agents are new class of antitumor drugs with demonstrated clinical activity in human malignancies, such as colorectal cancer and ovarian cancer. Currently, irinotecan and topotecan are the most widely used camptothecin analogs in clinical use and clinical trials are ongoing to better characterize their spectra of clinical activity, to determine their optimal schedules of administration and to define their use in combination with other chemotherapeutic agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI147211 and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. Other potential clinical applications include the use of camptothecin derivatives as radiation sensitizers or as antiviral agents. The successful development of the camptothecins as antitumor agents highlights the importance of topoisomerase I as a target for cancer chemotherapy. JF - Biochimica et biophysica acta AU - Takimoto, C H AU - Wright, J AU - Arbuck, S G AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 8, Room 5101, Bethesda Naval Hospital, Bethesda, MD 20892, USA. ctakim@helix.nih.gov Y1 - 1998/10/01/ PY - 1998 DA - 1998 Oct 01 SP - 107 EP - 119 VL - 1400 IS - 1-3 SN - 0006-3002, 0006-3002 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Molecular Structure KW - Enzyme Inhibitors -- therapeutic use KW - Clinical Trials, Phase I as Topic KW - Antineoplastic Agents -- pharmacokinetics KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- chemistry KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73941531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+applications+of+the+camptothecins.&rft.au=Takimoto%2C+C+H%3BWright%2C+J%3BArbuck%2C+S+G&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1998-10-01&rft.volume=1400&rft.issue=1-3&rft.spage=107&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 - 1998-12-04 N1 - Date created - 1998-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterogeneous neurochemical responses to different stressors: a test of Selye's doctrine of nonspecificity. AN - 73941354; 9756557 AB - Selye defined stress as the nonspecific response of the body to any demand. Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary responses. One can test Selye's concept by comparing magnitudes of responses at different stress intensities and assuming that the magnitudes vary with stress intensity, with the prediction that, at different stress intensities, ratios of increments neuroendocrine responses should be the same. We measured arterial plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage, intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization. Relative to ACTH increments, cold evoked large norepinephrine responses, insulin large epinephrine responses, and hemorrhage small norepinephrine and epinephrine responses, whereas immobilization elicited large increases in levels of all three compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%, and the epinephrine response to 25% hemorrhage was two times that to 10%. The ACTH response to 4% formaldehyde solution was two times that to 1%, and the epinephrine response to 4% formaldehyde solution exceeded four times that to 1%. These results are inconsistent with Selye's doctrine of nonspecificity and the existence of a unitary "stress syndrome," and they are more consistent with the concept that each stressor has its own central neurochemical and peripheral neuroendocrine "signature." JF - The American journal of physiology AU - Pacak, K AU - Palkovits, M AU - Yadid, G AU - Kvetnansky, R AU - Kopin, I J AU - Goldstein, D S AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - R1247 EP - R1255 VL - 275 IS - 4 Pt 2 SN - 0002-9513, 0002-9513 KW - Insulin KW - 0 KW - Formaldehyde KW - 1HG84L3525 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Norepinephrine KW - X4W3ENH1CV KW - Epinephrine KW - YKH834O4BH KW - Index Medicus KW - Animals KW - Restraint, Physical KW - Hypotension -- blood KW - Pain -- physiopathology KW - Pain -- blood KW - Hypoglycemia -- blood KW - Cold Temperature KW - Insulin -- pharmacology KW - Hemorrhage KW - Hypoglycemia -- chemically induced KW - Hypotension -- physiopathology KW - Mathematics KW - Rats KW - Handling (Psychology) KW - Rats, Sprague-Dawley KW - Hypoglycemia -- physiopathology KW - Time Factors KW - Male KW - Epinephrine -- secretion KW - Adrenocorticotropic Hormone -- secretion KW - Stress, Psychological -- physiopathology KW - Norepinephrine -- blood KW - Stress, Physiological -- blood KW - Norepinephrine -- secretion KW - Models, Biological KW - Epinephrine -- blood KW - Stress, Psychological -- blood KW - Stress, Physiological -- physiopathology KW - Adrenocorticotropic Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73941354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Heterogeneous+neurochemical+responses+to+different+stressors%3A+a+test+of+Selye%27s+doctrine+of+nonspecificity.&rft.au=Pacak%2C+K%3BPalkovits%2C+M%3BYadid%2C+G%3BKvetnansky%2C+R%3BKopin%2C+I+J%3BGoldstein%2C+D+S&rft.aulast=Pacak&rft.aufirst=K&rft.date=1998-10-01&rft.volume=275&rft.issue=4+Pt+2&rft.spage=R1247&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 - 1998-11-19 N1 - Date created - 1998-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD16 cross-linking blocks rearrangement of the TCR beta locus and development of alpha beta T cells and induces development of NK cells from thymic progenitors. AN - 73936415; 9759848 AB - Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus also contains precursor cells capable of developing into NK cells. Here, we describe conditions that induce pro-T cells to develop into NK cells. CD16 is expressed on thymic pro-T cells. We observed that CD16 cross-linking during culture of embryonic thymic organs suppressed rearrangement of the TCR beta locus (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR beta locus is normally required for development to the CD4+CD8+, and this development was also suppressed by CD16 cross-linking. The ability of CD16 cross-linking to block alpha beta T cell development was not attributable to toxic effects, but rather was accompanied by promotion of development into NK cells, identified based on molecular and functional criteria. These results suggest that common lymphoid precursors can respond to environmental signals to commit to the alpha beta T vs NK developmental pathways. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Durum, S K AU - Lee, C K AU - Geiman, T M AU - Murphy, W J AU - Muegge, K AD - Laboratory of Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA. durums@mail.ncifcrf.gov Y1 - 1998/10/01/ PY - 1998 DA - 1998 Oct 01 SP - 3325 EP - 3329 VL - 161 IS - 7 SN - 0022-1767, 0022-1767 KW - Antibodies, Blocking KW - 0 KW - Immune Sera KW - Receptors, Antigen, T-Cell, alpha-beta KW - Receptors, IgG KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Antibodies, Blocking -- pharmacology KW - Mice, Inbred C57BL KW - Cell Differentiation -- genetics KW - Mice KW - Immune Sera -- pharmacology KW - Cell Differentiation -- immunology KW - T-Lymphocyte Subsets -- cytology KW - Thymus Gland -- cytology KW - Receptors, IgG -- immunology KW - Receptors, IgG -- metabolism KW - Killer Cells, Natural -- cytology KW - T-Lymphocyte Subsets -- metabolism KW - Thymus Gland -- immunology KW - Receptors, Antigen, T-Cell, alpha-beta -- antagonists & inhibitors KW - Stem Cells -- immunology KW - Stem Cells -- cytology KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor -- immunology KW - Receptors, Antigen, T-Cell, alpha-beta -- genetics KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73936415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CD16+cross-linking+blocks+rearrangement+of+the+TCR+beta+locus+and+development+of+alpha+beta+T+cells+and+induces+development+of+NK+cells+from+thymic+progenitors.&rft.au=Durum%2C+S+K%3BLee%2C+C+K%3BGeiman%2C+T+M%3BMurphy%2C+W+J%3BMuegge%2C+K&rft.aulast=Durum&rft.aufirst=S&rft.date=1998-10-01&rft.volume=161&rft.issue=7&rft.spage=3325&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. AN - 73923474; 9753292 AB - Stimulation of beta3-adrenoceptors by selective agonists improves insulin action and stimulates energy metabolism in various rodent models of obesity and type 2 diabetes. Whether selective beta3-adrenoceptor stimulation exerts metabolic actions in humans remains to be proven. The effects of a highly selective beta3-adrenoceptor agonist on insulin action, energy metabolism, and body composition were assessed in 14 healthy young lean male volunteers (age 22.5 +/- 3.3 years, 15 +/- 5% body fat [mean +/- SD]) randomly assigned to 8 weeks of treatment with either 1,500 mg/day of CL 316,243 (n = 10) or placebo (n = 4). Insulin-mediated glucose disposal (IMGD), nonoxidative glucose disposal (NOGD), oxidative glucose disposal (OGD) (indirect calorimetry), and splanchnic glucose output (SGO; beta3-[H3]glucose) were determined during a 100-min hyperinsulinemic-euglycemic glucose clamp (40 mU x m(-2) x min(-1)) before and after 4 and 8 weeks of treatment. The 24-h energy expenditure (24-EE), 24-h respiratory quotient (24-RQ), and the oxidation rates of fat and carbohydrate were determined in a respiratory chamber before and after 8 weeks. After 4 weeks, treatment with CL 316,243 increased IMGD (+45%, P < 0.01) in a plasma concentration-dependent manner (r = 0.76, P < 0.02). This effect was due to an 82% increase in NOGD (P < 0.01), while OGD and SGO remained unchanged. The effects on insulin action were markedly diminished after 8 weeks; this was significantly related to an unexpected decline in the plasma concentrations of CL 316,243 (-36%, P = 0.08). At this time, 24-RQ was lowered (P < 0.001), corresponding to a 23% increase in fat oxidation (P < 0.01) and a 17% decrease in carbohydrate oxidation (P = 0.05). The 24-EE after 8 weeks did not differ from baseline, and there was no change in body weight or body composition. Plasma concentrations of glucose, insulin, and leptin were unaffected by treatment, while free fatty acid concentrations increased by 41% (P < 0.05), again linearly with the achieved plasma concentration of CL 316,243 (r = 0.67, P < 0.05). Treatment with CL 316,243 had no effect on heart rate or blood pressure and caused no cases of tremors. We conclude that treatment of lean male subjects with CL 316,243 increases insulin action and fat oxidation, both in a plasma concentration-dependent manner. This is the first study to demonstrate unequivocal metabolic effects of a highly selective beta3-adrenoceptor agonist in humans. JF - Diabetes AU - Weyer, C AU - Tataranni, P A AU - Snitker, S AU - Danforth, E AU - Ravussin, E AD - Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. cweyer@phx.niddk.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1555 EP - 1561 VL - 47 IS - 10 SN - 0012-1797, 0012-1797 KW - Adrenergic beta-Agonists KW - 0 KW - Blood Glucose KW - Dioxoles KW - Fatty Acids, Nonesterified KW - Insulin KW - Leptin KW - Proteins KW - disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate KW - 138908-40-4 KW - Abridged Index Medicus KW - Index Medicus KW - Oxidation-Reduction KW - Body Weight KW - Double-Blind Method KW - Blood Glucose -- metabolism KW - Humans KW - Glucose Clamp Technique KW - Adult KW - Body Composition KW - Fatty Acids, Nonesterified -- blood KW - Energy Metabolism KW - Proteins -- metabolism KW - Male KW - Adrenergic beta-Agonists -- pharmacology KW - Dioxoles -- adverse effects KW - Dioxoles -- blood KW - Insulin -- blood KW - Insulin -- pharmacology KW - Dioxoles -- pharmacology KW - Lipid Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73923474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increase+in+insulin+action+and+fat+oxidation+after+treatment+with+CL+316%2C243%2C+a+highly+selective+beta3-adrenoceptor+agonist+in+humans.&rft.au=Weyer%2C+C%3BTataranni%2C+P+A%3BSnitker%2C+S%3BDanforth%2C+E%3BRavussin%2C+E&rft.aulast=Weyer&rft.aufirst=C&rft.date=1998-10-01&rft.volume=47&rft.issue=10&rft.spage=1555&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-09 N1 - Date created - 1998-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct convective delivery of macromolecules to peripheral nerves. AN - 73913435; 9761055 AB - Although many macromolecules have treatment potential for peripheral nerve disease, clinical use of these agents has been restricted because of limitations of delivery including systemic toxicity, heterogeneous dispersion, and inadequate distribution. In an effort to overcome these obstacles, the authors examined the use of convection to deliver and distribute macromolecules into peripheral nerves. For convective delivery, the authors used a gas-tight, noncompliant system that provided continuous flow through a small silica cannula (inner diameter 100 microm, outer diameter 170 microm) inserted into a peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and 80 microl) of 14C-labeled (nine nerves) or gadolinium-labeled (two nerves) albumin were infused unilaterally or bilaterally into the tibial nerves of six primates (Macaca mulatta) at 0.5 microl/minute. The volume of distribution (Vd), percentage recovery, and delivery homogeneity were determined using quantitative autoradiography, an imaging program developed by the National Institutes of Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K) analysis. One animal that was infused bilaterally with gadolinium-bound albumin (40 microl to each nerve) underwent MR imaging and was observed for 16 weeks after infusion. The Vd increased with the Vi in a logarithmic fashion. The mean Vd/Vi ratio over all Vi was 3.7+/-0.8 (mean+/-standard deviation). The concentration across the perfused region was homogeneous (K=-1.07). The infusate, which was limited circumferentially by the epineurium, followed the parallel arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm). Recovery of radioactivity was 75.8+/-9%. No neurological deficits arose from infusion. Convective delivery of macromolecules to peripheral nerves is safe and reliable. It overcomes obstacles associated with current delivery methods and allows selective regional delivery of putative therapeutic agents to long sections of nerve. This technique should permit the development of new treatments for numerous types of peripheral nerve lesions. JF - Journal of neurosurgery AU - Lonser, R R AU - Weil, R J AU - Morrison, P F AU - Governale, L S AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 610 EP - 615 VL - 89 IS - 4 SN - 0022-3085, 0022-3085 KW - Carbon Radioisotopes KW - 0 KW - Contrast Media KW - Macromolecular Substances KW - Radiopharmaceuticals KW - Serum Albumin KW - Silicon Dioxide KW - 7631-86-9 KW - Gadolinium KW - AU0V1LM3JT KW - Abridged Index Medicus KW - Index Medicus KW - Magnetic Resonance Imaging KW - Nerve Fibers -- drug effects KW - Animals KW - Axons -- drug effects KW - Reproducibility of Results KW - Safety KW - Nerve Fibers -- metabolism KW - Catheterization -- instrumentation KW - Tissue Distribution KW - Autoradiography KW - Peripheral Nervous System Diseases -- drug therapy KW - Radionuclide Imaging KW - Equipment Design KW - Infusion Pumps KW - Axons -- metabolism KW - Follow-Up Studies KW - Macaca mulatta KW - Serum Albumin -- administration & dosage KW - Drug Delivery Systems -- instrumentation KW - Tibial Nerve -- metabolism KW - Tibial Nerve -- drug effects KW - Tibial Nerve -- diagnostic imaging KW - Serum Albumin -- pharmacokinetics KW - Drug Delivery Systems -- methods KW - Tibial Nerve -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73913435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+convective+delivery+of+macromolecules+to+peripheral+nerves.&rft.au=Lonser%2C+R+R%3BWeil%2C+R+J%3BMorrison%2C+P+F%3BGovernale%2C+L+S%3BOldfield%2C+E+H&rft.aulast=Lonser&rft.aufirst=R&rft.date=1998-10-01&rft.volume=89&rft.issue=4&rft.spage=610&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 - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Neurosurg. 1999 Mar;90(3):610-1 [10067944] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of human cytochrome P450 1A2 by flavones: a molecular modeling study. AN - 70129207; 9853678 AB - Cytochrome P450 1A2 metabolizes a number of important drugs, procarcinogens, and endogenous compounds. Several flavones, a class of phytochemicals consumed in the human diet, have been shown to differentially inhibit human P450 1A2-mediated methoxyresorufin demethylase. A molecular model of this P450 was constructed in order to elucidate the molecular basis of the P450-flavone interaction. Flavone and its 3,5,7-trihydroxy and 3,5,7-trimethoxy derivatives were docked into the active site to assess their mode of binding. The site is hydrophobic and includes several residues that hydrogen bond with substituents on the flavone nucleus. The binding interactions of these flavones in the modeled active side are consistent with their relative inhibitory potentials, namely 3,5,7-trihydroxylflavone > flavone > 3,5,7-trimethoxylflavone, toward P450 1A2-mediated methoxyresorufin demethylation. JF - Journal of protein chemistry AU - Dai, R AU - Zhai, S AU - Wei, X AU - Pincus, M R AU - Vestal, R E AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 643 EP - 650 VL - 17 IS - 7 SN - 0277-8033, 0277-8033 KW - Cytochrome P-450 CYP1A2 Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Index Medicus KW - Rats KW - Animals KW - Sequence Alignment KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Models, Chemical KW - Amino Acid Sequence KW - Substrate Specificity KW - Binding Sites KW - Enzyme Inhibitors -- pharmacology KW - Flavonoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70129207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+chemistry&rft.atitle=Inhibition+of+human+cytochrome+P450+1A2+by+flavones%3A+a+molecular+modeling+study.&rft.au=Dai%2C+R%3BZhai%2C+S%3BWei%2C+X%3BPincus%2C+M+R%3BVestal%2C+R+E%3BFriedman%2C+F+K&rft.aulast=Dai&rft.aufirst=R&rft.date=1998-10-01&rft.volume=17&rft.issue=7&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Journal+of+protein+chemistry&rft.issn=02778033&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 - Effect of glutathione depletion and metallothionein gene expression on arsenic-induced cytotoxicity and c-myc expression in vitro. AN - 70128204; 9848127 AB - Arsenic exposure is clearly linked to human cancer. In rodent cells, arsenic has been reported to induce aberrant gene expression, including activation of the proto-oncogene c-myc. Abnormal or altered expression of such oncogenes can be involved in the acquisition of a malignant phenotype. Although its mechanism of action is unclear, arsenic is known to exert at least some of its toxic effects through interaction with sulfhydryl groups, and the non-protein sulfhydryl glutathione (GSH) appears to play an important role in detoxication of arsenic. Similarly, metallothionein (MT), a metal-binding protein with high sulfhydryl content, often functions in defense against metal-induced or oxidative cellular injury. Therefore, we examined the relationship among GSH, MT gene expression, and arsenic-induced toxicity or c-myc expression in cultured rat myoblast (L6) cells. In initial toxicity studies, arsenic was used in both the trivalent (arsenite) and pentavalent (arsenate) forms. The role of GSH was studied by pretreating cells with L-buthionine sulfoximine (BSO), which induces a marked depletion of GSH. In vitro exposure of L6 cells to BSO (1 to 25 microM) resulted in dose-dependent decreases in GSH. GSH depletion sensitized cells to both arsenite and arsenate. Zinc pretreatment, at levels which highly activated MT expression, had no effect on arsenite-induced cytotoxicity. Arsenite (1 microM) alone modestly increased c-myc expression from 1 to 4 h after treatment (maximum of 2.0-fold over control). After GSH depletion cells responded to arsenite exposure with much larger increases in c-myc transcription (3.2-fold over control). Zinc pretreatment had no reductive effect on arsenite-induced c-myc expression despite markedly activating the MT gene. Thus, it appears that the cellular levels of GSH, but not MT gene expression, play an important role in resistance to arsenic toxicity and aberrant gene activation. Moreover, depletion of GSH enhances arsenic-induced proto-oncogene activation, which might contribute to subsequent transformation. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Shimizu, M AU - Hochadel, J F AU - Fulmer, B A AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 204 EP - 211 VL - 45 IS - 2 SN - 1096-6080, 1096-6080 KW - Arsenates KW - 0 KW - Arsenites KW - Proto-Oncogene Proteins c-myc KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 KW - sodium arsenate KW - 7631-89-2 KW - Metallothionein KW - 9038-94-2 KW - Glutathione KW - GAN16C9B8O KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Rats KW - Animals KW - Cell Line KW - Gene Expression -- drug effects KW - Arsenic -- toxicity KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Metallothionein -- physiology KW - Arsenates -- toxicity KW - Glutathione -- deficiency KW - Proto-Oncogene Proteins c-myc -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70128204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+glutathione+depletion+and+metallothionein+gene+expression+on+arsenic-induced+cytotoxicity+and+c-myc+expression+in+vitro.&rft.au=Shimizu%2C+M%3BHochadel%2C+J+F%3BFulmer%2C+B+A%3BWaalkes%2C+M+P&rft.aulast=Shimizu&rft.aufirst=M&rft.date=1998-10-01&rft.volume=45&rft.issue=2&rft.spage=204&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 - 1999-01-15 N1 - Date created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - The United States-Japan Cooperative Cancer Research Program seminar on "Cell cycle control and cancer". AN - 70115338; 9849591 JF - Japanese journal of cancer research : Gann AU - Thorgeirsson, S S AU - Okayama, H Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1093 EP - 1097 VL - 89 IS - 10 KW - Cyclins KW - 0 KW - Retinoblastoma Protein KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - United States KW - Cyclins -- physiology KW - Replication Origin KW - Humans KW - Retinoblastoma Protein -- metabolism KW - Cell Nucleus -- physiology KW - Tumor Suppressor Protein p53 -- metabolism KW - Japan KW - Neoplasms -- pathology KW - Neoplasms -- physiopathology KW - Cell Cycle KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70115338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=The+United+States-Japan+Cooperative+Cancer+Research+Program+seminar+on+%22Cell+cycle+control+and+cancer%22.&rft.au=Thorgeirsson%2C+S+S%3BOkayama%2C+H&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1998-10-01&rft.volume=89&rft.issue=10&rft.spage=1093&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-29 N1 - Date created - 1998-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [The current status of drug abuse and dependence in Japan]. AN - 70100680; 9844378 JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Wada, K AD - Div. of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, NCNP, Chiba, Japan. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 587 EP - 596 VL - 33 IS - 5 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Japan -- epidemiology KW - Age Factors KW - Iran -- ethnology KW - Humans KW - Korea -- ethnology KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Social Problems -- statistics & numerical data KW - Crime -- statistics & numerical data KW - Substance-Related Disorders -- ethnology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70100680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+current+status+of+drug+abuse+and+dependence+in+Japan%5D.&rft.au=Wada%2C+K&rft.aulast=Wada&rft.aufirst=K&rft.date=1998-10-01&rft.volume=33&rft.issue=5&rft.spage=587&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 - 1999-02-16 N1 - Date created - 1999-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibroblast growth factor-mediated angiogenesis for the treatment of ischemia. Lessons learned from experimental models and early human experience. AN - 70095224; 9835778 AB - Fibroblast growth factors (FGFs) are a family of nearly twenty heparin-binding growth factors. They are widely distributed throughout the body, but their activity is tightly controlled. This review will focus on fibroblast growth factor-1/FGF-1) and fibroblast growth factor-2 (FGF-2) which have been studied extensively in vitro and in vivo. These two growth factors stimulate the proliferation of cells of mesenchymal origin, including the three principal vascular cell types: fibroblasts, endothelial cells and smooth muscle cells. The molecular characteristics of these growth factors, their receptors, distribution, function, pharmacokinetics, hemodynamic effects and toxicity are reviewed herein. The experimental evidence for the potential for FGFs as therapeutic agents for the treatment of progressive myocardial ischemia, acute myocardial ischemia, and peripheral limb ischemia is also analyzed. It is not known to what extent the results of animal studies can be extrapolated to humans with ischemic cardiovascular disease. Clinical trials have been initiated, and there is a growing hope that the pharmacologic use of growth factors will represent a viable therapeutic alternative for patients with ischemic cardiovascular disease. JF - Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology AU - Gonçalves, L M AD - Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1518, USA. goncalvl@gwgate.nhlbi.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - II11 EP - II20 VL - 17 Suppl 2 SN - 0870-2551, 0870-2551 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Drug Evaluation KW - Animals KW - Humans KW - Drug Evaluation, Preclinical KW - Ischemia -- drug therapy KW - Myocardial Ischemia -- drug therapy KW - Ischemia -- physiopathology KW - Disease Models, Animal KW - Neovascularization, Physiologic -- drug effects KW - Fibroblast Growth Factors -- pharmacology KW - Extremities -- blood supply KW - Myocardial Ischemia -- physiopathology KW - Fibroblast Growth Factors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70095224?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Revista+portuguesa+de+cardiologia+%3A+orgao+oficial+da+Sociedade+Portuguesa+de+Cardiologia+%3D+Portuguese+journal+of+cardiology+%3A+an+official+journal+of+the+Portuguese+Society+of+Cardiology&rft.atitle=Fibroblast+growth+factor-mediated+angiogenesis+for+the+treatment+of+ischemia.+Lessons+learned+from+experimental+models+and+early+human+experience.&rft.au=Gon%C3%A7alves%2C+L+M&rft.aulast=Gon%C3%A7alves&rft.aufirst=L&rft.date=1998-10-01&rft.volume=17+Suppl+2&rft.issue=&rft.spage=II11&rft.isbn=&rft.btitle=&rft.title=Revista+portuguesa+de+cardiologia+%3A+orgao+oficial+da+Sociedade+Portuguesa+de+Cardiologia+%3D+Portuguese+journal+of+cardiology+%3A+an+official+journal+of+the+Portuguese+Society+of+Cardiology&rft.issn=08702551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of resistance against doxorubicin by a newly developed compound, oxalyl bis(N-phenyl)hydroxamic acid in vitro. AN - 70093307; 9840730 AB - A drug-resistant cell line (EAC/Dox) was developed by repeated exposure of Ehrlich ascites carcinoma cells to Doxorubicin (Dox) in vivo in male albino Swiss mice (6-8 weeks old). The weekly i.p. injections of Dox to mice (2 or 4 mg/kg/week for 4 months) gave rise to Dox-resistant cell line EAC/Dox, which displayed typical multidrug resistant (MDR) features of cross-resistance to a number of structurally and functionally unrelated drugs like doxorubicin, vinblastine and cisplatin. Moreover, the EAC/Dox cell line had lower drug accumulation than drug-sensitive (EAC/S) cells. Study of Western blots and immunofluorescence revealed that P-glycoprotein 170 kDa (P-gp) was absent in EAC/Dox cells. The drug resistance appeared to be due to the presence of a higher level of reduced glutathione (GSH) and glutathione S-transferase (GST) in EAC/Dox cells than in drug-sensitive (EAC/S) cells. The two structurally similar hydroxamic acid derivatives, i.e. oxalyl bis(N-phenyl)hydroxamic acid (X1) and succinyl bis(N-phenyl)hydroxamic acid (X2), having very low in vitro toxicity (IC50 value 250 microg/ ml), were investigated for their efficacy to reverse MDR. The compound X1 was able to reverse the effect of MDR and reduce GST in EAC/Dox cells. The compound X2 had no ability to reverse the effect of MDR. Further study on the mechanism of glutathione depletion and the resistance modifying property of X1 on other cell lines is warranted. JF - Anti-cancer drugs AU - Choudhuri, S K AU - Chatterjee, A AD - Department of Biochemistry, Chittaranjan National Cancer Institute (Research Wing), Calcutta, India. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 825 EP - 832 VL - 9 IS - 9 SN - 0959-4973, 0959-4973 KW - Antineoplastic Agents KW - 0 KW - Benzeneacetamides KW - Calcium Channel Blockers KW - Hydroxamic Acids KW - Oxalates KW - P-Glycoprotein KW - oxalyl bis(N-phenyl)hydroxamic acid KW - Doxorubicin KW - 80168379AG KW - Verapamil KW - CJ0O37KU29 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Drug Interactions KW - HeLa Cells KW - Glutathione -- metabolism KW - Humans KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Glutathione Transferase -- metabolism KW - Mice KW - Drug Resistance, Neoplasm KW - Verapamil -- pharmacology KW - Drug Resistance, Multiple KW - Carcinoma, Ehrlich Tumor -- metabolism KW - Calcium Channel Blockers -- pharmacology KW - P-Glycoprotein -- metabolism KW - Male KW - Doxorubicin -- pharmacokinetics KW - Oxalates -- pharmacology KW - Doxorubicin -- pharmacology KW - Antineoplastic Agents -- pharmacokinetics KW - Hydroxamic Acids -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70093307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Reversal+of+resistance+against+doxorubicin+by+a+newly+developed+compound%2C+oxalyl+bis%28N-phenyl%29hydroxamic+acid+in+vitro.&rft.au=Choudhuri%2C+S+K%3BChatterjee%2C+A&rft.aulast=Choudhuri&rft.aufirst=S&rft.date=1998-10-01&rft.volume=9&rft.issue=9&rft.spage=825&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of human cytochrome P450 3A4 and 3A5 in the metabolism of taxotere and its derivatives: enzyme specificity, interindividual distribution and metabolic contribution in human liver. AN - 70086661; 9825831 AB - Taxotere, a promising anticancer agent, is metabolized almost exclusively in liver and excreted from bile in all species. To determine which cytochrome P450 is involved in taxotere biotransformation, 11 cDNA-expressed human cytochrome P450s were examined for their activity in the metabolism of taxotere and its derivatives. Of all P450s, cytochrome P450 3A4 and 3A5 were the most active for the oxidation of taxotere to the primary metabolite RPR104952 and for subsequent oxidation of RPR104952 to RPR111059 and RPR111026. RP70617, an epimer of taxotere was also metabolized by both P450 3A enzymes to form metabolite XII. The activity of 3A4/5 enzymes for these substrates was 4-50-fold greater than the other P450s examined. The Kms of 3A4 and 3A5 for taxotere were 0.91 and 9.28 microM, and Vmax for the formation of RPR104952 were 1.17 and 1.36 m(-1), respectively. The contribution of the 3A enzyme complex to the metabolism of taxotere in human livers from 21 individuals was assessed with the inhibitory monoclonal antibody and ranged from 64-93%. The primary oxidative metabolism of taxotere by human liver microsomes was well correlated with 3A4-dependent reactions for testosterone 6beta-hydroxylation (r2 = 0.84), taxol aromatic hydroxylation (r2 = 0.67) and aflatoxin B1 3alpha-hydroxylation (r2 = 0.63); whereas a poor correlation was found for reactions specifically catalysed by other P450s (all r2 < or =O.17). The extent of taxotere metabolism also closely correlated with levels of 3A4 enzyme in human livers quantified with immunoblot monoclonal antibody (r2 = 0.61). These results demonstrate that the P450 3A4 and 3A5 enzymes are major determinants in taxotere oxidation and suggest that care must be taken when administering this drug with other drugs that are also substrates for these enzymes. JF - Pharmacogenetics AU - Shou, M AU - Martinet, M AU - Korzekwa, K R AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. magang_shou@merck.com Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 391 EP - 401 VL - 8 IS - 5 SN - 0960-314X, 0960-314X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Recombinant Proteins KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Oxidation-Reduction KW - Antineoplastic Agents, Phytogenic -- chemistry KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Humans KW - Microsomes, Liver -- enzymology KW - Adult KW - Aged KW - Middle Aged KW - Substrate Specificity KW - Adolescent KW - Antineoplastic Agents, Phytogenic -- metabolism KW - Paclitaxel -- chemistry KW - Paclitaxel -- metabolism KW - Liver -- enzymology KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Paclitaxel -- analogs & derivatives KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70086661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+human+cytochrome+P450+3A4+and+3A5+in+the+metabolism+of+taxotere+and+its+derivatives%3A+enzyme+specificity%2C+interindividual+distribution+and+metabolic+contribution+in+human+liver.&rft.au=Shou%2C+M%3BMartinet%2C+M%3BKorzekwa%2C+K+R%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1998-10-01&rft.volume=8&rft.issue=5&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine. AN - 70085945; 9829290 AB - 1. There is a large body of evidence indicating that fenfluramines damage brain serotonin neurons in animals. 2. Little is known about potential adverse neuropsychiatric consequences in humans associated with use of fenfluramines that could potentially be related to serotonergic dysfunction. 3. The authors now report numerous cases of severe and, sometimes persistent, neuropsychiatric syndromes associated with fenfluramine use. 4. Thirty one representative cases are presented and summarized in table form. 5. Several of the cases presented suggest long-lasting deleterious effects of fenfluramines on brain serotonin function. 6. Clinicians should be vigilant for disorders of mood, anxiety, cognitive function and impulse control in patients previously exposed to fenfluramines. JF - Progress in neuro-psychopharmacology & biological psychiatry AU - McCann, U D AU - Eligulashvili, V AU - Ricaurte, G A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1087 EP - 1102 VL - 22 IS - 7 SN - 0278-5846, 0278-5846 KW - Appetite Depressants KW - 0 KW - Serotonin Receptor Agonists KW - Fenfluramine KW - 2DS058H2CF KW - Phentermine KW - C045TQL4WP KW - Dexfenfluramine KW - E35R3G56OV KW - Index Medicus KW - Drug Therapy, Combination KW - Memory Disorders -- chemically induced KW - Anxiety KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Cognition Disorders -- chemically induced KW - Affect KW - Adolescent KW - Male KW - Female KW - Serotonin Receptor Agonists -- adverse effects KW - Fenfluramine -- adverse effects KW - Appetite Depressants -- adverse effects KW - Mental Disorders -- chemically induced KW - Dexfenfluramine -- adverse effects KW - Phentermine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70085945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.atitle=Adverse+neuropsychiatric+events+associated+with+dexfenfluramine+and+fenfluramine.&rft.au=McCann%2C+U+D%3BEligulashvili%2C+V%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1998-10-01&rft.volume=22&rft.issue=7&rft.spage=1087&rft.isbn=&rft.btitle=&rft.title=Progress+in+neuro-psychopharmacology+%26+biological+psychiatry&rft.issn=02785846&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 - Estrogen-induced hepatic toxicity and hepatic cancer: differences between two closely related hamster species. AN - 70073399; 9831364 AB - Estrogen is known to affect hepatobiliary function; however, it is unusual for high serum levels of estrogen to actually result in clinically detectable hyperbilirubinemia. Women affected by cholestatic jaundice during pregnancy share this genetic susceptibility with two Cricetulus hamsters, the Armenian hamster (Cricetulus migratorius) and the Chinese hamster (Cricetulus griseus). Nevertheless, the pathophysiologic process responsible for this estrogen induced icterus may be different in women and hamsters. The present study compares various facets of estrogen-induced icterus in these two closely related hamsters. Hamsters were injected with various estrogens and the acute and chronic effects on liver were monitored by measuring changes in serum constituents and by observing changes in hepatic structure as seen grossly and by light and electron microscopy. In previous studies, hepatic tumors developed in most Armenian hamsters after chronic estrogen treatment, but in the present study, the livers of Chinese hamsters were remarkably free of neoplastic change under similar conditions. Also, when compared with the responses in the Armenian hamsters, signs of hepatic destruction and regeneration were less prevalent in estrogen-treated Chinese hamsters, and they were less susceptible to the effects of estrogen (because larger doses of estrogen were required to produce icterus and the bilirubin levels were lower and of shorter duration). In contrast to the findings in Armenian hamsters, bile canaliculi were severely affected in livers of estrogen-treated Chinese hamsters, and hepatic microvesicular steatosis, indicative of an unusual lipodystrophy caused by estrogen, was prominent. An additional lesion peculiar to the Chinese hamster was striking sinusoidal dilatation, which may be analogous to the oral contraceptive-induced sinusoidal dilatation in humans. Although these two hamster species are genetically similar, the genes activated by the estrogen receptor show remarkable heterogeneity when their respective livers are examined. Comparisons within these species may provide information about the specific gene activation responsible for particular pathologic events. JF - Liver AU - Coe, J E AU - Ishak, K G AU - Ross, M J AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 343 EP - 351 VL - 18 IS - 5 SN - 0106-9543, 0106-9543 KW - Estrogens KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Mifepristone KW - 320T6RNW1F KW - Diethylstilbestrol KW - 731DCA35BT KW - Zeranol KW - 76LO2L2V39 KW - Medroxyprogesterone Acetate KW - C2QI4IOI2G KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Tamoxifen -- toxicity KW - Animals KW - Diethylstilbestrol -- toxicity KW - Inclusion Bodies -- drug effects KW - Inclusion Bodies -- ultrastructure KW - Zeranol -- toxicity KW - Mifepristone -- toxicity KW - Bilirubin -- blood KW - Species Specificity KW - Female KW - Male KW - Cricetinae KW - Medroxyprogesterone Acetate -- toxicity KW - Liver -- pathology KW - Liver Neoplasms, Experimental -- pathology KW - Cricetulus KW - Liver -- drug effects KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Adenoma, Liver Cell -- pathology KW - Adenoma, Liver Cell -- chemically induced KW - Estrogens -- toxicity KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70073399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver&rft.atitle=Estrogen-induced+hepatic+toxicity+and+hepatic+cancer%3A+differences+between+two+closely+related+hamster+species.&rft.au=Coe%2C+J+E%3BIshak%2C+K+G%3BRoss%2C+M+J&rft.aulast=Coe&rft.aufirst=J&rft.date=1998-10-01&rft.volume=18&rft.issue=5&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Liver&rft.issn=01069543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-22 N1 - Date created - 1999-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-deethylation in human liver. AN - 70070502; 9825829 AB - Human cytochrome P450 1A2 metabolizes a large number of common drugs and engages in carcinogen metabolism and activation. Baculovirus-expressed 1A2 was used to immunize mice producing hybridomas yielding monoclonal antibodies (MAbs). Three of 2050 clones assayed yielded the MAbs, MAb 26-7-5, MAb 951-5-1, MAb 1812-2-4, which were specific for 1A2 as assessed by enzyme-linked immunosorbent assay and immunoblots. The three MAbs inhibited 1A2-catalysed metabolism of phenacetin, 7-ethoxycoumarin, chlorzoxazone and phenanthrene by more than 85%. The MAbs were highly specific to 1A2 and did not inhibit 11 other human P450s. The phenancetin O-deethylation activity varied from 0.44-2.49 nmol/min/nmol P450 in eight human liver microsomes samples. MAb 26-7-5 inhibited 1A2-dependent phenacetin O-deethylation in these samples by 64-84% indicating the amount of 1A2 contribution to this reaction and in addition a role for other P450s in the O-deethylation. Independent analysis of recombinant human P450s showed that 1A1, 1A2, 2A6 and 2C19 exhibited phenacetin O-deethylation activity, with 1A1 and 1A2 being the most active followed by 2C19 and 2A6. Eight other P450s were inactive towards phenacetin O-deethylation. The role of different P450 in eight liver samples was analysed with specific individual inhibitory MAbs. Inhibitory antibodies to 1A2, 2C8/9/18/19, 2A6, 2D6, 2E1, and 1A1 were combinatorially added to the microsomes. The O-deethylation activity was inhibited by antibodies to 1A2 (64-84%), to 2C19 (4.6-20%) and to 2A6 (0-8.8%). The total activity inhibited by antibodies to P450 2E1, 2D6 and 1A1 was less than 4.5%, indicating a minor role for these P450s in phenancetin metabolism in human liver microsomes. Thus, 1A2, 2C 9 and 2A6 are the dominant P450s for phenacetin O-deethylation. These studies demonstrate the use of inhibitory MAbs to P450s for a simple and precise assessment of the quantitative role of each P450 in the metabolism of substrates, including drugs, carcinogens, mutagens, environmental chemicals and endobiotics. JF - Pharmacogenetics AU - Yang, T J AU - Sai, Y AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 375 EP - 382 VL - 8 IS - 5 SN - 0960-314X, 0960-314X KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 CYP1A2 Inhibitors KW - Cytochrome P-450 Enzyme Inhibitors KW - Isoenzymes KW - Phenanthrenes KW - phenanthrene KW - 448J8E5BST KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Phenacetin KW - ER0CTH01H9 KW - Index Medicus KW - Isoenzymes -- antagonists & inhibitors KW - Phenanthrenes -- metabolism KW - Antibody Specificity KW - Cytochrome P-450 CYP1A2 -- immunology KW - Microsomes, Liver -- metabolism KW - Humans KW - Isoenzymes -- immunology KW - Cytochrome P-450 Enzyme System -- immunology KW - Substrate Specificity KW - Antibodies, Monoclonal -- pharmacology KW - Liver -- enzymology KW - Phenacetin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitory+monoclonal+antibodies+to+human+cytochrome+P450+1A2%3A+analysis+of+phenacetin+O-deethylation+in+human+liver.&rft.au=Yang%2C+T+J%3BSai%2C+Y%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Yang&rft.aufirst=T&rft.date=1998-10-01&rft.volume=8&rft.issue=5&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Broad beneficial effects of cocaine abstinence reinforcement among methadone patients. AN - 70039077; 9803700 AB - Escalating reinforcement for sustained abstinence has been effective in treating cocaine abuse. Under this schedule, patients receive vouchers for cocaine-free urine samples; vouchers have monetary values that increase with the number of consecutive cocaine-free urine samples. Cocaine-abusing methadone patients were randomly assigned to receive vouchers for 12 weeks under (a) an escalating schedule (n = 20), (b) an escalating schedule with start-up bonuses (n = 20), or (c) a noncontingent schedule (n = 19). Start-up bonuses were designed to provide added reinforcement for initiating abstinence; however, they did not improve outcomes. Both contingent interventions significantly increased cocaine abstinence. In addition, the contingent interventions increased abstinence from opiates and decreased reports of cocaine craving. These results replicate the efficacy of cocaine abstinence reinforcement and show that it can have broad beneficial effects. JF - Journal of consulting and clinical psychology AU - Silverman, K AU - Wong, C J AU - Umbricht-Schneiter, A AU - Montoya, I D AU - Schuster, C R AU - Preston, K L AD - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. kpreston@irp.nida.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 811 EP - 824 VL - 66 IS - 5 SN - 0022-006X, 0022-006X KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Analysis of Variance KW - Methadone -- therapeutic use KW - Humans KW - Adult KW - Treatment Outcome KW - Narcotics -- therapeutic use KW - Substance Abuse Detection -- psychology KW - Longitudinal Studies KW - Time Factors KW - Male KW - Female KW - Reinforcement Schedule KW - Behavior Therapy -- standards KW - Token Economy KW - Opioid-Related Disorders -- complications KW - Opioid-Related Disorders -- rehabilitation KW - Behavior Therapy -- methods KW - Cocaine-Related Disorders -- complications KW - Cocaine-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70039077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+consulting+and+clinical+psychology&rft.atitle=Broad+beneficial+effects+of+cocaine+abstinence+reinforcement+among+methadone+patients.&rft.au=Silverman%2C+K%3BWong%2C+C+J%3BUmbricht-Schneiter%2C+A%3BMontoya%2C+I+D%3BSchuster%2C+C+R%3BPreston%2C+K+L&rft.aulast=Silverman&rft.aufirst=K&rft.date=1998-10-01&rft.volume=66&rft.issue=5&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Journal+of+consulting+and+clinical+psychology&rft.issn=0022006X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-08 N1 - Date created - 1999-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. AN - 70035544; 9806162 AB - Risk of oral cancer has been associated with exposure to tobacco smoke, alcohol and with genetic predisposition. The aromatic amines and their metabolites, a class of carcinogens present in tobacco smoke, undergo metabolism (activation or detoxification) through an N- or O-acetylation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2. The genes that encode these enzymes, NAT1 and NAT2, have a variety of high and low activity alleles and we analyzed these genetic polymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1*11(9 bp deletion), NAT1*14 (G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles (NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We observed significantly increased risk [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05) for non-smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P < 0.05) for smokers, but these risks were not significantly different from each other. Thus, we did not observe that NAT1*10 alleles confer differential risk among smokers and non-smokers. NAT2 rapid acetylation genotype was not a significant risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polymorphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma among Japanese people. JF - Carcinogenesis AU - Katoh, T AU - Kaneko, S AU - Boissy, R AU - Watson, M AU - Ikemura, K AU - Bell, D A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1803 EP - 1807 VL - 19 IS - 10 SN - 0143-3334, 0143-3334 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Index Medicus KW - Gene Frequency KW - Polymorphism, Genetic KW - Humans KW - Aged KW - Pilot Projects KW - Genotype KW - Japan -- epidemiology KW - Smoking KW - Acetylation KW - Alleles KW - Base Sequence KW - Risk Factors KW - Middle Aged KW - Female KW - Male KW - Carcinoma, Squamous Cell -- enzymology KW - Carcinoma, Squamous Cell -- epidemiology KW - Mouth Neoplasms -- enzymology KW - Carcinoma, Squamous Cell -- genetics KW - Isoenzymes -- genetics KW - Arylamine N-Acetyltransferase -- metabolism KW - Mouth Neoplasms -- genetics KW - Mouth Neoplasms -- epidemiology KW - Isoenzymes -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70035544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+pilot+study+testing+the+association+between+N-acetyltransferases+1+and+2+and+risk+of+oral+squamous+cell+carcinoma+in+Japanese+people.&rft.au=Katoh%2C+T%3BKaneko%2C+S%3BBoissy%2C+R%3BWatson%2C+M%3BIkemura%2C+K%3BBell%2C+D+A&rft.aulast=Katoh&rft.aufirst=T&rft.date=1998-10-01&rft.volume=19&rft.issue=10&rft.spage=1803&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-19 N1 - Date created - 1998-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Natural killer cell activity in Hodgkin's disease patients undergoing radiation therapy or chemotherapy and radiation therapy. AN - 70033895; 9807678 AB - Natural killer (NK) cell activity in peripheral blood mononuclear cells (PBMCs) from patients with Hodgkin's disease was studied using 4 h 51Cr release assay and K562 cells as sensitive targets. PBMCs were obtained from 15 previously untreated patients at different stages of their disease. PBMCs were also obtained from 46 patients treated by radiation therapy or combined chemotherapy and radiation therapy. Twenty healthy age-matched volunteer donors were used as controls to the treated patients. For these normal donors the mean cytotoxicity was 24.8 +/- 5.67% at a 100:1 effector-target cell ratio; and 43.7 +/- 12.1% for the treated cancer patients. Fifteen healthy age-matched volunteer donors were used as controls to the untreated patients. The mean cytotoxicity for these normal donors was 20.8 +/- 3.61% at a 100:1 effector-target cell ratio; and 37.6 +/- 6.65% for the previously untreated cancer patients. The mean cytotoxicity for all 35 normal donors was 23.1 +/- 5.22% at a 100:1 effector-target cell ratio. Most treated patients (93.5%) had a complete response to therapy and a significant difference was found between the mean cytotoxicity of the whole group (46 treated patients), compared with controls (P < 0.001). A significant difference (P < 0.05) was also observed when the same 11 patients were studied before and after treatment. JF - Clinical and laboratory haematology AU - Pinel, M I AU - Esteves, E B AU - Rumjanek, V M AD - Department of Radiation Therapy, National Cancer Institute, Rio de Janeiro, Brazil. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 303 EP - 306 VL - 20 IS - 5 SN - 0141-9854, 0141-9854 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Adult KW - Treatment Outcome KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Radiotherapy -- adverse effects KW - Hodgkin Disease -- immunology KW - Killer Cells, Natural -- radiation effects KW - Hodgkin Disease -- therapy KW - Killer Cells, Natural -- drug effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70033895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+laboratory+haematology&rft.atitle=Natural+killer+cell+activity+in+Hodgkin%27s+disease+patients+undergoing+radiation+therapy+or+chemotherapy+and+radiation+therapy.&rft.au=Pinel%2C+M+I%3BEsteves%2C+E+B%3BRumjanek%2C+V+M&rft.aulast=Pinel&rft.aufirst=M&rft.date=1998-10-01&rft.volume=20&rft.issue=5&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Clinical+and+laboratory+haematology&rft.issn=01419854&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-01 N1 - Date created - 1999-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deficient expression of mRNA for the putative inductive factor bone morphogenetic protein-7 in chemically initiated rat nephroblastomas. AN - 70027429; 9808158 AB - Wilms' tumor, or nephroblastoma, arises from metanephric blastema and caricatures renal organogenesis. An alteration in at least one of the genes involved in control of renal differentiation is therefore a likely event in tumorigenesis, and indeed some of the genes involved in renal development, for example, hepatocyte growth factor (HGF) and its receptor c-met, the transcription factor Wilms' tumor gene (WT1), and transforming growth factor-beta family member bone morphogenetic protein (BMP)-7, have also been implicated in various models of tumorigenesis. In a comparison of mRNA expression patterns for these genes in normal rat embryonic or fetal kidney and nephroblastoma, we found that the patterns for HGF, met, and WT1 detected by in situ hybridization or ribonuclease protection assay (RPA) in the nephroblastomas were similar to those of normal developing kidney. BMP-7 expression, on the other hand, was lower in most tumors examined both by in situ hybridization and RPA than in normal tissues. This deficiency in a defined inductive factor that has been shown to function in renal tubulogenesis may play a role in tumorigenesis by allowing the accumulation of blastemal populations typical of nephroblastomas. JF - Molecular carcinogenesis AU - Higinbotham, K G AU - Karavanova, I D AU - Diwan, B A AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 53 EP - 61 VL - 23 IS - 2 SN - 0899-1987, 0899-1987 KW - Bmp7 protein, rat KW - 0 KW - Bone Morphogenetic Protein 7 KW - Bone Morphogenetic Proteins KW - DNA Primers KW - DNA-Binding Proteins KW - RNA, Messenger KW - Transcription Factors KW - Transforming Growth Factor beta KW - WT1 Proteins KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Hepatocyte Growth Factor -- genetics KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - Ribonucleases -- metabolism KW - Rats KW - Proto-Oncogene Proteins c-met -- genetics KW - Base Sequence KW - In Situ Hybridization KW - Kidney -- growth & development KW - Female KW - Male KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Wilms Tumor -- chemically induced KW - Wilms Tumor -- pathology KW - RNA, Messenger -- genetics KW - Bone Morphogenetic Proteins -- genetics KW - Wilms Tumor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70027429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deficient+expression+of+mRNA+for+the+putative+inductive+factor+bone+morphogenetic+protein-7+in+chemically+initiated+rat+nephroblastomas.&rft.au=Higinbotham%2C+K+G%3BKaravanova%2C+I+D%3BDiwan%2C+B+A%3BPerantoni%2C+A+O&rft.aulast=Higinbotham&rft.aufirst=K&rft.date=1998-10-01&rft.volume=23&rft.issue=2&rft.spage=53&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 - 1998-11-19 N1 - Date created - 1998-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adduct levels associated with p53 induction and delay of MCF-7 cells in S phase after exposure to benzo[g]chrysene dihydrodiol epoxide enantiomers. AN - 70026869; 9808165 AB - Optically active isomers of a mammary carcinogen, anti-benzo[g]chrysene 11, 12-dihydrodiol 13, 14-epoxide, react to different extents with DNA and generate DNA adducts that differ in their stereochemistry. In the study reported here, the effect of these two enantiomers on the progress of human breast carcinoma MCF-7 cells through the cell cycle was investigated. Each enantiomer caused the cells to accumulate in the S phase, but a higher dose of the benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide than of its enantiomer was required to induce this effect. Similarly, induction of p53 also required a higher dose of benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide. Postlabeling studies indicated that the latter enantiomer also caused less modification of MCF-7 cell DNA for a given level of exposure than did benzo[g]chrysene 11R, 12S-dihydrodiol 13S, 14R-epoxide. These results suggest that p53 induction and delay in the S phase are similarly related to DNA binding and that a level of binding of the order of 1 adduct per 10(5) nucleotides is associated with these effects. JF - Molecular carcinogenesis AU - Khan, Q A AU - Agarwal, R AU - Seidel, A AU - Frank, H AU - Vousden, K H AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 115 EP - 120 VL - 23 IS - 2 SN - 0899-1987, 0899-1987 KW - Chrysenes KW - 0 KW - DNA Adducts KW - Tumor Suppressor Protein p53 KW - benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide KW - 132832-27-0 KW - Index Medicus KW - Stereoisomerism KW - Tumor Cells, Cultured KW - Humans KW - Tumor Suppressor Protein p53 -- biosynthesis KW - S Phase KW - Chrysenes -- chemistry KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70026869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+adduct+levels+associated+with+p53+induction+and+delay+of+MCF-7+cells+in+S+phase+after+exposure+to+benzo%5Bg%5Dchrysene+dihydrodiol+epoxide+enantiomers.&rft.au=Khan%2C+Q+A%3BAgarwal%2C+R%3BSeidel%2C+A%3BFrank%2C+H%3BVousden%2C+K+H%3BDipple%2C+A&rft.aulast=Khan&rft.aufirst=Q&rft.date=1998-10-01&rft.volume=23&rft.issue=2&rft.spage=115&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 - 1998-11-19 N1 - Date created - 1998-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcoholic beverage preference and risks of alcohol-related medical consequences: a preliminary report from the National Longitudinal Alcohol Epidemiologic Survey. AN - 70021641; 9802527 AB - In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered in this preliminary report. JF - Alcoholism, clinical and experimental research AU - Chou, S P AU - Grant, B F AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1450 EP - 1455 VL - 22 IS - 7 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Risk KW - Alcoholism -- epidemiology KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Alcoholic Beverages -- adverse effects KW - Alcohol-Related Disorders -- etiology KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70021641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alcoholic+beverage+preference+and+risks+of+alcohol-related+medical+consequences%3A+a+preliminary+report+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Chou%2C+S+P%3BGrant%2C+B+F%3BDawson%2C+D+A&rft.aulast=Chou&rft.aufirst=S&rft.date=1998-10-01&rft.volume=22&rft.issue=7&rft.spage=1450&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 - 1999-02-04 N1 - Date created - 1999-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of magnetite particles on photoinduced and nonphotoinduced free radical processes in human erythrocytes. AN - 70004082; 9796445 AB - Magnetite (Fe3O4) encapsulated in polystyrene microspheres dramatically decreased the time for 50% hemolysis (t1/2) of human erythrocytes irradiated (lambda > 300 nm) in the presence of ketoprofen (0.1 mM). The magnetic microspheres were present at a very low concentration (0.002%) such that on average there was only one particle per four erythrocytes. No such effect was seen when nonmagnetic microspheres were employed or when the equivalent concentration of soluble iron (FeCl3) was present. A decrease in t1/2 was also observed when the magnetic microspheres were added after UVA/ketoprofen treatment or when they were present during hemolysis initiated by thermolysis of 2,2'-azobis(2-amidinopropane). These findings may be attributed to an increase in the membrane concentration of lipid radicals as a result of a magnetic field-induced increase in radicals escaping from triplet radical pairs. JF - Photochemistry and photobiology AU - Chignell, C F AU - Sik, R H AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, NC 27709, USA. chignell@niehs.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 598 EP - 601 VL - 68 IS - 4 SN - 0031-8655, 0031-8655 KW - Amidines KW - 0 KW - Chlorides KW - Ferric Compounds KW - Free Radicals KW - Oxidants KW - Oxides KW - 2,2'-azobis(2-amidinopropane) KW - 7381JDR72F KW - Ketoprofen KW - 90Y4QC304K KW - Iron KW - E1UOL152H7 KW - ferric chloride KW - U38V3ZVV3V KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Index Medicus KW - Hemolysis -- drug effects KW - Hot Temperature KW - Amidines -- pharmacology KW - Oxidants -- pharmacology KW - Humans KW - Free Radicals -- blood KW - Ferric Compounds -- pharmacology KW - Hemolysis -- radiation effects KW - Microspheres KW - Ketoprofen -- pharmacology KW - Erythrocytes -- drug effects KW - Ultraviolet Rays KW - Iron -- pharmacology KW - Erythrocytes -- radiation effects KW - Oxides -- pharmacology KW - Erythrocytes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70004082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+magnetite+particles+on+photoinduced+and+nonphotoinduced+free+radical+processes+in+human+erythrocytes.&rft.au=Chignell%2C+C+F%3BSik%2C+R+H&rft.aulast=Chignell&rft.aufirst=C&rft.date=1998-10-01&rft.volume=68&rft.issue=4&rft.spage=598&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 - 1998-11-30 N1 - Date created - 1998-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Screening cloned PCR fragments by restriction endonuclease finger-printing to obtain wild-type sequences. AN - 70002193; 9793631 JF - BioTechniques AU - Hagiwara, K AU - Freeman, A A AU - McMenamin, M G AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 554 EP - 5, 558 VL - 25 IS - 4 SN - 0736-6205, 0736-6205 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - SMAD4 protein, human KW - Smad4 Protein KW - Trans-Activators KW - DNA Restriction Enzymes KW - EC 3.1.21.- KW - Index Medicus KW - Polymerase Chain Reaction KW - Bacteria KW - Trans-Activators -- genetics KW - Humans KW - DNA-Binding Proteins -- genetics KW - Sequence Analysis, DNA KW - Mutation KW - Molecular Weight KW - DNA Restriction Enzymes -- metabolism KW - Cloning, Molecular -- methods KW - DNA Fingerprinting -- methods KW - Polymorphism, Single-Stranded Conformational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70002193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=Screening+cloned+PCR+fragments+by+restriction+endonuclease+finger-printing+to+obtain+wild-type+sequences.&rft.au=Hagiwara%2C+K%3BFreeman%2C+A+A%3BMcMenamin%2C+M+G%3BHarris%2C+C+C&rft.aulast=Hagiwara&rft.aufirst=K&rft.date=1998-10-01&rft.volume=25&rft.issue=4&rft.spage=554&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness. AN - 69999033; 9790159 AB - Of 30 patients with treatment-refractory affective illness, 10 showed a moderate to marked response to blind nimodipine monotherapy compared with placebo on the Clinical Global Impressions Scale. Fourteen inadequately responsive patients (3 unipolar [UP], 11 bipolar [BP]) were treated with the blind addition of carbamazepine. Carbamazepine augmentation of nimodipine converted four (29%) of the partial responders to more robust responders. Patients who showed an excellent response to the nimodipine-carbamazepine combination included individual patients with patterns of rapid cycling, ultradian cycling, UP recurrent brief depression, and one with BP type II depression. When verapamil was blindly substituted for nimodipine, two BP patients failed to maintain improvement but responded again to nimodipine and remained well with a blind transition to another dihydropyridine L-type calcium channel blocker (CCB), isradipine. Mechanistic implications of the response to the dihydropyridine L-type CCB nimodipine alone and in combination with carbamazepine are discussed. JF - Journal of clinical psychopharmacology AU - Pazzaglia, P J AU - Post, R M AU - Ketter, T A AU - Callahan, A M AU - Marangell, L B AU - Frye, M A AU - George, M S AU - Kimbrell, T A AU - Leverich, G S AU - Cora-Locatelli, G AU - Luckenbaugh, D AD - Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1272, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 404 EP - 413 VL - 18 IS - 5 SN - 0271-0749, 0271-0749 KW - Antimanic Agents KW - 0 KW - Calcium Channel Blockers KW - Carbamazepine KW - 33CM23913M KW - Nimodipine KW - 57WA9QZ5WH KW - Isradipine KW - YO1UK1S598 KW - Index Medicus KW - Isradipine -- adverse effects KW - Drug Therapy, Combination KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Isradipine -- administration & dosage KW - Middle Aged KW - Male KW - Female KW - Bipolar Disorder -- diagnosis KW - Nimodipine -- adverse effects KW - Depressive Disorder -- psychology KW - Antimanic Agents -- adverse effects KW - Carbamazepine -- adverse effects KW - Nimodipine -- administration & dosage KW - Antimanic Agents -- administration & dosage KW - Bipolar Disorder -- drug therapy KW - Calcium Channel Blockers -- adverse effects KW - Calcium Channel Blockers -- administration & dosage KW - Carbamazepine -- administration & dosage KW - Depressive Disorder -- diagnosis KW - Bipolar Disorder -- psychology KW - Depressive Disorder -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69999033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychopharmacology&rft.atitle=Nimodipine+monotherapy+and+carbamazepine+augmentation+in+patients+with+refractory+recurrent+affective+illness.&rft.au=Pazzaglia%2C+P+J%3BPost%2C+R+M%3BKetter%2C+T+A%3BCallahan%2C+A+M%3BMarangell%2C+L+B%3BFrye%2C+M+A%3BGeorge%2C+M+S%3BKimbrell%2C+T+A%3BLeverich%2C+G+S%3BCora-Locatelli%2C+G%3BLuckenbaugh%2C+D&rft.aulast=Pazzaglia&rft.aufirst=P&rft.date=1998-10-01&rft.volume=18&rft.issue=5&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychopharmacology&rft.issn=02710749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Psychopharmacol. 2012 Feb;32(1):146-8 [22217956] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic exposure to MPTP as a primate model of progressive parkinsonism: a pilot study with a free radical scavenger. AN - 69998560; 9784281 AB - The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease. In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117) as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity, recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be "trait" markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential "state" markers for reaching endpoint. The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotective agents appear warranted. JF - Experimental neurology AU - Blanchet, P J AU - Konitsiotis, S AU - Hyland, K AU - Arnold, L A AU - Pettigrew, K D AU - Chase, T N AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 214 EP - 222 VL - 153 IS - 2 SN - 0014-4886, 0014-4886 KW - Biomarkers KW - 0 KW - Free Radical Scavengers KW - Indans KW - Piperazines KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - OPC 14117 KW - 103233-65-4 KW - Biopterin KW - 22150-76-1 KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - sapropterin KW - EGX657432I KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Biopterin -- analogs & derivatives KW - Biomarkers -- cerebrospinal fluid KW - Animals KW - Homovanillic Acid -- cerebrospinal fluid KW - Macaca fascicularis KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Disease Models, Animal KW - Biopterin -- cerebrospinal fluid KW - Pilot Projects KW - 3,4-Dihydroxyphenylacetic Acid -- cerebrospinal fluid KW - Male KW - Female KW - Parkinson Disease, Secondary -- physiopathology KW - Free Radical Scavengers -- blood KW - Indans -- blood KW - Indans -- pharmacology KW - Parkinson Disease, Secondary -- cerebrospinal fluid KW - Motor Activity -- drug effects KW - Piperazines -- pharmacology KW - Piperazines -- blood KW - Free Radical Scavengers -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69998560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+exposure+to+MPTP+as+a+primate+model+of+progressive+parkinsonism%3A+a+pilot+study+with+a+free+radical+scavenger.&rft.au=Blanchet%2C+P+J%3BKonitsiotis%2C+S%3BHyland%2C+K%3BArnold%2C+L+A%3BPettigrew%2C+K+D%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1998-10-01&rft.volume=153&rft.issue=2&rft.spage=214&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 - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in serotonergic responsiveness during cocaine withdrawal in rats: similarities to major depression in humans. AN - 69994456; 9787882 AB - Withdrawal from long-term cocaine use is accompanied by symptoms resembling major depression. Because acute cocaine affects serotonin (5-HT) neurons, and 5-HT dysfunction is implicated in the pathophysiology of depression, we evaluated the effects to 5-HT agonists in rats withdrawn from repeated injections of cocaine (15 mg/kg i.p., b.i.d., 7 days) or saline. In the first study, prolactin (PRL) responses elicited by the 5-HT-releasing agent fenfluramine, the 5-HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT2A/2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were examined as indices of postsynaptic 5-HT receptor function. In a second study, specific responses induced by 8-OH-DPAT, namely inhibition of brain 5-HT synthesis and stimulation of feeding, were examined as correlates of 5-HT1A autoreceptor function. Prior treatment with cocaine did not modify fenfluramine-evoked PRL release; however, the PRL secretory response to 8-OH-DPAT was blunted and the PRL response to DOI was potentiated after chronic cocaine treatment. Cocaine exposure did not alter the inhibitory effect of 8-OH-DPAT on 5-HT synthesis. 8-OH-DPAT-induced feeding was influenced by prior cocaine, but this effect was secondary to pronounced baseline hyperphagia in the cocaine-treated group. These data indicate that withdrawal from chronic cocaine renders specific subpopulations of postsynaptic 5-HT1A receptors subsensitive and 5-HT2A/2C receptors supersensitive. No evidence for cocaine-induced changes in 5-HT1A autoreceptor responsiveness was found. A survey of the literature reveals similarities in the profile of 5-HT dysfunction between rats withdrawn from cocaine and humans diagnosed with depression. We propose that withdrawal from chronic cocaine in rats may serve as a useful animal model of depressive disorders. JF - Biological psychiatry AU - Baumann, M H AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/10/01/ PY - 1998 DA - 1998 Oct 01 SP - 578 EP - 591 VL - 44 IS - 7 SN - 0006-3223, 0006-3223 KW - Amphetamines KW - 0 KW - Dopamine Uptake Inhibitors KW - Serotonin Receptor Agonists KW - Serotonin Uptake Inhibitors KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - 8-Hydroxy-2-(di-n-propylamino)tetralin KW - 78950-78-4 KW - Prolactin KW - 9002-62-4 KW - 5-Hydroxytryptophan KW - C1LJO185Q9 KW - Cocaine KW - I5Y540LHVR KW - 4-iodo-2,5-dimethoxyphenylisopropylamine KW - OOM10GW9UE KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Prolactin -- blood KW - Fenfluramine -- pharmacology KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - 8-Hydroxy-2-(di-n-propylamino)tetralin -- pharmacology KW - Amphetamines -- pharmacology KW - 5-Hydroxytryptophan -- metabolism KW - Serotonin Uptake Inhibitors -- pharmacology KW - Feeding Behavior -- drug effects KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Serotonin -- physiology KW - Serotonin -- biosynthesis KW - Depressive Disorder -- psychology KW - Dopamine Uptake Inhibitors -- adverse effects KW - Substance Withdrawal Syndrome -- psychology KW - Depressive Disorder -- metabolism KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69994456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+serotonergic+responsiveness+during+cocaine+withdrawal+in+rats%3A+similarities+to+major+depression+in+humans.&rft.au=Baumann%2C+M+H%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1998-10-01&rft.volume=44&rft.issue=7&rft.spage=578&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results. AN - 69994369; 9788521 AB - Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded. JF - Journal of analytical toxicology AU - Cone, E J AU - Lange, R AU - Darwin, W D AD - Addiction Research Center, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 460 EP - 473 VL - 22 IS - 6 SN - 0146-4760, 0146-4760 KW - Diuretics KW - 0 KW - Sodium Chloride Symporter Inhibitors KW - Hydrochlorothiazide KW - 0J48LPH2TH KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Sodium Chloride Symporter Inhibitors -- pharmacology KW - Osmolar Concentration KW - Beverages KW - Humans KW - Hydrogen-Ion Concentration KW - Marijuana Smoking -- urine KW - Specific Gravity KW - False Negative Reactions KW - Hydrochlorothiazide -- pharmacology KW - Creatinine -- metabolism KW - Adult KW - Female KW - Male KW - Drinking KW - Marijuana Abuse -- urine KW - Cocaine-Related Disorders -- diagnosis KW - Drug Contamination KW - Marijuana Abuse -- diagnosis KW - Substance Abuse Detection -- methods KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69994369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=In+vivo+adulteration%3A+excess+fluid+ingestion+causes+false-negative+marijuana+and+cocaine+urine+test+results.&rft.au=Cone%2C+E+J%3BLange%2C+R%3BDarwin%2C+W+D&rft.aulast=Cone&rft.aufirst=E&rft.date=1998-10-01&rft.volume=22&rft.issue=6&rft.spage=460&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 completed - 1998-12-17 N1 - Date created - 1998-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiating new marijuana use from residual drug excretion in occasional marijuana users. AN - 69990329; 9788519 AB - Increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as new drug use rather than carryover from previous drug exposure. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. A specimen ratio of 1.5 or greater between two creatinine normalized positive urine cannabinoid tests was previously proposed as an indicator of new marijuana use. This approach has received wide attention for potential use in treatment and employee assistance programs associated with workplace drug testing. Unfortunately, there has been limited evaluation of the usefulness of this ratio under controlled-dosing conditions with marijuana smokers. A controlled clinical study was conducted to examine the excretion profile of creatinine and marijuana metabolites in a group of six marijuana users who smoked two different doses of marijuana over a 4-week period. A relative operating characteristic curve was constructed from sensitivity and specificity data for 26 different specimen ratios ranging from 0.1 to 2.0. The most accurate specimen ratio (85.4%) for differentiating new use from residual excretion was 0.5. Use of this ratio provided a sensitivity of 80.1%, a specificity of 90.2%, and 5.6% false-positive and 7.4% false-negative predictions. To substantiate the validity of the 0.5 specimen ratio, urine cannabinoid and creatinine data from a controlled clinical trial specifically addressing water dilution as a means of specimen adulteration were evaluated. Sensitivity, specificity, accuracy, and percent false-positive and percent false-negative predictions were 71.9%, 91.6%, 83.9%, 5.4%, and 10.7%, respectively. These data compared favorably with the results from the first clinical study, with the exception of slightly lower sensitivity and higher false-negative percentages in the water dilution study. This would be expected because of the ingestion of large amounts of water and consequent dilution of urine drug concentration. These data indicated that selection of a specimen ratio to evaluate sequential creatinine normalized urine drug concentrations can improve the ability to distinguish residual excretion from new marijuana usage. The selection of an appropriate specimen ratio can be made based on the needs of a specific urine drug-testing program taking into account sensitivity, specificity, and accuracy data. JF - Journal of analytical toxicology AU - Huestis, M A AU - Cone, E J AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 445 EP - 454 VL - 22 IS - 6 SN - 0146-4760, 0146-4760 KW - Dronabinol KW - 7J8897W37S KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Sensitivity and Specificity KW - Drinking KW - Creatinine -- urine KW - ROC Curve KW - Drug Contamination KW - Humans KW - Adult KW - Time Factors KW - Male KW - Dronabinol -- urine KW - Marijuana Abuse -- urine KW - Marijuana Smoking -- urine KW - Marijuana Abuse -- diagnosis KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69990329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+analytical+toxicology&rft.atitle=Differentiating+new+marijuana+use+from+residual+drug+excretion+in+occasional+marijuana+users.&rft.au=Huestis%2C+M+A%3BCone%2C+E+J&rft.aulast=Huestis&rft.aufirst=M&rft.date=1998-10-01&rft.volume=22&rft.issue=6&rft.spage=445&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 completed - 1998-12-17 N1 - Date created - 1998-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the serotonin transporter promoter polymorphism in anxiety-related traits. AN - 69984025; 9783565 AB - The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4*C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in anxiety-related personality traits by sibpair analysis and association studies. Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 258 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire. The sibpair analysis revealed a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P = .003). However, there was no consistent association between SLC6A4*C and any Tridimensional Personality Questionnaire trait. In the present study we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLC6A4*C locus is itself affecting anxiety or is linked to another still unknown functional variant. JF - Archives of general psychiatry AU - Mazzanti, C M AU - Lappalainen, J AU - Long, J C AU - Bengel, D AU - Naukkarinen, H AU - Eggert, M AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 936 EP - 940 VL - 55 IS - 10 SN - 0003-990X, 0003-990X KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Serotonin KW - 333DO1RDJY KW - Abridged Index Medicus KW - Index Medicus KW - Genetic Linkage KW - Polymerase Chain Reaction KW - Crime KW - Polymorphism, Genetic KW - Humans KW - Alcoholism -- genetics KW - Transcription, Genetic -- physiology KW - Promoter Regions, Genetic -- physiology KW - Serotonin -- physiology KW - Membrane Glycoproteins -- physiology KW - Carrier Proteins -- genetics KW - Anxiety -- genetics KW - Carrier Proteins -- physiology KW - Promoter Regions, Genetic -- genetics KW - Personality -- genetics KW - Serotonin -- genetics KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69984025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+serotonin+transporter+promoter+polymorphism+in+anxiety-related+traits.&rft.au=Mazzanti%2C+C+M%3BLappalainen%2C+J%3BLong%2C+J+C%3BBengel%2C+D%3BNaukkarinen%2C+H%3BEggert%2C+M%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Mazzanti&rft.aufirst=C&rft.date=1998-10-01&rft.volume=55&rft.issue=10&rft.spage=936&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 - 1998-10-27 N1 - Date created - 1998-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration. AN - 69983622; 9783751 AB - The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 Mr dimer, has been solved by NMR, including extensive use of dipolar couplings which provide a priori long range structural information. BAF is a highly evolutionarily conserved DNA binding protein that is responsible for inhibiting autointegration of retroviral DNA, thereby promoting integration of retroviral DNA into the host chromosome. BAF is largely helical, and each subunit is composed of five helices. The dimer is elongated in shape and the dimer interface comprises principally hydrophobic contacts supplemented by a single salt bridge. Despite the absence of any sequence similarity to any other known protein family, the topology of helices 3-5 is similar to that of a number of DNA binding proteins, with helices 4 and 5 constituting a helix-turn-helix motif. A model for the interaction of BAF with DNA that is consistent with structural and mutagenesis data is proposed. JF - Nature structural biology AU - Cai, M AU - Huang, Y AU - Zheng, R AU - Wei, S Q AU - Ghirlando, R AU - Lee, M S AU - Craigie, R AU - Gronenborn, A M AU - Clore, G M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 903 EP - 909 VL - 5 IS - 10 SN - 1072-8368, 1072-8368 KW - BANF1 protein, human KW - 0 KW - DNA, Viral KW - DNA-Binding Proteins KW - Nuclear Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Models, Molecular KW - Dimerization KW - Humans KW - Retroviridae -- physiology KW - Amino Acid Sequence KW - Nucleic Acid Conformation KW - Nuclear Magnetic Resonance, Biomolecular KW - Molecular Sequence Data KW - Virus Integration -- physiology KW - DNA -- chemistry KW - Helix-Turn-Helix Motifs KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - DNA, Viral -- genetics KW - Protein Structure, Secondary KW - DNA-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69983622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+structural+biology&rft.atitle=Solution+structure+of+the+cellular+factor+BAF+responsible+for+protecting+retroviral+DNA+from+autointegration.&rft.au=Cai%2C+M%3BHuang%2C+Y%3BZheng%2C+R%3BWei%2C+S+Q%3BGhirlando%2C+R%3BLee%2C+M+S%3BCraigie%2C+R%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Cai&rft.aufirst=M&rft.date=1998-10-01&rft.volume=5&rft.issue=10&rft.spage=903&rft.isbn=&rft.btitle=&rft.title=Nature+structural+biology&rft.issn=10728368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 2EZX; PDB; 2EZY; 2EZZ; 2EZXMR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV risk behaviors associated with the injection process: multiperson use of drug injection equipment and paraphernalia in injection drug user networks. AN - 69973597; 9781822 AB - This study examines drug acquisition and multiperson use of paraphernalia, drugs, and needles/syringes. Ethnographers observed 54 injection episodes in which IDUs were linked by HIV risk behaviors, and developed a typology of higher-risk, lower-risk, and nonsharing-risk networks. Multiperson use of injection paraphernalia or drug solution occurred in most injection events (94%). Serial use of syringes/needles occurred infrequently (14%) relative to "backloading" (37%) and reuse of paraphernalia (cookers 84%, cotton 77%, water 77%). Higher-risk injection networks were characterized by larger size and pooling of resources for drugs. Prevention messages must include avoiding reuse of injection paraphernalia and transfer of drug solution. JF - Substance use & misuse AU - Needle, R H AU - Coyle, S AU - Cesari, H AU - Trotter, R AU - Clatts, M AU - Koester, S AU - Price, L AU - McLellan, E AU - Finlinson, A AU - Bluthenthal, R N AU - Pierce, T AU - Johnson, J AU - Jones, T S AU - Williams, M AD - National Institute on Drug Abuse, Rockville, Maryland 20857, USA. rh28e@nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 2403 EP - 2423 VL - 33 IS - 12 SN - 1082-6084, 1082-6084 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Health Knowledge, Attitudes, Practice KW - Observation KW - Urban Population KW - Male KW - Female KW - Anthropology, Cultural KW - Needle Sharing -- psychology KW - Needle Sharing -- statistics & numerical data KW - Risk-Taking KW - Interpersonal Relations KW - HIV Infections -- etiology KW - Substance Abuse, Intravenous -- complications KW - Substance Abuse, Intravenous -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69973597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+use+%26+misuse&rft.atitle=HIV+risk+behaviors+associated+with+the+injection+process%3A+multiperson+use+of+drug+injection+equipment+and+paraphernalia+in+injection+drug+user+networks.&rft.au=Needle%2C+R+H%3BCoyle%2C+S%3BCesari%2C+H%3BTrotter%2C+R%3BClatts%2C+M%3BKoester%2C+S%3BPrice%2C+L%3BMcLellan%2C+E%3BFinlinson%2C+A%3BBluthenthal%2C+R+N%3BPierce%2C+T%3BJohnson%2C+J%3BJones%2C+T+S%3BWilliams%2C+M&rft.aulast=Needle&rft.aufirst=R&rft.date=1998-10-01&rft.volume=33&rft.issue=12&rft.spage=2403&rft.isbn=&rft.btitle=&rft.title=Substance+use+%26+misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-10 N1 - Date created - 1998-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phylogenetic analysis of 22 complete genomes of the human polyomavirus JC virus. AN - 69972818; 9780056 AB - The polyomavirus JC (JCV) establishes a persistent infection in the kidneys, and is the virus agent that causes the demyelinating disease progressive multifocal leukoencephalopathy. PCR and DNA sequence analyses of partial JCV genomes have shown that there are at least four main JCV types, each associated with a specific geographical region. Type 1 is of European origin, Type 2 is Asian, Type 3 is found in individuals of African decent and Type 4 is a potential recombinant of Types 1 and 3, and is widely distributed throughout the population of the United States. A comprehensive phylogenetic analysis of 22 complete JCV genomes excluding part of the regulatory region was accomplished using neighbour-joining, UPGMA and maximum parsimony methods. The resulting UPGMA and parsimony phylogenies suggest that the European Type 1 strains diverged from the other types during the evolution of JCV and that each of the other genotypes (and subtypes) falls into well-supported clades. This is the first whole genome approach to phylogeny reconstruction for JCV and represents a significant improvement over earlier studies that were limited to partial JCV sequences and the neighbour-joining method. JF - The Journal of general virology AU - Jobes, D V AU - Chima, S C AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 2491 EP - 2498 VL - 79 ( Pt 10) SN - 0022-1317, 0022-1317 KW - Index Medicus KW - Phylogeny KW - Genotype KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - JC Virus -- genetics KW - JC Virus -- classification KW - Genome, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69972818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+general+virology&rft.atitle=Phylogenetic+analysis+of+22+complete+genomes+of+the+human+polyomavirus+JC+virus.&rft.au=Jobes%2C+D+V%3BChima%2C+S+C%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Jobes&rft.aufirst=D&rft.date=1998-10-01&rft.volume=79+%28+Pt+10%29&rft.issue=&rft.spage=2491&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-29 N1 - Date created - 1998-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. AN - 69971532; 9778212 JF - Arthritis and rheumatism AU - Cooper, G S AU - Dooley, M A AU - Treadwell, E L AU - St Clair, E W AU - Parks, C G AU - Gilkeson, G S AD - National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1714 EP - 1724 VL - 41 IS - 10 SN - 0004-3591, 0004-3591 KW - Estrogens KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Risk Factors KW - Humans KW - Female KW - Environmental Exposure KW - Bacterial Infections -- complications KW - Estrogens -- physiology KW - Lupus Erythematosus, Systemic -- epidemiology KW - Lupus Erythematosus, Systemic -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69971532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hormonal%2C+environmental%2C+and+infectious+risk+factors+for+developing+systemic+lupus+erythematosus.&rft.au=Cooper%2C+G+S%3BDooley%2C+M+A%3BTreadwell%2C+E+L%3BSt+Clair%2C+E+W%3BParks%2C+C+G%3BGilkeson%2C+G+S&rft.aulast=Cooper&rft.aufirst=G&rft.date=1998-10-01&rft.volume=41&rft.issue=10&rft.spage=1714&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 - 1998-11-03 N1 - Date created - 1998-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compartmental pharmacokinetics and tissue drug distribution of the pradimicin derivative BMS 181184 in rabbits. AN - 69968747; 9756780 AB - The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (Cmax) ranged from 120 microg/ml at 10 mg/kg to 648 microg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0-24) ranged from 726 to 2,130 microg . h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 to P < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0-24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing. JF - Antimicrobial agents and chemotherapy AU - Groll, A H AU - Sein, T AU - Petraitis, V AU - Petraitiene, R AU - Callender, D AU - Gonzalez, C E AU - Giri, N AU - Bacher, J AU - Piscitelli, S AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 2700 EP - 2705 VL - 42 IS - 10 SN - 0066-4804, 0066-4804 KW - Anthracyclines KW - 0 KW - Antibiotics, Antineoplastic KW - Antifungal Agents KW - 3'-hydroxybenanomicin A KW - 139272-69-8 KW - Index Medicus KW - Animals KW - Rabbits KW - Tissue Distribution KW - Female KW - Antifungal Agents -- pharmacokinetics KW - Antibiotics, Antineoplastic -- administration & dosage KW - Antibiotics, Antineoplastic -- pharmacokinetics KW - Antibiotics, Antineoplastic -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Compartmental+pharmacokinetics+and+tissue+drug+distribution+of+the+pradimicin+derivative+BMS+181184+in+rabbits.&rft.au=Groll%2C+A+H%3BSein%2C+T%3BPetraitis%2C+V%3BPetraitiene%2C+R%3BCallender%2C+D%3BGonzalez%2C+C+E%3BGiri%2C+N%3BBacher%2C+J%3BPiscitelli%2C+S%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=1998-10-01&rft.volume=42&rft.issue=10&rft.spage=2700&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 - 1998-11-09 N1 - Date created - 1998-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] J Infect. 1996 Jul;33(1):23-32 [8842991] J Antibiot (Tokyo). 1988 Nov;41(11):1701-4 [3198502] J Antibiot (Tokyo). 1990 Jun;43(6):715-21 [2199421] J Antibiot (Tokyo). 1990 Jul;43(7):763-70 [2167304] Antimicrob Agents Chemother. 1991 Nov;35(11):2185-90 [1803990] J Antibiot (Tokyo). 1992 Sep;45(9):1512-7 [1429237] J Infect Dis. 1993 May;167(5):1247-51 [8486965] Antimicrob Agents Chemother. 1995 Feb;39(2):295-300 [7726485] Antimicrob Agents Chemother. 1995 Aug;39(8):1683-7 [7486900] Clin Infect Dis. 1996 May;22 Suppl 2:S133-44 [8722841] Clin Infect Dis. 1996 May;22 Suppl 2:S148-53 [8722843] Clin Infect Dis. 1996 May;22 Suppl 2:S166-78 [8722846] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm. AN - 69965834; 9774373 AB - Insulin-mediated vasodilation has been proposed as an important determinant of whole-body insulin-stimulated glucose disposal. However, it is not clear whether the vasodilator effect of insulin results from a direct action of the hormone or whether alternative mechanisms are involved. To better characterize the mechanism of insulin-mediated vasorelaxation, we compared forearm blood flow (FBF) responses to local (intra-arterial) and systemic (intravenous, euglycemic clamp) hyperinsulinemia in 10 healthy lean subjects using venous occlusion plethysmography. In addition, we assessed the effect of nitric oxide (NO) synthase inhibition by NG-monomethyl-L-arginine (L-NMMA) on the vasodilator and metabolic responses to hyperinsulinemia. Similar forearm concentrations of insulin were achieved during local and systemic infusion (231+/-39 versus 265+/-22 microU/mL; P=0.54). Of note, FBF did not change significantly in response to local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/-0.3 mL . min-1 . dL-1; P=0.50). In contrast, systemic hyperinsulinemia caused a 52% increase in FBF (from 2.5+/-0.2 to 3. 8+/-0.5 mL . min-1 . dL-1; P<0.004), which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min-1 . dL-1; P=0. 004). We conclude that systemic, but not local, hyperinsulinemia induces vasodilation in the forearm. Our findings suggest that insulin-mediated vasodilation is not due solely to a direct stimulatory effect of insulin but involves additional mechanisms activated only during systemic hyperinsulinemia. JF - Hypertension (Dallas, Tex. : 1979) AU - Cardillo, C AU - Kilcoyne, C M AU - Nambi, S S AU - Cannon, R O AU - Quon, M J AU - Panza, J A AD - Cardiology Branch, Hypertension-Endocrine Branch, National Heart, Lung,and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 740 EP - 745 VL - 32 IS - 4 SN - 0194-911X, 0194-911X KW - Insulin KW - 0 KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Infusions, Intra-Arterial KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Humans KW - Hemodynamics KW - omega-N-Methylarginine -- pharmacology KW - Middle Aged KW - Male KW - Forearm KW - Female KW - Vasodilation -- physiology KW - Glucose -- metabolism KW - Hyperinsulinism -- chemically induced KW - Hyperinsulinism -- metabolism KW - Vasodilation -- drug effects KW - Insulin -- pharmacology KW - Glucose -- pharmacokinetics KW - Insulin -- administration & dosage KW - Glucose -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69965834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Vasodilator+response+to+systemic+but+not+to+local+hyperinsulinemia+in+the+human+forearm.&rft.au=Cardillo%2C+C%3BKilcoyne%2C+C+M%3BNambi%2C+S+S%3BCannon%2C+R+O%3BQuon%2C+M+J%3BPanza%2C+J+A&rft.aulast=Cardillo&rft.aufirst=C&rft.date=1998-10-01&rft.volume=32&rft.issue=4&rft.spage=740&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=0194911X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hypertension. 1999 Dec;34(6):e12-3 [10601136] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor-alpha stimulates human Clara cell secretory protein production by human airway epithelial cells. AN - 69959218; 9761760 AB - Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A2 which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of activating phospholipases and inducing the expression of a variety of genes in the airway epithelium which may modulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine could induce the production of a counterregulatory protein such as CCSP which might modulate the production of eicosanoid mediators in the airway. Using a human bronchial epithelial cell line (BEAS-2B), CCSP messenger RNA (mRNA) levels were detected by ribonuclease protection assay. TNF treatment of these cells increased CCSP mRNA levels in a time- and dose-dependent manner. The CCSP mRNA level increased in response to TNF-alpha (20 ng/ml) stimulation after 8 to 36 h with the peak increase at 18 h. Immunoblotting of CCSP protein released into the culture media demonstrated that TNF-alpha induced the synthesis and secretion of CCSP protein in a time-dependent manner over 8 to 18 h. The results of a CCSP reporter gene activity assay, nuclear run-on assay, and CCSP mRNA half-life assay indicated that the TNF-alpha-induced increases in CCSP gene expression are regulated at the post-transcriptional level. We conclude that TNF-alpha induces airway epithelial cell expression of human CCSP protein and may modulate airway inflammatory responses in this manner. JF - American journal of respiratory cell and molecular biology AU - Yao, X L AU - Levine, S J AU - Cowan, M J AU - Logun, C AU - Shelhamer, J H AD - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 629 EP - 635 VL - 19 IS - 4 SN - 1044-1549, 1044-1549 KW - Carcinogens KW - 0 KW - Proteins KW - RNA, Messenger KW - SCGB1A1 protein, human KW - Tumor Necrosis Factor-alpha KW - Uteroglobin KW - 9060-09-7 KW - Index Medicus KW - Cell Line, Transformed -- metabolism KW - Carcinogens -- metabolism KW - RNA, Messenger -- metabolism KW - Humans KW - Transcription, Genetic KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Bronchi -- cytology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Proteins -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69959218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+necrosis+factor-alpha+stimulates+human+Clara+cell+secretory+protein+production+by+human+airway+epithelial+cells.&rft.au=Yao%2C+X+L%3BLevine%2C+S+J%3BCowan%2C+M+J%3BLogun%2C+C%3BShelhamer%2C+J+H&rft.aulast=Yao&rft.aufirst=X&rft.date=1998-10-01&rft.volume=19&rft.issue=4&rft.spage=629&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 - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of random recombination between human MDR1 and mouse mdr1a cDNA in a pHaMDR-dihydrofolate reductase bicistronic expression system. AN - 69957632; 9765504 AB - Human P-glycoprotein (Pgp) confers multidrug resistance (MDR) to otherwise sensitive cells. The homologous mouse Pgps, which are encoded by mouse mdr1a (also known as mdr3) and mdr1b (also known as mdr1), confer different degrees of resistance to the same MDR drugs and inhibitors. To create recombinants for the study of sequences responsible for these differences in drug-resistance, chimeric cDNA libraries can be constructed by homologous recombination of pools of related sequences. This mutagenesis approach is called DNA shuffling. To select for chimeric Pgp with an altered resistance profile, DNA shuffling between the homologous but not identical drug interacting transmembrane domains 5 and 6 of human MDR1 and mouse mdr1a was used. The chimeric proteins were expressed in human KB-3-1 cells. One recombinant Pgp (clone 3-4) with a novel phenotype was analyzed in detail. Inhibitors of Pgp, including verapamil and cyclosporin A, were less effective in reversing resistance of the chimeric Pgp compared with wild-type Pgp, for certain drugs. However, [125I]iodoarylazidoprazosin photoaffinity labeling of the chimeric Pgp and its binding competition with cyclosporin A, showed that cyclosporin A competed for the photoaffinity labeling. The chimeric Pgp cells stained less well with human-specific anti-Pgp mAb MRK16 than wild-type Pgp, despite having the described epitopes for MRK16. Staining with human-specific mAb UIC2 was increased when the chimeric protein was compared with wild-type Pgp. These results suggest an alteration in exposure of human Pgp specific epitopes in this chimeric Pgp, as well as a change in the interaction of reversing agents with the chimeric protein. JF - Molecular pharmacology AU - Shoshani, T AU - Zhang, S AU - Dey, S AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 623 EP - 630 VL - 54 IS - 4 SN - 0026-895X, 0026-895X KW - Azides KW - 0 KW - DNA, Complementary KW - Iodine Radioisotopes KW - P-Glycoprotein KW - Photoaffinity Labels KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - azidoprazosin KW - 90990-97-9 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Prazosin KW - XM03YJ541D KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - KB Cells KW - Prazosin -- metabolism KW - Prazosin -- analogs & derivatives KW - Humans KW - Mice KW - Recombinant Proteins -- genetics KW - Azides -- metabolism KW - Photoaffinity Labels -- metabolism KW - Transfection KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Biological Transport -- physiology KW - Protein Structure, Tertiary KW - Recombinant Fusion Proteins -- metabolism KW - DNA, Complementary -- genetics KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - DNA, Complementary -- metabolism KW - Recombination, Genetic KW - Recombinant Fusion Proteins -- genetics KW - Tetrahydrofolate Dehydrogenase -- biosynthesis KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69957632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+random+recombination+between+human+MDR1+and+mouse+mdr1a+cDNA+in+a+pHaMDR-dihydrofolate+reductase+bicistronic+expression+system.&rft.au=Shoshani%2C+T%3BZhang%2C+S%3BDey%2C+S%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Shoshani&rft.aufirst=T&rft.date=1998-10-01&rft.volume=54&rft.issue=4&rft.spage=623&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 - 1998-10-30 N1 - Date created - 1998-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delta opioid peptide [D-Ala2,D-leu5]enkephalin blocks the long-term loss of dopamine transporters induced by multiple administrations of methamphetamine: involvement of opioid receptors and reactive oxygen species. AN - 69950633; 9765353 AB - Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopaminergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid antagonist naltrexone blocked this action of DADLE in both aspects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in body temperature induced by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was approximately equipotent to glutathione in inhibiting both superoxide anion formation induced by xanthine oxidase and hydroxyl radical formation evoked by ferrous/citrate complex. DADLE was only slightly less potent than glutathione in inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results suggest that DADLE can protect the terminal membranes of dopaminergic neurons against METH-induced insult but not the loss of dopaminergic content and tyrosine hydroxylase activity and that this action of DADLE might involve opioid receptors as well as the sequestration of free radical. JF - The Journal of pharmacology and experimental therapeutics AU - Tsao, L I AU - Ladenheim, B AU - Andrews, A M AU - Chiueh, C C AU - Cadet, J L AU - Su, T P AD - Molecular Neuropsychiatry Section, Cellular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 322 EP - 331 VL - 287 IS - 1 SN - 0022-3565, 0022-3565 KW - Antioxidants KW - 0 KW - Carrier Proteins KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Reactive Oxygen Species KW - Receptors, Opioid KW - Methamphetamine KW - 44RAL3456C KW - Naltrexone KW - 5S6W795CQM KW - Enkephalin, Leucine-2-Alanine KW - 63631-40-3 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Body Temperature -- drug effects KW - Naltrexone -- pharmacology KW - Mice KW - Glutathione -- pharmacology KW - Male KW - Antioxidants -- pharmacology KW - Carrier Proteins -- drug effects KW - Receptors, Opioid -- drug effects KW - Enkephalin, Leucine-2-Alanine -- pharmacology KW - Receptors, Opioid -- physiology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69950633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Delta+opioid+peptide+%5BD-Ala2%2CD-leu5%5Denkephalin+blocks+the+long-term+loss+of+dopamine+transporters+induced+by+multiple+administrations+of+methamphetamine%3A+involvement+of+opioid+receptors+and+reactive+oxygen+species.&rft.au=Tsao%2C+L+I%3BLadenheim%2C+B%3BAndrews%2C+A+M%3BChiueh%2C+C+C%3BCadet%2C+J+L%3BSu%2C+T+P&rft.aulast=Tsao&rft.aufirst=L&rft.date=1998-10-01&rft.volume=287&rft.issue=1&rft.spage=322&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 - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City. AN - 69948963; 9761765 AB - Platelet-derived growth factor (PDGF) and its receptor system regulate mesenchymal cell proliferation. We recently reported that emission-source fly-ash particles and asbestos fibers induce the PDGF alpha-receptor through a macrophage-dependent pathway, and upregulation of this receptor greatly enhances the mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Am. J. Respir. Cell Mol. Biol. 1997;16:283-292). In the present study we investigated the effect of particulate matter <= 10 micrometers in size (PM10) from the southern, central, and northern regions of Mexico City on PDGF receptor induction and compared these urban, ambient particles with Mt. St. Helen's volcanic ash particles as a negative control. All Mexico City PM10 samples, but not volcanic ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory factor(s) for the PDGF alpha-receptor on early passage rat lung myofibroblasts. The macrophage-derived upregulatory activity was blocked by the interleukin (IL)-1 receptor antagonist. The ability of PM10 to stimulate IL-1beta release was blocked in part by a recombinant endotoxin neutralizing protein (rENP). Lipopolysaccharide/endotoxin (LPS) and vanadium, both constituents that were present within these PM10 samples, also stimulated macrophages to secrete factor(s) that upregulated PDGF-Ralpha on lung myofibroblasts. Direct exposure of myofibroblasts to PM10 also elicited upregulation of the PDGF alpha-receptor, and this effect was blocked by rENP and mimicked by LPS, but not vanadium. These findings suggest that PM10 particles induce expression of the PDGF receptor system through macrophage-dependent and -independent mechanisms involving endotoxin and metals. JF - American journal of respiratory cell and molecular biology AU - Bonner, J C AU - Rice, A B AU - Lindroos, P M AU - O'Brien, P O AU - Dreher, K L AU - Rosas, I AU - Alfaro-Moreno, E AU - Osornio-Vargas, A R AD - Airway Inflammation Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. bonnerj@niehs.nih.gov Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 672 EP - 680 VL - 19 IS - 4 SN - 1044-1549, 1044-1549 KW - Air Pollutants KW - 0 KW - Culture Media, Conditioned KW - Endotoxins KW - Interleukin-1 KW - Vanadium Compounds KW - vanadium pentoxide KW - BVG363OH7A KW - Receptors, Platelet-Derived Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Vanadium Compounds -- pharmacology KW - Culture Media, Conditioned -- pharmacology KW - Animals KW - Fibroblasts -- drug effects KW - Interleukin-1 -- immunology KW - Endotoxins -- immunology KW - Fibroblasts -- metabolism KW - Rats KW - Macrophages, Alveolar -- metabolism KW - Bronchoalveolar Lavage Fluid -- immunology KW - Fibroblasts -- immunology KW - Cities KW - Rats, Sprague-Dawley KW - Mexico KW - Interleukin-1 -- metabolism KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Up-Regulation -- immunology KW - Vanadium Compounds -- immunology KW - Macrophages, Alveolar -- immunology KW - Bronchoalveolar Lavage Fluid -- cytology KW - Male KW - Volcanic Eruptions KW - Lung -- immunology KW - Air Pollutants -- pharmacology KW - Receptors, Platelet-Derived Growth Factor -- analysis KW - Receptors, Platelet-Derived Growth Factor -- immunology KW - Air Pollutants -- immunology KW - Lung -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69948963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+the+lung+myofibroblast+PDGF+receptor+system+by+urban+ambient+particles+from+Mexico+City.&rft.au=Bonner%2C+J+C%3BRice%2C+A+B%3BLindroos%2C+P+M%3BO%27Brien%2C+P+O%3BDreher%2C+K+L%3BRosas%2C+I%3BAlfaro-Moreno%2C+E%3BOsornio-Vargas%2C+A+R&rft.aulast=Bonner&rft.aufirst=J&rft.date=1998-10-01&rft.volume=19&rft.issue=4&rft.spage=672&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 - 1998-11-05 N1 - Date created - 1998-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-8 priming of human neutrophils is not associated with persistently altered calcium fluxes but is additive with lipopolysaccharide. AN - 69948168; 9766632 AB - Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency on altered calcium fluxes and for similarity to lipopolysaccharide (LPS). IL-8 caused a rapid rise in [Ca2+]i that returned to baseline values by 20 min. Peak [Ca2+]i transients in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) were unaltered in IL-8-primed compared with unprimed cells. In comparison to LPS and tumor necrosis factor (TNF), IL-8 was a much weaker priming agent as measured by either O2- or H2O2 production. Despite their large disparity in potency, IL-8 and LPS printing were additive using fMLP, a receptor-dependent stimulator, and synergistic using the post-receptor, protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) to trigger the respiratory burst. In contrast, IL-8 and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus, lasting alterations in [Ca2+]i are not a necessary characteristic of IL-8-primed cells. IL-8 and LPS appear to prime by non-overlapping pathways, whereas IL-8 and TNF appear to share mechanisms distal to protein kinase C activation. IL-8 and LPS may independently contribute to neutrophil-mediated host defense or injury by priming through distinct pathways. JF - Journal of leukocyte biology AU - Van Dervort, A L AU - Lam, C AU - Culpepper, S AU - Tuschil, A F AU - Wesley, R A AU - Danner, R L AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 511 EP - 518 VL - 64 IS - 4 SN - 0741-5400, 0741-5400 KW - Interleukin-8 KW - 0 KW - Lipopolysaccharides KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - N-Formylmethionine Leucyl-Phenylalanine KW - 59880-97-6 KW - Complement C5a KW - 80295-54-1 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Complement C5a -- pharmacology KW - Analysis of Variance KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Hydrogen Peroxide -- blood KW - N-Formylmethionine Leucyl-Phenylalanine -- pharmacology KW - Luminescent Measurements KW - Kinetics KW - In Vitro Techniques KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Drug Synergism KW - Superoxides -- blood KW - Respiratory Burst -- drug effects KW - Neutrophils -- drug effects KW - Calcium -- blood KW - Lipopolysaccharides -- pharmacology KW - Neutrophils -- physiology KW - Respiratory Burst -- physiology KW - Interleukin-8 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69948168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+leukocyte+biology&rft.atitle=Interleukin-8+priming+of+human+neutrophils+is+not+associated+with+persistently+altered+calcium+fluxes+but+is+additive+with+lipopolysaccharide.&rft.au=Van+Dervort%2C+A+L%3BLam%2C+C%3BCulpepper%2C+S%3BTuschil%2C+A+F%3BWesley%2C+R+A%3BDanner%2C+R+L&rft.aulast=Van+Dervort&rft.aufirst=A&rft.date=1998-10-01&rft.volume=64&rft.issue=4&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-26 N1 - Date created - 1998-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of rodent carcinogens and noncarcinogens using genetic toxicity tests: premises, promises, and performance. AN - 69162932; 9927558 AB - The basic premises that guide genetic toxicity testing for identifying carcinogens and to support administrative and regulatory decisions are: the Salmonella mutagenicity test is a necessary component of testing schemes; a chromosome aberration test is needed in addition to a gene mutation test; a mammalian cell mutagenicity test is needed in addition to the Salmonella test; in vivo tests are needed to confirm the results of in vitro tests; and test batteries are more predictive than the individual tests of the battery. Results from the Salmonella mutagenicity, in vitro chromosome aberration, mutations in mouse lymphoma cells, rodent bone marrow micronucleus, and rodent carcinogenicity tests, performed by the U.S. National Toxicology Program, were used to evaluate these premises. A positive Salmonella test was most predictive of carcinogenicity. However, the data do not support using the other tests in addition to Salmonella for predicting carcinogenicity. The genetic toxicity tests did not complement each other, and batteries or combinations of the tests were no more predictive of carcinogenicity than Salmonella alone. If a chemical is mutagenic in Salmonella it should be considered a potential rodent carcinogen, unless ancillary information suggests otherwise. Positive responses in the other in vitro or in vivo tests do not increase the probability that the chemical is a carcinogen, and negative responses in the other tests do not diminish the implications of the positive Salmonella response. JF - Regulatory toxicology and pharmacology : RTP AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 85 EP - 95 VL - 28 IS - 2 SN - 0273-2300, 0273-2300 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Micronucleus Tests KW - Chromosome Aberrations KW - Predictive Value of Tests KW - Mice KW - Salmonella typhimurium -- genetics KW - Mutagenicity Tests KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69162932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Identification+of+rodent+carcinogens+and+noncarcinogens+using+genetic+toxicity+tests%3A+premises%2C+promises%2C+and+performance.&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1998-10-01&rft.volume=28&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&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 - Phase III, large-scale chemoprevention trials. Approach to chemoprevention clinical trials and phase III clinical trial of tamoxifen as a chemopreventive for breast cancer--the US National Cancer Institute experience. AN - 69139795; 9888019 AB - Clinical trials to evaluate interventions for cancer prevention are designed as early (phase I, IIa, and IIb) or late-phase studies. Whereas the former are small and generally rely on intermediate endpoint biomarkers of carcinogenesis, the latter are large-scale, long-term, randomized, phase III studies that address endpoints such as cancer incidence. The Breast Cancer Prevention Trial, P-1, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), is discussed as an example of a large, extended, phase III trial designed to answer the question of whether tamoxifen reduces the incidence of breast cancer in women who are at increased risk for the disease. JF - Hematology/oncology clinics of North America AU - Dunn, B K AU - Kramer, B S AU - Ford, L G AD - Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 1019 EP - 36, vii VL - 12 IS - 5 SN - 0889-8588, 0889-8588 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - United States KW - Breast Neoplasms -- drug therapy KW - Tamoxifen -- therapeutic use KW - Humans KW - National Institutes of Health (U.S.) KW - Breast Neoplasms -- prevention & control KW - Chemoprevention KW - Female KW - Clinical Trials, Phase III as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69139795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=Phase+III%2C+large-scale+chemoprevention+trials.+Approach+to+chemoprevention+clinical+trials+and+phase+III+clinical+trial+of+tamoxifen+as+a+chemopreventive+for+breast+cancer--the+US+National+Cancer+Institute+experience.&rft.au=Dunn%2C+B+K%3BKramer%2C+B+S%3BFord%2C+L+G&rft.aulast=Dunn&rft.aufirst=B&rft.date=1998-10-01&rft.volume=12&rft.issue=5&rft.spage=1019&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=08898588&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical drug development paradigms for chemopreventives. AN - 69139748; 9888015 AB - Preclinical screening studies and animal efficacy testing models currently are used by the National Cancer Institute's chemoprevention drug discovery program to assess and identify chemical agents and natural products that may have the potential to prevent human cancer. Identification of potential cancer preventing agents begins by subjecting each compound to a sequential series of short-term, in vitro prescreens of mechanistic, biochemical assays to provide quantitative data to help establish an early indication of chemopreventive efficacy and to assist in prioritizing agents for further evaluation in longer-term, in vitro transformation bioassays and whole animal models. Promising chemical agents or combinations of agents that work through different inhibitory mechanisms subsequently are tested in well-established, chemically induced, animal tumor models, which include models of the lung, bladder, mammaries, prostate, and skin. These preclinical bioassays afford a strategic framework for evaluating agents according to defined criteria, and not only provide evidence of agent efficacy, but also serve to generate valuable dose-response, toxicity, and pharmacokinetic data required prior to phase I clinical safety testing. Based on preclinical efficacy and toxicity screening studies, only the most successful agents considered to have potential as human chemopreventives progress into clinical chemoprevention trials. JF - Hematology/oncology clinics of North America AU - Steele, V E AU - Boone, C W AU - Lubet, R A AU - Crowell, J A AU - Holmes, C A AU - Sigman, C C AU - Kelloff, G J AD - Chemoprevention Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 943 EP - 61, v-vi VL - 12 IS - 5 SN - 0889-8588, 0889-8588 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- prevention & control KW - Chemoprevention KW - Drug Screening Assays, Antitumor -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69139748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hematology%2Foncology+clinics+of+North+America&rft.atitle=Preclinical+drug+development+paradigms+for+chemopreventives.&rft.au=Steele%2C+V+E%3BBoone%2C+C+W%3BLubet%2C+R+A%3BCrowell%2C+J+A%3BHolmes%2C+C+A%3BSigman%2C+C+C%3BKelloff%2C+G+J&rft.aulast=Steele&rft.aufirst=V&rft.date=1998-10-01&rft.volume=12&rft.issue=5&rft.spage=943&rft.isbn=&rft.btitle=&rft.title=Hematology%2Foncology+clinics+of+North+America&rft.issn=08898588&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - American Genetic Association symposium on Conservation and genetics of marine organisms AN - 52530616; 1999-005872 JF - The Journal of Heredity A2 - O'Brien, Stephen J. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 377 EP - 472 PB - American Generic Association, Baltimore, MD VL - 89 IS - 5 SN - 0022-1503, 0022-1503 KW - genetics KW - Chordata KW - symposia KW - conservation KW - marine environment KW - paleobiology KW - Invertebrata KW - Vertebrata KW - biology KW - 08:General paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52530616?accountid=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=conference&rft.jtitle=The+Journal+of+Heredity&rft.atitle=American+Genetic+Association+symposium+on+Conservation+and+genetics+of+marine+organisms&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1998-10-01&rft.volume=89&rft.issue=5&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - American Genetic Association symposium on Conservation and genetics of marine organisms N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - PubXState - MD N1 - Document feature - illus. N1 - SuppNotes - Papers within scope are cited separately N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - biology; Chordata; conservation; genetics; Invertebrata; marine environment; paleobiology; symposia; Vertebrata ER - TY - JOUR T1 - Shallow population histories in deep evolutionary lineages of marine fishes; insights from sardines and anchovies and lessons for conservation AN - 52527708; 1999-005874 AB - Most surveys of mitochondrial DNA (mtDNA) in marine fishes reveal low levels of sequence divergence between haplotypes relative to the differentiation observed between sister taxa. It is nuclear whether this pattern is due to rapid lineage sorting accelerated by sweepstakes recruitment, historical bottlenecks in population size, founder events, or natural selection, any of which could retard the accumulation of deep mtDNA lineages. Recent advances in paleoclimate research prompt a reexamination of oceanographic processes as a fundamental influence on genetic diversity; evidence from ice cores and anaerobic marine sediments document strong regime shifts in the world's oceans in concert with periodic climatic changes. These changes in sea surface temperatures, current pathways, upwelling intensities, and retention eddies are likely harbingers of severe fluctuations in population size or regional extinctions. Sardines (Sardina, Sardinops) and anchovies (Engraulis) are used to assess the consequences of such oceanographic processes on marine fish intrageneric gene genealogies. Representatives of these two groups occur in temperate boundary currents on a global scale, and these regional populations are known to fluctuate markedly. Biogeographic and genetic data indicate that Sardinops has persisted for at least 20 million years, yet the mtDNA genealogy for this group coalesces in less than half a million years and points to a recent founding of populations around the rim of the Indian-Pacific Ocean. Phylogeographic analysis of Old World anchovies reveals a Pleistocene dispersal from the Pacific to the Atlantic, almost certainly via southern Africa, followed by a very recent recolonization from Europe to southern Africa. These results demonstrate that regional populations of sardines and anchovies are subject to periodic extinctions and recolonizations. Such climate-associated dynamics may explain the low levels of nucleotide diversity and the shallow coalescence of mtDNA genealogies. If these findings apply generally to marine fishes, management strategies should incorporate the idea that even extremely abundant populations may be relatively fragile on ecological and evolutionary time scales. JF - The Journal of Heredity AU - Grant, W S AU - Bowen, B W A2 - O'Brien, Stephen J. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 415 EP - 426 PB - American Generic Association, Baltimore, MD VL - 89 IS - 5 SN - 0022-1503, 0022-1503 KW - communities KW - Osteichthyes KW - paleo-oceanography KW - biogeography KW - paleoclimatology KW - Holocene KW - Sardina KW - Pisces KW - Cenozoic KW - spatial distribution KW - Indian Ocean KW - conservation KW - extinction KW - species diversity KW - biology KW - migration KW - Chordata KW - Actinopterygii KW - Quaternary KW - living taxa KW - biologic evolution KW - indicators KW - Teleostei KW - Engraulis KW - Sardinops KW - Pacific Ocean KW - DNA KW - Pleistocene KW - periodicity KW - Vertebrata KW - Atlantic Ocean KW - 24:Quaternary geology KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52527708?accountid=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=The+Journal+of+Heredity&rft.atitle=Shallow+population+histories+in+deep+evolutionary+lineages+of+marine+fishes%3B+insights+from+sardines+and+anchovies+and+lessons+for+conservation&rft.au=Grant%2C+W+S%3BBowen%2C+B+W&rft.aulast=Grant&rft.aufirst=W&rft.date=1998-10-01&rft.volume=89&rft.issue=5&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - American Genetic Association symposium on Conservation and genetics of marine organisms N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - Number of references - 126 N1 - PubXState - MD N1 - Document feature - illus. incl. 5 tables, sketch maps N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - Actinopterygii; Atlantic Ocean; biogeography; biologic evolution; biology; Cenozoic; Chordata; communities; conservation; DNA; Engraulis; extinction; Holocene; Indian Ocean; indicators; living taxa; migration; Osteichthyes; Pacific Ocean; paleo-oceanography; paleoclimatology; periodicity; Pisces; Pleistocene; Quaternary; Sardina; Sardinops; spatial distribution; species diversity; Teleostei; Vertebrata ER - TY - JOUR T1 - Low mitochondrial diversity and small effective population sizes of the copepods Calanus finmarchicus and Nannocalanus minor; possible impact of climatic variation during Recent glaciation AN - 52525752; 1999-005873 AB - Molecular population genetic diversity of two planktonic copepods of the North Atlantic, Calanus finmarchicus and Nannocalanus minor (Crustacea, Copepoda, Calanoida), was characterized using the sequence variation in a 350 bp region of the mitochondrial 16S rRNA gene. The subarctic species, C. finmarchicus, shows lower population genetic diversity (haplotype diversity, h = 0.368, SD = 0.043; nucleotide diversity, pi = 0.00370, SD = 0.0026) than the temperate/subtropical species, N. minor (h = 0.824, SD = 0.024; pi = 0.00502, SD = 0.0032). Effective population sizes (N (sub e) , estimated from numbers of haplotypes) and effective female population sizes (N (sub f(e)) , estimated from nucleotide diversities) for the two species are 10 (super 7) to 10 (super 10) smaller than census female population sizes (N (sub f) ) estimated from observed densities and areal distributions. For both C. finmarchicus and N. minor, N (sub f) approximately 10 (super 15) , N (sub e) approximately 10 (super 8) , and N (sub f(e)) approximately 10 (super 5) . We hypothesize that the cause of both low levels of molecular diversity and small effective population sizes of the two species is the impact of glaciation during the past 20,000 years. C. finmarchicus may have experienced 75% range reduction and latitudinal displacement during the last glacial maximum at 18,000 years BP, giving rise to a genetic bottleneck; this may explain low diversity and an L-shaped distribution of pairwise haplotype differences. In contrast, N. minor may have experienced range reduction of only 30% and less change in latitudinal extent, with less impact of levels of molecular diversity and the shape of the pairwise difference distribution. Although marine zooplankton species are highly abundant, conservation biologists should note that their numbers may vary significantly on climatic to evolutionary time scales, generating low levels of molecular genetic diversity. JF - The Journal of Heredity AU - Bucklin, A AU - Wiebe, P H A2 - O'Brien, Stephen J. Y1 - 1998/10// PY - 1998 DA - October 1998 SP - 383 EP - 392 PB - American Generic Association, Baltimore, MD VL - 89 IS - 5 SN - 0022-1503, 0022-1503 KW - last glacial maximum KW - glaciation KW - Holocene KW - Cenozoic KW - Copepoda KW - Invertebrata KW - species diversity KW - biology KW - Calanus finmarchicus KW - Quaternary KW - living taxa KW - Crustacea KW - statistical analysis KW - planktonic taxa KW - effects KW - Nannocalanus minor KW - populations KW - paleoenvironment KW - Arthropoda KW - RNA KW - Mandibulata KW - Pleistocene KW - North Atlantic KW - Atlantic Ocean KW - 10:Invertebrate paleontology KW - 24:Quaternary geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52525752?accountid=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=The+Journal+of+Heredity&rft.atitle=Low+mitochondrial+diversity+and+small+effective+population+sizes+of+the+copepods+Calanus+finmarchicus+and+Nannocalanus+minor%3B+possible+impact+of+climatic+variation+during+Recent+glaciation&rft.au=Bucklin%2C+A%3BWiebe%2C+P+H&rft.aulast=Bucklin&rft.aufirst=A&rft.date=1998-10-01&rft.volume=89&rft.issue=5&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - American Genetic Association symposium on Conservation and genetics of marine organisms N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - Number of references - 42 N1 - PubXState - MD N1 - Document feature - illus. incl. 2 tables, sketch maps N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - Arthropoda; Atlantic Ocean; biology; Calanus finmarchicus; Cenozoic; Copepoda; Crustacea; effects; glaciation; Holocene; Invertebrata; last glacial maximum; living taxa; Mandibulata; Nannocalanus minor; North Atlantic; paleoenvironment; planktonic taxa; Pleistocene; populations; Quaternary; RNA; species diversity; statistical analysis ER - TY - JOUR T1 - Fungicidal and binding properties of the natural peptides cecropin B and dermaseptin AN - 19637913; 7385380 AB - In vitro fungicidal properties of cecropin B and dermaseptin were explored using non-germinating and germinating conidia from Aspergillus flavus, A. fumigatus, A. niger, Fusarium moniliforme and F. oxysporum. Cecropin B produced LD sub(50) values for germinating A. flavus, A. fumigatus and A. niger conidia of 3 super(.)0, 0 super(.)5 and 2 super(.)0 mgrm, respectively, while dermaseptin gave LD sub(50) values of 4 super(.)0, 0 super(.)05 and 2 super(.)0 mgrm, respectively. Cecropin B produced an LD sub(50) value of 0 super(.)2 mgrm for non-germinating F. moniliforme and F. oxysporum conidia, while dermaseptin did not reduce either as much as 50% at any level tested. LD sub(50) levels for CB were 0 super(.)2 and 0 super(.)1 mgrm, respectively, for germinating F. moniliforme and F. oxysporum conidia. Dermaseptin was less effective, giving LD sub(50) values for germinating F. moniliforme and F. oxysporum conidia of 0 super(.)3 and 0 super(.)8 mgrm, respectively. Neither peptide reduced conidial viabilities of non-germinating Aspergillus spp. Physicochemical studies indicated cecropin B and dermaseptin bound to ergosterol and cholesterol, conidial wall constituents, but not to chitin or bgr-1,3- glucan. JF - Medical Mycology AU - De Lucca A.J. AU - Bland, J M AU - Jacks, T J AU - Grimm, C AU - Walsh, T J AD - National Cancer Institute, Pediatric Oncology Branch, 10 Center Drive MSC 1928, Bethseda, MD 20892-1928, USA Y1 - 1998/10/01/ PY - 1998 DA - 1998 Oct 01 SP - 291 EP - 298 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 36 IS - 5 SN - 1369-3786, 1369-3786 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - cecropin B KW - conidia KW - dermaseptin KW - fungicidal KW - peptides KW - Fusarium moniliforme KW - Cecropin KW - Aspergillus flavus KW - Chitin KW - Conidia KW - Cholesterol KW - Ergosterol KW - glucans KW - A 01380:Plant Protection, Fungicides & Seed Treatments KW - K 03340:Effects of Physical & Chemical Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19637913?accountid=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=Medical+Mycology&rft.atitle=Fungicidal+and+binding+properties+of+the+natural+peptides+cecropin+B+and+dermaseptin&rft.au=De+Lucca+A.J.%3BBland%2C+J+M%3BJacks%2C+T+J%3BGrimm%2C+C%3BWalsh%2C+T+J&rft.aulast=De+Lucca+A.J.&rft.aufirst=&rft.date=1998-10-01&rft.volume=36&rft.issue=5&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Medical+Mycology&rft.issn=13693786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Cecropin; Chitin; Conidia; Cholesterol; Ergosterol; glucans; Fusarium moniliforme; Aspergillus flavus ER - TY - JOUR T1 - Infant Feeding and Risk of Mother-to-Child Transmission of HIV-1 in Sao Paulo State, Brazil AN - 17584417; 4565275 AB - Although vertical transmission of HIV-1 can occur through breast-feeding, little is known about the effect of colostrum, duration of breast-feeding, mixing feeding, and nipple pathology. We used retrospective cohort data to examine the association between breast-feeding-related factors and transmission of HIV-1 from mother to child in Sao Paulo State, Brazil. Information on maternal and postnatal factors was collected by medical record review and interview. Infection status was determined for 434 children by anti-HIV-1 tests performed beyond 18 months of age or diagnosis of AIDS at any age. Among 168 breast-fed children, the risk of transmission of HIV-1 was 21%, compared with 13% (p = .01) among 264 children artificially fed. Breast-feeding was independently and significantly associated with mother-to-child transmission of HIV-1 after controlling for stage of maternal HIV-1 disease (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.3-3.8). A trend was shown toward an increased risk of transmission with longer duration of breast-feeding, a history of bleeding nipples, and introduction of other liquid food before weaning, but these associations were not statistically significant. History of colostrum intake or cracked nipples without bleeding were not associated with transmission. Most of the women who breast-fed were unaware of their HIV-1 infection status at the time of delivery. Avoidance of mixed feeding and withholding of breast-feeding in the presence of bleeding nipples should be considered in further research as strategies to reduce postnatal transmission of HIV-1 in settings in which safe and sustainable alternatives for breast-feeding are not yet available. JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology AU - Tess, B H AU - Rodrigues, L C AU - Newell, M-L AU - Dunn, D T AU - Lago, TDG AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6130 Executive Boulevard, EPN/434, Rockville, MD 20852, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 189 EP - 194 VL - 19 IS - 2 SN - 1077-9450, 1077-9450 KW - HIV-1 KW - Brazil KW - breast feeding KW - children KW - disease transmission KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Human immunodeficiency virus KW - Transmission (vertical) KW - Human immunodeficiency virus 1 KW - Colostrum KW - Breast feeding KW - Children 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/17584417?accountid=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+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.atitle=Infant+Feeding+and+Risk+of+Mother-to-Child+Transmission+of+HIV-1+in+Sao+Paulo+State%2C+Brazil&rft.au=Tess%2C+B+H%3BRodrigues%2C+L+C%3BNewell%2C+M-L%3BDunn%2C+D+T%3BLago%2C+TDG&rft.aulast=Tess&rft.aufirst=B&rft.date=1998-10-01&rft.volume=19&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Journal+of+Acquired+Immune+Deficiency+Syndromes+and+Human+Retrovirology&rft.issn=10779450&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; Human immunodeficiency virus; Children; Breast feeding; Transmission (vertical); Colostrum ER - TY - JOUR T1 - Acid-sensitive enteric pathogens are protected from killing under extremely acidic conditions of pH 2.5 when they are inoculated onto certain solid food sources AN - 17568773; 4432948 AB - Gastric acidity is recognized as the first line of defense against food-borne pathogens, and the ability of pathogens to resist this pH corresponds to their oral infective dose (ID). Naturally occurring and genetically engineered acid-sensitive enteric pathogens were examined for their ability to survive under acidic conditions of pH 2.5 for 2 h at 37 degree C when inoculated onto ground beef. Each of the strains displayed significantly high survival rates under these normally lethal conditions. The acid-sensitive pathogens Campylobacter jejuni and Vibrio cholerae, which were protected at lower levels from acid-induced killing by ground beef under these conditions, were sensitive to killing in acidified media at pH 5.0 but survived at pH 6.0. Salmonella inoculated onto the surface of preacidified ground beef could not survive if the pH on the surface of the beef was 2.61 or lower but was viable if the surface pH was 3.27. This implies that the pH of the microenvironment occupied by the bacteria on the surface of the food source is critical for their survival. Salmonella was also shown to be protected from killing when inoculated onto boiled egg white, a food source high in protein and low in fat. These results may explain why Salmonella species have a higher oral ID of approximately 10 super(5) cells when administered under defined conditions but have been observed to cause disease at doses as low as 50 to 100 organisms when consumed as part of a contaminated food source. They may also help explain why some pathogens are associated primarily with food-borne modes of transmission rather than fecal-oral transmission. JF - Applied and Environmental Microbiology AU - Waterman AU - Small, PLC AD - Rocky Mountain Laboratories, Microscopy Branch, 903 South 4th St., Hamilton, MT 59840, USA, pam-small@nih.gov Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 3882 EP - 3886 VL - 64 IS - 10 SN - 0099-2240, 0099-2240 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Meat KW - Vibrio cholerae KW - Beef KW - Campylobacter jejuni KW - Preservation KW - Acidity KW - pH effects KW - Food-borne diseases KW - A 01019:Sterilization, preservation & packaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17568773?accountid=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=Applied+and+Environmental+Microbiology&rft.atitle=Acid-sensitive+enteric+pathogens+are+protected+from+killing+under+extremely+acidic+conditions+of+pH+2.5+when+they+are+inoculated+onto+certain+solid+food+sources&rft.au=Waterman%3BSmall%2C+PLC&rft.aulast=Waterman&rft.aufirst=&rft.date=1998-10-01&rft.volume=64&rft.issue=10&rft.spage=3882&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 - Campylobacter jejuni; Vibrio cholerae; Preservation; Food-borne diseases; Meat; Beef; pH effects; Acidity ER - TY - JOUR T1 - Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene AN - 17432137; 4653334 AB - Animal inhalation studies and theoretical models suggest that the pattern of formation of benzene metabolites changes as exposure to benzene increases. To determine if this occurs in humans, benzene metabolites in urine samples collected as part of a cross sectional study of occupationally exposed workers in Shanghai, China were measured. With organic vapour monitoring badges, 38 subjects were monitored during their full workshift for inhalation exposure to benzene. The benzene urinary metabolites phenol, catechol, hydroquinone, and muconic acid were measured with an isotope dilution gas chromatography mass spectroscopy assay and strongly correlated with concentrations of benzene air. For the subgroup of workers (n=27) with urinary phenol >50 ng/g creatinine (above which phenol is considered to be a specific indicator of exposure to benzene), concentrations of each of the four metabolites were calculated as a ratio of the sum of the concentrations of all four metabolites (total metabolites) and were compared in workers exposed to >25 ppm \g?\ less than or equal to 25 ppm. The median, 8 hour time weighted average exposure to benzene was 25 ppm. Relative to the lower exposed workers, the ratio of phenol and catechol to total metabolites increased by 6.0% (p=0.04) and 22.2% (p=0.007), respectively, in the more highly exposed workers. By contrast, the ratio of hydroquinone and muconic acid to total metabolites decreased by 18.8% (p=0.04) and 26.7% (p=0.006), respectively. Similar patterns were found when metabolite ratios were analysed as a function of internal benzene dose (defined as total urinary benzene metabolites), although catechol showed a more complex, quadratic relation with increasing dose. These results, which are consistent with previous animal studies, show that the relative production of benzene metabolites is a function of exposure level. If the toxic benzene metabolites are assumed to be derived from hydroquinone, ring opened products, or both, these results suggests that the risk for adverse health outcomes due to exposure to benzene may have a supralinear relation with external dose, and that linear extrapolation of the toxic effects of benzene in highly exposed workers to lower levels of exposure may underestimate risk. JF - Occupational and Environmental Medicine AU - Rothman, N AU - Bechtold, W E AU - Yin, S-N AU - Dosemeci, M AU - Li, G-L AU - Wang, Y-Z AU - Griffith, W C AU - Smith, M T AU - Hayes, R B AD - NIH/NCI EPN 418, Bethesda, MD 20892, USA, rothmann@epndce.nci.nih.gov Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 705 EP - 711 VL - 55 IS - 10 SN - 1351-0711, 1351-0711 KW - man KW - catechol KW - hydroquinone KW - muconic acid KW - phenols KW - pyrocatechol KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Inhalation KW - Hydroquinone KW - Animal models KW - Phenols KW - Benzene KW - Urine KW - Excretion KW - Occupational exposure KW - X 24153:Metabolism KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17432137?accountid=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=Urinary+excretion+of+phenol%2C+catechol%2C+hydroquinone%2C+and+muconic+acid+by+workers+occupationally+exposed+to+benzene&rft.au=Rothman%2C+N%3BBechtold%2C+W+E%3BYin%2C+S-N%3BDosemeci%2C+M%3BLi%2C+G-L%3BWang%2C+Y-Z%3BGriffith%2C+W+C%3BSmith%2C+M+T%3BHayes%2C+R+B&rft.aulast=Rothman&rft.aufirst=N&rft.date=1998-10-01&rft.volume=55&rft.issue=10&rft.spage=705&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 - Animal models; Inhalation; Occupational exposure; Urine; Excretion; Benzene; Phenols; Hydroquinone ER - TY - JOUR T1 - Design strategies for variable-rate pricing of mixed solid waste AN - 17220944; 4508185 AB - Experience in the design and management of variable-rate mixed solid waste systems has helped practitioners to identify common difficulties and potential solutions. "Building-in" a number of the design strategies included here will enable the careful administrator to anticipate and manage negative externalities to give the variable-rate alternative its best possible chance of success. JF - Public Works Management & Policy AU - Kinner, J K AD - National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 155 EP - 166 VL - 3 IS - 2 SN - 1087-724X, 1087-724X KW - variable rate pricing KW - Pollution Abstracts KW - Economics KW - Environment management KW - Solid wastes KW - Waste management KW - P 4000:WASTE MANAGEMENT UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17220944?accountid=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=Public+Works+Management+%26+Policy&rft.atitle=Design+strategies+for+variable-rate+pricing+of+mixed+solid+waste&rft.au=Kinner%2C+J+K&rft.aulast=Kinner&rft.aufirst=J&rft.date=1998-10-01&rft.volume=3&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Public+Works+Management+%26+Policy&rft.issn=1087724X&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 - Economics; Environment management; Solid wastes; Waste management ER - TY - JOUR T1 - Cellular localization and temporal elevation of tumor necrosis factor- alpha , interleukin-1 alpha , and transforming growth factor- beta 1 mRNA in hippocampal injury response induced by trimethyltin AN - 17183494; 4483495 AB - In certain pathologic states, cytokine production may become spatially and temporally dysregulated, leading to their inappropriate production and potentially detrimental consequences. Tumor necrosis factor- alpha (TNF- alpha ), interleukin (IL)-1, IL-6, and transforming growth factor- beta (TGF- beta ) mediate a range of host responses affecting multiple cell types. To study the role of cytokines in the early stages of brain injury, we examined alterations in the 17-day-old mouse hippocampus during trimethyltin-induced neurodegeneration characterized by neuronal necrosis, microglia activation in the dentate, and astrocyte reactivity throughout the hippocampus. By 24 h after dosing, elevations in mRNA levels for TNF- alpha , IL-1 alpha , IL-1 beta , and IL-6 mRNA were seen. TGF- beta 1 mRNA was elevated at 72 h. In situ hybridization showed that TNF- alpha and IL-1 alpha were localized to the microglia, whereas TGF- beta 1 was expressed predominantly in hippocampal pyramidal cells. Intercellular adhesion molecule-1, EB-22, Mac-1, and glial fibrillary acidic protein mRNA levels were elevated within the first 3 days of exposure in the absence of increased inducible nitric oxide synthetase and interferon- gamma mRNA. These data suggest that pro-inflammatory cytokines contribute to the progression and pattern of neuronal degeneration in the hippocampus. JF - Journal of Neurochemistry AU - Bruccoleri, A AU - Brown, H AU - Harry, G J AD - National Institute of Environmental Health Sciences, MD C1-04, P.O. Box 12233, Research Triangle Park, NC 17709, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 1577 EP - 1587 VL - 71 IS - 4 SN - 0022-3042, 0022-3042 KW - mice KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Interleukin 6 KW - Hippocampus KW - Interleukin 1 KW - Neurodegeneration KW - Trimethyltin KW - Cytokines KW - Pyramidal cells KW - N3 11104:Mammals (except primates) KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17183494?accountid=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+Neurochemistry&rft.atitle=Cellular+localization+and+temporal+elevation+of+tumor+necrosis+factor-+alpha+%2C+interleukin-1+alpha+%2C+and+transforming+growth+factor-+beta+1+mRNA+in+hippocampal+injury+response+induced+by+trimethyltin&rft.au=Bruccoleri%2C+A%3BBrown%2C+H%3BHarry%2C+G+J&rft.aulast=Bruccoleri&rft.aufirst=A&rft.date=1998-10-01&rft.volume=71&rft.issue=4&rft.spage=1577&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytokines; Interleukin 1; Interleukin 6; Pyramidal cells; Neurodegeneration; Hippocampus; Trimethyltin ER - TY - JOUR T1 - Importance of Specific Native Lipids in Controlling the Photocycle of Bacteriorhodopsin AN - 17145477; 4437510 AB - Brief treatment of purple membrane (PM) with dilute detergent can cause major disruption of the BR photocycle without disrupting the trimer structure of BR [Mukhopadhyay et al. (1996) Biochemistry 35, 9245-9252]. Normal photocyle behavior can be recovered by incubating the damaged membranes with a total extract of the five types of native lipids present in PM. It is shown here that full restoration can also be obtained with combinations of squalene (SQ) and phosphatidyl glycerophosphate (PGP) which act synergistically. The addition of SQ to suboptimal levels of PGP induces complete reconstitution, principally by restoring the characteristics of the fast M intermediate, M sub(f) (as defined in Mukhopadhyay et al. (1996) Biochemistry 35, 9245-9252). The addition of small amounts of PGP to SQ, which alone is ineffective, also induces full reconstitution. At very high levels, full reconstitution can be obtained with PGP alone. These results, in combination with earlier studies which implicate an acidic amino acid residue [Bose et al. (1997) J. Phys. Chem. B 101, 10584-10587], suggest that a crucial interaction between a particular amino acid residue and a SQ-PGP lipid complex may be essential for normal BR photocycle activity. JF - Biochemistry (Washington) AU - Joshi, M K AU - Dracheva, S AU - Mukhopadhyay, A K AU - Bose, S AU - Hendler, R W AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0510, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 14463 EP - 14470 VL - 37 IS - 41 SN - 0006-2960, 0006-2960 KW - bacteriorhodopsin KW - phosphatidyl glycerophosphate KW - squalene KW - Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Photocycles KW - Membranes KW - Lipids KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17145477?accountid=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=Importance+of+Specific+Native+Lipids+in+Controlling+the+Photocycle+of+Bacteriorhodopsin&rft.au=Joshi%2C+M+K%3BDracheva%2C+S%3BMukhopadhyay%2C+A+K%3BBose%2C+S%3BHendler%2C+R+W&rft.aulast=Joshi&rft.aufirst=M&rft.date=1998-10-01&rft.volume=37&rft.issue=41&rft.spage=14463&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 - Membranes; Photocycles; Lipids; Bacteria ER - TY - JOUR T1 - Novel Families of Putative Protein Kinases in Bacteria and Archaea: Evolution of the "Eukaryotic" Protein Kinase Superfamily AN - 17135086; 4436329 AB - The central role of serine/threonine and tyrosine protein kinases in signal transduction and cellular regulation in eukaryotes is well established and widely documented. Considerably less is known about the prevalence and role of these protein kinases in bacteria and archaea. In order to examine the evolutionary origins of the eukaryotic-type protein kinase (ePK) superfamily, we conducted an extensive analysis of the proteins encoded by the completely sequenced bacterial and archaeal genomes. We detected five distinct families of known and predicted putative protein kinases with representatives in bacteria and archaea that share a common ancestry with the eukaryotic protein kinases. Four of these protein families have not been identified previously as protein kinases. From the phylogenetic distribution of these families, we infer the existence of an ancestral protein kinase(s) prior to the divergence of eukaryotes, bacteria, and archaea. JF - Genome Research AU - Leonard, C J AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 1038 EP - 1047 VL - 8 IS - 10 SN - 1088-9051, 1088-9051 KW - archaea KW - bacteria KW - eukaryotes KW - man KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Protein-serine/threonine kinase KW - Archaea KW - Protein kinase KW - Evolution KW - J 02728:Enzymes KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17135086?accountid=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=Novel+Families+of+Putative+Protein+Kinases+in+Bacteria+and+Archaea%3A+Evolution+of+the+%22Eukaryotic%22+Protein+Kinase+Superfamily&rft.au=Leonard%2C+C+J%3BAravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Leonard&rft.aufirst=C&rft.date=1998-10-01&rft.volume=8&rft.issue=10&rft.spage=1038&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10889051&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; Protein-serine/threonine kinase; Protein kinase; Evolution ER - TY - JOUR T1 - Occupational risk factors for cancer of the gastric cardia AN - 17134516; 4435705 AB - We evaluated the risk of gastric cardia cancer by occupation and industry in a case-control study using information from death certificates for 24 US states in 1984-1992. One thousand fifty-six cases of gastric cardia cancer were identified among men aged 20 years or more, including 1,023 whites and 33 blacks. Controls were 5,280 subjects who died of nonmalignant diseases, 5:1 matched to cases by geographic region, race, gender, and 5-year age group. Among white men, occupations with elevated risk included financial managers (odds ratio [OR] = 6.1; 95% confidence interval [CI], 1.3-28.8), janitors and cleaners (OR = 1.7; 95% CI, 1.0-2.9), production inspectors (OR = 3.2; 95% CI, 1.5-6.9), and truck drivers (OR = 1.5; 95% CI, 1.0-2.2). Industries with elevated risk included pulp and paper mills (OR = 2.0; 95% CI, 1.0-37), newspaper publishing and printing (OR = 2.6; 95% CI, 1.0-6.3), industrial and miscellaneous chemicals (OR = 2.0; 95% CI, 1.0-3.9), water supply and irrigation (OR = 5.6; 95% CI, 1.6-19.9). Among black men, risks were nonsignificantly increased for subjects employed in railroads (3 cases, 2 controls) and for carpenters (3 cases, 0 controls). We created job-exposure matrices for asbestos, inorganic dust, metal dust, lead, polycyclic aromatic hydrocarbons, nitrogen oxides, nitrosamines, sulfuric acid, fertilizers, herbicides, other pesticides, and wood dust. Among white men, a consistent pattern of risk increase by level and probability of exposure was observed only for sulfuric acid mists, with a twofold excess (95% CI, 0.6-7.3) associated with high probability of high intensity exposure. A significant 30% increase in risk was observed for those subjects with a high probability of exposure (all levels combined) to lead, and a 60% increase was observed for subjects with high-level exposure to lead (all probabilities combined). However, crosstabulation of gastric cardia cancer risk by probability and level of exposure to lead did not show consistent trends. Asbestos exposure also showed an overall 50% increase but no consistent trends among white men. None of the 12 occupational hazards showed an association with risk for black men. JF - Journal of Occupational and Environmental Medicine AU - Cocco, P AU - Ward, M H AU - Dosemeci, M AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics National Cancer Institute, 6130 Executive Boulevard, EPN Room 418, Bethesda, MD 20892, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 855 EP - 861 VL - 40 IS - 10 SN - 1076-2752, 1076-2752 KW - USA KW - gastric cardia KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Lead KW - occupational diseases KW - Occupational exposure KW - Asbestos KW - Cancer 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/17134516?accountid=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+Occupational+and+Environmental+Medicine&rft.atitle=Occupational+risk+factors+for+cancer+of+the+gastric+cardia&rft.au=Cocco%2C+P%3BWard%2C+M+H%3BDosemeci%2C+M&rft.aulast=Cocco&rft.aufirst=P&rft.date=1998-10-01&rft.volume=40&rft.issue=10&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&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 - Lead; Asbestos; Occupational exposure; Cancer; Risk assessment; occupational diseases ER - TY - JOUR T1 - Formation of single-stranded DNA during DNA transformation of Neisseria gonorrhoeae AN - 17133551; 4436503 AB - Neisseria gonorrhoeae is naturally competent for DNA transformation. In contrast to other natural prokaryotic DNA transformation systems, single-stranded donor DNA (ssDNA) has not previously been detected during transformation of N. gonorrhoeae. We have reassessed the physical nature of gonococcal transforming DNA by using a sensitive nondenaturing native blotting technique that detects ssDNA. Consistent with previous analyses, we found that the majority of donor DNA remained in the double-stranded form, and only plasmid DNAs that carried the genus-specific DNA uptake sequence were sequestered in a DNase I-resistant state. However, when the DNA was examined under native conditions, S1 nuclease-sensitive ssDNA was identified in all strains tested except for those bacteria that carried the dud-1 mutation. Surprisingly, ssDNA was also found during transformation of N. gonorrhoeae comA mutants, which suggested that ssDNA was initially formed within the periplasm. JF - Journal of Bacteriology AU - Chaussee AU - Hill, SA AD - 903 S. 4th St., Hamilton, MT 59840, USA, mchaussee@nih.gov Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 5117 EP - 5122 VL - 180 IS - 19 SN - 0021-9193, 0021-9193 KW - DNA KW - comA gene KW - transformation KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Transformation KW - Periplasmic space KW - Single-stranded KW - Hybridization analysis KW - Neisseria gonorrhoeae KW - N 14674:Transformation KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17133551?accountid=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=Formation+of+single-stranded+DNA+during+DNA+transformation+of+Neisseria+gonorrhoeae&rft.au=Chaussee%3BHill%2C+SA&rft.aulast=Chaussee&rft.aufirst=&rft.date=1998-10-01&rft.volume=180&rft.issue=19&rft.spage=5117&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 - Neisseria gonorrhoeae; Hybridization analysis; Single-stranded; Transformation; DNA; Periplasmic space ER - TY - JOUR T1 - Update on National Toxicology Program (NTP) assays with genetically altered or "transgenic" mice AN - 17132619; 4439013 AB - The NTP is evaluating several lines of genetically altered mice for possible use in identifying and assessing carcinogens. The NIEHS/NTP programs and progress in this area were recently reviewed by the NTP Board of Scientific Counselors (BSC). A number of comments and concerns were raised. This commentary summarizes and responds to the BSC review and offers some thoughts on future directions for this line of research as well as possible ways genetically altered mice might be integrated into a comprehensive testing strategy. JF - Environmental Health Perspectives AU - Bucher, J R AD - NIEHS, P.O. Box 12233, MD B3-04, Research Triangle Park, NC 27709, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 619 EP - 621 VL - 106 IS - 10 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - Bioassays KW - Genetic engineering KW - Carcinogenicity testing KW - Carcinogens KW - Transgenic mice KW - Toxicity testing KW - Research programs KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17132619?accountid=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=Update+on+National+Toxicology+Program+%28NTP%29+assays+with+genetically+altered+or+%22transgenic%22+mice&rft.au=Bucher%2C+J+R&rft.aulast=Bucher&rft.aufirst=J&rft.date=1998-10-01&rft.volume=106&rft.issue=10&rft.spage=619&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 - Bioassays; Research programs; Carcinogenicity testing; Transgenic mice; Genetic engineering; Carcinogens; Toxicity testing ER - TY - JOUR T1 - NMR structure determination of proteins and protein complexes larger than 20 kDa AN - 17119775; 4423218 AB - Recent advances in multidimensional nuclear magnetic resonance methodology to obtain super(1)H, super(15)N and super(13)C resonance assignments, interproton distance and torsion angle restraints, and restraints that characterize long-range order, coupled with new methods of structure refinement and novel methods for reducing linewidths, have permitted three-dimensional solution structures of single chain proteins in excess of 250 residues and multimeric proteins in excess of 40 kDa to be solved. These developments may permit the determination by nuclear magnetic resonance of macromolecular structures up to molecular weights in the 50-60 kDa range, thereby bringing into reach numerous systems of considerable biological interest, including a large variety of protein-protein and protein-nucleic acid complexes. JF - Current Opinion in Chemical Biology AU - Clore, G M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 564 EP - 570 VL - 2 IS - 5 SN - 1367-5931, 1367-5931 KW - protein structure KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Reviews KW - N.M.R. KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17119775?accountid=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+Chemical+Biology&rft.atitle=NMR+structure+determination+of+proteins+and+protein+complexes+larger+than+20+kDa&rft.au=Clore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Clore&rft.aufirst=G&rft.date=1998-10-01&rft.volume=2&rft.issue=5&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Chemical+Biology&rft.issn=13675931&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; N.M.R. ER - TY - JOUR T1 - Localization of a T-cell epitope of superantigen toxic shock syndrome toxin 1 to residues 125 to 158 AN - 17118304; 4423386 AB - Toxic shock syndrome toxin 1 (TSST-1) is a member of the staphylococcal enterotoxin superantigen family. So far, little is known about T-cell epitopes on superantigens. In this study, we developed an improved method for localizing T-cell epitopes on superantigens that involved synthetic peptides plus costimulation by CD28 or phorbol myristate acetate. Using this method, we localized a T-cell epitope to a 34-residue region, TSST-1 (residues 125 to 158), which possessed only two of four TSST-1-targeted beta -chain variable element (V beta ) specificities of T-cell receptors in humans and mice, human V beta 2 and murine V beta 15. JF - Infection and Immunity AU - Hu, W-G AU - Zhu, X-H AU - Wu, Y-Zh AU - Jia, Zh-C AD - Section on Experimental Immunology, Lab. of Immunology, NIDCD, 5 RC, 2A31, Rockville, MD 20850-3227 USA, wghu@hotmail.com Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 4971 EP - 4975 VL - 66 IS - 10 SN - 0019-9567, 0019-9567 KW - CD28 antigen KW - Phorbol myristate acetate KW - man KW - mice KW - toxic shock syndrome toxin 1 KW - Immunology Abstracts; Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Staphylococcus KW - Superantigens KW - Antigens KW - Lymphocytes T KW - Enterotoxins KW - Epitopes KW - Toxic shock syndrome KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial KW - F 06801:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17118304?accountid=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=Localization+of+a+T-cell+epitope+of+superantigen+toxic+shock+syndrome+toxin+1+to+residues+125+to+158&rft.au=Hu%2C+W-G%3BZhu%2C+X-H%3BWu%2C+Y-Zh%3BJia%2C+Zh-C&rft.aulast=Hu&rft.aufirst=W-G&rft.date=1998-10-01&rft.volume=66&rft.issue=10&rft.spage=4971&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; Superantigens; Toxic shock syndrome; Antigens; Epitopes; Lymphocytes T ER - TY - JOUR T1 - Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration AN - 17117562; 4425811 AB - 1. The disposition of super(14)C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO sub(2) (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO sub(2) (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles. JF - Xenobiotica AU - Burka, L T AU - Black AU - Mathews, J M AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 1005 EP - 1015 VL - 28 IS - 10 SN - 0049-8254, 0049-8254 KW - intravenous administration KW - methyl ethyl ketoxime KW - oral administration KW - pharmacokinetics KW - rats KW - Toxicology Abstracts KW - Anion-exchange chromatography KW - Skin KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17117562?accountid=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=Xenobiotica&rft.atitle=Disposition+of+methyl+ethyl+ketoxime+in+the+rat+after+oral%2C+intravenous+and+dermal+administration&rft.au=Burka%2C+L+T%3BBlack%3BMathews%2C+J+M&rft.aulast=Burka&rft.aufirst=L&rft.date=1998-10-01&rft.volume=28&rft.issue=10&rft.spage=1005&rft.isbn=&rft.btitle=&rft.title=Xenobiotica&rft.issn=00498254&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 - Anion-exchange chromatography; Skin ER - TY - JOUR T1 - Cocaine and metabolite concentrations in plasma during repeated oral administration: Development of a human laboratory model of chronic cocaine use AN - 17111410; 4420891 AB - Long-term use of cocaine may produce neurophysiological and metabolic alterations that differ from acute drug use. A laboratory model that was capable of evaluating the effects of chronic cocaine administration in human subjects was needed. Chronic oral administration of cocaine was considered a feasible route because of the ease of administration, control of dosing patterns, and possible reduction in medical risks compared with the intravenous and smoked routes. This clinical study was conducted to evaluate chronically administered oral cocaine as a means of studying cocaine addiction and withdrawal in humans. Cocaine-abusing volunteers were given multiple doses of oral cocaine each day in up to 16 daily sessions (including three placebo sessions). In each daily session, volunteers received five equal doses separated by hourly intervals. Across sessions, the dose was increased from an initial dose of 100 mg (500 mg/day) to 400 mg (2000 mg/day) in the last session. The dose for each consecutive cocaine session was increased by 25 mg/dose/session (125-mg total increase per session). Twelve subjects were enrolled in the study; however, three subjects dropped out prior to completion of at least three sessions. Two subjects completed all 13 cocaine sessions. The remaining seven subjects completed from 3 to 11 sessions; their participation was terminated early for safety and behavioral reasons. Plasma was collected during all sessions and analyzed for cocaine and metabolites by solid-phase extraction followed by gas chromatography-mass spectrometry. Oral cocaine administration resulted in peak plasma concentrations of cocaine approximately 1 h after administration. Accumulation of cocaine was evident between hourly doses and there was evidence of dose-proportional increases in area under the curve (AUC) measures across sessions. A variety of cocaine metabolites was measured in plasma including benzoylecgonine, ecgonine methyl ester, norcocaine, benzoylnorecgonine, and p- and m-hydroxy metabolites of cocaine and benzoylecgonine. During chronic oral dosing, there appeared to be a trend for AUC ratios (AUC sub(metabolite)/AUC sub(cocaine)) of benzoylecgonine and ecgonine methyl ester to decrease and norcocaine to increase, indicating the possibility of dose-, time-, or route-dependent changes in the absorption and/or metabolism of cocaine. Overall, this study demonstrated that chronic oral dosing of cocaine produced dose-related increases in plasma cocaine concentration, and this model could be useful for studying the effects of chronic cocaine use in human subjects. JF - Journal of Analytical Toxicology AU - Jufer, R A AU - Walsh, S L AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, National institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 435 EP - 444 VL - 22 IS - 6 SN - 0146-4760, 0146-4760 KW - metabolites KW - Toxicology Abstracts KW - Plasma KW - Withdrawal KW - Cocaine KW - Drug abuse KW - Drug addiction KW - Models KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17111410?accountid=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=Cocaine+and+metabolite+concentrations+in+plasma+during+repeated+oral+administration%3A+Development+of+a+human+laboratory+model+of+chronic+cocaine+use&rft.au=Jufer%2C+R+A%3BWalsh%2C+S+L%3BCone%2C+E+J&rft.aulast=Jufer&rft.aufirst=R&rft.date=1998-10-01&rft.volume=22&rft.issue=6&rft.spage=435&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 - Drug addiction; Withdrawal; Models; Plasma; Drug abuse; Cocaine ER - TY - JOUR T1 - Laboratory validation study of drug evaluation and classification program: Alprazolam, d-amphetamine, codeine, and marijuana AN - 17110245; 4420900 AB - The Drug Evaluation and Classification (DEC) program is used by police agencies to identify drivers impaired because of drug use and to determine the class(es) of drug causing the impairment. The primary goal of this study was to determine the validity of the DEC evaluation in predicting whether research volunteers were administered alprazolam, d-amphetamine, codeine, or marijuana. A secondary goal was to determine the accuracy of Drug Recognition Examiners (DREs) in detecting if subjects were dosed with these drugs. Community volunteers (n = 48) were administered alprazolam (0, 1, 2 mg), d-amphetamine (0, 12.5, 25 mg), codeine (0, 60, 120 mg), or marijuana (0, 3.58% THC) in a double-blind, randomized, between-subject design. A single drug dose or placebo was administered at each experimental session, and blood samples were obtained before and after dosing. With the exception of marijuana, plasma drug concentration was at or near maximum during the DEC evaluation. The ability of the DEC evaluation to predict the intake of alprazolam, d-amphetamine, codeine, or marijuana was optimal when using 2-7 variables from the evaluation. DREs' decisions of impairment were consistent with the administration of any active drug in 76% of cases, and their drug class decisions were consistent with toxicology in 32% of cases, according to standards of the International Association of Chiefs of Police. These findings suggest that the DEC evaluation can be used to predict accurately acute administration of alprazolam, d-amphetamine, codeine, and marijuana and that predictions of drug use may be improved by focusing on a subset of variables. JF - Journal of Analytical Toxicology AU - Heishman, S J AU - Singleton, E G AU - Crouch, D J AD - Clinical Pharmacology Branch, NIDA Addiction Research Center, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, Sheish@intra.nida.nih.gov Y1 - 1998/10// PY - 1998 DA - Oct 1998 SP - 503 EP - 514 VL - 22 IS - 6 SN - 0146-4760, 0146-4760 KW - alprazolam KW - drug testing KW - police KW - Toxicology Abstracts KW - Plasma levels KW - Driving ability KW - Cannabinoids KW - Amphetamine KW - Drug abuse KW - Codeine KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17110245?accountid=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=Laboratory+validation+study+of+drug+evaluation+and+classification+program%3A+Alprazolam%2C+d-amphetamine%2C+codeine%2C+and+marijuana&rft.au=Heishman%2C+S+J%3BSingleton%2C+E+G%3BCrouch%2C+D+J&rft.aulast=Heishman&rft.aufirst=S&rft.date=1998-10-01&rft.volume=22&rft.issue=6&rft.spage=503&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 - Cannabinoids; Plasma levels; Amphetamine; Drug abuse; Driving ability; Codeine ER - TY - JOUR T1 - Tumor induction in F344/N rats and B6C3F1 mice following inhalation exposure to ethylbenzene. AN - 70022321; 9801027 AB - Carcinogenesis studies of ethylbenzene were conducted because of its extensive use as a solvent and because it is structurally similar to the known carcinogen benzene. Groups of 50 male and 50 female Fischer rats and B6C3F1 mice were exposed to ethylbenzene by inhalation at 0, 75, 250, and 750 ppm 6 h per day, 5 days per week, for 2 years. The dose levels were selected based on the results of 13-week studies. In the 750 ppm group of male and female rats, body weights were slightly lower and incidences of renal hyperplasia and tubular neoplasms were significantly increased compared with controls. Incidence of testicular tumors was also significantly increased in male rats. Survival and body weights of the exposed groups of male and female mice and controls were comparable. Incidences of alveolar epithelium metaplasia, alveolar/bronchiolar adenoma, and hepatocyte hypertrophy and necrosis were significantly increased in the 750 ppm male mice and incidences of liver eosinophilic foci and hepatocellular neoplasms were significantly increased in the 750 ppm female mice compared with controls. Ethylbenzene is carcinogenic inducing neoplasms in kidneys and testes in Fischer rats and in lungs in male and liver in female B6C3F1 mice. JF - Toxicology letters AU - Chan, P C AU - Hasemani, J K AU - Mahleri, J AU - Aranyi, C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. chanp@niehs.nih.gov Y1 - 1998/09/30/ PY - 1998 DA - 1998 Sep 30 SP - 23 EP - 32 VL - 99 IS - 1 SN - 0378-4274, 0378-4274 KW - Benzene Derivatives KW - 0 KW - ethylbenzene KW - L5I45M5G0O KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemically induced KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Inhalation Exposure KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Carcinoma, Hepatocellular -- pathology KW - Mice KW - Male KW - Female KW - Carcinoma, Hepatocellular -- chemically induced KW - Benzene Derivatives -- administration & dosage KW - Thyroid Neoplasms -- chemically induced KW - Pituitary Neoplasms -- chemically induced KW - Kidney Neoplasms -- pathology KW - Benzene Derivatives -- toxicity KW - Pituitary Neoplasms -- pathology KW - Kidney Neoplasms -- chemically induced KW - Testicular Neoplasms -- pathology KW - Thyroid Neoplasms -- pathology KW - Testicular Neoplasms -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70022321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+letters&rft.atitle=Tumor+induction+in+F344%2FN+rats+and+B6C3F1+mice+following+inhalation+exposure+to+ethylbenzene.&rft.au=Chan%2C+P+C%3BHasemani%2C+J+K%3BMahleri%2C+J%3BAranyi%2C+C&rft.aulast=Chan&rft.aufirst=P&rft.date=1998-09-30&rft.volume=99&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&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 - Structural flexibility of the linker region of human P-glycoprotein permits ATP hydrolysis and drug transport. AN - 73945403; 9753453 AB - P-Glycoprotein (Pgp), an energy-dependent drug efflux pump responsible for multidrug resistance of many cancer cells, is comprised of two homologous halves connected by a peptide segment approximately 75 amino acids (aa) in length. The effects of length and composition of this connecting region on Pgp cell surface expression and the ability of the two halves to interact were explored using both stable transfections of Pgp mutants in mammalian cell lines and a vaccinia virus transient expression system. A 17 aa insertion of predicted flexible structure between amino acids 681 and 682 resulted in a functional Pgp molecule that was capable of conferring drug resistance. In contrast, an 18 aa peptide insertion with a predicted alpha-helical structure was unstable when expressed transiently. A 34 aa deletion from the central core of the linker region (Delta653-686) resulted in a protein expressed at the cell surface in amounts comparable to that of wild-type Pgp but unable to confer drug resistance. No apparent differences in drug or [alpha-32P]-8-azido-ATP photoaffinity labeling were observed. However, both ATP hydrolysis and drug transport activities of the deletion mutant were completely abrogated, indicating that the linker deletion disconnected substrate binding from ATP hydrolysis and transport. This mutant also failed to exhibit an ATP hydrolysis-dependent enhancement of binding of a conformation-sensitive monoclonal antibody, UIC2. Upon replacement with a 17 aa linker peptide having a predicted flexible secondary structure, but bearing no homology to the deleted 34 aa segment, normal Pgp transport and basal and drug-stimulated ATPase activities were restored along with increased UIC2 binding in the presence of substrate, suggesting a dramatic conformational change between the nonfunctional and functional molecules. Taken together, these data suggest a flexible secondary structure of the connector region is sufficient for the coordinate functioning of the two halves of Pgp, likely specifically required for the proper interaction of the two ATP binding sites. JF - Biochemistry AU - Hrycyna, C A AU - Airan, L E AU - Germann, U A AU - Ambudkar, S V AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 13660 EP - 13673 VL - 37 IS - 39 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Azides KW - Iodine Radioisotopes KW - P-Glycoprotein KW - Peptide Fragments KW - Recombinant Proteins KW - 8-azidoadenosine 5'-triphosphate KW - 53696-59-6 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - azidoprazosin KW - 90990-97-9 KW - Verapamil KW - CJ0O37KU29 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Prazosin KW - XM03YJ541D KW - Index Medicus KW - Animals KW - Prazosin -- metabolism KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Cell Membrane -- genetics KW - Biological Transport -- genetics KW - Verapamil -- pharmacology KW - Adenosine Triphosphatases -- drug effects KW - Tumor Cells, Cultured KW - Genetic Vectors KW - Molecular Sequence Data KW - Sequence Deletion KW - Protein Conformation KW - 3T3 Cells KW - Peptide Fragments -- genetics KW - Antibodies, Monoclonal -- metabolism KW - HeLa Cells KW - Prazosin -- analogs & derivatives KW - Adenosine Triphosphatases -- metabolism KW - Osteosarcoma KW - Amino Acid Sequence KW - Mice KW - Hydrolysis KW - Azides -- metabolism KW - Base Sequence KW - Protein Binding -- genetics KW - Cell Membrane -- metabolism KW - Mutagenesis, Insertional KW - P-Glycoprotein -- physiology KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - Adenosine Triphosphate -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - P-Glycoprotein -- chemistry KW - P-Glycoprotein -- biosynthesis KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73945403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+flexibility+of+the+linker+region+of+human+P-glycoprotein+permits+ATP+hydrolysis+and+drug+transport.&rft.au=Hrycyna%2C+C+A%3BAiran%2C+L+E%3BGermann%2C+U+A%3BAmbudkar%2C+S+V%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Hrycyna&rft.aufirst=C&rft.date=1998-09-29&rft.volume=37&rft.issue=39&rft.spage=13660&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-28 N1 - Date created - 1998-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic agents directed to peptide hormone receptors: defining the requirements for a successful drug. AN - 73931187; 9751698 AB - In principle, cell surface receptors that are overexpressed in tumor tissue could serve as targets for anticancer drugs attached to receptor ligands. The purpose of this paper is to identify the necessary elements for a successful receptor-targeted drug. We used the gastrin/cholecystokinin type B receptor as a model delivery system, and we report on the synthesis, trafficking, and in vitro and in vivo evaluation of heptagastrin, the C-terminal heptapeptide of gastrin, linked via an appropriate linker to a potently cytotoxic ellipticine derivative, 1-[3-[N-(3-aminopropyl)-N-methylamino]propyl]amino-9-methoxy-5, 11-dimethyl-6H-pyrido[4,3-b]carbazole. These data, and previous work from our laboratory, show that the drug-complexed ligand is sorted to lysosomes whereas the receptor is recycled to the plasma membrane. The lysosomal processing of the ligand/drug construct depends on the linker between the ligand sequence and the cytotoxic moiety. We show that heptagastrin linked to ellipticine via a succinoyl-substituted pentapeptide, AlaLeuAlaLeuAla, is at least 10(3) more toxic to cholecystokinin type B receptor-positive NIH/3T3 cells than to isogenic NIH/3T3 cells lacking the receptor. The conjugated drug eradicated all receptor-positive tumor cells in vivo without producing any general toxicity. The data indicate that the density of the cell surface receptor, the properties of the cytotoxic moiety, and the correct processing of the drug-conjugated ligand in lysosomes are crucial to the effectiveness of a receptor-targeted drug. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Czerwinski, G AU - Tarasova, N I AU - Michejda, C J AD - Molecular Aspects of Drug Design Section, Macromolecular Structure Laboratory, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 11520 EP - 11525 VL - 95 IS - 20 SN - 0027-8424, 0027-8424 KW - (1-(3-(N-(3-aminopropyl)-N-methylamino)propyl)amino-9-methoxy-5,11-dimethyl-6H-pyrido(4,3-b)carbazole)-Ala-Leu-Ala-Leu-Ala-Su-H-Ala-Try-Gly-Trp-Nle-Asp-Phe-NH2 KW - 0 KW - Antineoplastic Agents KW - Ellipticines KW - Gastrins KW - Ligands KW - Oligopeptides KW - Peptide Fragments KW - Receptor, Cholecystokinin B KW - Receptors, Cholecystokinin KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Microscopy, Confocal KW - 3T3 Cells KW - Animals KW - Gastrins -- chemical synthesis KW - Humans KW - Oligopeptides -- chemistry KW - Neoplasms, Experimental -- metabolism KW - Mice, Nude KW - Mice KW - Lysosomes -- metabolism KW - Amino Acid Sequence KW - Ellipticines -- chemistry KW - Ellipticines -- chemical synthesis KW - Oligopeptides -- chemical synthesis KW - Peptide Fragments -- chemical synthesis KW - Calcium -- metabolism KW - Gastrins -- chemistry KW - Peptide Fragments -- chemistry KW - Transfection KW - Kinetics KW - Peptide Fragments -- pharmacology KW - Gastrins -- pharmacology KW - Oligopeptides -- pharmacology KW - Neoplasms, Experimental -- drug therapy KW - Cell Membrane -- metabolism KW - Ellipticines -- pharmacology KW - Receptors, Cholecystokinin -- genetics KW - Receptors, Cholecystokinin -- metabolism KW - Antineoplastic Agents -- chemical synthesis KW - Receptors, Cholecystokinin -- drug effects KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73931187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxic+agents+directed+to+peptide+hormone+receptors%3A+defining+the+requirements+for+a+successful+drug.&rft.au=Czerwinski%2C+G%3BTarasova%2C+N+I%3BMichejda%2C+C+J&rft.aulast=Czerwinski&rft.aufirst=G&rft.date=1998-09-29&rft.volume=95&rft.issue=20&rft.spage=11520&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1982 Jan;79(2):626-9 [6952214] Nature. 1977 May 5;267(5606):56-8 [193043] Am J Physiol. 1986 Nov;251(5 Pt 1):G597-601 [3777167] Am J Surg. 1988 Mar;155(3):526-36 [3278641] Regul Pept. 1988 Jan;20(1):1-9 [3353523] Gastroenterology. 1988 Dec;95(6):1541-8 [2903111] Int J Cancer. 1989 Apr 15;43(4):692-6 [2703274] Exp Cell Res. 1990 Jan;186(1):15-21 [2298233] J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12 [2359136] Ann Intern Med. 1992 Jan 15;116(2):148-60 [1727619] Cancer Res. 1992 Mar 1;52(5):1114-22 [1310640] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3605-9 [1373504] Ann Surg. 1992 May;215(5):528-34 [1616389] J Cell Biol. 1992 Sep;118(6):1347-58 [1522111] Annu Rev Med. 1993;44:343-53 [8476255] Curr Opin Cell Biol. 1993 Apr;5(2):261-4 [8507498] J Biol Chem. 1993 Jun 25;268(18):13756-63 [8390469] Anticancer Res. 1994 Jan-Feb;14(1A):215-20 [8166452] J Med Chem. 1994 Oct 28;37(22):3812-8 [7966139] Cancer Res. 1995 Jan 1;55(1):71-7 [7805044] Breast Cancer Res Treat. 1994;32(1):97-103 [7819590] Anticancer Drug Des. 1995 Jan;10(1):1-9 [7695810] Gene Ther. 1995 Mar;2(2):116-23 [7719928] J Biol Chem. 1995 Apr 14;270(15):8429-38 [7721737] Am J Physiol. 1995 Nov;269(5 Pt 1):G628-46 [7491953] Cell Tissue Res. 1996 Jan;283(1):1-6 [8581949] Anticancer Drug Des. 1995 Dec;10(8):655-66 [8595124] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15063-8 [8986764] Cell Tissue Res. 1997 Feb;287(2):325-33 [8995203] J Biol Chem. 1997 Jun 6;272(23):14817-24 [9169450] Cancer Chemother Pharmacol. 1997;40 Suppl:S3-8 [9272126] Biochim Biophys Acta. 1997 Oct 24;1333(2):C1-6 [9395287] Adv Exp Med Biol. 1998;436:201-6 [9561220] J Biol Chem. 1998 Jun 26;273(26):15883-6 [9632631] J Med Chem. 1983 Feb;26(2):181-5 [6827534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of IL-10 in inflammation. Studies using cytokine knockout mice. AN - 69147765; 9917866 AB - Interleukin-10 (IL-10) inhibits the synthesis of proinflammatory cytokines known to be involved in fever, including IL-1, IL-6, and tumor necrosis factor-alpha. We hypothesized that IL-10 modulates lipopolysaccharide (LPS)-induced fever in mice. Body temperature was measured by biotelemetry. Swiss Webster mice injected with recombinant murine IL-10 (rmuIL-10) were resistant to fever induced by a low dose of LPS (100 micrograms/kg, i.p.) and to the hypothermic and febrile effects of a high (septic-like) dose of LPS (2.5 mg/kg, i.p.). Injection of rmuIL-10 alone had no effect on afebrile body temperature of Swiss Webster mice. IL-10 knockout mice showed an exacerbated and prolonged fever in response to a low dose of LPS (50 micrograms/kg, i.p.) compared to their wild-type counterparts. These data support the hypothesis that IL-10 acts as an endogenous cryogen during LPS-induced fever in mice. JF - Annals of the New York Academy of Sciences AU - Leon, L R AU - Kozak, W AU - Kluger, M J AD - Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA. lisale@intra.niddk.nih.gov Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 69 EP - 75 VL - 856 SN - 0077-8923, 0077-8923 KW - Analgesics, Non-Narcotic KW - 0 KW - Lipopolysaccharides KW - Recombinant Proteins KW - Interleukin-10 KW - 130068-27-8 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Escherichia coli KW - Lipopolysaccharides -- toxicity KW - Mice KW - Male KW - Mice, Knockout KW - Inflammation -- physiopathology KW - Analgesics, Non-Narcotic -- pharmacology KW - Body Temperature -- drug effects KW - Fever -- prevention & control KW - Fever -- immunology KW - Interleukin-10 -- pharmacology KW - Inflammation -- immunology KW - Fever -- physiopathology KW - Body Temperature -- immunology KW - Interleukin-10 -- physiology KW - Interleukin-10 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69147765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+IL-10+in+inflammation.+Studies+using+cytokine+knockout+mice.&rft.au=Leon%2C+L+R%3BKozak%2C+W%3BKluger%2C+M+J&rft.aulast=Leon&rft.aufirst=L&rft.date=1998-09-29&rft.volume=856&rft.issue=&rft.spage=69&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 - 1999-02-05 N1 - Date created - 1999-02-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial Lipopolysaccharide Increases Interleukin-6 and Prostaglandin Release in Rat Cortical Type I Astrocytes by Different Mechanisms: Role of Anti-inflammatory Agents AN - 17567324; 4460020 AB - LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical type I astrocytes. This stimulatory action was completely abolished by Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5-cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW 4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the release of PGE sub(2) from type I astrocytes, an effect completely inhibited by IND. To rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by blocking IL-6 gene expression, we tested the effect of DEX on interleukin 1 beta (IL-1)-induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6 release, while IL-1 releasing action on IL-6 was significantly reduced by IND. The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase, concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In conclusion, we provide evidence that LPS action on IL-6 and PGE sub(2) release can be ascribed to the activation of different transduction mechanisms, which can be pharmacologically dissected with the aid of anti-inflammatory drugs. JF - Biochemical and Biophysical Research Communications AU - Grimaldi, M AU - Navarra, P AU - Pozzoli, G AU - Preziosi, P AU - Schettini, G AD - Dipartimento di Neuroscienze e della Comunicazione Interumana, Universitadegli Studi di Napoli "Federico II", Via S. Pansini 5, Napoli, 80131, Italy, maurizio@codon.nih.gov Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 798 EP - 804 PB - Academic Press VL - 250 IS - 3 SN - 0006-291X, 0006-291X KW - rats KW - endotoxins KW - lipopolysaccharides KW - CSA Neurosciences Abstracts; Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Endotoxins KW - Interleukin 6 KW - Astrocytes KW - Prostaglandins KW - Antiinflammatory agents KW - Transduction 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/17567324?accountid=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=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Bacterial+Lipopolysaccharide+Increases+Interleukin-6+and+Prostaglandin+Release+in+Rat+Cortical+Type+I+Astrocytes+by+Different+Mechanisms%3A+Role+of+Anti-inflammatory+Agents&rft.au=Grimaldi%2C+M%3BNavarra%2C+P%3BPozzoli%2C+G%3BPreziosi%2C+P%3BSchettini%2C+G&rft.aulast=Grimaldi&rft.aufirst=M&rft.date=1998-09-29&rft.volume=250&rft.issue=3&rft.spage=798&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.1998.9378 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Astrocytes; Interleukin 6; Prostaglandins; Transduction; Endotoxins; Antiinflammatory agents DO - http://dx.doi.org/10.1006/bbrc.1998.9378 ER - TY - JOUR T1 - Melatonin attenuates hydrogen peroxide toxicity in MCF7 cells only at pharmacological concentrations AN - 17157458; 4459986 AB - Melatonin is proposed to be oncostatic in mammary tissue, and one mechanism by which this hormone may elicit its possible oncostatic effect is as an oxygen radical scavenger. Therefore, we examined melatonin's abilities to act as an oxygen radical scavenger at physiological or pharmacological concentrations. Hydrogen peroxide at 400 mu M killed 97% of treated MCF7 cells within 8 h, and following melatonin at 10 super(-5) and 10 super(-4) M concentrations only 76 and 64% of cells, respectively, were killed by hydrogen peroxide. However, melatonin at lower concentrations (10 super(-7) M) did not protect MCF7 cells. Moreover, pretreatment with melatonin (10 super(-5) or 10 super(-7) M) prior to hydrogen peroxide stress offered no further efficacy, and pretreatment with melatonin followed by the withdrawal of melatonin eliminated its protective effect from hydrogen peroxide toxicity. These findings indicate that melatonin acts directly as an antioxidant and does not stimulate antioxidant defenses in MCF7 cells that protect against hydrogen peroxide. Glutathione levels were examined to substantiate this hypothesis and were not altered by melatonin treatment. In conclusion, melatonin is an excellent oxygen radical scavenger at pharmacological concentrations, but not at physiological concentrations. Thus, loss of melatonin is unlikely to be important in oxidative scavenger mechanisms in human mammary cells. JF - Biochemical and Biophysical Research Communications AU - Baldwin, W S AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, 27709, North Carolina Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 602 EP - 605 PB - Academic Press VL - 250 IS - 3 SN - 0006-291X, 0006-291X KW - MCF7 cells KW - Toxicology Abstracts KW - Oxygen KW - Antioxidants KW - Hydrogen peroxide KW - Free radicals KW - Melatonin KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17157458?accountid=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=Melatonin+attenuates+hydrogen+peroxide+toxicity+in+MCF7+cells+only+at+pharmacological+concentrations&rft.au=Baldwin%2C+W+S%3BBarrett%2C+J+C&rft.aulast=Baldwin&rft.aufirst=W&rft.date=1998-09-29&rft.volume=250&rft.issue=3&rft.spage=602&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antioxidants; Melatonin; Hydrogen peroxide; Oxygen; Free radicals ER - TY - JOUR T1 - Reconsidering targeted toxins to eliminate HIV infection: You gotta have HAART AN - 16505493; 4401891 AB - The success of highly active anti-retroviral therapy (HAART) has inspired new concepts for eliminating HIV from infected individuals. A major obstacle is the persistence of long-lived reservoirs of latently infected cells that might become activated at some time after cessation of therapy. We propose that, in the context of treatment strategies to deliberately activate and eliminate these reservoirs, hybrid toxins targeted to kill HIV-infected cells be reconsidered in combination with HAART. Such combinations might also prove valuable in protocols aimed at preventing mother-to-child transmission and establishment of infection immediately after exposure to HIV. We suggest experimental approaches in vitro and in animal models to test various issues related to safety and efficacy of this concept. JF - Proceedings of the National Academy of Sciences, USA AU - Berger, E A AU - Moss, B AU - Pastan, I AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, edward_berger@nih.gov Y1 - 1998/09/29/ PY - 1998 DA - 1998 Sep 29 SP - 11511 EP - 11513 VL - 95 IS - 20 SN - 0027-8424, 0027-8424 KW - HIV KW - human immunodeficiency virus KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - W3 33372:Antiviral agents KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16505493?accountid=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=Reconsidering+targeted+toxins+to+eliminate+HIV+infection%3A+You+gotta+have+HAART&rft.au=Berger%2C+E+A%3BMoss%2C+B%3BPastan%2C+I&rft.aulast=Berger&rft.aufirst=E&rft.date=1998-09-29&rft.volume=95&rft.issue=20&rft.spage=11511&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 ER - TY - JOUR T1 - Identification of the start sites for the 1.9- and 1.4-kb rat transforming growth factor-beta1 transcripts and their effect on translational efficiency. AN - 73954362; 9757003 AB - Three distinct transforming growth factor-beta1 (TGF-beta1) transcripts of 2.5, 1.9 and 1.4kb have been described, but the start sites and functional significance of the shorter transcripts are unknown. Here, we have cloned and sequenced a rat genomic fragment encoding approximately 1250 bases upstream of the start of the TGF-beta1 open reading frame. Using a combination of ribonuclease protection and 5' RACE-PCR analysis, we have mapped the start sites for the two shorter TGF-beta1 transcripts in NRP152 cells, a rat prostatic epithelial cell line that expresses all three transcripts at high levels. The 1.4-kb mRNA starts 25 bases upstream of the initiator AUG, whereas the 1.9-kb mRNA has two start sites 366 and 401 bases upstream of the AUG. Polysome analysis of the NRP152 cells indicates that the 1.9-kb transcript is very efficiently translated, whereas the 2.5- and 1.4-kb transcripts appear to be poorly translated. Differential regulation of TGF-beta1 transcript size may therefore represent an important mechanism for regulating TGF-beta1 protein levels. JF - Gene AU - Yang, Y AU - Mumy, M AU - Romeo, D AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/09/28/ PY - 1998 DA - 1998 Sep 28 SP - 81 EP - 89 VL - 219 IS - 1-2 SN - 0378-1119, 0378-1119 KW - Codon KW - 0 KW - RNA, Messenger KW - Recombinant Proteins KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Open Reading Frames KW - Prostate -- metabolism KW - Polyribosomes -- metabolism KW - Mice KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Cloning, Molecular KW - Epithelial Cells -- metabolism KW - Polymerase Chain Reaction KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Cell Line KW - Male KW - Transforming Growth Factor beta -- biosynthesis KW - Protein Biosynthesis KW - Transcription, Genetic KW - Transforming Growth Factor beta -- genetics KW - Rats -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73954362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+the+start+sites+for+the+1.9-+and+1.4-kb+rat+transforming+growth+factor-beta1+transcripts+and+their+effect+on+translational+efficiency.&rft.au=Yang%2C+Y%3BMumy%2C+M%3BRomeo%2C+D%3BWakefield%2C+L+M&rft.aulast=Yang&rft.aufirst=Y&rft.date=1998-09-28&rft.volume=219&rft.issue=1-2&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-02 N1 - Date created - 1998-12-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF105069; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study. AN - 73951800; 9759683 AB - Several recent studies have suggested that calcium antagonist drugs, which are widely used for the treatment of hypertension, are associated with increased risk of cardiovascular disease. These studies have cast doubts on the long-term safety of calcium antagonists. To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study. We stratified 3539 subjects (mean+/-SD age, 64+/-13 years) from the Framingham Heart Study who had hypertension at routine clinic examinations, according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination. At each follow-up examination (every 2-4 years), subjects were reclassified with regard to the use of calcium antagonists. The end point of the study was all-cause mortality. Hazard ratios and 95% confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models. There were 970 deaths during follow-up. Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 (95% confidence interval, 0.72-1.21; P=.59) for subjects with hypertension without coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P=.58) for those with coronary heart disease at baseline. All models were adjusted for age, sex, current smoking, systolic and diastolic blood pressure, use of beta-blockers, and use of other antihypertensive medications. In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not. Results were similar among subjects with hypertension with and without coronary heart disease. The results of ongoing long-term, randomized clinical trials will provide more definitive data on the safety of calcium antagonists. JF - Archives of internal medicine AU - Abascal, V M AU - Larson, M G AU - Evans, J C AU - Blohm, A T AU - Poli, K AU - Levy, D AD - National Heart, Lung, and Blood Institute's Framingham Heart Study, Mass 01702, USA. Y1 - 1998/09/28/ PY - 1998 DA - 1998 Sep 28 SP - 1882 EP - 1886 VL - 158 IS - 17 SN - 0003-9926, 0003-9926 KW - Calcium Channel Blockers KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Coronary Disease -- etiology KW - Risk KW - Coronary Disease -- mortality KW - Massachusetts KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Hypertension -- complications KW - Hypertension -- mortality KW - Calcium Channel Blockers -- adverse effects KW - Calcium Channel Blockers -- therapeutic use KW - Hypertension -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73951800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internal+medicine&rft.atitle=Calcium+antagonists+and+mortality+risk+in+men+and+women+with+hypertension+in+the+Framingham+Heart+Study.&rft.au=Abascal%2C+V+M%3BLarson%2C+M+G%3BEvans%2C+J+C%3BBlohm%2C+A+T%3BPoli%2C+K%3BLevy%2C+D&rft.aulast=Abascal&rft.aufirst=V&rft.date=1998-09-28&rft.volume=158&rft.issue=17&rft.spage=1882&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-14 N1 - Date created - 1998-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys. AN - 73903778; 9739155 AB - Opiate receptor avidity, roughly equivalent to the ratio of unoccupied receptor density to the receptor dissociation constant (B'max/KD), was measured in four MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine)-lesioned rhesus monkeys and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. Although the MPTP-lesioned monkeys were dopamine deficient as measured with [18F]-L-fluorodopa ([18F]-DOPA) and PET [Doudet et al., 6-[18F]-L-DOPA imaging of the dopamine neostriatal system in normal and clinically normal-MPTP-treated rhesus monkeys, Exp. Brain Res. 78 (1989) 69-80], they had clinically recovered from the acute motor effects of MPTP exposure. Opiate receptor avidity was found to be reduced by 30-35% in the opiate-receptor rich areas of caudate, anterior putamen, thalamus, and amygdala of the MPTP-lesioned animals. The results suggest that opiate pathways make a significant contribution to the adjustment of cortico-striatal-thalamic pathway activity and thereby to behavior in rhesus monkeys following dopamine loss. Copyright 1998 Published by Elsevier Science B.V. JF - Brain research AU - Cohen, R M AU - Carson, R E AU - Aigner, T G AU - Doudet, D J AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bldg. 36, Room 1A05, 36 Convent Dr. MSC 4030, Bethesda, MD 20892-4030, USA. bob@shiloh.nimh.nih.go Y1 - 1998/09/28/ PY - 1998 DA - 1998 Sep 28 SP - 292 EP - 296 VL - 806 IS - 2 SN - 0006-8993, 0006-8993 KW - Dopamine Agents KW - 0 KW - Narcotic Antagonists KW - Receptors, Opioid KW - Naltrexone KW - 5S6W795CQM 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 - Reference Values KW - Naltrexone -- analogs & derivatives KW - In Vitro Techniques KW - Tomography, Emission-Computed KW - Macaca mulatta KW - Tissue Distribution KW - Receptors, Opioid -- metabolism KW - Brain -- drug effects KW - Dopamine Agents -- pharmacology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Brain -- metabolism KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73903778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Opiate+receptor+avidity+is+reduced+in+non-motor+impaired+MPTP-lesioned+rhesus+monkeys.&rft.au=Cohen%2C+R+M%3BCarson%2C+R+E%3BAigner%2C+T+G%3BDoudet%2C+D+J&rft.aulast=Cohen&rft.aufirst=R&rft.date=1998-09-28&rft.volume=806&rft.issue=2&rft.spage=292&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of antipsychotics, vitamin E, and MK-801 on dopamine dynamics in the rat brain following discontinuation of cocaine. AN - 70007688; 9796937 AB - Cocaine, 10 mg/kg, I.P., twice daily, was given to rats for 1 week. At 1 and 4 weeks following discontinuation of cocaine, the initial rate of 3,4-dihydroxyphenylacetic acid (DOPAC) formation was assessed. The initial rate of DOPAC formation was found to be decreased in the frontal and cingulate cortices at 1 week, but was only decreased in the frontal cortex at 4 weeks. When administered in conjunction with cocaine, haloperidol, clozapine, and vitamin E, but not MK-801, were found to prevent cocaine's effects. In addition to the potential value these findings have for further understanding cocaine abuse, it is proposed that the alteration in dopamine metabolism produced by cocaine, and the ability of haloperidol, clozapine and vitamin E to decrease cocaine's effects, model some biochemical aspects of schizophrenia. JF - Psychiatry research AU - Wyatt, R J AU - Karoum, F AU - Masserano, J AD - Neuropsychiatry Branch, Intramural Research Program, National Institute of Mental Health, Washington, DC 20032, USA. wyattr@dirpc.nimh.nih.gov Y1 - 1998/09/21/ PY - 1998 DA - 1998 Sep 21 SP - 213 EP - 225 VL - 80 IS - 3 SN - 0165-1781, 0165-1781 KW - Antipsychotic Agents KW - 0 KW - Neuroprotective Agents KW - Vitamin E KW - 1406-18-4 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Humans KW - Aged KW - Time Factors KW - Male KW - Brain -- drug effects KW - Antipsychotic Agents -- pharmacology KW - Vitamin E -- pharmacology KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Cocaine-Related Disorders -- metabolism KW - Neuroprotective Agents -- pharmacology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70007688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+antipsychotics%2C+vitamin+E%2C+and+MK-801+on+dopamine+dynamics+in+the+rat+brain+following+discontinuation+of+cocaine.&rft.au=Wyatt%2C+R+J%3BKaroum%2C+F%3BMasserano%2C+J&rft.aulast=Wyatt&rft.aufirst=R&rft.date=1998-09-21&rft.volume=80&rft.issue=3&rft.spage=213&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 - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autophosphorylation of Enzyme I of the Escherichia coli Phosphoenolpyruvate:Sugar Phosphotransferase System Requires Dimerization AN - 17098915; 4399267 AB - Enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system undergoes a slow monomer-dimer transition. In vitro autophosphorylation of Enzyme I by PEP was studied at limiting concentrations of the protein. Addition to incubation mixtures containing wild-type Enzyme I of inactive or low-activity mutant forms of Enzyme I resulted in stimulation of autophosphorylation activity. The kinetics of the activation fit well to a model in which the active form of Enzyme I is the dimer. These experiments provide support for the argument that only the dimeric form of Enzyme I can be autophosphorylated. JF - Biochemical and Biophysical Research Communications AU - Seok, Y AU - Zhu, P AU - Koo, B AU - Peterkofsky, A AD - Department of Microbiology, Seoul National University, Building 36, Room 4C-11, Seoul, 151-742, Maryland, Korea, alan@codon.nih.gov Y1 - 1998/09/18/ PY - 1998 DA - 1998 Sep 18 SP - 381 EP - 384 PB - Academic Press VL - 250 IS - 2 SN - 0006-291X, 0006-291X KW - phosphoenolpyruvate-sugar phosphotransferase KW - Microbiology Abstracts B: Bacteriology KW - Phosphorylation KW - Dimerization KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17098915?accountid=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=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Autophosphorylation+of+Enzyme+I+of+the+Escherichia+coli+Phosphoenolpyruvate%3ASugar+Phosphotransferase+System+Requires+Dimerization&rft.au=Seok%2C+Y%3BZhu%2C+P%3BKoo%2C+B%3BPeterkofsky%2C+A&rft.aulast=Seok&rft.aufirst=Y&rft.date=1998-09-18&rft.volume=250&rft.issue=2&rft.spage=381&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Phosphorylation; Dimerization ER - TY - JOUR T1 - Requirements for and Regulation of Origin Opening of Plasmid P1 AN - 17093827; 4404311 AB - Origin opening is essential for the initiation of DNA replication in the theta mode and requires binding of initiator proteins. Using reactivity to KMnO sub(4) in vivo as an assay, we find that, like initiation, origin opening of the Escherichia coli plasmid P1 requires the host initiators DnaA and HU and the plasmid-encoded initiator RepA. The ability to detect opening at the P1ori in vivo allowed us to study this activity at various copy numbers in chimeric replicons. The opening was prevented when the P1ori was cloned in high copy vectors or when excess RepA binding sites (iterons) were provided in trans. However, when RepA supply was also increased, the opening was efficient. A further increase in RepA prevented opening. Replication of an incoming P1 under these conditions correlated with opening. These results demonstrate that initiation is possible even at abnormally high origin concentrations and that oversupply of RepA relative to iterons, can prevent replication by blocking origin opening. It appears that plasmid overreplication can be prevented either by limiting RepA or by accumulating RepA at a rate higher than that of the origin. JF - Journal of Biological Chemistry AU - Park, K AU - Mukhopadhyay, S AU - Chattoraj, D K AD - Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255 Y1 - 1998/09/18/ PY - 1998 DA - 1998 Sep 18 SP - 24906 EP - 24911 VL - 273 IS - 38 SN - 0021-9258, 0021-9258 KW - DnaA protein KW - HU protein KW - RepA protein KW - double prime HU protein KW - plasmid P1 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA biosynthesis KW - J 02760:Plasmids KW - N 14650:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17093827?accountid=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=Requirements+for+and+Regulation+of+Origin+Opening+of+Plasmid+P1&rft.au=Park%2C+K%3BMukhopadhyay%2C+S%3BChattoraj%2C+D+K&rft.aulast=Park&rft.aufirst=K&rft.date=1998-09-18&rft.volume=273&rft.issue=38&rft.spage=24906&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 - DNA biosynthesis ER - TY - JOUR T1 - Caspase dependence of target cell damage induced by cytotoxic lymphocytes. AN - 73923458; 9743340 AB - Since the CTL secreted granule protease granzyme B can activate multiple target caspases, it has been proposed that this pathway is responsible for CTL-induced cytolysis of Fas-negative targets. However, target lysis via the granule exocytosis pathway is completely resistant to caspase inhibitors. To test the possibility that granzymes trigger a postcaspase cytoplasmic apoptotic pathway leading to lysis, we have examined the caspase dependence of several cytoplasmic changes associated with apoptotic death. Rapid prelytic phosphatidylserine externalization was induced in Jurkat target cells by both the Fas ligand (FasL)/Fas and the granule exocytosis effector pathways. This was specifically blocked by peptide ketone caspase inhibitors when induced by the former, but not by the latter, pathway. A rapid prelytic loss of target mitochondrial psi was also induced by both CTL effector pathways, and this was also specifically blocked by caspase inhibitors when induced by the FasL/Fas, but not by the granule exocytosis, pathway. Similarly, target membrane blebbing induced by CTL via the FasL/Fas, but not via the granule exocytosis, effector pathway was specifically blocked by caspase inhibitors. In contrast to the above nonnuclear damage, CTL-induced target staining by the lipid probe FM1-43 reflecting plasma membrane endocytosis was blocked by caspase inhibitors. Thus, when caspase activation is blocked, the granule exocytosis pathway triggers several parameters of target apoptotic damage in addition to lysis, suggesting that granzymes directly trigger a postcaspase cytoplasmic apoptotic death pathway. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Sarin, A AU - Haddad, E K AU - Henkart, P A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892-1360, USA. Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 2810 EP - 2816 VL - 161 IS - 6 SN - 0022-1767, 0022-1767 KW - Amino Acid Chloromethyl Ketones KW - 0 KW - Antigens, CD95 KW - Cysteine Proteinase Inhibitors KW - FASLG protein, human KW - Fas Ligand Protein KW - Ligands KW - Membrane Glycoproteins KW - Oligopeptides KW - Phosphatidylserines KW - benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Abridged Index Medicus KW - Index Medicus KW - Cytoplasmic Granules -- enzymology KW - Cell Nucleus -- pathology KW - Cell Membrane -- enzymology KW - Phosphatidylserines -- metabolism KW - Humans KW - Cell Nucleus -- immunology KW - Jurkat Cells KW - Apoptosis -- immunology KW - Antigens, CD95 -- immunology KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Leukemia, Erythroblastic, Acute KW - Cell Membrane -- immunology KW - Tumor Cells, Cultured KW - Mitochondria -- immunology KW - Cytoplasmic Granules -- immunology KW - Cytotoxicity Tests, Immunologic KW - Exocytosis -- immunology KW - Oligopeptides -- pharmacology KW - Amino Acid Chloromethyl Ketones -- pharmacology KW - Membrane Glycoproteins -- immunology KW - Cysteine Endopeptidases -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cytotoxicity, Immunologic -- drug effects KW - Cysteine Endopeptidases -- drug effects KW - T-Lymphocytes, Cytotoxic -- enzymology KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- enzymology KW - Killer Cells, Natural -- drug effects KW - T-Lymphocytes, Cytotoxic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73923458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caspase+dependence+of+target+cell+damage+induced+by+cytotoxic+lymphocytes.&rft.au=Sarin%2C+A%3BHaddad%2C+E+K%3BHenkart%2C+P+A&rft.aulast=Sarin&rft.aufirst=A&rft.date=1998-09-15&rft.volume=161&rft.issue=6&rft.spage=2810&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 - 1998-10-06 N1 - Date created - 1998-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of residues 286 and 289 as critical for conferring substrate specificity of human CYP2C9 for diclofenac and ibuprofen. AN - 73919573; 9735164 AB - Specificity of human CYP2C9 for two substrates, diclofenac and ibuprofen, was studied using chimeras and site-directed mutants of CYP2C9 and the highly related CYP2C19 expressed in Escherichia coli. Data were correlated with the presence of putative substrate recognition sites (SRS). A CYP2C19 chimera containing residues 228-340 (SRS 3 and 4) of 2C9 conferred both diclofenac hydroxylation and 2- and 3-hydroxylation of ibuprofen. The regiospecificity of this construct for metabolism of ibuprofen differed from that of CYP2C9 by favoring 2-hydroxylation over 3-hydroxylation. A CYP2C9 construct containing residues 228-340 of CYP2C19 lacked both diclofenac and ibuprofen hydroxylase activities. When residues 228-282 (containing SRS 3) of CYP2C9 were replaced by those of CYP2C19, the chimera retained appreciable activity for diclofenac and ibuprofen, and tolbutamide activity was inhibited by a specific CYP2C9 inhibitor, sulfaphenazole. This suggested that SRS 3 is not important in conferring specificity. CYP2C9 and CYP2C19 differ in five residues within the region 283-340 (within SRS 4). Mutations to analyze SRS 4 were made on a CYP2C19 chimera containing residues 228-282 of CYP2C9. A single I289N mutation conferred a dramatic increase in diclofenac hydroxylation and a small increase in ibuprofen 2-hydroxylation. A second mutation (N286S and I289N) increased diclofenac hydroxylation and conferred a dramatic increase in ibuprofen 2-hydroxylation. A V288E mutation did not increase activity toward either substrate and decreased activity toward the two substrates in combination with the I289N or the N286S, I289N mutants. Therefore residues 286 and 289 of CYP2C9 are important in conferring specificity for diclofenac and ibuprofen. JF - Archives of biochemistry and biophysics AU - Klose, T S AU - Ibeanu, G C AU - Ghanayem, B I AU - Pedersen, L G AU - Li, L AU - Hall, S D AU - Goldstein, J A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 240 EP - 248 VL - 357 IS - 2 SN - 0003-9861, 0003-9861 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Recombinant Fusion Proteins KW - Diclofenac KW - 144O8QL0L1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Tolbutamide KW - 982XCM1FOI KW - Mixed Function Oxygenases KW - EC 1.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Steroid 16-alpha-Hydroxylase KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Humans KW - Escherichia coli -- genetics KW - Substrate Specificity -- genetics KW - Enzyme Activation -- genetics KW - Hydroxylation KW - Mutagenesis, Site-Directed KW - Tolbutamide -- metabolism KW - Protein Binding -- drug effects KW - Recombinant Fusion Proteins -- genetics KW - Enzyme Activation -- drug effects KW - Protein Binding -- genetics KW - Mixed Function Oxygenases -- genetics KW - Ibuprofen -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Diclofenac -- metabolism KW - Steroid Hydroxylases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Steroid Hydroxylases -- genetics KW - Steroid Hydroxylases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73919573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+residues+286+and+289+as+critical+for+conferring+substrate+specificity+of+human+CYP2C9+for+diclofenac+and+ibuprofen.&rft.au=Klose%2C+T+S%3BIbeanu%2C+G+C%3BGhanayem%2C+B+I%3BPedersen%2C+L+G%3BLi%2C+L%3BHall%2C+S+D%3BGoldstein%2C+J+A&rft.aulast=Klose&rft.aufirst=T&rft.date=1998-09-15&rft.volume=357&rft.issue=2&rft.spage=240&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 - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis in the developing cerebellum of the thyroid hormone deficient rat. AN - 73908114; 9740554 AB - The mechanism underlying transient reduction of cell number in the developing cerebellum have been studied for several decades. In this study we analyzed cell death by apoptosis in the developing cerebellum of euthyroid and hypothyroid rats. Results showed that in both groups the apoptotic activity is limited to the internal granular layer from postnatal (p) day 2 to day 12 in euthyroid animals, with the peak at 8 days. No apoptotic cells were detected in the cerebellum of 22 days old euthyroid rats. The level of apoptosis in the cerebellum of hypothyroid rats also reached a peak at 8 days but was four times higher than in control animals. Apoptosis in hypothyroid animals was also observed at p22 and corresponds to the value found in the time of the apoptotic peak in euthyroid cerebellum. At the age of 42 days, no apoptotic cells were found in the cerebellum of either group. Furthermore, it appears that the hormone also plays a role in the disappearance of the external germinal layer, since its presence is still apparent in 42 day old hypothyroid cerebellum. Hence, our results suggest that the deficiency of thyroid hormone (TH) not only increases, but also extends apoptosis during rat cerebellum development and affects the disappearance of the external germinal layer. JF - Frontiers in bioscience : a journal and virtual library AU - Xiao, Q AU - Nikodem, V M AD - Mechanism of Gene Regulation Section, Genetics and Biochemistry Branch, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 10 Center Dr. MSC 1766, Bethesda, MD 20892-1766, USA. Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - A52 EP - A57 VL - 3 SN - 1093-9946, 1093-9946 KW - Antithyroid Agents KW - 0 KW - Thyroid Hormones KW - Methimazole KW - 554Z48XN5E KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Thyroid Hormones -- physiology KW - Aging KW - Hypothyroidism -- pathology KW - Thyroid Hormones -- deficiency KW - Hypothyroidism -- chemically induced KW - Antithyroid Agents -- pharmacology KW - Methimazole -- pharmacology KW - DNA Fragmentation KW - Thyroid Gland -- physiology KW - Apoptosis KW - Cerebellum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73908114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apoptosis+in+the+developing+cerebellum+of+the+thyroid+hormone+deficient+rat.&rft.au=Xiao%2C+Q%3BNikodem%2C+V+M&rft.aulast=Xiao&rft.aufirst=Q&rft.date=1998-09-15&rft.volume=3&rft.issue=&rft.spage=A52&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 - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis. AN - 73900751; 9740093 AB - Tumor necrosis factor (TNF), hyperthermia, and cisplatin have synergistic cytotoxicity against cancer cells in vitro. This combination may be well suited to the regional treatment of peritoneal tumor spread in patients. Continuous hyperthermic peritoneal perfusion (CHPP) is a technique that allows uniform delivery of cytotoxic agents and heat to the peritoneal surface. A Phase I trial of CHPP with TNF and cisplatin was conducted to define the maximum tolerated dose (MTD) for TNF and cisplatin under moderate hyperthermia in the treatment of peritoneal carcinomatosis. Twenty-seven patients with peritoneal carcinomatosis underwent exploratory laparotomy and tumor debulking followed by a 90-minute CHPP with cisplatin (100-350 mg/m2) and TNF (0-0.3 mg/L). Perfusion parameters included a perfusate volume of 3-9 L, a peritoneal temperature of 42-43 degrees C, and a flow rate of 1.5 L/minute. Sodium thiosulfate was administered systemically during and after the perfusion as a cisplatin binding agent. There was no operative or treatment-related mortality in this study. CHPP resulted in a 14-fold higher area under the concentration versus time curve (AUC) for cisplatin in the perfusate compared with plasma, and a 4854-fold higher AUC for TNF. The MTD was defined as 250 mg/m2 cisplatin plus 0.1 mg/L TNF. The dose-limiting toxicity was renal insufficiency. No other systemic toxicity was identified, and no significant regional toxicity was identified. The median time to toleration of a regular diet was 8 days (range, 5-20 days). The favorable regional pharmacologic profile of the combination of cisplatin and TNF suggests that these agents administered via CHPP warrant further evaluation as prophylaxis against or treatment for peritoneal carcinomatosis. JF - Cancer AU - Bartlett, D L AU - Buell, J F AU - Libutti, S K AU - Reed, E AU - Lee, K B AU - Figg, W D AU - Venzon, D J AU - Alexander, H R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 1251 EP - 1261 VL - 83 IS - 6 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Cisplatin KW - Q20Q21Q62J KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Area Under Curve KW - Combined Modality Therapy KW - Humans KW - Chemotherapy, Cancer, Regional Perfusion KW - Adult KW - Middle Aged KW - Infusions, Parenteral KW - Male KW - Female KW - Cisplatin -- pharmacokinetics KW - Carcinoma -- therapy KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Hyperthermia, Induced KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Cisplatin -- adverse effects KW - Peritoneal Neoplasms -- therapy KW - Cisplatin -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73900751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=A+phase+I+trial+of+continuous+hyperthermic+peritoneal+perfusion+with+tumor+necrosis+factor+and+cisplatin+in+the+treatment+of+peritoneal+carcinomatosis.&rft.au=Bartlett%2C+D+L%3BBuell%2C+J+F%3BLibutti%2C+S+K%3BReed%2C+E%3BLee%2C+K+B%3BFigg%2C+W+D%3BVenzon%2C+D+J%3BAlexander%2C+H+R&rft.aulast=Bartlett&rft.aufirst=D&rft.date=1998-09-15&rft.volume=83&rft.issue=6&rft.spage=1251&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer 1998 Nov 15;83(10):2241 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. AN - 73872917; 9722641 AB - Iterative profile searches and structural modeling show that bacterial DnaG-type primases, small primase-like proteins from bacteria and archaea, type IA and type II topoisomerases, bacterial and archaeal nucleases of the OLD family and bacterial DNA repair proteins of the RecR/M family contain a common domain, designated Toprim (topoisomerase-primase) domain. The domain consists of approximately 100 amino acids and has two conserved motifs, one of which centers at a conserved glutamate and the other one at two conserved aspartates (DxD). Examination of the structure of Topo IA and Topo II and modeling of the Toprim domains of the primases reveal a compact beta/alpha fold, with the conserved negatively charged residues juxtaposed, and inserts seen in Topo IA and Topo II. The conserved glutamate may act as a general base in nucleotide polymerization by primases and in strand rejoining by topoisomerases and as a general acid in strand cleavage by topoisomerases and nucleases. The role of this glutamate in catalysis is supported by site-directed mutagenesis data on primases and Topo IA. The DxD motif may coordinate Mg2+that is required for the activity of all Toprim-containing enzymes. The common ancestor of all life forms could encode a prototype Toprim enzyme that might have had both nucleotidyl transferase and polynucleotide cleaving activity. JF - Nucleic acids research AU - Aravind, L AU - Leipe, D D AU - Koonin, E V AD - Department of Biology, Texas A&M University, College Station, TX 70843, USA, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 4205 EP - 4213 VL - 26 IS - 18 SN - 0305-1048, 0305-1048 KW - Bacterial Proteins KW - 0 KW - RecR protein, Bacteria KW - 125524-02-9 KW - DNA Primase KW - EC 2.7.7.- KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Space life sciences KW - Bacteria -- genetics KW - Sequence Alignment KW - Conserved Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Evolution, Molecular KW - Archaea -- genetics KW - Catalysis KW - Binding Sites KW - Bacterial Proteins -- genetics KW - DNA Topoisomerases, Type II -- genetics KW - Bacterial Proteins -- metabolism KW - DNA Topoisomerases, Type II -- metabolism KW - DNA Topoisomerases, Type I -- genetics KW - DNA Topoisomerases, Type I -- chemistry KW - DNA Primase -- genetics KW - Bacterial Proteins -- chemistry KW - DNA Primase -- chemistry KW - DNA Topoisomerases, Type I -- metabolism KW - DNA Topoisomerases, Type II -- chemistry KW - Protein Conformation KW - DNA Primase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73872917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toprim--a+conserved+catalytic+domain+in+type+IA+and+II+topoisomerases%2C+DnaG-type+primases%2C+OLD+family+nucleases+and+RecR+proteins.&rft.au=Aravind%2C+L%3BLeipe%2C+D+D%3BKoonin%2C+E+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=1998-09-15&rft.volume=26&rft.issue=18&rft.spage=4205&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 - 1998-11-02 N1 - Date created - 1998-11-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 1998 Apr;18(4):313-8 [9537411] J Biol Chem. 1998 Apr 10;273(15):8783-9 [9535856] Mol Cell. 1997 Dec;1(1):89-97 [9659906] Mol Cell. 1998 Apr;1(5):741-8 [9660957] Protein Eng. 1993 Jan;6(1):37-40 [8433969] J Mol Biol. 1970 Mar;48(3):443-53 [5420325] Cell. 1980 Nov;22(1 Pt 1):269-76 [6253080] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2264-8 [2315319] J Mol Biol. 1990 Jun 20;213(4):583-91 [2162963] Curr Top Microbiol Immunol. 1990;163:93-123 [2242683] Proteins. 1991;9(3):180-90 [2006136] Annu Rev Biochem. 1991;60:39-71 [1883199] J Mol Evol. 1992 Apr;34(4):351-7 [1569588] J Biol Chem. 1992 Jun 25;267(18):13062-72 [1618804] Protein Seq Data Anal. 1992;5(1):43-5 [1492096] J Bacteriol. 1995 Feb;177(3):497-501 [7836278] Science. 1995 Mar 24;267(5205):1817-20 [7892605] Nat Struct Biol. 1995 Jan;2(1):25-6 [7719848] J Mol Biol. 1995 Apr 7;247(4):536-40 [7723011] J Biol Chem. 1995 Jun 9;270(23):14148-53 [7775476] Curr Opin Genet Dev. 1995 Apr;5(2):174-9 [7613086] Protein Sci. 1995 Aug;4(8):1618-32 [8520488] J Gen Virol. 1995 Dec;76 ( Pt 12):2923-32 [8847496] Indian J Biochem Biophys. 1995 Aug;32(4):171-8 [8655184] Biochemistry. 1995 Dec 26;34(51):16708-14 [8527445] Methods Enzymol. 1995;262:405-14 [8594364] Nature. 1996 Jan 18;379(6562):225-32 [8538787] Biochem Soc Trans. 1996 Feb;24(1):274-9 [8674685] Curr Opin Struct Biol. 1996 Feb;6(1):84-90 [8696977] Nucleic Acids Res. 1996 Jul 1;24(13):2488-97 [8692686] J Biol Chem. 1996 Aug 9;271(32):19563-70 [8702650] Methods Enzymol. 1996;266:460-80 [8743700] Methods Enzymol. 1996;266:513-25 [8743703] Methods Enzymol. 1996;266:554-71 [8743706] J Biol Chem. 1996 Aug 30;271(35):21391-7 [8702920] Curr Biol. 1996 Mar 1;6(3):279-91 [8805245] Annu Rev Biochem. 1996;65:635-92 [8811192] Nucleic Acids Res. 1996 Nov 1;24(21):4171-5 [8932368] Biosystems. 1993;30(1-3):241-68 [8374079] J Biol Chem. 1994 Feb 11;269(6):4675-82 [8308039] Nature. 1994 Jan 13;367(6459):138-46 [8114910] Nat Genet. 1994 Feb;6(2):119-29 [8162065] Comput Appl Biosci. 1994 Feb;10(1):53-60 [8193956] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12091-5 [7991589] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14468-73 [8962075] Nucleic Acids Res. 1997 Jan 1;25(1):236-9 [9016544] Comput Appl Biosci. 1996 Dec;12(6):543-8 [9021275] Virus Genes. 1996;13(3):229-37 [9035367] J Mol Biol. 1997 Mar 7;266(4):688-702 [9102462] Nature. 1997 Mar 27;386(6623):414-7 [9121560] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3714-9 [9108043] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5831-6 [9159160] Cell. 1997 Jun 27;89(7):995-8 [9215620] J Mol Biol. 1997 Jul 18;270(3):471-80 [9237912] Nature. 1997 Aug 7;388(6642):598-602 [9252192] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] Proc Int Conf Intell Syst Mol Biol. 1997;5:234-6 [9322042] Proc Int Conf Intell Syst Mol Biol. 1997;5:333-9 [9322058] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10606-11 [9380682] Science. 1997 Oct 24;278(5338):631-7 [9381173] Mol Microbiol. 1997 Aug;25(4):619-37 [9379893] Cell. 1997 Oct 31;91(3):347-56 [9363943] J Mol Biol. 1997 Oct 17;273(1):355-68 [9367768] J Bacteriol. 1997 Nov;179(22):7135-55 [9371463] Nucleic Acids Res. 1998 Jan 1;26(1):316-9 [9399863] Nature. 1998 Jan 15;391(6664):231-2 [9440683] J Biol Chem. 1998 Mar 13;273(11):6050-6 [9497321] J Mol Biol. 1998 Mar 27;277(2):257-71 [9514760] Cell. 1998 Mar 20;92(6):841-50 [9529259] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of Human Cytolytic T Lymphocyte Lines Directed Against Prostate-Specific Antigen (PSA) Employing a PSA Oligoepitope Peptide AN - 16501884; 4403562 AB - Prostate-specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity. T cell lines from different HLA-A2 and HLA-A3 donors were established by in vitro stimulation with PSA-OP; the CTL lines lysed PSA-OP as well as PSA-1- or PSA-3-pulsed C1R-A2 cells, and PSA-OP and PSA-9-pulsed C1R-A3 cells, respectively. The CTL lines derived from the PSA-OP peptide also lysed PSA-positive prostate cancer cells. PSA-OP-derived T cell lines also lysed recombinant vaccinia-PSA-infected targets but not targets infected with wild-type vaccinia. PSA-OP did not bind HLA-A2 and HLA-A3 molecules. The decrease in cytotoxicity in the presence of protease inhibitors suggests that the PSA-OP is cleaved into shorter peptides, which in turn can interact with HLA-class I molecules and, as a consequence, induce CTL-mediated lysis. We have also demonstrated that it is possible to induce CTL responses in HLA-A2.1/K super(b) transgenic mice by immunization with PSA-OP with adjuvant. These studies thus provide evidence that oligopeptides such as PSA-OP may be useful candidates for peptide-based cancer vaccines. JF - Journal of Immunology AU - Correale, P AU - Walmsley, K AU - Zaremba, S AU - Zhu, M AU - Schlom, J AU - Tsang, KY AD - Laboratory of Tumor Immunology and Biology, Division of Basic Science, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 8B07, Bethesda, MD 20892, USA, js141c@nih.gov Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 3186 EP - 3194 VL - 161 IS - 6 SN - 0022-1767, 0022-1767 KW - prostate-specific antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06725:Leukocyte isolation, characterization & preservation KW - W3 33235:New cell lines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16501884?accountid=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+Human+Cytolytic+T+Lymphocyte+Lines+Directed+Against+Prostate-Specific+Antigen+%28PSA%29+Employing+a+PSA+Oligoepitope+Peptide&rft.au=Correale%2C+P%3BWalmsley%2C+K%3BZaremba%2C+S%3BZhu%2C+M%3BSchlom%2C+J%3BTsang%2C+KY&rft.aulast=Correale&rft.aufirst=P&rft.date=1998-09-15&rft.volume=161&rft.issue=6&rft.spage=3186&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 ER - TY - JOUR T1 - Activation of Cutaneous Dendritic Cells by CpG-Containing Oligodeoxynucleotides: A Role for Dendritic Cells in the Augmentation of Th1 Responses by Immunostimulatory DNA AN - 16501572; 4403544 AB - Genetic vaccination depends at least in part on the adjuvant properties of plasmids, properties that have been ascribed to unmethylated CpG dinucleotides in bacterial DNA. Because dendritic cells (DC) participate in the T cell priming that occurs during genetic vaccination, we reasoned that CpG-containing DNA might activate DC. Thus, we assessed the effects of CpG oligodeoxynucleotides (CpG ODN) on Langerhans cell (LC)-like murine fetal skin-derived DC (FSDDC) in vitro and on LC in vivo. Treatment with CpG ODN as well as LPS induced FSDDC maturation, manifested by decreased E-cadherin-mediated adhesion, up-regulation of MHC class II and costimulator molecule expression, and acquisition of enhanced accessory cell activity. In contrast to LPS, CpG ODN stimulated FSDDC to produce large amounts of IL-12 but only small amounts of IL-6 and TNF- alpha . Injection of CpG ODN into murine dermis also led to enhanced expression of MHC class II and CD86 Ag by LC in overlying epidermis and intracytoplasmic IL-12 accumulation in a subpopulation of activated LC. We conclude that immunostimulatory CpG ODN stimulate DC in vitro and in vivo. Bacterial DNA-based vaccines may preferentially elicit Th1-predominant immune responses because they activate and mobilize DC and induce them to produce large amounts of IL-12. JF - Journal of Immunology AU - Jakob, T AU - Walker, P S AU - Krieg, A M AU - Udey, M C 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, USA, jonvogel@box-j.nih.gov Y1 - 1998/09/15/ PY - 1998 DA - 1998 Sep 15 SP - 3042 EP - 3049 VL - 161 IS - 6 SN - 0022-1767, 0022-1767 KW - DNA vaccines KW - oligodeoxynucleotides KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06807:Active immunization 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/16501572?accountid=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=Activation+of+Cutaneous+Dendritic+Cells+by+CpG-Containing+Oligodeoxynucleotides%3A+A+Role+for+Dendritic+Cells+in+the+Augmentation+of+Th1+Responses+by+Immunostimulatory+DNA&rft.au=Jakob%2C+T%3BWalker%2C+P+S%3BKrieg%2C+A+M%3BUdey%2C+M+C%3BVogel%2C+J+C&rft.aulast=Jakob&rft.aufirst=T&rft.date=1998-09-15&rft.volume=161&rft.issue=6&rft.spage=3042&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 ER - TY - JOUR T1 - The appetite suppressant d-fenfluramine induces apoptosis in human serotonergic cells. AN - 70025298; 9804303 AB - Fenfluramine is an amphetamine analogue which has been widely used in the treatment of obesity. In rodents, non-human primates, and humans, fenfluramine is associated with some indices of neurotoxicity, as well as pulmonary hypertension and cardiac valve pathology. In the present study, d-fenfluramine was found to be cytotoxic to the serotonin (5-HT) transporter (5-HTT) expressing human placental choriocarcinoma cells. d-Fenfluramine caused DNA fragmentation and apoptosis. Apoptosis was not observed after the 5-HTT had been blocked by fluoxetine, indicating that intact 5-HTT function is required for d-fenfluramine to induce programmed cell death. These observations in a human cell line may reflect a possible mechanism associated with the risks of fenfluramine administration in several species, including humans. JF - Neuroreport AU - Bengel, D AU - Isaacs, K R AU - Heils, A AU - Lesch, K P AU - Murphy, D L AD - Section on Clinical Neuropharmacology, Laboratory of Clinical Science, NIMH, NIH Clinical Center, Bethesda, MD 20892, USA. Y1 - 1998/09/14/ PY - 1998 DA - 1998 Sep 14 SP - 2989 EP - 2993 VL - 9 IS - 13 SN - 0959-4965, 0959-4965 KW - Appetite Depressants KW - 0 KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Agents KW - Serotonin Plasma Membrane Transport Proteins KW - Fluoxetine KW - 01K63SUP8D KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Fluoxetine -- pharmacology KW - Carrier Proteins -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Choriocarcinoma KW - Cell Nucleus -- drug effects KW - Biological Transport -- drug effects KW - Cell Size -- drug effects KW - Tumor Cells, Cultured KW - DNA Fragmentation -- drug effects KW - Serotonin Agents -- toxicity KW - Time Factors KW - Female KW - Membrane Glycoproteins -- metabolism KW - Fenfluramine -- toxicity KW - Fenfluramine -- antagonists & inhibitors KW - Apoptosis -- drug effects KW - Serotonin -- metabolism KW - Appetite Depressants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+appetite+suppressant+d-fenfluramine+induces+apoptosis+in+human+serotonergic+cells.&rft.au=Bengel%2C+D%3BIsaacs%2C+K+R%3BHeils%2C+A%3BLesch%2C+K+P%3BMurphy%2C+D+L&rft.aulast=Bengel&rft.aufirst=D&rft.date=1998-09-14&rft.volume=9&rft.issue=13&rft.spage=2989&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The future of transgenic mutation models: Introduction to the panel discussion AN - 17129890; 4437284 AB - There has been an impressive amount of R&D during the past few years into the development and validation of transgenic rodent models for mutagenesis, and new models continue to be proposed and developed. We all acknowledge that there is a need for such tools, but may not yet be sure as to how they should be used, or whether they are more effective than our old-fashioned, non-transgenic tools. One of the driving forces behind the development of transgenic mutation systems has been the difficulties, both physiological and psychological, in extrapolating mutagenic effects from cells in vitro to hazard and risk parameters in vivo. These difficulties arise from the recognition that in vitro metabolic activation systems can, at best, only approximate the reactions occurring in the intact animal, and that reaction kinetics cannot be extrapolated from in vitro conditions to in vivo. Transgenic animals promise a number of uses for genetic and mutagenesis studies. These uses range from addressing basic research questions about how the body and its various systems work and respond to internal and external stimuli, to questions that come under the general rubrics of "research and development" and "testing." The possibility of being able to measure mutation in any tissue of the body under normal conditions or as a function of chemical treatment or other stress conditions, and to measure the kinetics of mutation induction as a function of time and physiology, and to be able to relate these mutagenic effects to acute and chronic disease, is very attractive and enticing. JF - Environmental and Molecular Mutagenesis AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA Y1 - 1998/09/14/ PY - 1998 DA - 1998 Sep 14 SP - 103 VL - 32 IS - 2 SN - 0893-6692, 0893-6692 KW - Toxicology Abstracts; Genetics Abstracts KW - Animal models KW - Genotoxicity testing KW - Mutagenesis KW - Transgenic animals KW - Genetic engineering KW - Reviews KW - Toxicity testing KW - G 07220:General theory/testing systems KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17129890?accountid=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+and+Molecular+Mutagenesis&rft.atitle=The+future+of+transgenic+mutation+models%3A+Introduction+to+the+panel+discussion&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1998-09-14&rft.volume=32&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Environmental+and+Molecular+Mutagenesis&rft.issn=08936692&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 - Mutagenesis; Reviews; Genetic engineering; Animal models; Transgenic animals; Toxicity testing; Genotoxicity testing ER - TY - JOUR T1 - A novel mutation in the switch 3 region of Gsalpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation. AN - 73885735; 9727013 AB - Albright hereditary osteodystrophy (AHO), a disorder characterized by skeletal abnormalities and obesity, is associated with heterozygous inactivating mutations in the gene for Gsalpha. A novel Gsalpha mutation encoding the substitution of tryptophan for a nonconserved arginine within the switch 3 region (Gsalpha R258W) was identified in an AHO patient. Although reverse transcription-polymerase chain reaction studies demonstrated that mRNA expression from wild type and mutant alleles was similar, Gsalpha expression in erythrocyte membranes from the affected patient was reduced by 50%. A Gsalpha R258W cDNA, as well as one with arginine replaced by alanine (Gsalpha R258A), was generated, and the biochemical properties of in vitro transcription/translation products were examined. When reconstituted with cyc- membranes, both mutant proteins were able to stimulate adenylyl cyclase normally in the presence of guanosine- 5'-O-(3-thiotriphosphate) (GTPgammaS) but had decreased ability in the presence of isoproterenol or AlF4- (a mixture of 10 microM AlCl3 and 10 mM NaF). The ability of each mutant to bind and be activated by GTPgammaS or AlF4- was assessed by trypsin protection assays. Both mutants were protected normally by GTPgammaS but showed reduced protection in the presence of AlF4-. The addition of excess GDP (2 mM) was able to rescue the ability of AlF4- to protect the mutants, suggesting that they might have reduced affinity for GDP. A Gsalpha R258A mutant purified from Escherichia coli had decreased affinity for GDP and an apparent rate of GDP release that was 10-fold greater than that of wild type Gsalpha. Sucrose density gradient analysis demonstrated that both Gsalpha R258W and Gsalpha R258A were thermolabile at higher temperatures and that denaturation of both mutants was prevented by the presence of 0.1 mM GTPgammaS or 2 mM GDP. The crystal structure of Gsalpha demonstrates that Arg258 interacts with a conserved residue in the helical domain (Gln170). Arg258 substitutions would be predicted to open the cleft between the GTPase and helical domains, allowing for increased GDP release in the inactive state, resulting in enhanced thermolability and reduced AlF4--induced adenylyl cyclase stimulation and trypsin protection, since activation by AlF4- requires bound GDP. JF - The Journal of biological chemistry AU - Warner, D R AU - Weng, G AU - Yu, S AU - Matalon, R AU - Weinstein, L S AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. dwarner@helix.nih.gov Y1 - 1998/09/11/ PY - 1998 DA - 1998 Sep 11 SP - 23976 EP - 23983 VL - 273 IS - 37 SN - 0021-9258, 0021-9258 KW - Aluminum Compounds KW - 0 KW - RNA, Messenger KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Guanosine Diphosphate KW - 146-91-8 KW - tetrafluoroaluminate KW - 21340-02-3 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Tryptophan KW - 8DUH1N11BX KW - Arginine KW - 94ZLA3W45F KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Alanine KW - OF5P57N2ZX KW - Fluorides KW - Q80VPU408O KW - Index Medicus KW - Protein Structure, Secondary KW - Humans KW - Adenylyl Cyclases -- metabolism KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Mutagenesis, Site-Directed KW - Receptors, Cell Surface -- metabolism KW - Recombinant Proteins -- metabolism KW - Adult KW - Escherichia coli KW - Molecular Sequence Data KW - Aluminum Compounds -- pharmacology KW - Male KW - Protein Biosynthesis KW - Exons KW - Models, Molecular KW - Fluorides -- pharmacology KW - Amino Acid Sequence KW - Cloning, Molecular KW - Binding Sites KW - Polymerase Chain Reaction KW - Base Sequence KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Female KW - Guanosine Diphosphate -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- genetics KW - Fibrous Dysplasia, Polyostotic -- genetics KW - Point Mutation KW - GTP-Binding Protein alpha Subunits, Gs -- chemistry KW - GTP-Binding Protein alpha Subunits, Gs -- blood KW - Erythrocyte Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73885735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+novel+mutation+in+the+switch+3+region+of+Gsalpha+in+a+patient+with+Albright+hereditary+osteodystrophy+impairs+GDP+binding+and+receptor+activation.&rft.au=Warner%2C+D+R%3BWeng%2C+G%3BYu%2C+S%3BMatalon%2C+R%3BWeinstein%2C+L+S&rft.aulast=Warner&rft.aufirst=D&rft.date=1998-09-11&rft.volume=273&rft.issue=37&rft.spage=23976&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 - 1998-10-13 N1 - Date created - 1998-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gonococcal invasion of epithelial cells driven by P.IA, a bacterial ion channel with GTP binding properties. AN - 73912024; 9730895 AB - The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine. JF - The Journal of experimental medicine AU - van Putten, J P AU - Duensing, T D AU - Carlson, J AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840-2999, USA. jos_van_putten@nih.gov Y1 - 1998/09/07/ PY - 1998 DA - 1998 Sep 07 SP - 941 EP - 952 VL - 188 IS - 5 SN - 0022-1007, 0022-1007 KW - Antigens, Bacterial KW - 0 KW - Bacterial Outer Membrane Proteins KW - Ion Channels KW - Phosphates KW - Porins KW - Rmp protein, Neisseria KW - opacity proteins KW - porin protein, Neisseria KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Alleles KW - Phosphates -- pharmacology KW - Humans KW - Bacterial Outer Membrane Proteins -- genetics KW - Mutagenesis, Insertional KW - Cell Line KW - Porins -- genetics KW - Antigens, Bacterial -- metabolism KW - Neisseria gonorrhoeae -- pathogenicity KW - Ion Channels -- immunology KW - Porins -- metabolism KW - Epithelial Cells -- microbiology KW - Ion Channels -- drug effects KW - GTP-Binding Proteins -- drug effects KW - Ion Channels -- metabolism KW - Neisseria gonorrhoeae -- drug effects KW - Epithelial Cells -- drug effects KW - Porins -- drug effects KW - GTP-Binding Proteins -- metabolism KW - Antigens, Bacterial -- physiology KW - Epithelial Cells -- immunology KW - GTP-Binding Proteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73912024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gonococcal+invasion+of+epithelial+cells+driven+by+P.IA%2C+a+bacterial+ion+channel+with+GTP+binding+properties.&rft.au=van+Putten%2C+J+P%3BDuensing%2C+T+D%3BCarlson%2C+J&rft.aulast=van+Putten&rft.aufirst=J&rft.date=1998-09-07&rft.volume=188&rft.issue=5&rft.spage=941&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1998 Mar 2;187(5):743-52 [9480984] Biochem J. 1998 Aug 15;334 ( Pt 1):133-9 [9693112] Mol Microbiol. 1998 Jul;29(1):369-79 [9701828] J Infect Dis. 1989 Dec;160(6):1012-7 [2511251] Biochim Biophys Acta. 1990 May 9;1024(1):111-21 [1692483] Vaccine. 1990 Jun;8(3):225-30 [1694611] Mol Microbiol. 1990 Jun;4(6):1009-18 [2170812] EMBO J. 1991 Feb;10(2):477-88 [1671354] EMBO J. 1991 Jun;10(6):1307-15 [1673923] J Exp Med. 1991 Jun 1;173(6):1395-405 [1903430] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3831-5 [6407021] Sex Transm Dis. 1984 Apr-Jun;11(2):77-80 [6431621] Infect Immun. 1984 Oct;46(1):202-12 [6207109] Nature. 1985 May 9-15;315(6015):156-8 [2859529] J Infect Dis. 1985 Aug;152(2):339-43 [3928769] Cell. 1986 Jan 17;44(1):107-15 [2866848] J Gen Microbiol. 1986 Feb;132(2):503-12 [2872268] Cell. 1986 Oct 10;47(1):61-71 [3093085] J Exp Med. 1986 Nov 1;164(5):1735-48 [3095479] J Gen Microbiol. 1986 Jun;132(6):1621-9 [2433385] J Exp Med. 1987 Apr 1;165(4):1016-25 [2435829] J Biol Chem. 1988 Jan 15;263(2):945-51 [2826469] J Clin Microbiol. 1988 Feb;26(2):358-63 [3125223] J Gen Microbiol. 1987 Sep;133(9):2639-46 [2452228] Graefes Arch Clin Exp Ophthalmol. 1988;226(4):341-5 [3139497] J Gen Microbiol. 1987 Dec;133(12):3393-401 [2460579] Cell. 1989 Feb 24;56(4):539-47 [2492905] J Clin Invest. 1989 May;83(5):1472-6 [2496142] Clin Microbiol Rev. 1989 Apr;2 Suppl:S41-8 [2497962] Immunobiology. 1993 Apr;187(3-5):382-402 [8330904] EMBO J. 1993 Nov;12(11):4043-51 [7693451] Gene. 1994 Jan 28;138(1-2):43-50 [8125316] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2456-63 [8146139] J Infect Dis. 1994 Mar;169(3):532-7 [8158024] Ann N Y Acad Sci. 1994 Aug 15;730:7-14 [8080215] Methods Enzymol. 1994;236:420-37 [7968627] Mol Microbiol. 1994 Aug;13(3):403-16 [7997158] Infect Immun. 1995 Jan;63(1):160-7 [7806353] J Cell Biol. 1991 Aug;114(3):433-42 [1907286] J Exp Med. 1991 Sep 1;174(3):705-15 [1908511] EMBO J. 1992 Mar;11(3):933-41 [1547789] Res Microbiol. 1991 Nov-Dec;142(9):985-93 [1725221] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4633-7 [1533934] FEBS Lett. 1992 Jun 15;304(2-3):216-20 [1377642] J Infect Dis. 1992 Sep;166(3):551-5 [1323620] J Biol Chem. 1992 Sep 25;267(27):19266-71 [1326549] Mol Microbiol. 1992 Nov;6(22):3439-50 [1362447] EMBO J. 1993 Feb;12(2):641-50 [8440254] J Clin Invest. 1976 Nov;58(5):1163-73 [825532] Proc Natl Acad Sci U S A. 1978 Aug;75(8):3751-5 [358202] J Bacteriol. 1980 Mar;141(3):1183-91 [6767703] J Clin Microbiol. 1980 Apr;11(4):363-9 [6768768] Infect Immun. 1980 Jun;28(3):785-91 [6772567] Infect Immun. 1982 Nov;38(2):668-72 [6183218] Prog Allergy. 1983;33:298-313 [6828470] Infect Immun. 1983 May;40(2):816-9 [6404835] Nature. 1995 Jan 26;373(6512):357-9 [7830772] Curr Top Microbiol Immunol. 1994;192:283-317 [7859510] EMBO J. 1995 May 15;14(10):2144-54 [7774572] J Exp Med. 1995 Aug 1;182(2):511-7 [7629509] Clin Microbiol Rev. 1995 Jul;8(3):376-88 [7553571] J Exp Med. 1996 Jan 1;183(1):323-7 [8551240] Trends Microbiol. 1995 Dec;3(12):469-74 [8800838] Am J Obstet Gynecol. 1996 Feb;174(2):659-66 [8623803] Cell. 1996 May 3;85(3):391-402 [8616894] Mol Microbiol. 1996 Dec;22(5):941-50 [8971715] Infect Immun. 1997 Mar;65(3):964-70 [9038304] J Exp Med. 1997 May 5;185(9):1557-64 [9151893] Infect Immun. 1997 Jun;65(6):2094-9 [9169737] Infect Immun. 1997 Jun;65(6):2353-61 [9169774] Infect Immun. 1997 Aug;65(8):3203-8 [9234776] Infect Immun. 1997 Sep;65(9):3857-66 [9284164] Infect Immun. 1997 Dec;65(12):5028-34 [9393792] Mol Microbiol. 1997 Dec;26(5):971-80 [9426134] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The base substitution and frameshift fidelity of Escherichia coli DNA polymerase III holoenzyme in vitro. AN - 73866679; 9722597 AB - We have investigated the in vitro fidelity of Escherichia coli DNA polymerase III holoenzyme from a wild-type and a proofreading-impaired mutD5 strain. Exonuclease assays showed the mutD5 holoenzyme to have a 30-50-fold reduced 3'-->5'-exonuclease activity. Fidelity was assayed during gap-filling synthesis across the lacId forward mutational target. The error rate for both enzymes was lowest at low dNTP concentrations (10-50 microM) and highest at high dNTP concentration (1000 microM). The mutD5 proofreading defect increased the error rate by only 3-5-fold. Both enzymes produced a high level of (-1)-frameshift mutations in addition to base substitutions. The base substitutions were mainly C-->T, G-->T, and G-->C, but dNTP pool imbalances suggested that these may reflect misincorporations opposite damaged template bases and that, instead, T-->C, G-->A, and C-->T transitions represent the normal polymerase III-mediated base.base mispairs. The frequent (-1)-frameshift mutations do not result from direct slippage but may be generated via a mechanism involving "misincorporation plus slippage." Measurements of the fidelity of wild-type and mutD5 holoenzyme during M13 in vivo replication revealed significant differences between the in vivo and in vitro fidelity with regard to both the frequency of frameshift errors and the extent of proofreading. JF - The 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, USA. Y1 - 1998/09/04/ PY - 1998 DA - 1998 Sep 04 SP - 23575 EP - 23584 VL - 273 IS - 36 SN - 0021-9258, 0021-9258 KW - DNA, Bacterial KW - 0 KW - Deoxyribonucleotides KW - DNA Polymerase III KW - EC 2.7.7.- KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - Index Medicus KW - Base Sequence KW - Models, Genetic KW - DNA, Bacterial -- biosynthesis KW - Molecular Sequence Data KW - Deoxyribonucleotides -- metabolism KW - Exodeoxyribonucleases -- metabolism KW - Frameshift Mutation KW - DNA Polymerase III -- genetics KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - DNA Polymerase III -- metabolism KW - DNA Replication KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73866679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+base+substitution+and+frameshift+fidelity+of+Escherichia+coli+DNA+polymerase+III+holoenzyme+in+vitro.&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=1998-09-04&rft.volume=273&rft.issue=36&rft.spage=23575&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 - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells. AN - 73865132; 9722577 AB - ERCC-1 is a critical gene within the nucleotide excision repair pathway, and cells without a functional ERCC-1 do not perform cisplatin-DNA adduct repair. We therefore investigated the cisplatin effect on ERCC-1 mRNA expression in vitro. In response to a 1-h cisplatin exposure, A2780/CP70 human ovarian cancer cells showed a 6-fold increase in steady-state level of ERCC-1 mRNA. This rise was attributable to increased transcription as measured by nuclear run-on assays and a 60% increase in ERCC-1 mRNA half-life. The increase in ERCC-1 mRNA was preceded by a 4-5-fold rise in mRNA expressions of c-fos and c-jun, a 14-fold increase in c-Jun protein phosphorylation, and an increase in in vitro nuclear extract binding activity to the AP-1-like site of ERCC-1. These data suggest that the induction of ERCC-1 expression in A2780/CP70 cells exposed to cisplatin results from two major factors: (a) an increase in the expression of transactivating factors that bind the AP-1-like site in the 5'-flanking region of ERCC-1 and (b) an increase in the level of c-Jun phosphorylation that enhances its transactivation property. JF - The Journal of biological chemistry AU - Li, Q AU - Gardner, K AU - Zhang, L AU - Tsang, B AU - Bostick-Bruton, F AU - Reed, E AD - Medical Ovarian Cancer Section, Department of Developmental Therapeutics, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/09/04/ PY - 1998 DA - 1998 Sep 04 SP - 23419 EP - 23425 VL - 273 IS - 36 SN - 0021-9258, 0021-9258 KW - Amanitins KW - 0 KW - DNA Adducts KW - DNA-Binding Proteins KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Transcription Factor AP-1 KW - cisplatin-DNA adduct KW - Cycloheximide KW - 98600C0908 KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Half-Life KW - Transcription Factor AP-1 -- metabolism KW - Amanitins -- pharmacology KW - Humans KW - Cycloheximide -- pharmacology KW - Up-Regulation -- drug effects KW - RNA, Messenger -- pharmacokinetics KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - Protein Binding KW - Female KW - DNA Adducts -- metabolism KW - Proto-Oncogene Proteins c-fos -- biosynthesis KW - Gene Expression Regulation, Neoplastic KW - Protein Biosynthesis KW - Ovarian Neoplasms -- genetics KW - Cisplatin -- pharmacology KW - Cisplatin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73865132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cisplatin+induction+of+ERCC-1+mRNA+expression+in+A2780%2FCP70+human+ovarian+cancer+cells.&rft.au=Li%2C+Q%3BGardner%2C+K%3BZhang%2C+L%3BTsang%2C+B%3BBostick-Bruton%2C+F%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=1998-09-04&rft.volume=273&rft.issue=36&rft.spage=23419&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 - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved stability and yield of a Fv-toxin fusion protein by computer design and protein engineering of the Fv. AN - 73862567; 9719644 AB - The conversion of the anti-mesothelin monoclonal antibody K1 to a single-chain Fv (scFv) that is fused to a truncated form of Pseudomonas exotoxin A (PE) results in a fusion protein (immunotoxin) that is unstable and refolds very inefficiently. We have devised a method that identifies candidate residues in the framework region of K1 Fv that, when mutated, improved the yield and stability of the protein. The method works by initially aligning the framework sequences of K1 VH and VL with those of other scFvs that are stable and give a good yield as immunotoxins. Then we assigned a character to each residue that indicates its state of exposure based on the known crystal structures of Fabs. This identifies residues that are not compatible with their environment in the folded state of the protein. Next we calculated the frequencies of different amino acids for each position of the Fvs based on the available sequence database. This identifies residues that are not commonly present in the conserved positions. If these residues are compatible with their exposure profile they are left unaltered. Otherwise, they are identified as candidate residues for mutation. We identified two such residues in the VH (T82 and A85) and two in the VL (H36 and V60) of K1 that did not seem appropriate for their respective positions. By mutating these residues in K1 into those that occur most commonly in the sequence database or in stable scFvs, we significantly improved the stability and yield of the K1 scFv immunotoxins. By making single and combined mutations we assessed the relative contribution of mutations at these four sites towards the stability and yield of K1 scFv immunotoxins. The method we devised is probably general and can be used to improve other scFvs. Copyright 1998 Academic Press JF - Journal of molecular biology AU - Chowdhury, P S AU - Vasmatzis, G AU - Beers, R AU - Lee, B AU - Pastan, I AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Bethesda, MD, 20892-4255, USA. Y1 - 1998/09/04/ PY - 1998 DA - 1998 Sep 04 SP - 917 EP - 928 VL - 281 IS - 5 SN - 0022-2836, 0022-2836 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - GPI-Linked Proteins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Membrane Glycoproteins KW - Recombinant Fusion Proteins KW - mesothelin KW - Index Medicus KW - Computer Simulation KW - Models, Molecular KW - Amino Acid Sequence KW - Antibodies, Monoclonal -- chemistry KW - Mutagenesis -- genetics KW - Protein Binding -- immunology KW - Recombinant Fusion Proteins -- chemistry KW - Biosensing Techniques KW - Immunoglobulin Fragments -- chemistry KW - Protein Engineering KW - Molecular Sequence Data KW - Bacterial Toxins -- chemistry KW - Protein Structure, Tertiary KW - Membrane Glycoproteins -- immunology KW - Pseudomonas -- chemistry KW - Immunotoxins -- chemistry KW - Exotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73862567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Improved+stability+and+yield+of+a+Fv-toxin+fusion+protein+by+computer+design+and+protein+engineering+of+the+Fv.&rft.au=Chowdhury%2C+P+S%3BVasmatzis%2C+G%3BBeers%2C+R%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Chowdhury&rft.aufirst=P&rft.date=1998-09-04&rft.volume=281&rft.issue=5&rft.spage=917&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 - 1998-10-02 N1 - Date created - 1998-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of MutS ATPase activity in MutS,L- dependent block of in vitro strand transfer AN - 16555419; 4368656 AB - In addition to mismatch recognition, Escherichia coli MutS has an associated ATPase activity that is fundamental to repair.Hence, we have characterized two MutS mutant gene products todefine the role of ATP hydrolysis in homeologous recombination.These mutants, denoted MutS501 and MutS506, have single pointmutations within the Walker A motif, and rate constants for ATPhydrolysis are down 60-100-fold as compared with wild type. BothMutS501 and MutS506 retain mismatch binding and, unlike wild type,fail to relinquish this specificity in the presence of ATP, adenosine5'-O-(thiotriphosphate), and adenosine 5'-( beta , gamma -imino)triphosphate. Both MutS501 and MutS506 blocked the level of strand transfer between M13 and fd DNAs. The level of inhibition varied betweenthe mutants and corresponded with the relative affinities to aG/T mispair. Neither MutS501 nor MutS506, however, would affordcomplete block of full-length heteroduplex in the presence ofMutL. DNase I footprinting data are consistent with these results,as the region of protection by MutS501 and MutS506 was unchangedin the presence of ATP and MutL. Taken together, these studiessuggest that 1) MutS impedes RecA-mediated homeologous exchangeas a distinct mismatch- provoked event and 2) the role of MutLis coupled to MutS-dependent ATP hydrolysis. These observationsare in good agreement with the present model for E. coli methyl-directedmismatch repair. JF - Journal of Biological Chemistry AU - Worth, L AU - Bader, T AU - Yang, J AU - Clark, S AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, P.O. Box 12233, Research Triangle, North Carolina 27709 Y1 - 1998/09/04/ PY - 1998 DA - 1998 Sep 04 SP - 23176 EP - 23182 VL - 273 IS - 36 SN - 0021-9258, 0021-9258 KW - MutS protein KW - Microbiology Abstracts B: Bacteriology KW - Adenosinetriphosphatase KW - Escherichia coli KW - DNA repair KW - RecA protein KW - Mutants KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16555419?accountid=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=Role+of+MutS+ATPase+activity+in+MutS%2CL-+dependent+block+of+in+vitro+strand+transfer&rft.au=Worth%2C+L%3BBader%2C+T%3BYang%2C+J%3BClark%2C+S&rft.aulast=Worth&rft.aufirst=L&rft.date=1998-09-04&rft.volume=273&rft.issue=36&rft.spage=23176&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; Mutants; RecA protein; Adenosinetriphosphatase; DNA repair ER - TY - JOUR T1 - Cancer: Has the smart bomb been defused? AN - 16472354; 4389558 AB - A goal of cancer research is to develop therapies that can selectively kill tumour cells without adversely affecting normal cells--this is crucial for both the short-term comfort and long-term survival of patients. One such agent is a genetically engineered adenovirus from ONYX Pharmaceuticals, called ONYX-015, which is thought to selectively replicate in (and kill) tumour cells deficient for the p53 tumour-suppressor pathway, having little toxicity to normal cells. Because p53 is mutated in over half of all human cancers, and is probably functionally deficient in many others owing to mutations in associated genes, ONYX-015 could prove useful in treating a range of tumours. But a report by Hall et al. in Nature Medicine raises a serious question about the efficacy of this virus. JF - Nature AU - Linke, S P AD - Lab. Hum. Carcinog., Natl. Cancer Inst., Natl. Inst. Health, 9000 Rockville Pike, Bethesda, MD 20892-4255, USA, slinke@helix.nih.gov Y1 - 1998/09/03/ PY - 1998 DA - 1998 Sep 03 SP - 13 EP - 15 PB - Macmillan Journals Ltd. VL - 395 IS - 6697 SN - 0028-0836, 0028-0836 KW - adenovirus KW - cancer therapy KW - p53 gene KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/16472354?accountid=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&rft.atitle=Cancer%3A+Has+the+smart+bomb+been+defused%3F&rft.au=Linke%2C+S+P&rft.aulast=Linke&rft.aufirst=S&rft.date=1998-09-03&rft.volume=395&rft.issue=6697&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&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 - Evolution of adaptive neural networks: the role of voltage-dependent K+ channels. AN - 85411032; pmid-9743076 AB - The vestibular pathway of the mollusk Hermissenda crassicornis mediates a reflexive, unconditioned response to disorientation, clinging, that has been conserved during evolution even to the emergence of our own species. This response becomes associated with a visual stimulus (mediated by a precisely ordered visual-vestibular synaptic network) according to principles of Pavlovian conditioning that are also followed in human learning. It is not entirely surprising therefore that molecular and biophysical cascades responsible for this associative learning appear to function in both mollusks and mammals. In brief, combinational elevation of (Ca2+)i, diacylglycerol, and arachidonic acid activates protein kinase C to phosphorylate the Ca2+ and guanosine triphosphate-binding protein, cp20 (now called calexcitin (Nelson T, et al. Proc Natl Acad Sci USA 1996;93:13808-13)), which potently inactivates postsynaptic voltage-dependent K+ currents and thereby increases synaptic weight. Longer term changes included rearrangement of synaptic terminals and modified protein synthesis. This cascade has also been implicated in other associative-learning paradigms (e.g., spatial maze, olfactory discrimination) and as a pathophysiologic target in early Alzheimer's disease. Recent molecular biologic experiments also demonstrate the dependence of associative memory (but not long-term potentiation) on voltage-dependent K+ currents. Theoretic learning models based on these findings focus on dendritic spine clusters and yield computer implementations with powerful pattern-recognition capabilities. JF - Otolaryngology and head and neck surgery AU - Alkon, D L AU - Favit, A AU - Nelson, T AD - Laboratory of Adaptive Systems, National Institutes of Health, Bethesda, Maryland 20892-4124, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 204 EP - 211 VL - 119 IS - 3 SN - 0194-5998, 0194-5998 KW - Index Medicus; Space life sciences KW - National Library of Medicine KW - Snails KW - Animals KW - Second Messenger Systems -- physiology KW - Alzheimer Disease -- physiopathology KW - Humans KW - Conditioning (Psychology) -- physiology KW - Electrophysiology KW - Fibroblasts -- physiology KW - Nerve Net -- physiology KW - Potassium Channels -- physiology KW - Adaptation, Physiological KW - Evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85411032?accountid=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=Otolaryngology+and+head+and+neck+surgery&rft.atitle=Evolution+of+adaptive+neural+networks%3A+the+role+of+voltage-dependent+K%2B+channels.&rft.au=Alkon%2C+D+L%3BFavit%2C+A%3BNelson%2C+T&rft.aulast=Alkon&rft.aufirst=D&rft.date=1998-09-01&rft.volume=119&rft.issue=3&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Otolaryngology+and+head+and+neck+surgery&rft.issn=01945998&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. AN - 85409775; pmid-9756148 AB - The antidyskinetic potential of the glutamate NMDA receptor channel blocker amantadine was evaluated in four levodopa-primed parkinsonian monkeys using two different regimens (1.25 or 2.5 mg/kg administered subcutaneously twice daily for 3-6 days). When administered with a relatively low dose of levodopa, amantadine produced a near-total suppression of choreiform dyskinesias and a substantial reduction in dystonic dyskinesias at the expense of a significant reduction in antiparkinsonian response. With a high dose of levodopa, amantadine had a smaller but still significant effect on dyskinesias without altering the antiparkinsonian response. These results lend support to the view that glutamate receptor-mediated mechanisms contribute to levodopa-induced dyskinesias. They also suggest that amantadine could alleviate such complications in parkinsonian patients, especially with careful dose optimization. JF - Movement disorders : official journal of the Movement Disorder Society AU - Blanchet, P J AU - Konitsiotis, S AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1406, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 798 EP - 802 VL - 13 IS - 5 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Antiparkinson Agents -- adverse effects KW - Animals KW - Parkinson Disease, Secondary -- chemically induced KW - Macaca fascicularis KW - Antiparkinson Agents -- administration & dosage KW - Dose-Response Relationship, Drug KW - Parkinson Disease, Secondary -- drug therapy KW - Parkinson Disease, Secondary -- physiopathology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Levodopa -- administration & dosage KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - Injections, Subcutaneous KW - Neurologic Examination -- drug effects KW - Levodopa -- adverse effects KW - Amantadine -- administration & dosage KW - Dyskinesia, Drug-Induced -- drug therapy KW - Amantadine -- adverse effects KW - Dopamine Agents -- adverse effects KW - Dyskinesia, Drug-Induced -- physiopathology KW - Dopamine Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85409775?accountid=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=Amantadine+reduces+levodopa-induced+dyskinesias+in+parkinsonian+monkeys.&rft.au=Blanchet%2C+P+J%3BKonitsiotis%2C+S%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1998-09-01&rft.volume=13&rft.issue=5&rft.spage=798&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 - 2008-01-14 N1 - SuppNotes - Comment in: Mov Disord. 1998 Sep;13(5):851 [9756161] N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3). AN - 85274494; pmid-9788564 AB - It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis. Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA were present in 40 and 20%, respectively. Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%. In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome. JF - American Journal of Medical Genetics AU - Stratakis, C A AU - Lin, J P AU - Rennert, O M AD - Unit on Genetics and Endocrinology, Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, US. PY - 1998 SP - 209 EP - 214 VL - 79 IS - 3 SN - 0148-7299, 0148-7299 KW - Branchial Region KW - Pedigree KW - Linkage (Genetics) KW - Human KW - Genetic Markers KW - Chromosomes, Human, Pair 8 KW - Ear KW - Hearing Disorders KW - Genes, Dominant KW - Branchio-Oto-Renal Syndrome KW - Trans-Activators KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85274494?accountid=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=Description+of+a+large+kindred+with+autosomal+dominant+inheritance+of+branchial+arch+anomalies%2C+hearing+loss%2C+and+ear+pits%2C+and+exclusion+of+the+branchio-oto-renal+%28BOR%29+syndrome+gene+locus+%28chromosome+8q13.3%29.&rft.au=Stratakis%2C+C+A%3BLin%2C+J+P%3BRennert%2C+O+M&rft.aulast=Stratakis&rft.aufirst=C&rft.date=1998-09-01&rft.volume=79&rft.issue=3&rft.spage=209&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 update on drug interactions with zidovudine. AN - 79630421; 15468442 AB - Zidovudine remains one of the most commonly prescribed agents for patients with HIV infection. A variety of drug interactions have been reported that may alter blood levels of zidovudine and concomitantly administered drugs or may involve overlapping toxicities. Several concomitant medications have been shown to alter the plasma concentrations of zidovudine, although most of these interactions are not thought to be clinically important. Use of agents that share the bone marrow-suppressive properties of zidovudine require additional monitoring for the development of hematologic toxicity. An understanding of potential mechanisms and important zidovudine-related interactions will aid in the optimal care of the HIV-infected patient. JF - AIDS patient care and STDs AU - Piscitelli, S C AU - Polis, M A AD - Department of Pharmacy, Clinical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 687 EP - 690 VL - 12 IS - 9 SN - 1087-2914, 1087-2914 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - AIDS/HIV KW - Drug Interactions KW - Humans KW - Zidovudine -- therapeutic use KW - Anti-HIV Agents -- therapeutic use KW - Zidovudine -- adverse effects KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79630421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+patient+care+and+STDs&rft.atitle=An+update+on+drug+interactions+with+zidovudine.&rft.au=Piscitelli%2C+S+C%3BPolis%2C+M+A&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1998-09-01&rft.volume=12&rft.issue=9&rft.spage=687&rft.isbn=&rft.btitle=&rft.title=AIDS+patient+care+and+STDs&rft.issn=10872914&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-28 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comments on "The moral economies of homeless heroin addicts: confronting ethnography, HIV risk, and everyday violence in San Francisco shooting encampments," by Phillippe Bourgois. AN - 73995190; 9758021 JF - Substance use & misuse AU - Leshner, A I AD - National Institute on Drug Abuse, Rockville, Maryland 20857, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2369 EP - 2374 VL - 33 IS - 11 SN - 1082-6084, 1082-6084 KW - Index Medicus KW - AIDS/HIV KW - San Francisco KW - Humans KW - Adult KW - Health Knowledge, Attitudes, Practice KW - Social Support KW - Male KW - Female KW - Homeless Persons -- statistics & numerical data KW - Violence -- statistics & numerical data KW - HIV Infections -- transmission KW - Urban Population -- statistics & numerical data KW - Anthropology, Cultural KW - Morals KW - Heroin Dependence -- epidemiology KW - HIV Infections -- prevention & control KW - Homeless Persons -- psychology KW - Social Facilitation KW - Heroin Dependence -- psychology KW - HIV Infections -- psychology KW - Violence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73995190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+use+%26+misuse&rft.atitle=Comments+on+%22The+moral+economies+of+homeless+heroin+addicts%3A+confronting+ethnography%2C+HIV+risk%2C+and+everyday+violence+in+San+Francisco+shooting+encampments%2C%22+by+Phillippe+Bourgois.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1998-09-01&rft.volume=33&rft.issue=11&rft.spage=2369&rft.isbn=&rft.btitle=&rft.title=Substance+use+%26+misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-19 N1 - Date created - 1999-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions of Nickel(II) with histones: interactions of Nickel(II) with CH3CO-Thr-Glu-Ser-His-His-Lys-NH2, a peptide modeling the potential metal binding site in the "C-Tail" region of histone H2A. AN - 73975167; 9760275 AB - A combined pH-metric and spectroscopic (UV/vis, CD, NMR) study of the Ni(II) binding to CH3CO-Thr-Glu-Ser-His-His-Lys-NH2 (AcTESHHKam), a blocked hexapeptide modeling a part of the C-terminal sequence of the major variant of histone H2A (residues 120-125), revealed the formation of a pseudo-octahedral NiHL complex in weakly acidic and neutral solutions. Ni(II) is bound to the peptide through imidazole nitrogens on both of its histidine residues and the carboxylate of the side chain of glutamic acid. At higher pH, a series of square-planar complexes are formed. This process is accompanied by hydrolytic degradation of the peptide. At pH 7.4, the peptide hydrolyzes in a Ni(II)-assisted fashion, yielding the square-planar Ni(II) complex of SHHKam as the sole product detected by CD, MALDI-TOF MS, and HPLC. Quantitative analysis of complex stabilities indicates that the -TESHHK- motif is a very likely binding site for carcinogenic Ni(II) ions in the cell nucleus. The Ni(II)-assisted hydrolysis of the C-terminal chain of histone H2A may provide a novel mechanism of genotoxicity combining the damage to the nucleosome with the generation of further toxic Ni(II) species. JF - Chemical research in toxicology AU - Bal, W AU - Lukszo, J AU - Bialkowski, K AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland 21702, Maryland 20852. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1014 EP - 1023 VL - 11 IS - 9 SN - 0893-228X, 0893-228X KW - Cations, Divalent KW - 0 KW - Histones KW - Oligopeptides KW - Solutions KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Oxidation-Reduction KW - Chemistry, Physical KW - Nuclear Magnetic Resonance, Biomolecular KW - Kinetics KW - Hydrogen-Ion Concentration KW - Chemical Phenomena KW - Spectrophotometry, Ultraviolet KW - Circular Dichroism KW - Hydrolysis KW - Catalysis KW - Binding Sites KW - Histones -- metabolism KW - Oligopeptides -- chemistry KW - Histones -- chemistry KW - Oligopeptides -- metabolism KW - Nickel -- metabolism KW - Nickel -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73975167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interactions+of+Nickel%28II%29+with+histones%3A+interactions+of+Nickel%28II%29+with+CH3CO-Thr-Glu-Ser-His-His-Lys-NH2%2C+a+peptide+modeling+the+potential+metal+binding+site+in+the+%22C-Tail%22+region+of+histone+H2A.&rft.au=Bal%2C+W%3BLukszo%2C+J%3BBialkowski%2C+K%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1998-09-01&rft.volume=11&rft.issue=9&rft.spage=1014&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 - 1998-11-09 N1 - Date created - 1998-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compliance with treatment and follow-up protocols in project MATCH: predictors and relationship to outcome. AN - 73960170; 9756050 AB - Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator. JF - Alcoholism, clinical and experimental research AU - Mattson, M E AU - Del Boca, F K AU - Carroll, K M AU - Cooney, N L AU - DiClemente, C C AU - Donovan, D AU - Kadden, R M AU - McRee, B AU - Rice, C AU - Rycharik, R G AU - Zweben, A AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892-7003, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1328 EP - 1339 VL - 22 IS - 6 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Adult KW - Temperance -- psychology KW - Outcome and Process Assessment (Health Care) KW - Psychotherapy -- methods KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Aftercare KW - Ambulatory Care KW - Alcoholism -- rehabilitation KW - Alcoholism -- diagnosis KW - Patient Care Planning KW - Alcoholism -- psychology KW - Quality Assurance, Health Care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73960170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Compliance+with+treatment+and+follow-up+protocols+in+project+MATCH%3A+predictors+and+relationship+to+outcome.&rft.au=Mattson%2C+M+E%3BDel+Boca%2C+F+K%3BCarroll%2C+K+M%3BCooney%2C+N+L%3BDiClemente%2C+C+C%3BDonovan%2C+D%3BKadden%2C+R+M%3BMcRee%2C+B%3BRice%2C+C%3BRycharik%2C+R+G%3BZweben%2C+A&rft.aulast=Mattson&rft.aufirst=M&rft.date=1998-09-01&rft.volume=22&rft.issue=6&rft.spage=1328&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 - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reappraisal of progressive multifocal leukoencephalopathy due to simian virus 40. AN - 73935457; 9754960 AB - Several cases of progressive multifocal leukoencephalopathy (PML) have been associated with simian virus 40 (SV40), rather than with JC virus (JCV), the polyomavirus originally isolated from PML tissue. PML has, therefore, been defined as a demyelinating syndrome with possible multiple viral etiologies. Tissues from three of the cases thought to be associated with SV40 were available for reexamination. Monoclonal antibodies specific for SV40 capsid antigen VPI, virus-specific biotinylated DNA probes for in situ hybridization, and virus-specific primers in the polymerase chain reaction (PCR) were used. Macaque PML brain served as a positive control tissue for SV40 brain infection. Monoclonal antibodies to SV40 VPI failed to recognize viral antigen in lesions from all three human PML cases. The biotinylated DNA probe, which reacted with SV40 in macaque PML, failed to detect SV40 in human PML. However, JCV could be detected by in situ hybridization with a JCV-specific DNA probe. Moreover, JCV DNA sequences were amplified by PCR from the human PML tissues, whereas SV40 DNA sequences were amplified only from the macaque brain. Thus, we could not confirm the original reports that the demyelinating agent in these three cases of PML was SV40, rather than JCV. We conclude that SV40 infection of the central nervous system need not be ruled out in the differential diagnosis of PML. JF - Acta neuropathologica AU - Stoner, G L AU - Ryschkewitsch, C F AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. stoner@helix.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 271 EP - 278 VL - 96 IS - 3 SN - 0001-6322, 0001-6322 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Viral, Tumor KW - Capsid Proteins KW - DNA, Viral KW - Oligonucleotide Probes KW - VP1 protein, polyomavirus KW - Index Medicus KW - Animals KW - BK Virus -- genetics KW - JC Virus -- genetics KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Tumor Virus Infections -- genetics KW - Antigens, Viral, Tumor -- analysis KW - Brain -- virology KW - BK Virus -- chemistry KW - JC Virus -- immunology KW - Genotype KW - Polymerase Chain Reaction KW - In Situ Hybridization KW - Capsid -- analysis KW - JC Virus -- chemistry KW - DNA, Viral -- analysis KW - Brain -- pathology KW - Oligonucleotide Probes -- metabolism KW - Cell Line KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - Leukoencephalopathy, Progressive Multifocal -- etiology KW - Simian virus 40 -- chemistry KW - Simian virus 40 -- genetics KW - Leukoencephalopathy, Progressive Multifocal -- pathology KW - Simian virus 40 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73935457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropathologica&rft.atitle=Reappraisal+of+progressive+multifocal+leukoencephalopathy+due+to+simian+virus+40.&rft.au=Stoner%2C+G+L%3BRyschkewitsch%2C+C+F&rft.aulast=Stoner&rft.aufirst=G&rft.date=1998-09-01&rft.volume=96&rft.issue=3&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Acta+neuropathologica&rft.issn=00016322&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High dose versus low dose fludarabine in the treatment of patients with severe refractory rheumatoid arthritis. AN - 73928717; 9733448 AB - Fludarabine, a nucleoside analog that targets both resting and proliferating lymphocytes, is a promising drug for the treatment of autoimmune diseases. We conducted a 2 dose, open label clinical trial to evaluate the toxicity/safety of the fludarabine treatment and its clinical and immunological effects. Twenty-six patients with severe rheumatoid arthritis (RA) refractory to treatment with at least one slow acting antirheumatic drug were treated with intravenous fludarabine [20 mg/m2 body surface area (n=12) or 30 mg/m2 body surface area (n=14) per day for 3 consecutive days] given monthly for 6 months. Second line agents with the exception of glucocorticoids were discontinued at least 4 weeks before study entry. Measurements included toxicity and tolerability monitored at monthly intervals: efficacy, by both a 50% reduction in tender or swollen joint count and American College of Rheumatology (ACR) criteria for 20% response; and phenotypic analysis of peripheral blood mononuclear cells and T cell functional assays. Using intention-to-treat analysis, 2 of 12 (17%) patients in the low dose and 7 of 14 (50%) in the high dose groups had 50% or greater reduction in tender and/or swollen joint count after 6 months of therapy compared to baseline (p=0.09). Two of 12 (17%) in the low dose group and 5 of 14 (36%) in the high dose group met ACR criteria for 20% improvement (p=0.28). No immediate toxicity was observed. Several infections occurred, including 4 episodes of limited Herpes zoster, which responded to standard therapy. Significant lymphopenia involving T and B cells was observed in all patients. Both naive (CD4+CD45RA+) and memory CD4+ T cells (CD4+CD45RO+) were reduced (naive > memory). No significant regeneration of naive T cells was observed, which may suggest limited thymic regenerative capacity. Fludarabine decreased the proliferative response of peripheral blood lymphocytes to mitogens, as well as the production of T cell (interleukin 2 and interferon-gamma) and monocyte derived (tumor necrosis factor-alpha and IL-10) cytokines. Fludarabine treatment of patients with severe, refractory RA resulted in significant lymphopenia, suppression of lymphocyte function, and clinical improvement in the high dose group. There was no immediate toxicity; however, several infections occurred. Controlled trials are needed to substantiate the clinical improvement observed in this open label trial. JF - The Journal of rheumatology AU - Davis, J C AU - Fessler, B J AU - Tassiulas, I O AU - McInnes, I B AU - Yarboro, C H AU - Pillemer, S AU - Wilder, R AU - Fleisher, T A AU - Klippel, J H AU - Boumpas, D T AD - Clinical Investigation Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1694 EP - 1704 VL - 25 IS - 9 SN - 0315-162X, 0315-162X KW - Antigens, CD KW - 0 KW - Immunosuppressive Agents KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Phenotype KW - Lymphocyte Count -- drug effects KW - Leukocytes, Mononuclear -- physiology KW - Antigens, CD -- analysis KW - Dose-Response Relationship, Drug KW - Humans KW - Treatment Outcome KW - Platelet Count -- drug effects KW - Middle Aged KW - Leukocytes, Mononuclear -- drug effects KW - Time Factors KW - Male KW - Female KW - Arthritis, Rheumatoid -- drug therapy KW - Vidarabine -- analogs & derivatives KW - Vidarabine -- therapeutic use KW - Vidarabine -- administration & dosage KW - Vidarabine -- adverse effects KW - Immunosuppressive Agents -- therapeutic use KW - Arthritis, Rheumatoid -- immunology KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73928717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+dose+versus+low+dose+fludarabine+in+the+treatment+of+patients+with+severe+refractory+rheumatoid+arthritis.&rft.au=Davis%2C+J+C%3BFessler%2C+B+J%3BTassiulas%2C+I+O%3BMcInnes%2C+I+B%3BYarboro%2C+C+H%3BPillemer%2C+S%3BWilder%2C+R%3BFleisher%2C+T+A%3BKlippel%2C+J+H%3BBoumpas%2C+D+T&rft.aulast=Davis&rft.aufirst=J&rft.date=1998-09-01&rft.volume=25&rft.issue=9&rft.spage=1694&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 - 1998-11-19 N1 - Date created - 1998-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifungal activity of the pradimicin derivative BMS 181184 in the treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits. AN - 73927792; 9736570 AB - The activity of the pradimicin derivative BMS 181184 was evaluated in a model of invasive pulmonary aspergillosis in persistently neutropenic rabbits and compared with that of amphotericin B deoxycholate. BMS 181184 at total daily doses of 50 and 150 mg/kg of body weight was at least as effective as amphotericin B at 1 mg/kg once a day in conferring survival and had comparable activity in reducing organism-mediated tissue injury and excess lung weight. Although treatment at all dosing regimens of BMS 181184 resulted in significant reductions in fungal tissue burden compared to untreated controls, equivalence to amphotericin B occurred only at the higher dosage level. Similar observations were made in bronchoalveolar lavage fluid cultures obtained postmortem. Monitoring of the animals through ultrafast computerized tomography scan revealed a marked resolution of pulmonary lesions during treatment with BMS 181184. The compound was well tolerated at all dosing regimens, and no toxicity was noted. Pharmacokinetic studies revealed nonlinear drug disposition with increased clearance at higher dosages and some evidence for extravascular drug accumulation. BMS 181184 had excellent activity in the treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits, thus underscoring the potential of pradimicin derivatives in therapy of invasive aspergillosis in the neutropenic host. JF - Antimicrobial agents and chemotherapy AU - Gonzalez, C E AU - Groll, A H AU - Giri, N AU - Shetty, D AU - Al-Mohsen, I AU - Sein, T AU - Feuerstein, E AU - Bacher, J AU - Piscitelli, S AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2399 EP - 2404 VL - 42 IS - 9 SN - 0066-4804, 0066-4804 KW - Anthracyclines KW - 0 KW - Antibiotics, Antineoplastic KW - Antifungal Agents KW - 3'-hydroxybenanomicin A KW - 139272-69-8 KW - Index Medicus KW - Animals KW - Rabbits KW - Aspergillosis -- microbiology KW - Lung Diseases, Fungal -- microbiology KW - Lung Diseases, Fungal -- drug therapy KW - Lung Diseases, Fungal -- pathology KW - Aspergillosis -- drug therapy KW - Aspergillosis -- pathology KW - Antibiotics, Antineoplastic -- pharmacokinetics KW - Antibiotics, Antineoplastic -- adverse effects KW - Antifungal Agents -- therapeutic use KW - Antibiotics, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73927792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antifungal+activity+of+the+pradimicin+derivative+BMS+181184+in+the+treatment+of+experimental+pulmonary+aspergillosis+in+persistently+neutropenic+rabbits.&rft.au=Gonzalez%2C+C+E%3BGroll%2C+A+H%3BGiri%2C+N%3BShetty%2C+D%3BAl-Mohsen%2C+I%3BSein%2C+T%3BFeuerstein%2C+E%3BBacher%2C+J%3BPiscitelli%2C+S%3BWalsh%2C+T+J&rft.aulast=Gonzalez&rft.aufirst=C&rft.date=1998-09-01&rft.volume=42&rft.issue=9&rft.spage=2399&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Microbiol. 1968;22:87-108 [4879523] Eur J Clin Microbiol Infect Dis. 1997 Jan;16(1):93-7 [9063679] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] J Antibiot (Tokyo). 1988 Nov;41(11):1701-4 [3198502] J Antibiot (Tokyo). 1990 Jun;43(6):715-21 [2199421] J Antibiot (Tokyo). 1990 Jul;43(7):763-70 [2167304] J Clin Oncol. 1991 Jan;9(1):77-84 [1845875] Medicine (Baltimore). 1992 Jan;71(1):24-43 [1549057] Antimicrob Agents Chemother. 1991 Nov;35(11):2185-90 [1803990] Clin Infect Dis. 1992 Mar;14 Suppl 1:S43-53 [1562695] J Antibiot (Tokyo). 1992 Sep;45(9):1512-7 [1429237] J Antibiot (Tokyo). 1993 Feb;46(2):265-74 [8468241] Clin Infect Dis. 1993 Sep;17(3):397-404 [8218680] Antimicrob Agents Chemother. 1995 Feb;39(2):295-300 [7726485] Antimicrob Agents Chemother. 1995 Feb;39(2):314-9 [7726488] Antimicrob Agents Chemother. 1995 May;39(5):1065-9 [7625790] J Am Soc Nephrol. 1995 Aug;6(2):154-64 [7579079] Clin Infect Dis. 1996 May;22 Suppl 2:S133-44 [8722841] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] J Infect. 1996 Jul;33(1):23-32 [8842991] Clin Infect Dis. 1996 Sep;23(3):608-15 [8879787] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma. AN - 73917884; 9738568 AB - Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Sandor, V AU - Stark-Vancs, V AU - Pearson, D AU - Nussenblat, R AU - Whitcup, S M AU - Brouwers, P AU - Patronas, N AU - Heiss, J AU - Jaffe, E AU - deSmet, M AU - Kohler, D AU - Simon, R AU - Wittes, R AD - Medicine and Pediatric Branches, Department of Neurosurgery, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-2440, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 3000 EP - 3006 VL - 16 IS - 9 SN - 0732-183X, 0732-183X KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Dexamethasone KW - 7S5I7G3JQL KW - Thiotepa KW - 905Z5W3GKH KW - Leucovorin KW - Q573I9DVLP KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Leucovorin -- administration & dosage KW - Vincristine -- administration & dosage KW - Dexamethasone -- administration & dosage KW - Aged KW - Pilot Projects KW - Cytarabine -- administration & dosage KW - Adult KW - Thiotepa -- administration & dosage KW - Middle Aged KW - Methotrexate -- administration & dosage KW - Female KW - Male KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Eye Neoplasms -- drug therapy KW - Central Nervous System Neoplasms -- 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/73917884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+II+trial+of+chemotherapy+alone+for+primary+CNS+and+intraocular+lymphoma.&rft.au=Sandor%2C+V%3BStark-Vancs%2C+V%3BPearson%2C+D%3BNussenblat%2C+R%3BWhitcup%2C+S+M%3BBrouwers%2C+P%3BPatronas%2C+N%3BHeiss%2C+J%3BJaffe%2C+E%3BdeSmet%2C+M%3BKohler%2C+D%3BSimon%2C+R%3BWittes%2C+R&rft.aulast=Sandor&rft.aufirst=V&rft.date=1998-09-01&rft.volume=16&rft.issue=9&rft.spage=3000&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 - 1998-09-29 N1 - Date created - 1998-09-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 1999 Apr;17(4):1329 [10561199] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. AN - 73916877; 9751121 AB - The hormonal stimulation of mammary gland morphogenesis is believed to occur through growth factor receptor signaling pathways. To determine the importance of the epidermal growth factor receptor (EGFR) pathway, we examined extracts of inguinal mammary glands from prepubertal and pubertal mice for tyrosine-phosphorylated EGFR and other erbB receptors. Tyrosine phosphorylation of both EGFR and erbB-2 was detected in normal female BALB/c mice at 5-6 weeks of age, but not during the prepubertal stage, e.g., 24 days of age. Treatment of mice with estradiol or epidermal growth factor also stimulated the formation of mammary EGFR/erbB-2 phosphotyrosine. Waved-2 mice, which have impaired EGFR kinase activity, exhibited less mammary development than did wild-type (wt) mice when both were evaluated at 36 days of age. Because EGFR knockout (KO) mice die shortly after birth, glands from the newborns were implanted under the renal capsules of female nude mice. Under these conditions, extensive ductal growth was observed in mammary glands from wt animals; in contrast, glands from EGFR KO mice failed to grow beyond rudimentary structures. Tissue recombinants revealed that the wt fat pad supported the morphogenesis of EGFR KO epithelium, whereas the EGFR KO fat pad did not. Taken together, these data suggest that EGFR is essential for morphogenesis of the mammary ducts and functions during this period of mammary development as a heterodimer with erbB-2 in the mammary stroma. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Sebastian, J AU - Richards, R G AU - Walker, M P AU - Wiesen, J F AU - Werb, Z AU - Derynck, R AU - Hom, Y K AU - Cunha, G R AU - DiAugustine, R P AD - Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 777 EP - 785 VL - 9 IS - 9 SN - 1044-9523, 1044-9523 KW - Estradiol KW - 4TI98Z838E KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Phosphorylation KW - Morphogenesis KW - Estradiol -- pharmacology KW - Mice, Nude KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Mice, Inbred BALB C KW - Female KW - Receptor, Epidermal Growth Factor -- drug effects KW - Receptor, ErbB-2 -- physiology KW - Receptor, Epidermal Growth Factor -- metabolism KW - Mammary Glands, Animal -- drug effects KW - Receptor, ErbB-2 -- metabolism KW - Mammary Glands, Animal -- metabolism KW - Mammary Glands, Animal -- growth & development KW - Receptor, Epidermal Growth Factor -- physiology KW - Receptor, ErbB-2 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73916877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+and+function+of+the+epidermal+growth+factor+receptor+and+erbB-2+during+mammary+gland+morphogenesis.&rft.au=Sebastian%2C+J%3BRichards%2C+R+G%3BWalker%2C+M+P%3BWiesen%2C+J+F%3BWerb%2C+Z%3BDerynck%2C+R%3BHom%2C+Y+K%3BCunha%2C+G+R%3BDiAugustine%2C+R+P&rft.aulast=Sebastian&rft.aufirst=J&rft.date=1998-09-01&rft.volume=9&rft.issue=9&rft.spage=777&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 - 1998-12-11 N1 - Date created - 1998-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excretory transport of xenobiotics by dogfish shark rectal gland tubules. AN - 73911141; 9728065 AB - Marine elasmobranch rectal gland is a specialized, osmoregulatory organ composed of numerous blind-ended, branched tubules emptying into a central duct. To date, NaCl excretion has been its only described function. Here we use isolated rectal gland tubule fragments from dogfish shark (Squalus acanthias), fluorescent xenobiotics, and confocal microscopy to describe a second function, xenobiotic excretion. Isolated rectal gland tubules rapidly transported the fluorescent organic anion sulforhodamine 101 from bath to lumen. Luminal accumulation was concentrative, saturable, and inhibited by cyclosporin A (CSA), chlorodinitrobenzene, leukotriene C4, and KCN. Inhibitors of renal organic anion transport (probenecid, p-aminohippurate), organic cation transport (tetraethylammonium and verapamil), and P-glycoprotein (verapamil) were without effect. Cellular accumulation of sulforhodamine 101 was not concentrative, saturable, or inhibitable. Rectal gland tubules did not secrete fluorescein, daunomycin, or a fluorescent CSA derivative. Finally, frozen rectal gland sections stained with an antibody to a hepatic canalicular multispecific organic anion transporter (cMOAT or MRP2) showed heavy and specific staining on the luminal membrane of the epithelial cells. We conclude that rectal gland is capable of active and specific excretion of xenobiotics and that such transport is mediated by a shark analog of MRP2, an ATP-driven xenobiotic transporter, but not by P-glycoprotein. JF - The American journal of physiology AU - Miller, D S AU - Masereeuw, R AU - Henson, J AU - Karnaky, K J AD - Intracellular Regulation Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - R697 EP - R705 VL - 275 IS - 3 Pt 2 SN - 0002-9513, 0002-9513 KW - Fluorescent Dyes KW - 0 KW - Rhodamines KW - Xenobiotics KW - Leukotriene C4 KW - 2CU6TT9V48 KW - Cyclosporine KW - 83HN0GTJ6D KW - sulforhodamine 101 KW - FX0ES3271V KW - Dinitrochlorobenzene KW - GE3IBT7BMN KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - Microscopy, Fluorescence KW - Microscopy, Confocal KW - Animals KW - Rhodamines -- metabolism KW - Leukotriene C4 -- pharmacology KW - Dinitrochlorobenzene -- pharmacology KW - Cyclosporine -- pharmacology KW - Biological Transport KW - Potassium Cyanide -- pharmacology KW - Male KW - Female KW - Salt Gland -- metabolism KW - Xenobiotics -- metabolism KW - Dogfish -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73911141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Excretory+transport+of+xenobiotics+by+dogfish+shark+rectal+gland+tubules.&rft.au=Miller%2C+D+S%3BMasereeuw%2C+R%3BHenson%2C+J%3BKarnaky%2C+K+J&rft.aulast=Miller&rft.aufirst=D&rft.date=1998-09-01&rft.volume=275&rft.issue=3+Pt+2&rft.spage=R697&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 - 1998-10-01 N1 - Date created - 1998-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor. AN - 73910467; 9730951 AB - The incretin hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is best known for its antidiabetogenic actions mediated via a GLP-1 receptor present on pancreatic endocrine cells. To investigate the molecular mechanisms of GLP-1 action in muscle, we used cultured L6 myotubes. In L6 myotubes, GLP-1 enhanced insulin-stimulated glycogen synthesis by 140% while stimulating CO2 production and lactate formation by 150%. In the presence of IBMX, GLP-1 diminished cAMP levels to 83% of IBMX alone. In L6 myotubes transfected with pancreatic GLP-1 receptor, GLP-1 increased cAMP levels and inhibited glycogen synthesis by 60%. An antagonist of pancreatic GLP-1 receptor, exendin-4-(9-39), inhibited GLP-1-mediated glycogen synthesis in GLP-1 receptor-transfected L6 myotubes. However, in parental L6 myotubes, exendin-4-(9-39) and GLP-1-(1-36) amide, an inactive peptide on pancreatic GLP-1 receptor, displaced 125I-labeled GLP-1 binding and stimulated glycogen synthesis by 186 and 130%, respectively. These results suggest that the insulinomimetic effects of GLP-1 in L6 cells are likely to be mediated by a receptor that is different from the GLP-1 receptor found in the pancreas. JF - The American journal of physiology AU - Yang, H AU - Egan, J M AU - Wang, Y AU - Moyes, C D AU - Roth, J AU - Montrose, M H AU - Montrose-Rafizadeh, C AD - Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - C675 EP - C683 VL - 275 IS - 3 Pt 1 SN - 0002-9513, 0002-9513 KW - Glp1r protein, rat KW - 0 KW - Glucagon-Like Peptide-1 Receptor KW - Insulin KW - Peptide Fragments KW - Protein Precursors KW - Receptors, Glucagon KW - Recombinant Proteins KW - Venoms KW - exendin (9-39) KW - 5313W10MYT KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Carbachol KW - 8Y164V895Y KW - Glycogen KW - 9005-79-2 KW - Glucagon KW - 9007-92-5 KW - Cyclic AMP KW - E0399OZS9N KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Insulin -- pharmacology KW - Cloning, Molecular KW - Rats KW - Glycolysis -- drug effects KW - Transfection KW - Kinetics KW - Cyclic AMP -- metabolism KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Carbachol -- pharmacology KW - Cell Line KW - Venoms -- pharmacology KW - Peptide Fragments -- metabolism KW - Protein Precursors -- metabolism KW - Protein Precursors -- physiology KW - Muscle, Skeletal -- physiology KW - Glucagon -- pharmacology KW - Receptors, Glucagon -- physiology KW - Peptide Fragments -- physiology KW - Pancreas -- physiology KW - Receptors, Glucagon -- biosynthesis KW - Protein Precursors -- pharmacology KW - Glucagon -- metabolism KW - Muscle, Skeletal -- cytology KW - Glucagon -- physiology KW - Pancreas -- metabolism KW - Peptide Fragments -- pharmacology KW - Glycogen -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73910467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=GLP-1+action+in+L6+myotubes+is+via+a+receptor+different+from+the+pancreatic+GLP-1+receptor.&rft.au=Yang%2C+H%3BEgan%2C+J+M%3BWang%2C+Y%3BMoyes%2C+C+D%3BRoth%2C+J%3BMontrose%2C+M+H%3BMontrose-Rafizadeh%2C+C&rft.aulast=Yang&rft.aufirst=H&rft.date=1998-09-01&rft.volume=275&rft.issue=3+Pt+1&rft.spage=C675&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 - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of a five-day dose schedule of 4-Ipomeanol in patients with non-small cell lung cancer. AN - 73909702; 9748125 AB - The mammalian pulmonary toxin 4-ipomeanol (IPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has in vitro and in vivo antitumor activity in non-small cell lung cancer (NSCLC) and thus was proposed as a lung cancer-specific antitumor agent. We have completed a directed Phase I trial in patients with NSCLC. Forty-four patients (34 men and 10 women) with NSCLC were treated with IPO. All but two patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. They received 91 courses of therapy with i.v. IPO; 82 courses were administered daily for five days, and 9 were single bolus doses. The dose-limiting toxicity of elevated serum transaminases was observed in three of seven patients at 922 mg/m2/day. The maximum tolerated dose was 693 mg/m2/day on 5 consecutive days every 3 weeks. One patient developed grade 4 pulmonary toxicity at 167 mg/m2/day. There was no significant hematological or renal toxicity. No objective antitumor responses were observed. Pharmacokinetic analysis of 39 patients from day 1 of IPO administration showed biexponential elimination with mean half-lives of 8.6 (alpha half-life) and 76 min (beta half-life). There was a linear relationship between the area under the plasma drug concentration-time curve and the dose of IPO. There was no significant difference between the pharmacokinetic parameters measured on day 1 and day 5. Using a 4-day in vitro cytotoxicity assay, two tumor cell lines established from patients treated at 693 mg/m2/day had IC50s of approximately 6 mM, a concentration more than 75-fold higher than the plasma levels measured in these patients. Thus, although the total amount of drug administered per cycle on a daily times five dose schedule is more than 2.5-fold higher than the recommended single daily dose, IPO is unlikely to be a useful drug for patients with lung cancer. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kasturi, V K AU - Dearing, M P AU - Piscitelli, S C AU - Russell, E K AU - Sladek, G G AU - O'Neil, K AU - Turner, G A AU - Morton, T L AU - Christian, M C AU - Johnson, B E AU - Kelley, M J AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889-5105, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2095 EP - 2102 VL - 4 IS - 9 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Terpenes KW - 4-ipomeanol KW - 32954-58-8 KW - Index Medicus KW - Drug Administration Schedule KW - Lung Diseases -- chemically induced KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Partial Thromboplastin Time KW - Terpenes -- administration & dosage KW - Terpenes -- pharmacokinetics KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Terpenes -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73909702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+study+of+a+five-day+dose+schedule+of+4-Ipomeanol+in+patients+with+non-small+cell+lung+cancer.&rft.au=Kasturi%2C+V+K%3BDearing%2C+M+P%3BPiscitelli%2C+S+C%3BRussell%2C+E+K%3BSladek%2C+G+G%3BO%27Neil%2C+K%3BTurner%2C+G+A%3BMorton%2C+T+L%3BChristian%2C+M+C%3BJohnson%2C+B+E%3BKelley%2C+M+J&rft.aulast=Kasturi&rft.aufirst=V&rft.date=1998-09-01&rft.volume=4&rft.issue=9&rft.spage=2095&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma. AN - 73908087; 9758369 AB - Mitogen-activated protein kinase (MAPK) is a serine-threonine kinase that is activated by various extracellular stimuli. Extracellular signal-regulated kinases (ERK1 and ERK2), an MAPK subfamily, are activated by many oncogenes, such as ras and raf, and they induce cell proliferation. myc is also an oncogene and one of the targets of ERKs. Mutations of ras and overexpression of myc were found in various human cancers, and ERKs were also reported to play a role in carcinogenesis. In this study, we examined 39 biopsy specimens of oral squamous cell carcinoma (OSCC) and 5 of normal gingival mucosa for the expression of ERK protein and the proliferation marker, MIB-1 (Ki-67 antibody). Thirteen OSCC specimens and five normal gingival biopsies were also examined for the expression of ERKs mRNA by in situ hybridization. Double staining for ERKs and MIB-1 was also performed. Histologically, 18 patients (46%) were diagnosed with well-differentiated SCC, 17 (44%) with moderately differentiated SCC, and 4 (10%) with poorly differentiated SCC. The histologic grade correlated with the MIB-1 index. The localization of ERK1 was similar to that of ERK2. Positive signals for ERK proteins were localized in superficial keratinocytes in normal gingival mucosa, whereas these mRNAs were weakly positive in the basal and spinous layer. Basal and suprabasal cells were positive for MIB-1. In well-differentiated and moderately differentiated OSCC, positive signals for ERK mRNA and proteins were found at higher levels than in normal gingival mucosa in keratotic cells around cancer pearls. Some cells showed positive signals for ERKs and MIB-1. Furthermore, most cancer cells in poorly differentiated SCC were positive for both ERK and MIB-1. The histologic grade was statistically related to the percentage of cells positive for both ERK and MIB-1. This suggested that ERKs might be related to proliferation in OSCC. JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc AU - Mishima, K AU - Yamada, E AU - Masui, K AU - Shimokawara, T AU - Takayama, K AU - Sugimura, M AU - Ichijima, K AD - Department of Pathology, Nara Medical University, Kashihara, Japan. kmishima@yoda.nidr.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 886 EP - 891 VL - 11 IS - 9 SN - 0893-3952, 0893-3952 KW - Antigens, Nuclear KW - 0 KW - Ki-67 Antigen KW - Nuclear Proteins KW - RNA, Messenger KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Humans KW - Gene Expression KW - Nuclear Proteins -- metabolism KW - Mouth Mucosa -- metabolism KW - Immunoenzyme Techniques KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Mouth Neoplasms -- metabolism KW - Carcinoma, Squamous Cell -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73908087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Modern+pathology+%3A+an+official+journal+of+the+United+States+and+Canadian+Academy+of+Pathology%2C+Inc&rft.atitle=Overexpression+of+the+ERK%2FMAP+kinases+in+oral+squamous+cell+carcinoma.&rft.au=Mishima%2C+K%3BYamada%2C+E%3BMasui%2C+K%3BShimokawara%2C+T%3BTakayama%2C+K%3BSugimura%2C+M%3BIchijima%2C+K&rft.aulast=Mishima&rft.aufirst=K&rft.date=1998-09-01&rft.volume=11&rft.issue=9&rft.spage=886&rft.isbn=&rft.btitle=&rft.title=Modern+pathology+%3A+an+official+journal+of+the+United+States+and+Canadian+Academy+of+Pathology%2C+Inc&rft.issn=08933952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-02 N1 - Date created - 1998-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients. AN - 73907673; 9736569 AB - The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections. JF - Antimicrobial agents and chemotherapy AU - Walsh, T J AU - Yeldandi, V AU - McEvoy, M AU - Gonzalez, C AU - Chanock, S AU - Freifeld, A AU - Seibel, N I AU - Whitcomb, P O AU - Jarosinski, P AU - Boswell, G AU - Bekersky, I AU - Alak, A AU - Buell, D AU - Barret, J AU - Wilson, W AD - Pediatric Oncology Branch, National Institutes of Health, Bethesda, Maryland, USA. walsht@pbmac.nci.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2391 EP - 2398 VL - 42 IS - 9 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Amphotericin B -- pharmacokinetics KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Antifungal Agents -- administration & dosage KW - Neutropenia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73907673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+tolerance%2C+and+pharmacokinetics+of+a+small+unilamellar+liposomal+formulation+of+amphotericin+B+%28AmBisome%29+in+neutropenic+patients.&rft.au=Walsh%2C+T+J%3BYeldandi%2C+V%3BMcEvoy%2C+M%3BGonzalez%2C+C%3BChanock%2C+S%3BFreifeld%2C+A%3BSeibel%2C+N+I%3BWhitcomb%2C+P+O%3BJarosinski%2C+P%3BBoswell%2C+G%3BBekersky%2C+I%3BAlak%2C+A%3BBuell%2C+D%3BBarret%2C+J%3BWilson%2C+W&rft.aulast=Walsh&rft.aufirst=T&rft.date=1998-09-01&rft.volume=42&rft.issue=9&rft.spage=2391&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 1994 Feb;169(2):356-68 [8106769] Biochim Biophys Acta. 1992 Jun 30;1107(2):271-82 [1504072] Antimicrob Agents Chemother. 1994 Feb;38(2):223-7 [8192447] Antimicrob Agents Chemother. 1994 Apr;38(4):713-8 [8031034] Br J Haematol. 1994 Apr;86(4):754-60 [7918068] Bone Marrow Transplant. 1994;14 Suppl 5:S8-9 [7703929] Eur J Clin Microbiol Infect Dis. 1995 Jan;14(1):41-3 [7729451] J Antimicrob Chemother. 1994 Dec;34(6):975-87 [7730240] Arch Intern Med. 1995 May 22;155(10):1093-8 [7748054] Arch Intern Med. 1995 Jun 12;155(11):1177-84 [7763123] J Antimicrob Chemother. 1995 Apr;35(4):509-19 [7628985] Clin Infect Dis. 1996 May;22 Suppl 2:S133-44 [8722841] Mycoses. 1995 Nov-Dec;38(11-12):459-65 [8720196] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] Ther Drug Monit. 1996 Oct;18(5):604-9 [8885127] J Antimicrob Chemother. 1980 Mar;6(2):241-9 [6769895] Drug Metab Dispos. 1981 Jan-Feb;9(1):25-9 [6111427] Biochim Biophys Acta. 1984 Mar 14;770(2):230-4 [6696909] Antimicrob Agents Chemother. 1989 Sep;33(9):1544-8 [2684010] Rev Infect Dis. 1990 Mar-Apr;12(2):308-29 [2184499] Ann Intern Med. 1991 Apr 15;114(8):664-6 [2003714] J Antimicrob Chemother. 1991 Oct;28 Suppl B:49-61 [1778892] J Antimicrob Chemother. 1991 Oct;28 Suppl B:73-82 [1778894] J Antimicrob Chemother. 1991 Oct;28 Suppl B:83-91 [1778895] Cancer. 1992 Jun 1;69(11):2653-62 [1315207] Bone Marrow Transplant. 1993 Dec;12(6):577-82 [8136741] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients. AN - 73906938; 9738569 AB - To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity. The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-up of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional follow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AU - Sorensen, J M AU - Vena, D A AU - Montello, M J AU - Barrett, J A AU - Damasio, E AU - Tallman, M AU - Annino, L AU - Connors, J AU - Coiffier, B AU - Lauria, F AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. chesonb@ctep.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 3007 EP - 3015 VL - 16 IS - 9 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Cladribine KW - 47M74X9YT5 KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - Neoplasms, Second Primary -- diagnosis KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Survival Analysis KW - Cladribine -- adverse effects KW - Cladribine -- therapeutic use KW - Leukemia, Hairy Cell -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73906938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+hairy+cell+leukemia+with+2-chlorodeoxyadenosine+via+the+Group+C+protocol+mechanism+of+the+National+Cancer+Institute%3A+a+report+of+979+patients.&rft.au=Cheson%2C+B+D%3BSorensen%2C+J+M%3BVena%2C+D+A%3BMontello%2C+M+J%3BBarrett%2C+J+A%3BDamasio%2C+E%3BTallman%2C+M%3BAnnino%2C+L%3BConnors%2C+J%3BCoiffier%2C+B%3BLauria%2C+F&rft.aulast=Cheson&rft.aufirst=B&rft.date=1998-09-01&rft.volume=16&rft.issue=9&rft.spage=3007&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 - 1998-09-29 N1 - Date created - 1998-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photocarcinogenesis and susceptibility to UV radiation in the v-Ha-ras transgenic Tg.AC mouse. AN - 73906930; 9740239 AB - The v-Ha-ras transgenic Tg.AC mouse line has proven to be a useful model for the study of chemical carcinogenic potential. We undertook experiments designed to study the effect of the physical carcinogen, UV radiation, on tumorigenesis in this mouse strain. Following a total of three exposures on alternating days to a radiation source covering a cumulative UVR exposure range of 2.6-42.6 kJ per m2, squamous papillomas developed by 4 wk after initial exposure in a dose-dependent manner. Malignancies developed within 18-30 wk following the initial UVR exposure and were all diagnosed as squamous cell carcinoma or spindle cell tumors. In contrast to other mouse stains used in photocarcinogenesis studies, few p53 mutations were found in Tg.AC malignancies upon polymerase chain reaction-single stranded conformational polymorphism analysis of exons 4-8 followed by sequencing of suspicious bands; however, all tumors analyzed by in situ hybridization expressed the v-Ha-ras transgene. Immunohistochemical analysis of UVR-exposed skin taken 24 h after the last of three exposures (13.1 kJ per m2 total UVR) showed expression of p53 in hair follicles and in interfollicular epidermis, which indicates that the gene was functional. Thus, although there are some differences between the Tg.AC and other mouse models, these results suggest that the Tg.AC mouse may be a useful model for the study of acute exposure photocarcinogenesis. JF - The Journal of investigative dermatology AU - Trempus, C S AU - Mahler, J F AU - Ananthaswamy, H N AU - Loughlin, S M AU - French, J E AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 445 EP - 451 VL - 111 IS - 3 SN - 0022-202X, 0022-202X KW - Index Medicus KW - Phenotype KW - Animals KW - Genes, p53 KW - Disease Models, Animal KW - Mice KW - Dose-Response Relationship, Radiation KW - Mice, Transgenic KW - Mutation KW - Female KW - Genes, ras KW - Ultraviolet Rays KW - Papilloma -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Radiation Tolerance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73906930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Photocarcinogenesis+and+susceptibility+to+UV+radiation+in+the+v-Ha-ras+transgenic+Tg.AC+mouse.&rft.au=Trempus%2C+C+S%3BMahler%2C+J+F%3BAnanthaswamy%2C+H+N%3BLoughlin%2C+S+M%3BFrench%2C+J+E%3BTennant%2C+R+W&rft.aulast=Trempus&rft.aufirst=C&rft.date=1998-09-01&rft.volume=111&rft.issue=3&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-02 N1 - Date created - 1998-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. AN - 73901937; 9731712 AB - Insulin-like growth factor-I (IGF-I) is essential for cell growth, differentiation and postnatal development. A null mutation in igf-1 causes intrauterine growth retardation and perinatal lethality. The present study was designed to test the lower limit of igf-1 gene dosage that ensures survival and postnatal growth by using the Cre/loxP system. Mice with variable reductions in IGF-I levels were generated by crossing EIIa-cre transgenic mice and mice with loxP-flanked igf-1 locus (igf-1/flox). EIIa-cre mice express bacteriophage P1 Cre (causes recombination) recombinase under the adenovirus promoter EIIa, during early embryonic development before implantation, and cause genomic recombination of the igf-1/flox locus. Mice with the most extensive recombination die immediately after birth, while the survivors have significant growth retardation in proportion to the reduction in their igf-1 gene. Interestingly, this gene dosage effect on body weight was not very significant before weaning. However, when the young animals were weaned at 3 weeks, the igf-1 gene dosage was the only independent predictor of the weight gain between 3 and 6 weeks among the parameters tested. Although growth retarded, mice with Cre-induced partial igf-1 deficiency were fertile and gave birth to null mice. Thus Cre-induced genomic recombination using the EIIa promoter occurs during development and creates distinct phenotypes compared with the conventional null mutation. This variability allows for postnatal survival and will enable one to begin to explore the role of the endocrine vs. paracrine effects of IGF-I. JF - Molecular endocrinology (Baltimore, Md.) AU - Liu, J L AU - Grinberg, A AU - Westphal, H AU - Sauer, B AU - Accili, D AU - Karas, M AU - LeRoith, D AD - Section on Cellular and Molecular Physiology, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1452 EP - 1462 VL - 12 IS - 9 SN - 0888-8809, 0888-8809 KW - RNA, Messenger KW - 0 KW - Viral Proteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Growth Disorders -- genetics KW - RNA, Messenger -- metabolism KW - Liver -- growth & development KW - Humans KW - Recombination, Genetic KW - Infant, Newborn KW - Liver -- metabolism KW - Mice KW - Mice, Transgenic KW - Gene Expression Regulation, Developmental KW - Insulin-Like Growth Factor I -- genetics KW - Insulin-Like Growth Factor I -- physiology KW - Integrases -- genetics KW - Infant Mortality KW - Gene Dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73901937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Insulin-like+growth+factor-I+affects+perinatal+lethality+and+postnatal+development+in+a+gene+dosage-dependent+manner%3A+manipulation+using+the+Cre%2FloxP+system+in+transgenic+mice.&rft.au=Liu%2C+J+L%3BGrinberg%2C+A%3BWestphal%2C+H%3BSauer%2C+B%3BAccili%2C+D%3BKaras%2C+M%3BLeRoith%2C+D&rft.aulast=Liu&rft.aufirst=J&rft.date=1998-09-01&rft.volume=12&rft.issue=9&rft.spage=1452&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 - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae. AN - 73901823; 9728538 AB - Multidrug-resistant Streptococcus pneumoniae strains have emerged over the past decade at an alarming rate. The molecular mechanism of trimethoprim resistance was investigated in 5 pneumococcal strains isolated in the Washington, DC, area from patients with invasive infections. Cloning and sequencing of the trimethoprim resistance determinant from these pneumococci indicated that an altered chromosome-encoded dihydrofolate reductase (DHFR) was responsible for the observed resistance. Comparison of DHFR sequences from pneumococcal strains with various susceptibilities to trimethoprim, together with site-directed mutagenesis, revealed that substitution of isoleucine-100 with a leucine residue resulted in trimethoprim resistance. Hydrogen bonding between the carbonyl oxygen of isoleucine-100 and the 4-amino group of trimethoprim is proposed to play a critical role in the inhibition of DHFR by trimethoprim. This enzyme-substrate model should facilitate the design of new antibacterial agents with improved activity against S. pneumoniae. JF - The Journal of infectious diseases AU - Pikis, A AU - Donkersloot, J A AU - Rodriguez, W J AU - Keith, J M AD - Vaccine and Therapeutic Development Section, Oral Infection and Immunity Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-4350, USA. apikis@yoda.nidr.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 700 EP - 706 VL - 178 IS - 3 SN - 0022-1899, 0022-1899 KW - Anti-Bacterial Agents KW - 0 KW - DNA, Bacterial KW - Trimethoprim KW - AN164J8Y0X KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Abridged Index Medicus KW - Index Medicus KW - Base Sequence KW - Humans KW - Drug Resistance, Microbial -- genetics KW - Chromosomes, Bacterial KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Streptococcus pneumoniae -- enzymology KW - Trimethoprim -- pharmacology KW - Conserved Sequence KW - Anti-Bacterial Agents -- pharmacology KW - Streptococcus pneumoniae -- isolation & purification KW - Mutation KW - Streptococcus pneumoniae -- drug effects KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Streptococcus pneumoniae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73901823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+conservative+amino+acid+mutation+in+the+chromosome-encoded+dihydrofolate+reductase+confers+trimethoprim+resistance+in+Streptococcus+pneumoniae.&rft.au=Pikis%2C+A%3BDonkersloot%2C+J+A%3BRodriguez%2C+W+J%3BKeith%2C+J+M&rft.aulast=Pikis&rft.aufirst=A&rft.date=1998-09-01&rft.volume=178&rft.issue=3&rft.spage=700&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 - 1998-09-29 N1 - Date created - 1998-09-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF055726; GENBANK; AF055727; AF055721; AF055720; AF055723; AF055722; AF055725; AF055724 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. AN - 73898283; 9741580 AB - There has been confusion as to what role(s) nitric oxide (NO) has in different physiological and pathophysiological mechanisms. Some studies imply that NO has cytotoxic properties and is the genesis of numerous diseases and degenerative states, whereas other reports suggest that NO prevents injurious conditions from developing and promotes events which return tissue to homeostasis. The primary determinant(s) of how NO affects biological systems centers on its chemistry. The chemistry of NO in biological systems is extensive and complex. To simplify this discussion, we have formulated the "chemical biology of NO" to describe the pertinent chemical reactions under specific biological conditions. The chemical biology of NO is divided into two major categories, direct and indirect. Direct effects are defined as those reactions fast enough to occur between NO and specific biological molecules. Indirect effects do not involve NO, but rather are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. RNOS formed from NO can mediate either nitrosative or oxidative stress. This report discusses various aspects of the chemical biology of NO relating to biological molecules such as guanylate cyclase, cytochrome P450, nitric oxide synthase, catalase, and DNA and explores the potential roles of NO in different biological events. Also, the implications of different chemical reactions of NO with cellular processes such as mitochondrial respiration, metal homeostasis, and lipid metabolism are discussed. Finally, a discussion of the chemical biology of NO in different cytotoxic mechanisms is presented. JF - Free radical biology & medicine AU - Wink, D A AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 434 EP - 456 VL - 25 IS - 4-5 SN - 0891-5849, 0891-5849 KW - Superoxides KW - 11062-77-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Superoxides -- chemistry KW - Animals KW - Superoxides -- metabolism KW - Apoptosis KW - Oxygen -- metabolism KW - Humans KW - Oxygen -- chemistry KW - Nitric Oxide -- toxicity KW - Cell Death KW - Cytoprotection KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- metabolism KW - Nitric Oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73898283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+biology+of+nitric+oxide%3A+Insights+into+regulatory%2C+cytotoxic%2C+and+cytoprotective+mechanisms+of+nitric+oxide.&rft.au=Wink%2C+D+A%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1998-09-01&rft.volume=25&rft.issue=4-5&rft.spage=434&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 - 1998-11-24 N1 - Date created - 1998-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. AN - 73897398; 9732415 AB - A genetic polymorphism in the metabolism of the anticonvulsant drug S-mephenytoin has been attributed to defective CYP2C19 alleles. This genetic polymorphism displays large interracial differences with the poor metabolizer (PM) phenotype representing 2-5% of Caucasian and 13-23% of Oriental populations. In the present study, we identified two new mutations in CYP2C19 in a single Swiss Caucasian PM outlier (JOB 1) whose apparent genotype (CYP2C19*1/CYP2C19*2) did not agree with his PM phenotype. These mutations consisted of a single base pair mutation (G395A) in exon 3 resulting in an Arg132-->Gln coding change and a (G276C) mutation in exon 2 resulting in a coding change Glu92-->Asp. However, the G276C mutation and the G395A mutation resided on separate alleles. Genotyping tests of a family study of JOB1 showed that the exon 2 change occurred on the CYP2C19*2 allele, which also contained the known splice mutation in exon 5 (this variant is termed CYP2C19*2B to distinguish it from the original splice variant now termed CYP2C19*2A). The exon 3 mutation resided on a separate allele (termed CYP2C19*6). In all other respects this allele was identical to one of two wild-type alleles, CYP2C19*1B. The incidence of CYP2C19*6 in a European Caucasian population phenotyped for mephenytoin metabolism was 0/344 (99% confidence limits of 0 to 0.9%). Seven of 46 Caucasian CYP2C19*2 alleles were CYP2C19*2B(15%) and 85% were CYP2C19*2A. The Arg132Gln mutation was produced by site-directed mutatgenesis and the recombinant protein expressed in a bacterial cDNA expression system. Recombinant CYP2C19 6 had negligible catalytic activity toward S-mephenytoin compared with CYP2C19 1B, which is consistent with the conclusion that CYP2C19*6 represents a PM allele. Thus, the new CYP2C19*6 allele contributes to the PM phenotype in Caucasians. JF - The Journal of pharmacology and experimental therapeutics AU - Ibeanu, G C AU - Goldstein, J A AU - Meyer, U AU - Benhamou, S AU - Bouchardy, C AU - Dayer, P AU - Ghanayem, B I AU - Blaisdell, J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1490 EP - 1495 VL - 286 IS - 3 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 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 - Mutagenesis, Site-Directed KW - Humans KW - Alleles KW - Cytochrome P-450 Enzyme System -- genetics KW - Anticonvulsants -- metabolism KW - European Continental Ancestry Group -- genetics KW - Mixed Function Oxygenases -- genetics KW - Mephenytoin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73897398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+new+human+CYP2C19+alleles+%28CYP2C19*6+and+CYP2C19*2B%29+in+a+Caucasian+poor+metabolizer+of+mephenytoin.&rft.au=Ibeanu%2C+G+C%3BGoldstein%2C+J+A%3BMeyer%2C+U%3BBenhamou%2C+S%3BBouchardy%2C+C%3BDayer%2C+P%3BGhanayem%2C+B+I%3BBlaisdell%2C+J&rft.aulast=Ibeanu&rft.aufirst=G&rft.date=1998-09-01&rft.volume=286&rft.issue=3&rft.spage=1490&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 - 1998-10-08 N1 - Date created - 1998-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell-cycle arrest and inhibition of G1 cyclin translation by iron in AFT1-1(up) yeast. AN - 73896043; 9724638 AB - Although iron is an essential nutrient, it is also a potent cellular toxin, and the acquisition of iron is a highly regulated process in eukaryotes. In yeast, iron uptake is homeostatically regulated by the transcription factor encoded by AFT1. Expression of AFT1-1(up), a dominant mutant allele, results in inappropriately high rates of iron uptake, and AFT1-1(up) mutants grow slowly in the presence of high concentrations of iron. We present evidence that when Aft1-1(up) mutants are exposed to iron, they arrest the cell division cycle at the G1 regulatory point Start. This arrest is dependent on high-affinity iron uptake and does not require the activation of the DNA damage checkpoint governed by RAD9. The iron-induced arrest is bypassed by overexpression of a mutant G1 cyclin, cln3-2, and expression of the G1-specific cyclins Cln1 and Cln2 is reduced when yeast are exposed to increasing amounts of iron, which may account for the arrest. This reduction is not due to changes in transcription of CLN1 or CLN2, nor is it due to accelerated degradation of the protein. Instead, this reduction occurs at the level of Cln2 translation, a recently recognized locus of cell-cycle control in yeast. JF - The EMBO journal AU - Philpott, C C AU - Rashford, J AU - Yamaguchi-Iwai, Y AU - Rouault, T A AU - Dancis, A AU - Klausner, R D AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA. carolinep@intra.niddk.nih.gov Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 5026 EP - 5036 VL - 17 IS - 17 SN - 0261-4189, 0261-4189 KW - AFT1 protein, S cerevisiae KW - 0 KW - CLN1 protein, S cerevisiae KW - CLN2 protein, S cerevisiae KW - CLN3 protein, S cerevisiae KW - Cyclins KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Models, Genetic KW - Biological Transport KW - G1 Phase -- drug effects KW - Homeostasis KW - Mutation KW - Gene Expression Regulation, Fungal KW - Protein Biosynthesis KW - Cyclins -- biosynthesis KW - Fungal Proteins -- biosynthesis KW - Fungal Proteins -- genetics KW - Iron -- toxicity KW - Transcription Factors -- genetics KW - Saccharomyces cerevisiae -- drug effects KW - Saccharomyces cerevisiae -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73896043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell-cycle+arrest+and+inhibition+of+G1+cyclin+translation+by+iron+in+AFT1-1%28up%29+yeast.&rft.au=Philpott%2C+C+C%3BRashford%2C+J%3BYamaguchi-Iwai%2C+Y%3BRouault%2C+T+A%3BDancis%2C+A%3BKlausner%2C+R+D&rft.aulast=Philpott&rft.aufirst=C&rft.date=1998-09-01&rft.volume=17&rft.issue=17&rft.spage=5026&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms. AN - 73888696; 9738567 AB - We conducted a phase I trial of the cyclin-dependent kinase inhibitor, flavopiridol (National Service Center [NSC] 649890), to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacology of flavopiridol given as a 72-hour infusion every 2 weeks. Seventy-six patients with refractory malignancies with prior disease progression were treated with flavopiridol, with first-cycle pharmacokinetic sampling. Forty-nine patients defined our first MTD, 50 mg/m2/d x 3 with dose-limiting toxicity (DLT) of secretory diarrhea at 62.5 mg/kg/d x 3. Subsequent patients received antidiarrheal prophylaxis (ADP) to define a second MTD, 78 mg/m2/d x 3 with DLT of hypotension at 98 mg/m2/d x 3. Other toxicities included a proinflammatory syndrome with alterations in acute-phase reactants, particularly at doses >50 mg/ m2/d x 3, which in some patients prevented chronic therapy every 2 weeks. In some patients, ADP was not successful, requiring dose-deescalation. Although approximately 70% of patients displayed predictable flavopiridol pharmacology, we observed unexpected interpatient variability and postinfusion peaks in approximately 30% of cases. At the two MTDs, we achieved a mean plasma flavopiridol concentration of 271 nM (50 mg/m2/d x 3) and 344 nM (78 mg/m2/d x 3), respectively. One partial response in a patient with renal cancer and minor responses (n=3) in patients with non-Hodgkin's lymphoma, colon, and renal cancer occurred. The MTD of infusional flavopiridol is 50 mg/m2/d x 3 with dose-limiting secretory diarrhea at 62.5 mg/m2/d x 3. With ADP, 78 mg/m2/d x 3 was the MTD, with dose-limiting hypotension at 98 mg/m2/d x 3. Based on chronic tolerability, 50 mg/m2/d x 3 is the recommended phase II dose without ADP. Antitumor effect was observed in certain patients with renal, prostate, and colon cancer, and non-Hodgkin's lymphoma. Concentrations of flavopiridol (200 to 400 nM) needed for cyclin-dependent kinase inhibition in preclinical models were achieved safely. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Senderowicz, A M AU - Headlee, D AU - Stinson, S F AU - Lush, R M AU - Kalil, N AU - Villalba, L AU - Hill, K AU - Steinberg, S M AU - Figg, W D AU - Tompkins, A AU - Arbuck, S G AU - Sausville, E A AD - Developmental Therapeutics Program Clinical Trials Unit, Medicine Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, USA. sendero@helix.nih.gov Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2986 EP - 2999 VL - 16 IS - 9 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Drug Administration Schedule KW - Diarrhea -- chemically induced KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Aged, 80 and over KW - Humans KW - Adult KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Aged KW - Middle Aged KW - Male KW - Female KW - Enzyme Inhibitors -- adverse effects KW - Neoplasms -- drug therapy KW - Enzyme Inhibitors -- therapeutic use KW - Antineoplastic Agents -- pharmacokinetics KW - Flavonoids -- adverse effects KW - Piperidines -- pharmacokinetics KW - Piperidines -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Flavonoids -- therapeutic use KW - Piperidines -- therapeutic use KW - Enzyme Inhibitors -- pharmacokinetics KW - Antineoplastic Agents -- therapeutic use KW - Flavonoids -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73888696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+trial+of+continuous+infusion+flavopiridol%2C+a+novel+cyclin-dependent+kinase+inhibitor%2C+in+patients+with+refractory+neoplasms.&rft.au=Senderowicz%2C+A+M%3BHeadlee%2C+D%3BStinson%2C+S+F%3BLush%2C+R+M%3BKalil%2C+N%3BVillalba%2C+L%3BHill%2C+K%3BSteinberg%2C+S+M%3BFigg%2C+W+D%3BTompkins%2C+A%3BArbuck%2C+S+G%3BSausville%2C+E+A&rft.aulast=Senderowicz&rft.aufirst=A&rft.date=1998-09-01&rft.volume=16&rft.issue=9&rft.spage=2986&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 - 1998-09-29 N1 - Date created - 1998-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7. AN - 73887885; 9748126 AB - Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Steller, M A AU - Gurski, K J AU - Murakami, M AU - Daniel, R W AU - Shah, K V AU - Celis, E AU - Sette, A AU - Trimble, E L AU - Park, R C AU - Marincola, F M AD - Section of Gynecologic Oncology, Surgery Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892, USA. msteller@wihri.org Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 2103 EP - 2109 VL - 4 IS - 9 SN - 1078-0432, 1078-0432 KW - Cancer Vaccines KW - 0 KW - Epitopes KW - Epitopes, T-Lymphocyte KW - Lipids KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Peptides KW - oncogene protein E7, Human papillomavirus type 16 KW - Index Medicus KW - Lipids -- administration & dosage KW - Peptides -- administration & dosage KW - Humans KW - Peptides -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Epitopes, T-Lymphocyte -- immunology KW - Immunity, Cellular -- immunology KW - Neoplasm Recurrence, Local -- immunology KW - Adult KW - Immunotherapy, Active KW - Middle Aged KW - Neoplasm Recurrence, Local -- therapy KW - Epitopes, T-Lymphocyte -- biosynthesis KW - Female KW - Uterine Cervical Neoplasms -- therapy KW - Carcinoma, Squamous Cell -- immunology KW - Cancer Vaccines -- immunology KW - Vaginal Neoplasms -- immunology KW - Epitopes -- administration & dosage KW - Oncogene Proteins, Viral -- immunology KW - Cancer Vaccines -- therapeutic use KW - Epitopes -- therapeutic use KW - Uterine Cervical Neoplasms -- immunology KW - Epitopes -- immunology KW - Vaginal Neoplasms -- therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73887885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell-mediated+immunological+responses+in+cervical+and+vaginal+cancer+patients+immunized+with+a+lipidated+epitope+of+human+papillomavirus+type+16+E7.&rft.au=Steller%2C+M+A%3BGurski%2C+K+J%3BMurakami%2C+M%3BDaniel%2C+R+W%3BShah%2C+K+V%3BCelis%2C+E%3BSette%2C+A%3BTrimble%2C+E+L%3BPark%2C+R+C%3BMarincola%2C+F+M&rft.aulast=Steller&rft.aufirst=M&rft.date=1998-09-01&rft.volume=4&rft.issue=9&rft.spage=2103&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Footprints on the viral DNA ends in moloney murine leukemia virus preintegration complexes reflect a specific association with integrase. AN - 73881361; 9724738 AB - Retroviral DNA integration is mediated by the preintegration complex, a large nucleoprotein complex derived from the core of the infecting virion. We previously have used Mu-mediated PCR to probe the nucleoprotein organization of Moloney murine leukemia virus preintegration complexes. A region of protection spans several hundred base pairs at each end of the viral DNA, and strong enhancements are present near the termini. Here, we show that these footprints reflect a specific association between integrase and the viral DNA ends in functional preintegration complexes. Barrier-to-autointegration factor, a cellular protein that blocks autointegration of Moloney murine leukemia virus DNA, also plays an indirect role in generating the footprints at the ends of the viral DNA. We have exploited Mu-mediated PCR to examine the effect of mutations at the viral DNA termini on complex formation. We find that a replication competent mutant with a deletion at one end of the viral DNA still exhibits a strong enhancement about 20 bp from the terminus of the mutant DNA end. The site of the enhancement therefore appears to be at a fixed distance from the ends of the viral DNA. We also find that a mutation at one end of the viral DNA, which renders the virus incompetent for replication, abolishes the enhancements and protection at both the U3 and U5 ends. A pair of functional viral DNA ends therefore are required to interact before the chemical step of 3' end processing. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wei, S Q AU - Mizuuchi, K AU - Craigie, R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 10535 EP - 10540 VL - 95 IS - 18 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - Integrases KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Animals KW - 3T3 Cells KW - Base Sequence KW - Mice KW - Leukemia Virus, Murine -- genetics KW - Integrases -- metabolism KW - DNA Footprinting KW - Virus Integration KW - Leukemia Virus, Murine -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73881361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Footprints+on+the+viral+DNA+ends+in+moloney+murine+leukemia+virus+preintegration+complexes+reflect+a+specific+association+with+integrase.&rft.au=Wei%2C+S+Q%3BMizuuchi%2C+K%3BCraigie%2C+R&rft.aulast=Wei&rft.aufirst=S&rft.date=1998-09-01&rft.volume=95&rft.issue=18&rft.spage=10535&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 - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1987 May 8;49(3):347-56 [3032450] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1528-33 [9465049] Cell. 1988 Aug 12;54(4):497-504 [3401925] Genes Dev. 1989 Apr;3(4):469-78 [2721960] J Virol. 1990 Jun;64(6):2711-5 [2335814] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4164-8 [2349226] J Virol. 1990 Dec;64(12):5958-65 [2173775] Mol Cell Biol. 1991 Mar;11(3):1419-30 [1847499] J Virol. 1992 Aug;66(8):5092-5 [1629963] Annu Rev Genet. 1992;26:527-44 [1482125] Virology. 1993 Aug;195(2):432-40 [8393234] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9823-7 [7937898] Annu Rev Biochem. 1994;63:133-73 [7526778] J Virol. 1996 Jun;70(6):3571-80 [8648691] Cell. 1997 Feb 21;88(4):483-92 [9038339] EMBO J. 1997 Dec 15;16(24):7511-20 [9405379] J Mol Biol. 1988 Jan 5;199(1):47-59 [3351923] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Copy number control of IncIalpha plasmid ColIb-P9 by competition between pseudoknot formation and antisense RNA binding at a specific RNA site. AN - 73881293; 9724656 AB - Replication of a low-copy-number IncIalpha plasmid ColIb-P9 depends on expression of the repZ gene encoding the replication initiator protein. repZ expression is negatively controlled by the small antisense Inc RNA, and requires formation of a pseudoknot in the RepZ mRNA consisting of stem-loop I, the Inc RNA target, and a downstream sequence complementary to the loop I. The loop I sequence comprises 5'-rUUGGCG-3', conserved in many prokaryotic antisense systems, and was proposed to be the important site of copy number control. Here we show that the level of repZ expression is rate-limiting for replication and thus copy number, by comparing the levels of repZ expression and copy number from different mutant ColIb-P9 derivatives defective in Inc RNA and pseudoknot formation. Kinetic analyses using in vitro transcribed RNAs indicate that Inc RNA binding and the pseudoknot formation are competitive at the level of initial base paring to loop I. This initial interaction is stimulated by the presence of the loop U residue in the 5'-rUUGGCG-3' motif. These results indicate that the competition between the two RNA-RNA interactions at the specific site is a novel regulatory mechanism for establishing the constant level of repZ expression and thus copy number. JF - The EMBO journal AU - Asano, K AU - Mizobuchi, K AD - Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113. kasano@aghmac1.nichd.nih.gov Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 5201 EP - 5213 VL - 17 IS - 17 SN - 0261-4189, 0261-4189 KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - DNA-Binding Proteins KW - RNA, Antisense KW - RNA, Bacterial KW - RNA, Double-Stranded KW - RNA, Messenger KW - RepZ protein, plasmid ColIb-P9 KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Models, Genetic KW - Molecular Sequence Data KW - DNA-Binding Proteins -- biosynthesis KW - RNA, Antisense -- metabolism KW - Nucleic Acid Conformation KW - Mutagenesis KW - Plasmids -- genetics KW - DNA, Bacterial -- biosynthesis KW - RNA, Bacterial -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73881293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Copy+number+control+of+IncIalpha+plasmid+ColIb-P9+by+competition+between+pseudoknot+formation+and+antisense+RNA+binding+at+a+specific+RNA+site.&rft.au=Asano%2C+K%3BMizobuchi%2C+K&rft.aulast=Asano&rft.aufirst=K&rft.date=1998-09-01&rft.volume=17&rft.issue=17&rft.spage=5201&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 - 1998-11-23 N1 - Date created - 1998-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Biophys Res Commun. 1970 Oct 9;41(1):150-6 [4918011] J Biol Chem. 1998 May 8;273(19):11826-38 [9565607] J Bacteriol. 1978 Jun;134(3):1141-56 [149110] J Mol Biol. 1980 Apr;138(2):179-207 [6997493] J Bacteriol. 1980 Aug;143(2):971-80 [6162838] J Mol Biol. 1983 May 5;166(1):1-19 [6304321] Microbiol Rev. 1984 Mar;48(1):1-23 [6201704] Cell. 1984 Oct;38(3):861-70 [6207934] Cell. 1984 Oct;38(3):879-87 [6386179] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Cell. 1985 Mar;40(3):527-35 [2578886] Mol Gen Genet. 1986 Apr;203(1):143-9 [2423846] Nucleic Acids Res. 1986 Oct 24;14(20):8027-46 [2430262] Methods Enzymol. 1987;153:3-11 [3323803] Microbiol Rev. 1987 Dec;51(4):381-95 [3325793] Protein Eng. 1986 Oct-Nov;1(1):67-74 [3507689] Cell. 1989 Oct 20;59(2):395-404 [2478296] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7942-6 [2682632] J Bacteriol. 1990 Apr;172(4):1983-91 [1690704] J Bacteriol. 1990 Apr;172(4):1992-7 [1690705] J Biol Chem. 1990 Jun 25;265(18):10666-73 [2191957] Cell. 1990 Aug 10;62(3):591-8 [1696181] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7668-72 [2217199] Cell. 1990 Dec 21;63(6):1121-4 [2261636] J Biol Chem. 1991 Feb 25;266(6):3774-81 [1704893] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1389-93 [1996339] Annu Rev Biochem. 1991;60:631-52 [1715680] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9011-5 [1924364] Nucleic Acids Res. 1992 Jun 11;20(11):2705-10 [1614857] EMBO J. 1992 Jul;11(7):2675-83 [1378398] J Bacteriol. 1992 Dec;174(23):7620-8 [1447133] J Bacteriol. 1993 Oct;175(20):6476-83 [7691796] Annu Rev Microbiol. 1994;48:713-42 [7826024] DNA Res. 1994;1(5):201-12 [7584042] Mol Microbiol. 1995 Jul;17(2):291-301 [7494478] Mol Microbiol. 1997 Jan;23(1):95-108 [9004224] Cell. 1997 Jul 11;90(1):43-53 [9230301] J Biol Chem. 1998 May 8;273(19):11815-25 [9565606] Nature. 1976 Apr 15;260(5552):645-6 [772447] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. AN - 73867728; 9725260 AB - IL-12 and IL-10, respectively, stimulate Th1 and Th2 immune responses. The development of some allergic reactions, infections, and tumors are associated with excessive histamine production and a shift toward Th2 responses. Here we address the possibility that this association is causally linked, at least in part, to modulation of IL-12 and IL-10 production by histamine. We report that histamine dose-dependently inhibited the secretion of human IL-12 (p70) and increased the production of IL-10 in LPS-stimulated whole blood cultures. These effects of histamine were antagonized by cimetidine, an H2 receptor antagonist, but not by selective H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. The effects of histamine on IL-12 and IL-10 secretion were independent of endogenous secretion of IL-10 or exogenous addition of IL-12, while Ro 20-1724, a phosphodiesterase inhibitor, potentiated the effects of histamine on IL-12 and IL-10 production, implicating cAMP in its actions. Similar modulatory effects of histamine on IL-12 and IL-10 production, which were reversed by the H2 antagonist cimetidine, were observed in PBMC and isolated monocytes stimulated by Staphylococcus aureus Cowan strain 1 and LPS, respectively. Thus, histamine, via stimulation of H2 receptors on peripheral monocytes and subsequent elevation of cAMP, suppresses IL-12 and stimulates IL-10 secretion, changes that may result in a shift of Th1/Th2 balance toward Th2-dominance. This may represent a novel mechanism by which excessive secretion of histamine potentiates Th2-mediated allergic reactions and contributes to the development of certain infections and tumors normally eliminated by Th1-dependent immune mechanisms. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Elenkov, I J AU - Webster, E AU - Papanicolaou, D A AU - Fleisher, T A AU - Chrousos, G P AU - Wilder, R L AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. ElenkovI@cc1.nichd.nih.gov Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 2586 EP - 2593 VL - 161 IS - 5 SN - 0022-1767, 0022-1767 KW - Histamine Agonists KW - 0 KW - Histamine H2 Antagonists KW - Lipopolysaccharides KW - Receptors, Histamine H2 KW - Interleukin-10 KW - 130068-27-8 KW - Interleukin-12 KW - 187348-17-0 KW - Cimetidine KW - 80061L1WGD KW - Histamine KW - 820484N8I3 KW - Cyclic AMP KW - E0399OZS9N KW - Dimaprit KW - ZZQ699148P KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Histamine H2 Antagonists -- pharmacology KW - Histamine Agonists -- pharmacology KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Th1 Cells -- metabolism KW - Dimaprit -- pharmacology KW - Th2 Cells -- metabolism KW - Cells, Cultured KW - Monocytes -- metabolism KW - Adult KW - Cyclic AMP -- pharmacology KW - Monocytes -- drug effects KW - Cimetidine -- pharmacology KW - Drug Synergism KW - Female KW - Male KW - Receptors, Histamine H2 -- blood KW - Interleukin-12 -- biosynthesis KW - Histamine -- physiology KW - Histamine -- blood KW - Interleukin-10 -- pharmacology KW - Interleukin-10 -- blood KW - Interleukin-10 -- biosynthesis KW - Interleukin-12 -- blood KW - Interleukin-12 -- antagonists & inhibitors KW - Receptors, Histamine H2 -- physiology KW - Receptors, Histamine H2 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73867728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Histamine+potently+suppresses+human+IL-12+and+stimulates+IL-10+production+via+H2+receptors.&rft.au=Elenkov%2C+I+J%3BWebster%2C+E%3BPapanicolaou%2C+D+A%3BFleisher%2C+T+A%3BChrousos%2C+G+P%3BWilder%2C+R+L&rft.aulast=Elenkov&rft.aufirst=I&rft.date=1998-09-01&rft.volume=161&rft.issue=5&rft.spage=2586&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 - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel Escherichia coli umuD' mutants: structure-function insights into SOS mutagenesis. AN - 73866610; 9721309 AB - Although it has been 10 years since the discovery that the Escherichia coli UmuD protein undergoes a RecA-mediated cleavage reaction to generate mutagenically active UmuD', the function of UmuD' has yet to be determined. In an attempt to elucidate the role of UmuD' in SOS mutagenesis, we have utilized a colorimetric papillation assay to screen for mutants of a hydroxylamine-treated, low-copy-number umuD' plasmid that are unable to promote SOS-dependent spontaneous mutagenesis. Using such an approach, we have identified 14 independent umuD' mutants. Analysis of these mutants revealed that two resulted from promoter changes which reduced the expression of wild-type UmuD', three were nonsense mutations that resulted in a truncated UmuD' protein, and the remaining nine were missense alterations. In addition to the hydroxylamine-generated mutants, we have subcloned the mutations found in three chromosomal umuD1, umuD44, and umuD77 alleles into umuD'. All 17 umuD' mutants resulted in lower levels of SOS-dependent spontaneous mutagenesis but varied in the extent to which they promoted methyl methanesulfonate-induced mutagenesis. We have attempted to correlate these phenotypes with the potential effect of each mutation on the recently described structure of UmuD'. JF - Journal of bacteriology AU - McLenigan, M AU - Peat, T S AU - Frank, E G AU - McDonald, J P AU - Gonzalez, M AU - Levine, A S AU - Hendrickson, W A 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, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 4658 EP - 4666 VL - 180 IS - 17 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Phenotype KW - Genes, Dominant KW - Dimerization KW - Plasmids KW - Genes, Recessive KW - Structure-Activity Relationship KW - Mutagenesis KW - Cloning, Molecular KW - Bacterial Proteins -- genetics KW - SOS Response (Genetics) KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73866610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+Escherichia+coli+umuD%27+mutants%3A+structure-function+insights+into+SOS+mutagenesis.&rft.au=McLenigan%2C+M%3BPeat%2C+T+S%3BFrank%2C+E+G%3BMcDonald%2C+J+P%3BGonzalez%2C+M%3BLevine%2C+A+S%3BHendrickson%2C+W+A%3BWoodgate%2C+R&rft.aulast=McLenigan&rft.aufirst=M&rft.date=1998-09-01&rft.volume=180&rft.issue=17&rft.spage=4658&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1995;254:241-63 [8531690] Mutat Res. 1993 Oct;292(2):175-85 [7692254] Nature. 1996 Apr 25;380(6576):727-30 [8614470] J Bacteriol. 1996 Jun;178(12):3550-6 [8655553] Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10291-6 [8816793] Gene. 1996 Oct 24;177(1-2):77-81 [8921848] J Bacteriol. 1996 Dec;178(24):7295-303 [8955415] Cancer Surv. 1996;28:117-40 [8977032] Structure. 1996 Dec 15;4(12):1401-12 [8994967] J Bacteriol. 1997 Dec;179(23):7435-45 [9393709] Nat Struct Biol. 1997 Dec;4(12):979-83 [9406544] J Bacteriol. 1994 Aug;176(16):5011-21 [8051014] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4331-5 [2989816] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6226-30 [2994067] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] J Bacteriol. 1988 May;170(5):2163-73 [2834329] Nature. 1989 Jul 20;340(6230):245-6 [2547163] Curr Genet. 1989 Dec;16(5-6):339-46 [2692852] J Bacteriol. 1990 Jun;172(6):3030-6 [2188949] J Bacteriol. 1990 Sep;172(9):4964-78 [2144275] J Bacteriol. 1990 Sep;172(9):4979-87 [2203737] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190-4 [2205854] Nucleic Acids Res. 1990 Dec 25;18(24):7367-72 [2259628] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] Nucleic Acids Res. 1991 Oct 25;19(20):5791 [1945859] Proteins. 1991;11(4):281-96 [1758883] J Bacteriol. 1992 May;174(10):3133-9 [1349601] Mol Gen Genet. 1992 Jun;233(3):443-8 [1320188] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] J Bacteriol. 1993 Sep;175(17):5411-9 [8366028] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] J Bacteriol. 1996 May;178(9):2580-5 [8626325] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of a neurovirulence determinant within the envelope protein of a polytropic murine retrovirus: induction of central nervous system disease by low levels of virus. AN - 73857407; 9721229 AB - Murine leukemia virus (MuLV) clone Fr98 is a recombinant polytropic virus that causes neurological disease characterized by ataxia in susceptible mouse strains. The envelope gene of Fr98 has been previously shown to encode at least two separate neurovirulence determinants. In the present study, the determinant encoded within the EcoRI/AvrII fragment of the envelope gene was further defined. In these experiments, neurovirulence was associated with a change from a serine to an arginine at position 195 and a glycine to an alanine at position 198 within the envelope protein. Neurovirulent and nonvirulent virus clones, which differed only at these two amino acid residues, showed no difference in the type or location of cells infected. Furthermore, equivalent levels of viral p30 capsid protein were detected in the brains of mice infected with either the neurovirulent or nonvirulent virus clones. These results were consistent with the interpretation that the envelope protein of the neurovirulent virus differed from that of the nonvirulent virus by having a greater toxic effect on central nervous system function. JF - Virology AU - Poulsen, D J AU - Robertson, S J AU - Favara, C A AU - Portis, J L AU - Chesebro, B W AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana, 59840, USA. Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 199 EP - 207 VL - 248 IS - 2 SN - 0042-6822, 0042-6822 KW - Viral Envelope Proteins KW - 0 KW - Index Medicus KW - Animals KW - Virulence -- genetics KW - Tumor Virus Infections -- pathology KW - Astrocytes -- physiology KW - Capsid -- metabolism KW - Mice KW - Immunohistochemistry KW - Retroviridae Infections -- pathology KW - Leukemia, Experimental -- pathology KW - Protein Conformation KW - Leukemia Virus, Murine -- genetics KW - Viral Envelope Proteins -- physiology KW - Viral Envelope Proteins -- analysis KW - Central Nervous System Diseases -- virology KW - Leukemia Virus, Murine -- chemistry KW - Leukemia Virus, Murine -- pathogenicity KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73857407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mapping+of+a+neurovirulence+determinant+within+the+envelope+protein+of+a+polytropic+murine+retrovirus%3A+induction+of+central+nervous+system+disease+by+low+levels+of+virus.&rft.au=Poulsen%2C+D+J%3BRobertson%2C+S+J%3BFavara%2C+C+A%3BPortis%2C+J+L%3BChesebro%2C+B+W&rft.aulast=Poulsen&rft.aufirst=D&rft.date=1998-09-01&rft.volume=248&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor promoter arsenite activates extracellular signal-regulated kinase through a signaling pathway mediated by epidermal growth factor receptor and Shc. AN - 73847234; 9710602 AB - Although arsenite is an established carcinogen, the mechanisms underlying its tumor-promoting properties are poorly understood. Previously, we reported that arsenite treatment leads to the activation of the extracellular signal-regulated kinase (ERK) in rat PC12 cells through a Ras-dependent pathway. To identify potential mediators of the upstream signaling cascade, we examined the tyrosine phosphorylation profile in cells exposed to arsenite. Arsenite treatment rapidly stimulated tyrosine phosphorylation of several proteins in a Ras-independent manner, with a pattern similar to that seen in response to epidermal growth factor (EGF) treatment. Among these phosphorylated proteins were three isoforms of the proto-oncoprotein Shc as well as the EGF receptor (EGFR). Tyrosine phosphorylation of Shc allowed for enhanced interactions between Shc and Grb2 as identified by coimmunoprecipitation experiments. The arsenite-induced tyrosine phosphorylation of Shc, enhancement of Shc and Grb2 interactions, and activation of ERK were all drastically reduced by treatment of cells with either the general growth factor receptor poison suramin or the EGFR-selective inhibitor tyrphostin AG1478. Down-regulation of EGFR expression through pretreatment of cells with EGF also attenuated ERK activation and Shc tyrosine phosphorylation in response to arsenite treatment. These results demonstrate that the EGFR and Shc are critical mediators in the activation of the Ras/ERK signaling cascade by arsenite and suggest that arsenite acts as a tumor promoter largely by usurping this growth factor signaling pathway. JF - Molecular and cellular biology AU - Chen, W AU - Martindale, J L AU - Holbrook, N J AU - Liu, Y AD - Gene Expression and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, Maryland 21224, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 5178 EP - 5188 VL - 18 IS - 9 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Arsenites KW - Carcinogens KW - GRB2 Adaptor Protein KW - Grb2 protein, rat KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 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 - arsenite KW - N5509X556J KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Phosphotyrosine -- metabolism KW - Genes, ras KW - Rats KW - Down-Regulation KW - Phosphorylation KW - Transfection KW - Glutathione Transferase -- biosynthesis KW - PC12 Cells KW - Phosphoproteins -- metabolism KW - Signal Transduction -- physiology KW - Protein Biosynthesis KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Signal Transduction -- drug effects KW - Arsenites -- toxicity KW - Carcinogens -- toxicity KW - Receptor, Epidermal Growth Factor -- physiology KW - src Homology Domains KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+promoter+arsenite+activates+extracellular+signal-regulated+kinase+through+a+signaling+pathway+mediated+by+epidermal+growth+factor+receptor+and+Shc.&rft.au=Chen%2C+W%3BMartindale%2C+J+L%3BHolbrook%2C+N+J%3BLiu%2C+Y&rft.aulast=Chen&rft.aufirst=W&rft.date=1998-09-01&rft.volume=18&rft.issue=9&rft.spage=5178&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 - Evaluation of the conditioned reinforcing effects of phentermine and fenfluramine in the rat: concordance with clinical studies. AN - 73838025; 9704887 AB - An unbiased place-preference conditioning procedure was used to characterize the conditioned reinforcing effects of phentermine (PHEN), fenfluramine (FEN), and their combination (PHEN/FEN) in previously drug-naive rats. Animals exhibited marked preferences for an environment previously associated with the administration of phentermine. The minimum dose producing a significant effect was 3.0 mg/kg. In contrast, FEN produced dose-related place aversions. In animals which received a subthreshold dose of FEN in combination with a dose of PHEN that produced a conditioned place preference, no preference or aversion for the drug-paired place was seen. Similarly, no significant conditioning in response to administration of PHEN (3.0 mg/kg) and FEN (3.0 mg/kg) was seen. The failure of PHEN/FEN to produce conditioned reinforcing effects is in line with recent clinical studies, and suggests that PHEN/FEN and drug combinations sharing the same neurochemical mechanisms of action will have low potential for abuse. JF - Synapse (New York, N.Y.) AU - Rea, W P AU - Rothman, R B AU - Shippenberg, T S AD - Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 107 EP - 111 VL - 30 IS - 1 SN - 0887-4476, 0887-4476 KW - Fenfluramine KW - 2DS058H2CF KW - Phentermine KW - C045TQL4WP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Male KW - Phentermine -- pharmacology KW - Choice Behavior -- drug effects KW - Reinforcement (Psychology) KW - Conditioning (Psychology) -- physiology KW - Choice Behavior -- physiology KW - Fenfluramine -- pharmacology KW - Conditioning (Psychology) -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73838025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+the+conditioned+reinforcing+effects+of+phentermine+and+fenfluramine+in+the+rat%3A+concordance+with+clinical+studies.&rft.au=Rea%2C+W+P%3BRothman%2C+R+B%3BShippenberg%2C+T+S&rft.aulast=Rea&rft.aufirst=W&rft.date=1998-09-01&rft.volume=30&rft.issue=1&rft.spage=107&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice. AN - 70123967; 9848111 AB - Inhalation studies of molybdenum trioxide (MoO3) were conducted because of its wide use in industry, human exposure, and lack of data on carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MoO3 by inhalation at 0, 10, 30, or 100 mg/m3, 6 h/day, 5 days/week, for 2 years. In both rats and mice, survival and mean body weights of exposed groups of males and females were similar to those of their respective controls. There were significant exposure-dependent increases in blood molybdenum concentration in exposed rats and mice. There were no toxicological differences in bone density or curvature between exposed animals and their respective controls. In rats, dose-dependent increases in incidence of hyaline degeneration in the nasal olfactory epithelium and squamous metaplasia of the epithelium lining the base of the epiglottis were observed. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) was marginally increased in males but not in females compared with controls. In mice, the incidences of squamous metaplasia of the epithelium lining the base of the epiglottis, hyperplasia of the laryngeal epithelium, and metaplasia of the alveolar epithelium were significantly increased in all exposed males and females compared with controls. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) in exposed groups of males and females was significantly greater than that in the control groups. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chan, P C AU - Herbert, R A AU - Roycroft, J H AU - Haseman, J K AU - Grumbein, S L AU - Miller, R A AU - Chou, B J AD - National Institute of Environmental Health Sciences, North Carolina 27709, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 58 EP - 65 VL - 45 IS - 1 SN - 1096-6080, 1096-6080 KW - Air Pollutants KW - 0 KW - Oxides KW - molybdenum trioxide KW - 22FQ3F03YS KW - Molybdenum KW - 81AH48963U KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Pneumonia -- chemically induced KW - Inhalation Exposure KW - Carcinogenicity Tests KW - Mice KW - Pneumonia -- pathology KW - Male KW - Female KW - Molybdenum -- administration & dosage KW - Oxides -- administration & dosage KW - Adenocarcinoma, Bronchiolo-Alveolar -- chemically induced KW - Adenocarcinoma, Bronchiolo-Alveolar -- pathology KW - Lung -- drug effects KW - Oxides -- toxicity KW - Lung Neoplasms -- chemically induced KW - Lung -- pathology KW - Air Pollutants -- toxicity KW - Molybdenum -- toxicity KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70123967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lung+tumor+induction+by+inhalation+exposure+to+molybdenum+trioxide+in+rats+and+mice.&rft.au=Chan%2C+P+C%3BHerbert%2C+R+A%3BRoycroft%2C+J+H%3BHaseman%2C+J+K%3BGrumbein%2C+S+L%3BMiller%2C+R+A%3BChou%2C+B+J&rft.aulast=Chan&rft.aufirst=P&rft.date=1998-09-01&rft.volume=45&rft.issue=1&rft.spage=58&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 - 1999-01-15 N1 - Date created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subchronic toxicity of human immunodeficiency virus and tuberculosis combination therapies in B6C3F1 mice. AN - 70111031; 9848118 AB - Combination therapy with anti-HIV drugs and opportunistic infection drugs is a common practice in treatment of AIDS patients. Although toxic effects of most individual therapies are known, the toxic potential of most combination therapies has not been established. To understand the toxic consequences of combination therapies, the commonly used anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) and tuberculosis infection therapies pyrazinamide, isoniazid, and rifampicin were evaluated by 13-week gavage studies in B6C3F1 mice, either alone or AZT in combination with one of the antituberculosis drugs. The doses include AZT 100, 200, and 400; pyrazinamide 1000 and 1500; isoniazid 50, 100, and 150; and rifampicin 100, 200, and 400 mg/kg/day. AZT alone caused hematopoietic toxicity with dose-related bone marrow suppression, macrocytic anemia, and thrombocytosis. Pyrazinamide or isoniazid alone at the doses tested did not cause significant toxicity. Rifampicin alone caused hematopoietic toxicity and possibly mild hepatic toxicity. Pyrazinamide below 10 times the therapeutic dose when given with AZT did not increase the hematological toxicity of AZT. Isoniazid markedly increased the hematological toxicity of AZT and contributed to mortality at 3 to 4 times the therapeutic dose combinations. Administration of rifampicin with AZT at the calculated therapeutic doses resulted in toxicity of far greater magnitude than that caused by AZT or rifampicin alone. Combination treatment with AZT and rifampicin caused severe anemia with mortality at 2 to 4 times the therapeutic dose combinations. However, AZT did not enhance the hepatotoxicity of rifampicin. Increased hematopoietic toxicity of AZT when given in combination with the above antituberculosis drugs may be due to changes in the metabolism of AZT. Results of these studies indicate that toxicological effects of combination therapies could be considerably more severe than and different from the toxicity of individual therapies. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Rao, G N AU - Lindamood, C AU - Heath, J E AU - Farnell, D R AU - Giles, H D AD - National Institute of Environmental Health Sciences, North Carolina 27709, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 113 EP - 127 VL - 45 IS - 1 SN - 1096-6080, 1096-6080 KW - Anti-HIV Agents KW - 0 KW - Antibiotics, Antitubercular KW - Hemoglobins KW - Pyrazinamide KW - 2KNI5N06TI KW - Zidovudine KW - 4B9XT59T7S KW - Isoniazid KW - V83O1VOZ8L KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Drug Interactions KW - Blood Platelets KW - Erythrocytes KW - Toxicity Tests KW - Mice KW - Male KW - Female KW - Rifampin -- toxicity KW - Anti-HIV Agents -- toxicity KW - Bone Marrow -- pathology KW - Zidovudine -- toxicity KW - Pyrazinamide -- toxicity KW - Antibiotics, Antitubercular -- toxicity KW - Isoniazid -- toxicity KW - Bone Marrow -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70111031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Subchronic+toxicity+of+human+immunodeficiency+virus+and+tuberculosis+combination+therapies+in+B6C3F1+mice.&rft.au=Rao%2C+G+N%3BLindamood%2C+C%3BHeath%2C+J+E%3BFarnell%2C+D+R%3BGiles%2C+H+D&rft.aulast=Rao&rft.aufirst=G&rft.date=1998-09-01&rft.volume=45&rft.issue=1&rft.spage=113&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 - 1999-01-15 N1 - Date created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of human polyomavirus JC in the Biaka Pygmies and Bantu of Central Africa. AN - 70070936; 9830527 AB - Polyomavirus JC (JCV) is ubiquitous in humans and causes a chronic demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy which is common in AIDS. JCV is excreted in urine of 30-70% of adults worldwide. Based on sequence analysis of JCV complete genomes or fragments thereof, JCV can be classified into geographically derived genotypes. Types 1 and 2 are of European and Asian origin respectively while Types 3 and 6 are African in origin. Type 4, a possible recombinant of European and African genotypes (1 and 3) is common in the USA. To delineate the JCV genotypes in an aboriginal African population, random urine samples were collected from the Biaka Pygmies and Bantu from the Central African Republic. There were 43 males and 25 females aged 4-55 years, with an average age of 26 years. After PCR amplification of JCV in urine, products were directly cycle sequenced. Five of 23 Pygmy adults (22%) and four of 20 Bantu adults (20%) were positive for JC viruria. DNA sequence analysis revealed JCV Type 3 (two), Type 6 (two) and one Type 1 variant in Biaka Pygmies. All the Bantu strains were Type 6. Type 3 and 6 strains of JCV are the predominant strains in central Africa. The presence of multiple subtypes of JCV in Biaka Pygmies may be a result of extensive interactions of Pygmies with their African tribal neighbors during their itinerant movements in the equatorial forest. JF - Memorias do Instituto Oswaldo Cruz AU - Chima, S C AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. chimasc@helix.nih.gov PY - 1998 SP - 615 EP - 623 VL - 93 IS - 5 SN - 0074-0276, 0074-0276 KW - Index Medicus KW - Humans KW - Continental Population Groups KW - Urine -- virology KW - Oceanic Ancestry Group KW - Africa, Central KW - Child KW - Child, Preschool KW - Genotype KW - Molecular Epidemiology KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - JC Virus -- genetics KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70070936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Memorias+do+Instituto+Oswaldo+Cruz&rft.atitle=Molecular+epidemiology+of+human+polyomavirus+JC+in+the+Biaka+Pygmies+and+Bantu+of+Central+Africa.&rft.au=Chima%2C+S+C%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Chima&rft.aufirst=S&rft.date=1998-09-01&rft.volume=93&rft.issue=5&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Memorias+do+Instituto+Oswaldo+Cruz&rft.issn=00740276&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 - Melanoma-specific cytotoxicity induced by a tyrosinase promoter-enhancer/herpes simplex virus thymidine kinase adenovirus. AN - 70062297; 9824047 AB - The ability to specifically and efficiently express selected genes in tumor cells is an important goal for cancer gene therapy. Transcriptional targeting of adenovirus to tumor cells, thereby limiting their expression to specific cell types, represents one experimental approach to this problem. We have previously shown that a recombinant adenovirus containing the murine tyrosinase promoter coupled to a dimer of the tyrosinase-enhancer element can target the expression of beta-galactosidase cDNA to melanoma cells. We now report that this same promoter/enhancer cassette can efficiently drive the expression of the herpes simplex virus thymidine kinase gene in melanoma cells. Infection of melanoma cells with the AdmTyr-tk virus along with subsequent ganciclovir treatment induces S phase cell cycle arrest associated with a profound change in cell size and morphology. Treated cells remain viable for prolonged periods, but clonogenic assays demonstrate that the cell cycle arrest is irreversible. In contrast, nonmelanoma cells are unaffected by this treatment regimen, exhibiting normal growth kinetics, metabolic activity, and cell cycle progression. The therapeutic efficacy of the AdmTyr-tk virus was tested in vivo using a xenograft model of human melanoma. The injection of the AdmTyr-tk virus into established subcutaneous tumor nodules in combination with systemic ganciclovir administration led to a decreased tumor growth rate and to complete tumor regressions in some cases. These studies demonstrate the feasibility of selectively targeting growth-inhibitory genes to melanoma cells in vitro and in vivo. JF - Cancer gene therapy AU - Siders, W M AU - Halloran, P J AU - Fenton, R G AD - Department of Experimental Transplantation and Immunology, Division of Clinical Sciences, the National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 27102, USA. PY - 1998 SP - 281 EP - 291 VL - 5 IS - 5 SN - 0929-1903, 0929-1903 KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Animals KW - S Phase -- drug effects KW - Neoplasms, Experimental -- therapy KW - Humans KW - Simplexvirus -- enzymology KW - Mice KW - Mice, Nude KW - Cell Death -- drug effects KW - Genetic Vectors -- pharmacology KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Enhancer Elements, Genetic KW - Carcinogenicity Tests KW - Cell Death -- genetics KW - Genetic Vectors -- genetics KW - Cell Cycle -- drug effects KW - Ganciclovir -- pharmacology KW - Melanoma -- pathology KW - Genetic Therapy -- methods KW - Melanoma -- therapy KW - Monophenol Monooxygenase -- genetics KW - Melanoma -- metabolism KW - Thymidine Kinase -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70062297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gene+therapy&rft.atitle=Melanoma-specific+cytotoxicity+induced+by+a+tyrosinase+promoter-enhancer%2Fherpes+simplex+virus+thymidine+kinase+adenovirus.&rft.au=Siders%2C+W+M%3BHalloran%2C+P+J%3BFenton%2C+R+G&rft.aulast=Siders&rft.aufirst=W&rft.date=1998-09-01&rft.volume=5&rft.issue=5&rft.spage=281&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 completed - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Congenital disorders sharing oxidative stress and cancer proneness as phenotypic hallmarks: prospects for joint research in pharmacology. AN - 70012265; 9792204 AB - In spite of very distinct genotypic assets, a number of congenital conditions include oxidative stress as a phenotypic hallmark. These disorders include Fanconi's anaemia, ataxia telangiectasia, xeroderma pigmentosum and Bloom's syndrome, as well as two frequent congenital conditions: Down's syndrome and cystic fibrosis. Cancer proneness is a clinical feature shared by these disorders, while other manifestations include early ageing, neurological symptoms or congenital malformations. The onset of oxidative stress has been related to excess formation, or defective detoxification, of reactive oxygen species (ROS). This can arise from either the abnormal expression or inducibility of ROS-detoxifying enzymes, or by defective absorption of nutrient antioxidants. Resulting oxidative injury has been characterized through: (i) DNA, protein or lipid oxidative damage; (ii) excess ROS formation (in vitro and ex vivo); (iii) sensitivity to oxygen-related toxicity; (iv) improvement of cellular defects by either hypoxia or antioxidants; and (v) circumstantial evidence for in vivo oxidative stress (as e.g. clastogenic factors). Investigations conducted so far have been confined to individual disorders. Comparative studies of selected indicators for oxidative stress could provide further insights into the pathogenesis of each individual condition. Such a unified approach may have wide-ranging consequences for studies of ageing and cancer. JF - Medical hypotheses AU - Pagano, G AU - Korkina, L G AU - Brunk, U T AU - Chessa, L AU - Degan, P AU - del Principe, D AU - Kelly, F J AU - Malorni, W AU - Pallardó, F AU - Pasquier, C AU - Scovassi, I AU - Zatterale, A AU - Franceschi, C AD - Italian National Cancer Institute, Fondazione G. Pascale, Naples, Italy. airfa@italsoft.it Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 253 EP - 266 VL - 51 IS - 3 SN - 0306-9877, 0306-9877 KW - Index Medicus KW - Phenotype KW - Animals KW - Apoptosis KW - Humans KW - Aging KW - Disease Susceptibility KW - Genetic Diseases, Inborn -- genetics KW - Oxidative Stress -- genetics KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70012265?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hypotheses&rft.atitle=Congenital+disorders+sharing+oxidative+stress+and+cancer+proneness+as+phenotypic+hallmarks%3A+prospects+for+joint+research+in+pharmacology.&rft.au=Pagano%2C+G%3BKorkina%2C+L+G%3BBrunk%2C+U+T%3BChessa%2C+L%3BDegan%2C+P%3Bdel+Principe%2C+D%3BKelly%2C+F+J%3BMalorni%2C+W%3BPallard%C3%B3%2C+F%3BPasquier%2C+C%3BScovassi%2C+I%3BZatterale%2C+A%3BFranceschi%2C+C&rft.aulast=Pagano&rft.aufirst=G&rft.date=1998-09-01&rft.volume=51&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Medical+hypotheses&rft.issn=03069877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-05 N1 - Date created - 1999-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequency of ras mutations in liver neoplasms from B6C3F1 mice exposed to tetrafluoroethylene for two years. AN - 69999381; 9789951 AB - Tetrafluoroethylene (TFE) was evaluated for carcinogenicity in inhalation studies because of its high use in the production of Teflon. There was clear evidence of hepatocarcinogenic activity in B6C3F1 mice after 2 yr of TFE exposure. The present study was designed to characterize the mutation profiles of H- and K-ras oncogenes in liver neoplasms in mice after exposure to 0, 312, 625, or 1,250 ppm TFE. ras mutations were identified by restriction fragment length polymorphism, single-stranded conformation polymorphism analysis, and direct sequencing of polymerase chain reaction amplified-DNA isolated from frozen or paraffin-embedded liver neoplasms. A low frequency (15%, 9/59) of H-ras codon 61 mutations was detected in hepatocellular neoplasms when compared with the higher frequency (59% of this study and 56% of historical data) in spontaneously occurring liver neoplasms. There was no difference in the mutation frequency or spectrum among exposure groups or between benign and malignant hepatocellular neoplasms. K-ras mutations at codons 12, 13, and 61 and H-ras mutations at codon 117 were not detected in hepatocellular neoplasms. These data suggest that TFE-induced hepatocellular neoplasms are developed by pathways that are mostly independent of ras mutations. The ras mutation frequency and spectrum were similar to those of the structurally related chemical tetrachloroethylene. JF - Toxicologic pathology AU - Hong, H H AU - Devereux, T R AU - Roycroft, J H AU - Boorman, G A AU - Sills, R C AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. hong@niehs.nih.gov PY - 1998 SP - 646 EP - 650 VL - 26 IS - 5 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Fluorocarbons KW - tetrafluoroethylene KW - OMW63Z518S KW - Index Medicus KW - Signal Transduction -- physiology KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Division -- physiology KW - Mice KW - Time Factors KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Male KW - Female KW - Cell Transformation, Neoplastic KW - Genes, ras KW - Liver Neoplasms, Experimental -- genetics KW - Point Mutation KW - Fluorocarbons -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69999381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequency+of+ras+mutations+in+liver+neoplasms+from+B6C3F1+mice+exposed+to+tetrafluoroethylene+for+two+years.&rft.au=Hong%2C+H+H%3BDevereux%2C+T+R%3BRoycroft%2C+J+H%3BBoorman%2C+G+A%3BSills%2C+R+C&rft.aulast=Hong&rft.aufirst=H&rft.date=1998-09-01&rft.volume=26&rft.issue=5&rft.spage=646&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 - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impact of Helicobacter hepaticus infection in B6C3F1 mice from twelve National Toxicology Program two-year carcinogenesis studies. AN - 69996918; 9789946 AB - Male and female B6C3F1 mice from 12 National Toxicology Program (NTP) 2-yr carcinogenesis studies were found to be infected with Helicobacter hepaticus. Many of the male mice from 9 of these studies had an associated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis and hepatocellular neoplasms in the A/JCr male mouse. We attempted to determine if the data from the Helicobacter-affected NTP B6C3F1 mouse studies were compromised and unsuitable for cancer hazard identification. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F1 mice were increased in affected studies as compared with control males from unaffected studies. The increased incidence of hepatocellular neoplasms was observed in those males exhibiting H. hepaticus-associated hepatitis. Other observations further differentiated control male mice from affected and unaffected studies. H-ras codon 61 CAA to AAA mutations were less common in liver neoplasms from males from affected studies as compared with historical and study controls. In addition, increases in cell proliferation rates and apoptosis were observed in the livers of male mice with H. hepaticus-associated hepatitis. These data support the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in the pathogenesis. Therefore, interpretation of carcinogenic effects in the liver of B6C3F1 mice may be confounded if there is H. hepaticus-associated hepatitis. JF - Toxicologic pathology AU - Hailey, J R AU - Haseman, J K AU - Bucher, J R AU - Radovsky, A E AU - Malarkey, D E AU - Miller, R T AU - Nyska, A AU - Maronpot, R R AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. hailey@niehs.nih.gov PY - 1998 SP - 602 EP - 611 VL - 26 IS - 5 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Hepatitis -- microbiology KW - Animals KW - Cell Cycle -- physiology KW - Mice KW - Rats KW - Genes, ras KW - Mice, Inbred Strains KW - Polymerase Chain Reaction KW - Rats, Inbred F344 KW - Polymorphism, Restriction Fragment Length KW - Carcinogenicity Tests KW - Mutation KW - Female KW - Male KW - Liver Neoplasms, Experimental -- genetics KW - Liver Neoplasms, Experimental -- microbiology KW - Helicobacter KW - Helicobacter Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69996918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Impact+of+Helicobacter+hepaticus+infection+in+B6C3F1+mice+from+twelve+National+Toxicology+Program+two-year+carcinogenesis+studies.&rft.au=Hailey%2C+J+R%3BHaseman%2C+J+K%3BBucher%2C+J+R%3BRadovsky%2C+A+E%3BMalarkey%2C+D+E%3BMiller%2C+R+T%3BNyska%2C+A%3BMaronpot%2C+R+R&rft.aulast=Hailey&rft.aufirst=J&rft.date=1998-09-01&rft.volume=26&rft.issue=5&rft.spage=602&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 - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute immunosuppression and syngeneic bone marrow transplantation in ocular autoimmunity abort disease, but do not result in induction of long-term protection. AN - 69995749; 9785606 AB - Acute immunosuppression induced by total body irradiation (TBI) or cyclophosphamide (Cy) treatment, followed by syngeneic bone marrow transplantation (SBMT), was reported to be effective in inducing long-term tolerance in some autoimmune disease models. We examined the efficacy of this approach in the mouse model of experimental autoimmune uveoretinitis (EAU). Development of EAU induced by the interphotoreceptor retinoid binding protein (IRBP) was abolished almost completely by either TBI or Cy treatment, followed by SBMT, instituted one week after priming. In parallel, IRBP-specific delayed-type hypersensitivity (DTH) responses and lymph node cell proliferation were strongly suppressed or abolished. However, when these IRBP-immunized, lymphoablated and BM reconstituted mice were rechallenged with the immunizing antigen seven weeks after the primary immunization, they were not protected from developing disease, despite the fact that DTH and lymph node cell proliferation to the antigen were suppressed relative to controls. TBI treatment appeared somewhat more effective than Cy treatment as judged by its more profound effect on immunological responses. These results demonstrate the ability of acute immunosuppression followed by reconstitution of the immune system to inhibit the development of EAU, although long-term protection from disease was not achieved. JF - Ocular immunology and inflammation AU - Savion, S AU - Silver, P B AU - Chan, C C AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. shoshans@plato.tau.ac.il Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 163 EP - 172 VL - 6 IS - 3 SN - 0927-3948, 0927-3948 KW - Autoantigens KW - 0 KW - Eye Proteins KW - Immunosuppressive Agents KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Animals KW - Autoantigens -- pharmacology KW - Retinol-Binding Proteins -- pharmacology KW - Hypersensitivity, Delayed -- chemically induced KW - Transplantation, Isogeneic KW - Mice KW - Hypersensitivity, Delayed -- prevention & control KW - Immunosuppressive Agents -- pharmacology KW - Eye Proteins -- pharmacology KW - Whole-Body Irradiation KW - Hypersensitivity, Delayed -- pathology KW - Lymphocyte Activation -- immunology KW - Immune Tolerance -- immunology KW - Bone Marrow -- radiation effects KW - Bone Marrow -- drug effects KW - Bone Marrow -- immunology KW - Female KW - Lymph Nodes -- immunology KW - Cyclophosphamide -- pharmacology KW - Autoimmunity -- immunology KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Bone Marrow Transplantation -- immunology KW - Uveitis -- therapy KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- therapy KW - Autoimmune Diseases -- chemically induced KW - Retinitis -- therapy KW - Retinitis -- chemically induced KW - Uveitis -- chemically induced KW - Immunosuppression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69995749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=Acute+immunosuppression+and+syngeneic+bone+marrow+transplantation+in+ocular+autoimmunity+abort+disease%2C+but+do+not+result+in+induction+of+long-term+protection.&rft.au=Savion%2C+S%3BSilver%2C+P+B%3BChan%2C+C+C%3BCaspi%2C+R+R&rft.aulast=Savion&rft.aufirst=S&rft.date=1998-09-01&rft.volume=6&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trials of reducing low-density lipoprotein concentrations. AN - 69990664; 9785054 AB - Much diverse evidence suggests that the plasma levels of low-density lipoprotein (LDL) cholesterol play a causal role in the pathogenesis of atherosclerotic coronary heart disease. Until recently, clinical trials of LDL lowering, while showing significant reductions in coronary heart disease (CHD) rates, were not entirely convincing and left some questions of long-term toxicity unresolved. The results of a series of new trials using members of the powerful statin class of drugs are now being reported. Whether they are primary or secondary prevention studies, they have been uniformly successful in reducing mortality and morbidity from CHD and even total mortality, and have decreased the need for revascularization procedures. Their effectiveness is apparent in many different subgroups such as women, diabetics, hypertensives, and in stroke prevention. Statin drugs also have proven to be remarkably safe over the duration of the studies. Angiographic studies show an impact on coronary or carotid lesions. JF - Endocrinology and metabolism clinics of North America AU - Rifkind, B M AD - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 585 EP - 95, viii-ix VL - 27 IS - 3 SN - 0889-8529, 0889-8529 KW - Hypolipidemic Agents KW - 0 KW - Lipoproteins, LDL KW - Index Medicus KW - Hypolipidemic Agents -- therapeutic use KW - Coronary Disease -- mortality KW - Angiography KW - Coronary Disease -- prevention & control KW - Humans KW - Clinical Trials as Topic KW - Cerebrovascular Disorders -- prevention & control KW - Male KW - Female KW - Lipoproteins, LDL -- blood KW - Arteriosclerosis -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69990664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+metabolism+clinics+of+North+America&rft.atitle=Clinical+trials+of+reducing+low-density+lipoprotein+concentrations.&rft.au=Rifkind%2C+B+M&rft.aulast=Rifkind&rft.aufirst=B&rft.date=1998-09-01&rft.volume=27&rft.issue=3&rft.spage=585&rft.isbn=&rft.btitle=&rft.title=Endocrinology+and+metabolism+clinics+of+North+America&rft.issn=08898529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-11 N1 - Date created - 1998-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of xenobiotics in the central nervous system: implications and challenges. AN - 69983626; 9783722 AB - The metabolism of drugs and other xenobiotics in situ in the brain has far-reaching implications in the pharmacological and pharmacodynamic effects of drugs acting on the CNS, particularly with respect to psychoactive drugs wherein a wide range of therapeutic response is typically seen in the patient population. An entirely functional cytochrome P450 (P450) monooxygenase system is known to exist in the rodent and human brain, wherein it is preferentially localized in the neuronal cells, which are the sites of action of psychoactive drugs. Further, bioactivation of xenobiotics, in situ, in the CNS would result in the formation of reactive, toxic metabolites in the neuronal cells that have limited regenerative capability. The presence of P450 enzymes in selective cell populations within distinctive regions of the brain that are affected in certain neurodegenerative disorders implies the potential role of P450-mediated bioactivation as a causative factor in the etiopathogenesis of these diseases. The characterization of brain-specific P450s and their regulation and localization within the CNS assume importance for understanding the potential role of these enzymes in the pathogenesis of neurodegenerative disorders and psychopharmacological modulation of drugs acting on the CNS. JF - Biochemical pharmacology AU - Ravindranath, V AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore, India. vijaravi@nimhans.ren.nic.in Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 547 EP - 551 VL - 56 IS - 5 SN - 0006-2952, 0006-2952 KW - Psychotropic Drugs KW - 0 KW - Xenobiotics KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Sex Characteristics KW - Humans KW - Neurodegenerative Diseases -- metabolism KW - Psychotropic Drugs -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Organ Specificity KW - Central Nervous System -- metabolism KW - Xenobiotics -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69983626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolism+of+xenobiotics+in+the+central+nervous+system%3A+implications+and+challenges.&rft.au=Ravindranath%2C+V&rft.aulast=Ravindranath&rft.aufirst=V&rft.date=1998-09-01&rft.volume=56&rft.issue=5&rft.spage=547&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 - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice. AN - 69968692; 9772215 AB - Acetaminophen (APAP) hepatotoxicity is due to its biotransformation to a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), that is capable of binding to cellular macromolecules. At least two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated in this reaction in mice. To test the combined roles of CYP1A2 and CYP2E1 in an intact animal model, a double-null mouse line lacking functional expression of CYP1A2 and CYP2E1 was produced by cross-breeding Cyp1a2-/- mice with Cyp2e1-/- mice. Animals deficient in the expression of both P450s developed normally and exhibited no obvious phenotypic abnormalities. Comparison of the dose-response to APAP (200-1200 mg/kg) indicated that double-null animals were highly resistant to APAP-induced toxicity whereas the wild-type animals were sensitive. Administration of 600 to 800 mg/kg of this drug to male wild-type animals resulted in increased plasma concentrations of liver enzymes (alanine aminotransferase, sorbitol dehydrogenase), lipidosis, hepatic necrosis, and renal tubular necrosis. In contrast, when APAP of equivalent or higher dose was administered to the double-null mice, plasma levels of liver enzymes and liver histopathology were normal. However, administration of 1200 mg of APAP/kg to the double-null mice resulted in infrequent liver lipidosis and mild kidney lesions. Consistent with the protection from hepatotoxicity, the expected depletion of hepatic glutathione (GSH) content was significantly retarded and APAP covalent binding to hepatic cytosolic proteins was not detectable in the double-null mice. Likewise, in vitro activation of APAP by liver microsomes from the double-null mice was approximately one tenth of that in microsomes from wild-type mice. Thus, the protection against APAP toxicity afforded by deletion of both CYP2E1 and CYP1A2 likely reflects greatly diminished production of the toxic electrophile, NAPQI. Copyright 1998 Academic Press. JF - Toxicology and applied pharmacology AU - Zaher, H AU - Buters, J T AU - Ward, J M AU - Bruno, M K AU - Lucas, A M AU - Stern, S T AU - Cohen, S D AU - Gonzalez, F J AD - Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 193 EP - 199 VL - 152 IS - 1 SN - 0041-008X, 0041-008X KW - Analgesics, Non-Narcotic KW - 0 KW - Sulfhydryl Compounds KW - Acetaminophen KW - 362O9ITL9D KW - DNA KW - 9007-49-2 KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Sulfhydryl Compounds -- metabolism KW - Dose-Response Relationship, Drug KW - Lipidoses -- metabolism KW - Alanine Transaminase -- metabolism KW - Glutathione -- metabolism KW - DNA -- analysis KW - Mice KW - L-Iditol 2-Dehydrogenase -- metabolism KW - Mice, Knockout KW - Gene Deletion KW - Genotype KW - Necrosis KW - Survival Rate KW - Mice, Inbred C57BL KW - Male KW - Liver -- enzymology KW - Liver -- pathology KW - Kidney Tubules -- pathology KW - Cytochrome P-450 CYP2E1 -- genetics KW - Cytochrome P-450 CYP1A2 -- physiology KW - Cytochrome P-450 CYP1A2 -- genetics KW - Kidney Tubules -- drug effects KW - Liver -- drug effects KW - Microsomes, Liver -- enzymology KW - Analgesics, Non-Narcotic -- toxicity KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 CYP2E1 -- physiology KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protection+against+acetaminophen+toxicity+in+CYP1A2+and+CYP2E1+double-null+mice.&rft.au=Zaher%2C+H%3BButers%2C+J+T%3BWard%2C+J+M%3BBruno%2C+M+K%3BLucas%2C+A+M%3BStern%2C+S+T%3BCohen%2C+S+D%3BGonzalez%2C+F+J&rft.aulast=Zaher&rft.aufirst=H&rft.date=1998-09-01&rft.volume=152&rft.issue=1&rft.spage=193&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 - 1998-11-20 N1 - Date created - 1998-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in development of medications for alcoholism treatment. AN - 69953296; 9768539 AB - Over the past decade, research on medications to treat alcohol problem has flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and each has now earned approval in a large number of countries. Recent studies on naltrexone indicate that patient compliance is important if full benefits are to be achieved. Several laboratory studies with human subjects are beginning to elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining variability of response among subpopulations of drinkers. In addition to these two agents, recent investigations have also demonstrated that the antidepressants desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some extent, drinking itself in alcoholics who are depressed. Research to date suggests that opioid antagonists and selective serotonin reuptake inhibitors are more effective in reducing alcohol intake when used in combination. Clinical issues, methodology, and directions for future research are also reviewed in this article. In particular, issues addressed include alternative dosage regimens, necessary duration of treatment, employment of medications in combination, integration of pharmacologic agents with behavioral interventions, enhancement of patient compliance, and concurrent treatment of psychiatric comorbidity. JF - Psychopharmacology AU - Litten, R Z AU - Allen, J P AD - Treatment Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852-7003, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 20 EP - 33 VL - 139 IS - 1-2 SN - 0033-3158, 0033-3158 KW - Alcohol Deterrents KW - 0 KW - Antidepressive Agents KW - Taurine KW - 1EQV5MLY3D KW - Naltrexone KW - 5S6W795CQM KW - acamprosate KW - N4K14YGM3J KW - Index Medicus KW - Drug Therapy, Combination KW - Taurine -- analogs & derivatives KW - Humans KW - Antidepressive Agents -- therapeutic use KW - Taurine -- therapeutic use KW - Naltrexone -- therapeutic use KW - Alcoholism -- drug therapy KW - Alcohol Deterrents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69953296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Advances+in+development+of+medications+for+alcoholism+treatment.&rft.au=Litten%2C+R+Z%3BAllen%2C+J+P&rft.aulast=Litten&rft.aufirst=R&rft.date=1998-09-01&rft.volume=139&rft.issue=1-2&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-09 N1 - Date created - 1998-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant toxins in haematologic malignancies and solid tumours. AN - 69260631; 15992040 AB - Recombinant toxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. They are fusion proteins, which contain toxin and ligand regions, and are produced in Escherichia coli. The ligand may be a growth factor or a fragment of an antibody, and the toxin is usually one of the two bacterial toxins: Pseudomonas exotoxin and diphtheria toxin. Compared to the earlier generation chemical conjugates of ligands and toxins, recombinant toxins have many advantages, including homogeneity with respect to the connection between the ligand and toxin, ease and yield of production and small size. A variety of chemotherapy-resistant haematologic and solid tumours have been targeted with recombinant toxins, and clinical trials with many of them have recently demonstrated their effectiveness. Moreover, their unwanted toxic effects are different from those of most chemotherapeutic agents, supporting the expectation that they can be combined with existing modalities to improve the clinical resources available to treat cancer in humans. JF - Expert opinion on investigational drugs AU - Kreitman, R J AD - Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4B27, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 1405 EP - 1427 VL - 7 IS - 9 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69260631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Recombinant+toxins+in+haematologic+malignancies+and+solid+tumours.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1998-09-01&rft.volume=7&rft.issue=9&rft.spage=1405&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2005-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of upstream regulatory elements that repress expression of adult beta-like globin genes in a primitive erythroid environment. AN - 69187364; 10087993 AB - Our investigations have focused on localizing cis-elements responsible for the down regulation of the adult beta-like globin genes (delta and beta) in immature, or primitive erythroid tissues. We studied their activity after transfection into K562 cells, an erythroleukemia cell line with an embryonic-fetal phenotype. Analyzed DNA sequences included delta and beta 5' flanking regions extending from approximately -500 to +50bp (promoter regions), truncated delta and beta 5' flanking regions extending from approximately -250 to +50 bp, and chimeric promoter constructions, which consisted of a distal delta or beta fragment fused to a proximal beta or delta sequence. In CAT reporter constructions no appreciable level of CAT activity was supported by the beta globin promoter, and only low level activity by the delta promoter. Truncation of the beta globin promoter led to a 2-3 fold increase in promoter activity. In contrast, deletion of the upstream portion of the delta promoter led to a 10 fold decrease in expression. Coupling of the upstream beta globin sequence from approximately -500 to -250 bp to the truncated delta promoter fragment led to complete extinction of transcription activity, consistent with a negative regulatory effect of the beta globin gene upstream element(s). Fusion of the upstream portion of the delta promoter to the truncated beta globin promoter yielded a modest increase in promoter strength relative to the truncated beta gene promoter, indicating the presence of a positive transcriptional element(s) in the upstream delta globin regulatory region. Site-directed mutagenesis of binding sites for the repressor proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking region led to a 4-6 fold increase in promoter activity. DNase I footprinting of the upstream delta-globin region revealed protected sequences corresponding to consensus binding sites for GATA-1 and BP2. These results confirm that sequences in the upstream promoter region of the adult beta globin gene contribute to its factor-mediated suppression early in development and then may modulate its expression at a later stage. JF - Blood cells, molecules & diseases AU - Ebb, D AU - Tang, D C AU - Drew, L AU - Chin, K AU - Berg, P E AU - Rodgers, G P AD - National Institutes of Health, Bethesda, MD 20892-1822, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 356 EP - 369 VL - 24 IS - 3 SN - 1079-9796, 1079-9796 KW - DNA-Binding Proteins KW - 0 KW - Nerve Tissue Proteins KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Transcription Factors KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Humans KW - Repressor Proteins -- metabolism KW - Transcription, Genetic KW - Gene Expression Regulation, Leukemic KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - Locus Control Region KW - Genes, Reporter KW - K562 Cells -- metabolism KW - Nerve Tissue Proteins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Regulatory Sequences, Nucleic Acid KW - Globins -- genetics KW - Erythroid Precursor Cells -- metabolism KW - Globins -- biosynthesis KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69187364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cells%2C+molecules+%26+diseases&rft.atitle=Identification+of+upstream+regulatory+elements+that+repress+expression+of+adult+beta-like+globin+genes+in+a+primitive+erythroid+environment.&rft.au=Ebb%2C+D%3BTang%2C+D+C%3BDrew%2C+L%3BChin%2C+K%3BBerg%2C+P+E%3BRodgers%2C+G+P&rft.aulast=Ebb&rft.aufirst=D&rft.date=1998-09-01&rft.volume=24&rft.issue=3&rft.spage=356&rft.isbn=&rft.btitle=&rft.title=Blood+cells%2C+molecules+%26+diseases&rft.issn=10799796&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-03 N1 - Date created - 1999-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [A cohort study of art glass workers in the Empoli area]. TT - Studio di coorte dei lavoratori del vetro artistico nel territorio empolese. AN - 69182548; 10064947 AB - The investigation aimed at studying cause-specific mortality of art glass workers employed in 17 industrial facilities in Tuscany, Italy. A cohort of 3390 workers employed for at least 1 year was obtained from company payrolls. Follow-up was between the year each factory started operations, mostly in the mid-fifties, and the end of 1993. The cause specific expected mortality was computed relative to Tuscany rates, specified for gender, 5-year age groups and calendar year. Separate analyses were carried out for the job titles of makers, batch mixers and grinders. For males, 3180 individuals, the observed mortality for cancer causes was above the expected for the lung [standardized mortality ratio (SMR) 123, 10 observed (Obs)], larynx (SMR 166, 10 Obs), stomach (SMR 105, 30 Obs) and brain (SMR 150, 7 Obs). For non-cancer causes observed mortality was above expected for hypertensive diseases (SMR 178, 10 Obs) and diseases of the genitourinary system (SMR 169, 11 Obs). Increases for the above listed causes were shown also among makers. Mortality for larynx and lung cancer increased with time since first exposure and significantly increased SMRs were observed for 21 or more years since first exposure: this pattern was still present with smoking adjustment. The results showed consistently increased mortality for lung and larynx cancer in the overall cohort and among makers. Stomach cancer, brain cancer, hypertensive diseases and diseases of the genitourinary system were also increased in the overall cohort and among makers. JF - La Medicina del lavoro AU - Bartoli, D AU - Battista, G AU - Bertoncini, S AU - De Santis, M AU - Giusti, S AU - Orsi, D AU - Pirastu, R AU - Zingoni, A AU - Valiani, M AD - Azienda USL 11, Toscana U.O. Igiene e salute nei luoghi di lavoro, Empoli. PY - 1998 SP - 424 EP - 436 VL - 89 IS - 5 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Neoplasms -- mortality KW - Humans KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Italy -- epidemiology KW - Sex Distribution KW - Male KW - Female KW - Cause of Death KW - Occupational Diseases -- mortality KW - Art KW - Glass UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69182548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BA+cohort+study+of+art+glass+workers+in+the+Empoli+area%5D.&rft.au=Bartoli%2C+D%3BBattista%2C+G%3BBertoncini%2C+S%3BDe+Santis%2C+M%3BGiusti%2C+S%3BOrsi%2C+D%3BPirastu%2C+R%3BZingoni%2C+A%3BValiani%2C+M&rft.aulast=Bartoli&rft.aufirst=D&rft.date=1998-09-01&rft.volume=89&rft.issue=5&rft.spage=424&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 - 1999-03-23 N1 - Date created - 1999-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances. AN - 69081762; 9858067 AB - Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials. JF - Journal of affective disorders AU - Winokur, G AU - Turvey, C AU - Akiskal, H AU - Coryell, W AU - Solomon, D AU - Leon, A AU - Mueller, T AU - Endicott, J AU - Maser, J AU - Keller, M AD - The National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies, Iowa, USA. Y1 - 1998/09// PY - 1998 DA - September 1998 SP - 81 EP - 89 VL - 50 IS - 2-3 SN - 0165-0327, 0165-0327 KW - Central Nervous System Stimulants KW - 0 KW - Index Medicus KW - Age of Onset KW - Humans KW - Adult KW - Diagnosis, Dual (Psychiatry) KW - Middle Aged KW - Male KW - Female KW - Comorbidity KW - Depressive Disorder -- psychology KW - Bipolar Disorder -- psychology KW - Genetic Predisposition to Disease KW - Substance-Related Disorders -- psychology KW - Alcoholism -- genetics KW - Alcoholism -- psychology KW - Substance-Related Disorders -- genetics KW - Depressive Disorder -- complications KW - Bipolar Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69081762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+affective+disorders&rft.atitle=Alcoholism+and+drug+abuse+in+three+groups--bipolar+I%2C+unipolars+and+their+acquaintances.&rft.au=Winokur%2C+G%3BTurvey%2C+C%3BAkiskal%2C+H%3BCoryell%2C+W%3BSolomon%2C+D%3BLeon%2C+A%3BMueller%2C+T%3BEndicott%2C+J%3BMaser%2C+J%3BKeller%2C+M&rft.aulast=Winokur&rft.aufirst=G&rft.date=1998-09-01&rft.volume=50&rft.issue=2-3&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Journal+of+affective+disorders&rft.issn=01650327&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-08 N1 - Date created - 1999-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relations Between Family Predictors and Child Outcomes: Are They Weaker for Children in Child Care? AN - 1791715255 JF - Developmental Psychology Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 1119 CY - Washington PB - American Psychological Association VL - 34 IS - 5 SN - 0012-1649 KW - Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791715255?accountid=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=Relations+Between+Family+Predictors+and+Child+Outcomes%3A+Are+They+Weaker+for+Children+in+Child+Care%3F&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1998-09-01&rft.volume=34&rft.issue=5&rft.spage=1119&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 - Case-control study of occupational exposures and male breast cancer AN - 17434306; 4653317 AB - The objective was to investigate whether risk of male breast cancer is associated with workplace exposures. A case-control study of 178 cases of male breast cancer and 1041 controls was carried out with data from the United States national mortality followback survey, which collected questionnaire information from proxy respondents of a 1% sample of all 1986 United States deaths among subjects aged 25-74 years. Occupational exposure to electromagnetic fields, high temperatures, polycyclic aromatic hydrocarbons (PAHs), herbicides, other pesticides, and organic solvents was assessed by applying job-exposure matrices, based on the 1980 United States census occupation and industry codes, to the longest job held by study subjects as reported by the informants. A socioeconomic status index was created by combining information on annual family income, education, assets, and occupation to assess the association of socioeconomic status with male breast cancer. Relative risks were derived from logistic regression modelling, which included age, socioeconomic status, marital status, and body mass index, as well as occupational exposures. Risk of male breast cancer increased significantly with increasing socioeconomic status index (test for trend: p< 0.01), but the risks associated with individual socioeconomic status variables were smaller and the trends were not significant. A significant increase in risk of male breast cancer was associated with employment in blast furnaces, steel works, and rolling mills (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.1 to 10.1, based on six cases), and motor vehicle manufacturing (OR 3.1; 95% CI 1.2 to 8.2, based on seven cases). However, exposures to electromagnetic fields, high temperature, PAHs, herbicides, other pesticides, and organic solvents were not associated with risk of male breast cancer. The role of workplace exposures in increasing risk of breast cancer among men employed in motor vehicle manufacturing and in blast furnaces, steel works, and rolling mills deserves further investigation. The finding on socioeconomic status suggests that, as well as reproductive factors, other lifestyle factors such as diet that may be related to high socioeconomic status in men should be investigated further. JF - Occupational and Environmental Medicine AU - Cocco, P AU - Figgs, L AU - Dosemeci, M AU - Hayes, R AU - Linet AU - Hsing, A W AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6130 Executive Boulevard, EPN room 443 Bethesda, MD 20892, USA, HsingA@epndce.nci.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 599 EP - 604 VL - 55 IS - 9 SN - 1351-0711, 1351-0711 KW - man KW - males KW - blast furnaces KW - steel workers KW - Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Motor vehicles KW - Socioeconomics KW - Occupational exposure KW - Diets KW - Solvents KW - Metal industry KW - Socio-economic aspects KW - Pesticides KW - Breast cancer KW - R2 23080:Industrial and labor KW - X 24240:Miscellaneous KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17434306?accountid=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=Occupational+and+Environmental+Medicine&rft.atitle=Case-control+study+of+occupational+exposures+and+male+breast+cancer&rft.au=Cocco%2C+P%3BFiggs%2C+L%3BDosemeci%2C+M%3BHayes%2C+R%3BLinet%3BHsing%2C+A+W&rft.aulast=Cocco&rft.aufirst=P&rft.date=1998-09-01&rft.volume=55&rft.issue=9&rft.spage=599&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 - males; Occupational exposure; Breast cancer; Solvents; Pesticides; Socioeconomics; Metal industry; Socio-economic aspects; Risk assessment; Motor vehicles; Diets ER - TY - JOUR T1 - Circulating leptin levels during acute experimental endotoxemia and antiinflammatory therapy in humans AN - 17160541; 4456799 AB - Leptin, a newly discovered adipose tissue-derived weight-reducing hormone, is increased in acute inflammation and may be involved in the anorexia and wasting syndrome associated with infection. To determine whether this hormone responds to an acute inflammatory stimulus, plasma leptin concentrations were measured in 12 healthy subjects after intravenous administration of endotoxin. These subjects were randomized to receive concurrently ibuprofen or placebo normal saline (6 in each group). Endotoxin administration resulted in fever, leukocytosis, and an increase in plasma levels of the stress hormones adrenocorticotropic hormone (3.2 plus or minus 0.3 to 132.6 plus or minus 75.5 pmol/L, P = 0.001) and cortisol (431.6 plus or minus 44 to 796.9 plus or minus 99 mmol/L, P = 0.001). Plasma leptin levels, however, did not change significantly from baseline values after administration of endotoxin (0 h: 6.9 plus or minus 3.1 ng/mL; 6 h: 6.0 plus or minus 2.2; 24 h: 6.5 plus or minus 2.8). While ibuprofen suppressed fever and symptoms associated with endotoxemia, it had no effect on the plasma levels of leptin. In conclusion, acute experimental human endotoxinemia is not associated with acute changes in circulating leptin levels. JF - Journal of Infectious Diseases AU - Bornstein AU - Preas, H L AU - Chrousos, G P AU - Suffredini, A F AD - National Institute of Child Health and Human Development, NIH Clinical Center, Bldg. 10, Room 10N242, 9000 Rockville Pike, Bethesda, MD 20892, USA, bornstes@cc1.nichd.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 887 EP - 890 VL - 178 IS - 3 SN - 0022-1899, 0022-1899 KW - Leptin KW - Microbiology Abstracts B: Bacteriology KW - Endotoxins KW - Plasma levels KW - Ibuprofen KW - Escherichia coli KW - Adrenocorticotropic hormone KW - Inflammation KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17160541?accountid=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=Circulating+leptin+levels+during+acute+experimental+endotoxemia+and+antiinflammatory+therapy+in+humans&rft.au=Bornstein%3BPreas%2C+H+L%3BChrousos%2C+G+P%3BSuffredini%2C+A+F&rft.aulast=Bornstein&rft.aufirst=&rft.date=1998-09-01&rft.volume=178&rft.issue=3&rft.spage=887&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 - Escherichia coli; Endotoxins; Ibuprofen; Plasma levels; Inflammation; Adrenocorticotropic hormone ER - TY - JOUR T1 - Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol AN - 17152123; 4446927 AB - Prenatal exposure to diethylstilbestrol (DES) has been associated with the subsequent development of reproductive tract abnormalities, including poor reproductive outcome and neoplasia, in experimental animals and humans. Experimental animal studies with chemical carcinogens have raised the possibility that adverse effects of DES may be transmitted to succeeding generations. To evaluate this possibility and to determine if there is a sensitive window of developmental exposure, outbred CD-1 mice were treated with DES during three stages of development: group 1 was treated on days 9-16 of gestation (2.5, 5 or 10 mu g/kg maternal body wt), the time of major organogenesis; group II was treated once on day 18 of gestation (1000 mu g/kg maternal body wt) just prior to birth; group III was treated on days 1-5 of neonatal life (0.002 mu g/pup/day). Female mice (F1) in each group were raised to sexual maturity and bred to control males. As previously reported, fertility of the F1 DES-exposed females was decreased in all groups. Female offspring (DES lineage or F2) from these matings were raised to maturity and housed with control males for 20 weeks. The fertility of these DES lineage female mice was not affected by DES exposure of their `grandmothers'. DES lineage mice were killed at 17-19 and 22-24 months of age. An increased incidence of malignant reproductive tract tumors, including uterine adenocarcinoma, was seen in DES lineage mice but not in corresponding controls; the range and prevalence of tumors increased with age. Because uterine adenocarcinomas were seen in all three DES groups, all developmental exposure periods were considered susceptible to the adverse effects of DES. These data suggest that the reduced fertility observed in the DES F1 female mice was not transmitted to their descendants; however, increased susceptibility to tumor formation is apparently transmitted to subsequent generations. JF - Carcinogenesis AU - Newbold, R R AU - Hanson, R B AU - Jefferson, W N AU - Bullock, B C AU - Haseman, J AU - McLachlan, JA AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, newbold1@niehs.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 1655 EP - 1663 VL - 19 IS - 9 SN - 0143-3334, 0143-3334 KW - mice KW - Toxicology Abstracts KW - Fertility KW - Prenatal experience KW - Tumors KW - Diethylstilbestrol KW - X 24112:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17152123?accountid=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=Increased+tumors+but+uncompromised+fertility+in+the+female+descendants+of+mice+exposed+developmentally+to+diethylstilbestrol&rft.au=Newbold%2C+R+R%3BHanson%2C+R+B%3BJefferson%2C+W+N%3BBullock%2C+B+C%3BHaseman%2C+J%3BMcLachlan%2C+JA&rft.aulast=Newbold&rft.aufirst=R&rft.date=1998-09-01&rft.volume=19&rft.issue=9&rft.spage=1655&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 - Diethylstilbestrol; Fertility; Prenatal experience; Tumors ER - TY - JOUR T1 - IS481 and IS1002 of Bordetella pertussis create a 6-base-pair duplication upon insertion at a consensus target site AN - 17131690; 4436483 AB - The insertion sequence IS481 and its isoform IS1002 have been observed to transpose into the bvgAS locus of Bordetella pertussis, for which the DNA sequence has previously been determined. Upon insertion of IS481 at three different sites and IS1002 at one site, a 6-bp sequence originally present was found at the junction of bvg and insertion sequence DNA. This indicates that, contrary to prior reports, IS481 and IS1002 do create a duplication upon insertion. In this light, examination of these and other examples of IS481 and IS1002 reported in the literature leads to the observation that the 6-bp recognition sequence usually fits the consensus NCTAGN. The near-palindromic nature of this sequence, when directly repeated at the ends of IS481 or IS1002, apparently led to the interpretation that 5 of these base pairs were part of the terminal inverted repeats flanking these elements. JF - Journal of Bacteriology AU - Stibitz, S AD - Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA, stibitz@helix.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 4963 EP - 4966 VL - 180 IS - 18 SN - 0021-9193, 0021-9193 KW - bvg gene KW - bvgAS locus KW - insertion sequence IS1002 KW - insertion sequence IS481 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Duplication KW - Site location KW - Bordetella pertussis KW - Palindromes KW - DNA KW - Junctions KW - Base pairs KW - J 02725:DNA KW - N 14675:Transposition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17131690?accountid=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=IS481+and+IS1002+of+Bordetella+pertussis+create+a+6-base-pair+duplication+upon+insertion+at+a+consensus+target+site&rft.au=Stibitz%2C+S&rft.aulast=Stibitz&rft.aufirst=S&rft.date=1998-09-01&rft.volume=180&rft.issue=18&rft.spage=4963&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; Palindromes; Site location; Duplication; DNA; Base pairs; Junctions ER - TY - JOUR T1 - BG-1 ovarian cell line: An alternative model for examining estrogen-dependent growth in vitro AN - 17120539; 4423283 AB - Examination of estrogen-responsive processes in cell culture is used to investigate hormonal influence on cancer cell growth and gene expression. Most experimental studies have used breast cancer cell lines, in particular MCF7 cells, to investigate estrogen responsiveness. In this study we examined an ovarian cancer cell line, BG-1, which is highly estrogen-responsive in vitro. This observation, plus the fact that the cells are of ovarian rather than mammary gland origin, makes it an attractive alternative model. 17 beta -Estradiol, epidermal growth factor, and insulin-like growth factor induced proliferation of BG-1 and MCF7 cells. Viability was dependent on these growth factors in BG-1 cells, but not in MCF7 cells. Therefore, we examined the differences between these two cell lines with respect to estrogen and growth factor receptors. BG-1 cells have twice as many estrogen receptors as MCF7 cells, and BG-1 cells have higher insulin-like growth factor-1 and epidermal growth factor receptor levels than MCF7 cells. This may also explain why BG-1 cells proliferate 56% more robustly in serum and show more serum dependence in culture. In both BG-1 and MCF7 cells, epidermal growth factor receptor number is low ( MDA-MB-435 > HBL100). In conclusion, BG-1 cells are an excellent model for understanding hormone responsiveness in ovarian tissue and an alternative for examining estrogen receptor-mediated and insulin-like growth factor-1/epidermal growth factor/estrogen cross-talk processes because of their sensitivity to these factors. JF - In Vitro Cellular & Developmental Biology - Animal AU - Baldwin, W S AU - Curtis, S W AU - Cauthen, CA AU - Risinger, JI AU - Korach, K S AU - Barrett, J C AD - National Institute of Environmental Health Sciences, P.O. Box 12233, MD C2-15, Research Triangle Park, NC 27709, USA Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 649 EP - 654 VL - 34 IS - 8 SN - 1071-2690, 1071-2690 KW - BG-1 cells KW - Epidermal growth factor receptors KW - insulin-like growth factor I receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Estrogens KW - Cell lines KW - Cell culture KW - Ovaries KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17120539?accountid=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=In+Vitro+Cellular+%26+Developmental+Biology+-+Animal&rft.atitle=BG-1+ovarian+cell+line%3A+An+alternative+model+for+examining+estrogen-dependent+growth+in+vitro&rft.au=Baldwin%2C+W+S%3BCurtis%2C+S+W%3BCauthen%2C+CA%3BRisinger%2C+JI%3BKorach%2C+K+S%3BBarrett%2C+J+C&rft.aulast=Baldwin&rft.aufirst=W&rft.date=1998-09-01&rft.volume=34&rft.issue=8&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=In+Vitro+Cellular+%26+Developmental+Biology+-+Animal&rft.issn=10712690&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 - Cell culture; Cell lines; Ovaries; Estrogens ER - TY - JOUR T1 - Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8 super(+) T Cells after Gene Gun Immunization AN - 17112793; 4421462 AB - Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8 super(+) T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50-100 cells in an individual draining LN. However, over this same time period, the total number of CD11c super(+) DC increases more than twofold, by an average of 20,000-30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8 super(+) T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming. JF - Journal of Experimental Medicine AU - Porgador, A AU - Irvine, K R AU - Iwasaki, A U AU - Barber, B H AU - Restifo, N P AU - Germain, R N AD - Laboratory of Immunology, Bldg. 10, Rm. 11N311, 10 Center Dr. MSC-1892, Bethesda, MD 20892-1892, USA, ronald_germain@nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 1075 EP - 1082 VL - 188 IS - 6 SN - 0022-1007, 0022-1007 KW - CD4 antigen KW - gene guns KW - particle bombardment KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antigen presentation KW - Immunization KW - Dendritic cells KW - Lymphocytes T KW - F 06776:Cell cooperation (antigen presentation) 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/17112793?accountid=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+Experimental+Medicine&rft.atitle=Predominant+Role+for+Directly+Transfected+Dendritic+Cells+in+Antigen+Presentation+to+CD8+super%28%2B%29+T+Cells+after+Gene+Gun+Immunization&rft.au=Porgador%2C+A%3BIrvine%2C+K+R%3BIwasaki%2C+A+U%3BBarber%2C+B+H%3BRestifo%2C+N+P%3BGermain%2C+R+N&rft.aulast=Porgador&rft.aufirst=A&rft.date=1998-09-01&rft.volume=188&rft.issue=6&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=Journal+of+Experimental+Medicine&rft.issn=00221007&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 - Immunization; Lymphocytes T; Dendritic cells; Antigen presentation ER - TY - JOUR T1 - Migration of a Holliday Junction through a Nucleosome Directed by the E. coli RuvAB Motor Protein AN - 17094791; 4411097 AB - Chromatin plays a critical role in regulating access to DNA by proteins that direct recombination and repair. The E. coli RuvAB protein complex promotes branch migration of the Holliday junction recombination intermediate. The ability of RuvAB to negotiate passage of the junction through nucleosomal DNA is examined. The model system involves the formation of a Holliday junction positioned upstream of a nucleosome. Unassisted, the junction is blocked by a histone octamer. In the presence of RuvAB and ATP, rapid branch migration through the nucleosome is observed. It results in disruption of the histone-DNA interactions leading to the removal of the octamer from the junction intermediate. These results suggest that eukaryotic DNA motor proteins analogous to RuvAB could function during recombination to promote branch migration through chromatin. JF - Molecular Cell AU - Grigoriev, M AU - Hsieh, P AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1810, USA, hsieh@ncifcrf.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 373 EP - 381 VL - 2 IS - 3 SN - 1097-4164, 1097-4164 KW - Holliday junctions KW - RuvAB protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Nucleosomes KW - histones KW - Escherichia coli KW - DNA repair KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17094791?accountid=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+Cell&rft.atitle=Migration+of+a+Holliday+Junction+through+a+Nucleosome+Directed+by+the+E.+coli+RuvAB+Motor+Protein&rft.au=Grigoriev%2C+M%3BHsieh%2C+P&rft.aulast=Grigoriev&rft.aufirst=M&rft.date=1998-09-01&rft.volume=2&rft.issue=3&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Molecular+Cell&rft.issn=10974164&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; histones; Nucleosomes ER - TY - JOUR T1 - Mutational analysis of the 3' arrow right 5' proofreading exonuclease of Escherichia coli DNA polymerase III AN - 16560197; 4399983 AB - The epsilon subunit of Escherichia coli DNA polymerase III holoenzyme, the enzyme primarily responsible for the duplication of the bacterial chromosome, is a 3' arrow right 5' exonuclease that functions as a proofreader for polymerase errors. In addition, it plays an important structural role within the pol III core. To gain further insight into how epsilon performs these joint structural and catalytic functions, we have investigated a set of 20 newly isolated dnaQ mutator mutants. The mutator effects ranged from strong (700-8000 fold enhancement) to moderate (6-20-fold enhancement), reflecting the range of proofreading deficiencies. Complementation assays revealed most mutators to be partially or fully dominant, suggesting that they carried an exonucleolytic defect but retained binding to the pol III core subunits. One allele, containing a stop codon 3 amino acids from the C-terminal end of the protein, was fully recessive. Sequence analysis of the mutants revealed mutations in the Exo I, Exo II and recently proposed Exo III epsilon motifs, as well as in the intervening regions. Together, the data support the functional significance of the proposed motifs, presumably in catalysis, and suggest that the C-terminus of epsilon may be specifically involved in binding to the alpha (polymerase) subunit. JF - Nucleic Acids Research AU - Taft-Benz, SA AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Science, PO Box 12233, Research Triangle Park, NC 27709, USA, schaaper@niehs.nih.gov Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 4005 EP - 4011 VL - 26 IS - 17 SN - 0305-1048, 0305-1048 KW - mutational analysis KW - proofreading 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 KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16560197?accountid=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=Mutational+analysis+of+the+3%27+arrow+right+5%27+proofreading+exonuclease+of+Escherichia+coli+DNA+polymerase+III&rft.au=Taft-Benz%2C+SA%3BSchaaper%2C+R+M&rft.aulast=Taft-Benz&rft.aufirst=SA&rft.date=1998-09-01&rft.volume=26&rft.issue=17&rft.spage=4005&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 - Escherichia coli; DNA-directed DNA polymerase ER - TY - JOUR T1 - The APC I1307K allele and cancer risk in a community-based study of Ashkenazi Jews AN - 16559669; 4399957 AB - Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer (CRC). APC is a tumour-suppressor gene, and somatic loss occurs in tumours. The germline T-to-A transversion responsible for the APC I1307K allele converts the wild-type sequence to a homopolymer tract (A sub(8)) that is genetically unstable and prone to somatic mutation. The I1307K allele was found in 6.1% of unselected Ashkenazi Jews and higher proportions of Ashkenazim with family or personal histories of CRC. To evaluate the role of I1307K in cancer, we genotyped 5,081 Ashkenazi volunteers in a community survey. Risk of developing colorectal, breast and other cancers were compared between genotyped I1307K carriers and non-carriers and their first-degree relatives. JF - Nature Genetics AU - Woodage, T AU - King, S M AU - Wacholder, S AU - Hartge, P AU - Struewing, J P AU - McAdams, M AU - Laken, S J AU - Tucker, MA AU - Brody, L C AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA, lbrody@helix.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 62 EP - 65 VL - 20 IS - 1 SN - 1061-4036, 1061-4036 KW - APC gene KW - Ashkenazi Jews KW - familial adenomatous polyposis KW - man KW - tumors KW - Risk Abstracts; Genetics Abstracts KW - Tumors KW - Risks KW - Cancer KW - Genetics KW - Colorectal carcinoma KW - Ethnic groups KW - G 07470:Cytogenetics & general KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16559669?accountid=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=Nature+Genetics&rft.atitle=The+APC+I1307K+allele+and+cancer+risk+in+a+community-based+study+of+Ashkenazi+Jews&rft.au=Woodage%2C+T%3BKing%2C+S+M%3BWacholder%2C+S%3BHartge%2C+P%3BStruewing%2C+J+P%3BMcAdams%2C+M%3BLaken%2C+S+J%3BTucker%2C+MA%3BBrody%2C+L+C&rft.aulast=Woodage&rft.aufirst=T&rft.date=1998-09-01&rft.volume=20&rft.issue=1&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Nature+Genetics&rft.issn=10614036&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 - Ethnic groups; Tumors; Genetics; Cancer; Colorectal carcinoma; Risks ER - TY - JOUR T1 - Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis AN - 16554879; 4393898 AB - Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues. The expression of virulence factors in B. pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR. The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown. The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice. JF - Infection and Immunity AU - Merkel, T J AU - Stibitz, S AU - Keith, J M AU - Leef, M AU - Shahin, R AD - OIIB/NIDR/NIH, Building 30, Rm. 303, 30 Convent Dr., MSC 4350, Bethesda, MD 20892-4350, USA, merkel@yoda.nidr.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 4367 EP - 4373 VL - 66 IS - 9 SN - 0019-9567, 0019-9567 KW - BvgA protein KW - BvgS protein KW - bvg gene KW - bvgA gene KW - bvgR gene KW - bvgS gene KW - mice KW - mutants KW - promoters KW - repression KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Pertussis KW - Virulence KW - Gene expression KW - Respiratory tract diseases KW - Bordetella pertussis KW - Gene regulation KW - Transcription activation KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16554879?accountid=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=Contribution+of+regulation+by+the+bvg+locus+to+respiratory+infection+of+mice+by+Bordetella+pertussis&rft.au=Merkel%2C+T+J%3BStibitz%2C+S%3BKeith%2C+J+M%3BLeef%2C+M%3BShahin%2C+R&rft.aulast=Merkel&rft.aufirst=T&rft.date=1998-09-01&rft.volume=66&rft.issue=9&rft.spage=4367&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 - Bordetella pertussis; Transcription activation; Gene expression; Virulence; Pertussis; Gene regulation; Respiratory tract diseases ER - TY - JOUR T1 - A novel DNA-binding motif in MarA: The first structure for an AraC family transcriptional activator AN - 16551665; 4368833 AB - A crystal structure for a member of the AraC prokaryotic transcriptional activator family, MarA, in complex with its cognate DNA-binding site is described. MarA consists of two similar subdomains, each containing a helix-turn-helix DNA-binding motif. The two recognition helices of the motifs are inserted into adjacent major groove segments on the same face of the DNA but are separated by only 27 Aa thereby bending the DNA by ~35 degree . Extensive interactions between the recognition helices and the DNA major groove provide the sequence specificity. JF - Proceedings of the National Academy of Sciences, USA AU - Rhee, S AU - Martin, R G AU - Rosner, J L AU - Davies AD - Laboratory of Molecular Biology, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, david.davies@nih.gov Y1 - 1998/09/01/ PY - 1998 DA - 1998 Sep 01 SP - 10413 EP - 10418 VL - 95 IS - 18 SN - 0027-8424, 0027-8424 KW - AraC operon KW - DNA-binding protein KW - MarA protein KW - helix-turn-helix KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Crystal structure KW - Transcription activators KW - J 02725:DNA KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16551665?accountid=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=A+novel+DNA-binding+motif+in+MarA%3A+The+first+structure+for+an+AraC+family+transcriptional+activator&rft.au=Rhee%2C+S%3BMartin%2C+R+G%3BRosner%2C+J+L%3BDavies&rft.aulast=Rhee&rft.aufirst=S&rft.date=1998-09-01&rft.volume=95&rft.issue=18&rft.spage=10413&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 - Transcription activators; Crystal structure ER - TY - JOUR T1 - Genomic microbiology: Right on target? AN - 16533055; 4396970 AB - Is a gene conserved in evolution because its function is of critical importance for an organism's survival? By extension, are genes conserved in all species likely to be essential for each of them under any conditions? In this issue, Arigoni et al. investigate the validity of these predictions in direct experimental tests. Genome sequencing became a tangible reality a mere three years ago, but already it has changed the way we do microbiology. A great deal of research can now be accomplished using a computer alone - or as the saying goes these days, "in silico." Indeed, a quick look at the description of gene functions in any of the 14 completely sequenced bacterial and archaeal genomes suggests that a whole lot is known about them, with precise functional assignments given for at least one half of the genes. And yet, how do we know all that, given that the number of molecular studies on most of these organisms has been negligibly small? The answer is obvious - by transfer of functional information from those model systems on which experimentation has been extensive. JF - Nature Biotechnology 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 - 1998/09// PY - 1998 DA - Sep 1998 SP - 821 EP - 822 VL - 16 IS - 9 SN - 1087-0156, 1087-0156 KW - genomics KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - G 07320:Bacterial genetics KW - W2 32060:Microorganisms KW - W2 32000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16533055?accountid=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+Biotechnology&rft.atitle=Genomic+microbiology%3A+Right+on+target%3F&rft.au=Koonin%2C+E+V&rft.aulast=Koonin&rft.aufirst=E&rft.date=1998-09-01&rft.volume=16&rft.issue=9&rft.spage=821&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 ER - TY - JOUR T1 - Skin tumorigenesis and Ki-ras and Ha-ras mutations in tumors from adult mice exposed in utero to 3'-azido-2',3'-dideoxythymidine AN - 16529946; 4408781 AB - This study was designed to evaluate the potential initiating effects of transplacental 3'-azido-2',3'-dideoxythymine (AZT) and the role of ras mutational activation in skin tumors induced in a two-stage mouse skin model. In addition, mouse liver and lung tumors from a transplacental AZT tumorigenicity study reported elsewhere were examined for evidence of ras activation. For both tumor studies, pregnant CD-1 mice were given either vehicle or 25 mg of AZT daily on days 12-18 of gestation. In the 1997 study, the offspring were given no further exposure and were killed at 1 yr of age. For the skin tumor study, all mice received twice-weekly topical 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment from weeks 5-35; half of the mice had been exposed to AZT in utero. At weeks 16-18, 30, 31, and 34-41, the skin tumor incidences in mice given AZT and TPA were significantly higher than in mice given TPA alone (P less than or equal to 0.05). At week 41, the average numbers of tumors per mouse were 1.44 plus or minus 0.36 (mean plus or minus standard error of the mean) and 0.57 plus or minus 0.13 for mice given AZT plus TPA and TPA alone, respectively (P = 0.006). Mutagenesis in ras exons I and II was determined by polymerase chain reaction (PCR) and dye-terminator cycling sequencing of PCR products. Ha-ras exon I codons 12 and 13 were mutated in 11 of 19 tumors (58%) from mice given AZT and TPA and in one of 15 tumors (7%) from mice given TPA alone (P = 0.004). The only mutation in Ha-ras codon 12 (four in four tumors examined) was a G arrow right A transition in the second base, and the major mutation in codon 13 (six in seven tumors examined) was a G arrow right T transversion in the second base. In skin tumors, AZT exposure did not increase the number of Ha-ras codon 61 mutations, and no Ki-ras mutations were observed. Analysis of ras mutations in liver and lung tumors from mice exposed to AZT in utero with no TPA promotion showed no significant AZT-related increases. JF - Molecular Carcinogenesis AU - Zhang, Z AU - Diwan, BA AU - Anderson, L M AU - Logsdon, D AU - Olivero, O A AU - Haines, D C AU - Rice, J M AU - Yuspa, SH AU - Poirier, M C AD - National Cancer Institute, Bldg. 37, Rm. 3B12, NIH, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 45 EP - 51 VL - 23 IS - 1 SN - 0899-1987, 0899-1987 KW - 3'-Azido-2',3'-dideoxythymidine KW - 3'-azido-2',3'-dideoxythymidine KW - H-ras gene KW - K-ras gene KW - azidobudine KW - mice KW - zidovudine KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - X 24240:Miscellaneous KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16529946?accountid=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=Skin+tumorigenesis+and+Ki-ras+and+Ha-ras+mutations+in+tumors+from+adult+mice+exposed+in+utero+to+3%27-azido-2%27%2C3%27-dideoxythymidine&rft.au=Zhang%2C+Z%3BDiwan%2C+BA%3BAnderson%2C+L+M%3BLogsdon%2C+D%3BOlivero%2C+O+A%3BHaines%2C+D+C%3BRice%2C+J+M%3BYuspa%2C+SH%3BPoirier%2C+M+C&rft.aulast=Zhang&rft.aufirst=Z&rft.date=1998-09-01&rft.volume=23&rft.issue=1&rft.spage=45&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 ER - TY - JOUR T1 - The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis AN - 16518393; 4423537 AB - There are three major structural classes of mycolic acids in the cell envelope of Mycobacterium tuberculosis (MTB): alpha-, methoxy- and ketomycolate. The two oxygen-containing classes are biosynthetically related through a common alpha -methyl hydroxymycolate intermediate. BCG strains that fail to produce methoxymycolate and instead produce only keto- and alpha-mycolic acids show apparent defects in the O-methyltransferase MMAS-3. Overproduction of MMAS-3 from MTB resulted in a complete replacement of ketomycolate by methoxymycolate in both BCG and MTB. In vitro growth of these recombinant strains lacking ketomycolate was impaired at reduced temperatures but appeared to be normal at 37 degree C. Glucose uptake was significantly decreased in such strains, but uptake of chenodeoxycholate and glycine was unaffected. Although sensitivity to INH remained unchanged, these cells were found to be hypersensitive to ampicillin and rifampicin. Infectivity of BCG and H37Rv wild type or MMAS-3 overproducers in THP-1 cells was somewhat affected, but the ability of the strains lacking ketomycolate to grow within this macrophage-like cell line was severely compromised. In vivo labeling of mycolic acids during growth of H37Rv within THP-1 cells revealed a substantial increase in ketomycolate and alphamycolate synthesized by intracellularly grown mycobacteria. These results establish a critical role for mycolate composition in proper cell wall function during the growth of MTB in vivo. JF - Molecular Microbiology AU - Yuan, Y AU - Zhu, Y AU - Crane, D D AU - Barry, CE III AD - Tuberculosis Research Section, Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Disease, National Institutes of Health, 903 S. Fourth St., Hamilton, MT 59840-2999, USA, clifton-barry@nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 1449 EP - 1458 VL - 29 IS - 6 SN - 0950-382X, 0950-382X KW - Alphamycolate KW - Ketomycolate KW - Methoxymycolate KW - O-Methyltransferase KW - chenodeoxycholic acid KW - chenodiol KW - mycolic acids KW - Microbiology Abstracts B: Bacteriology KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16518393?accountid=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=The+effect+of+oxygenated+mycolic+acid+composition+on+cell+wall+function+and+macrophage+growth+in+Mycobacterium+tuberculosis&rft.au=Yuan%2C+Y%3BZhu%2C+Y%3BCrane%2C+D+D%3BBarry%2C+CE+III&rft.aulast=Yuan&rft.aufirst=Y&rft.date=1998-09-01&rft.volume=29&rft.issue=6&rft.spage=1449&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 ER - TY - JOUR T1 - Vaccination against Chlamydial Genital Tract Infection after Immunization with Dendritic Cells Pulsed Ex Vivo with Nonviable Chlamydiae AN - 16507907; 4407063 AB - Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4 super(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed similar to 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop. JF - Journal of Experimental Medicine AU - Su, Hua AU - Messer, R AU - Whitmire, W AU - Fischer, E AU - Portis, J C AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratory, Hamilton, MT 59840, USA, hcaldwell@atlas.niaid.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 809 EP - 818 VL - 188 IS - 5 SN - 0022-1007, 0022-1007 KW - CD4 antigen KW - Chlamydia trachomatis KW - mice KW - p40 protein KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16507907?accountid=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=Vaccination+against+Chlamydial+Genital+Tract+Infection+after+Immunization+with+Dendritic+Cells+Pulsed+Ex+Vivo+with+Nonviable+Chlamydiae&rft.au=Su%2C+Hua%3BMesser%2C+R%3BWhitmire%2C+W%3BFischer%2C+E%3BPortis%2C+J+C%3BCaldwell%2C+H+D&rft.aulast=Su&rft.aufirst=Hua&rft.date=1998-09-01&rft.volume=188&rft.issue=5&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Journal+of+Experimental+Medicine&rft.issn=00221007&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 - Abrogation of TGF- beta activity during retroviral transduction improves murine hematopoietic progenitor and repopulating cell gene transfer efficiency AN - 16507419; 4400008 AB - Transforming growth factor- beta has complex activities on hematopoietic cells. We have previously shown that murine long-term repopulating activity is compromised by ex vivo culture in TGF- beta 1 and conversely is increased by abrogating endogenous TGF- beta activity with a neutralizing antibody. In the current study, we investigated the effect of abrogation of autocrine or paracrine TGF- beta present during retroviral transduction on gene transfer efficiency to primitive hematopoietic cells. Murine marrow cells were cultured and retrovirally transduced for 4 days in the presence of interleukin-3, interleukin-6 and stem cell factor, and either a neutralizing anti-TGF- beta antibody or an isotype control. Committed progenitor cells were analyzed for gene transfer efficiency, and cells were also injected into W/W super(v) recipient mice for analysis of transduction of long-term repopulating cells. The progenitor (CFU-C) transduction efficiency in the presence of anti-TGF- beta was significantly greater. Semiquantitative PCR analysis and Southern blot analysis for the retroviral marker gene in the blood and bone marrow of recipient mice revealed a significant increase in the transduction efficiency of long-term repopulating cells after culture and transduction in the presence of the anti-TGF- beta . Thus neutralization of TGF- beta activity during retroviral transduction allows more efficient gene transfer into primitive murine hematopoietic cells and may prove beneficial in future clinical gene transfer or therapy trials. JF - Gene Therapy AU - Yu, J AU - Soma, T AU - Hanazono, Y AU - Dunbar, CE AD - Hematology Branch, Building 10, Room 7C103, NHLBI, NIH, Bethesda, MD 20892, USA Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 1265 EP - 1271 VL - 5 IS - 9 SN - 0969-7128, 0969-7128 KW - Hemopoiesis KW - Interleukins KW - Marrow cells KW - Stem cell factor KW - transforming growth factor- beta KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/16507419?accountid=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=Abrogation+of+TGF-+beta+activity+during+retroviral+transduction+improves+murine+hematopoietic+progenitor+and+repopulating+cell+gene+transfer+efficiency&rft.au=Yu%2C+J%3BSoma%2C+T%3BHanazono%2C+Y%3BDunbar%2C+CE&rft.aulast=Yu&rft.aufirst=J&rft.date=1998-09-01&rft.volume=5&rft.issue=9&rft.spage=1265&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 ER - TY - JOUR T1 - The identification of Mycobacterium marinum genes differentially expressed in macrophage phagosomes using promoter fusions to green fluorescent protein AN - 16497048; 4402538 AB - Mycobacterium marinum, like Mycobacterium tuberculosis, is a slow-growing pathogenic mycobacteria that is able to survive and replicate in macrophages. Using the promoter-capture vector pFPV27, we have constructed a library of 200-1000 bp fragments of M. marinum genomic DNA inserted upstream of a promoterless green fluorescent protein (GFP) gene. Only those plasmids that contain an active promoter will express GFP. Macrophages were infected with this fusion library, and phagosomes containing fluorescent bacteria were isolated. Promoter constructs that were more active intracellularly were isolated with a fluorescence-activated cell sorter, and inserts were partially sequenced. The promoter fusions expressed intracellularly exhibited homology to mycobacterial genes encoding, among others, membrane proteins and biosynthetic enzymes. Intracellular expression of GFP was 2-20 times that of the same clones grown in media. Several promoter constructs were transformed into Mycobacterium smegmatis, Mycobacterium bovis BCG and Mycobacterium tuberculosis. These constructs were positive for GFP expression in all mycobacterial strains tested. Sorting fluorescent bacteria in phagosomes circumvents the problem of isolating a single clone from macrophages, which may contain a mixed bacterial population. This method has enabled us to isolate 12 M. marinum clones that contain promoter constructs differentially expressed in the macrophage. JF - Molecular Microbiology AU - Barker, L P AU - Brooks, D M AU - Small, PLC AD - Microscopy Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South 4th Street, Hamilton, MT 59840, USA, LBARKER@NIH.GOV Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 1167 EP - 1177 VL - 29 IS - 5 SN - 0950-382X, 0950-382X KW - green fluorescent protein KW - phagosomes KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14640:Structure & sequence KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16497048?accountid=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=The+identification+of+Mycobacterium+marinum+genes+differentially+expressed+in+macrophage+phagosomes+using+promoter+fusions+to+green+fluorescent+protein&rft.au=Barker%2C+L+P%3BBrooks%2C+D+M%3BSmall%2C+PLC&rft.aulast=Barker&rft.aufirst=L&rft.date=1998-09-01&rft.volume=29&rft.issue=5&rft.spage=1167&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 ER - TY - JOUR T1 - 5-HT sub(3) receptor activation is required for induction of striatal c-Fos and phosphorylation of ATF-1 by amphetamine AN - 16492562; 4379612 AB - Dopamine (DA) has been shown to be required for the induction of striatal gene expression by psychostimulants. However, direct DA agonists or selective inhibitors of DA reuptake are relatively weak inducers of striatal gene expression compared with cocaine or amphetamine. So although necessary, DA alone is not sufficient to mediate the full gene induction response to psychostimulants. In addition to its actions on the DA transporter, amphetamine also enhances serotonin (5-HT) release in the striatum. In this study, we investigated the mechanism by which 5-HT contributes to the regulation of striatal gene expression by amphetamine. We found that selective lesions of serotonergic terminals in the rat forebrain using 5,7-dihydroxytryptamine prevented the full induction of striatal c-Fos by 4 mg/kg amphetamine. Furthermore, amphetamine-induced striatal c-Fos was completely inhibited by administration of the 5-HT sub(3) receptor antagonist, MDL-72222, but not by the 5-HT sub(2A/2C) receptor antagonist, ritanserin. Consistent with this finding, the induction of c-Fos by 5-HT in primary cultures of E18 striatal neurons devoid of DA input was blocked by the 5-HT sub(3) receptor antagonists, MDL-72222 and ICS 205-930, but not by 5-HT sub(2A/2C) antagonism. Additionally, blockade of 5-HT sub(3) receptors by MDL-72222 inhibited the phosphorylation of activating transcription factor-1 (ATF-1) at Ser super(63) by amphetamine, but not the phosphorylation of cAMP response element binding protein (CREB) at Ser super(133). These results suggest that 5-HT3 receptor activation may be required for amphetamine-induced expression of ATF-1-regulated target genes in the striatum, which may include c-Fos. JF - Synapse AU - Genova, L M AU - Hyman, SE AD - MPS/NINDS/NIH, Bldg. 36, Rm. 4C/24, 36 Convent Drive, Bethesda, MD 20892-4135, USA, genova@codon.nih.gov Y1 - 1998/09// PY - 1998 DA - Sep 1998 SP - 71 EP - 78 VL - 30 IS - 1 SN - 0887-4476, 0887-4476 KW - Fos protein KW - activating transcription factor-1 KW - amphetamine KW - rats KW - serotonin S3 receptors KW - serotonin receptors KW - Toxicology Abstracts; CSA Neurosciences Abstracts 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/16492562?accountid=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=Synapse&rft.atitle=5-HT+sub%283%29+receptor+activation+is+required+for+induction+of+striatal+c-Fos+and+phosphorylation+of+ATF-1+by+amphetamine&rft.au=Genova%2C+L+M%3BHyman%2C+SE&rft.aulast=Genova&rft.aufirst=L&rft.date=1998-09-01&rft.volume=30&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Synapse&rft.issn=08874476&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 - Studies of structure-activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage. AN - 73878217; 9719601 AB - The protective effects of stable nitroxides, as well as their hydroxylamine and amine precursors, have been tested in Chinese hamster V79 cells subjected to H2O2 exposure at fixed concentration or exposure to ionizing radiation. Cytotoxicity was evaluated by monitoring the viability of the cells assessed by the clonogenic assay. The compounds tested at fixed concentration varied in terms of ring size, oxidation state, and ring substituents. Electrochemical studies were carried out to measure the redox midpoint potentials. The studies show that in the case of protection against H2O2 exposure, the protection was determined by the ring size, oxidation state, and redox midpoint potentials. In general the protection factors followed the order nitroxides > hydroxylamines > amines. Both the six-membered ring nitroxides and substituted five-membered ring nitroxides were efficient protectors. For six-membered ring nitroxides, the compounds exhibiting the lowest midpoint potentials exhibited maximal protection. In the case of X-radiation, nitroxides were the most protective though some hydroxylamines were also efficient. The amines were in some cases found to sensitize the toxicity of aerobic radiation exposure. The protection observed by the nitroxides was not dependent on the ring size. However, the ring substituents had significant influence on the protection. Compounds containing a basic side chain were found to provide enhanced protection. The results in this study suggest that these compounds are novel antioxidants which can provide cytoprotection in mammalian cells against diverse types of oxidative insult and identify structural determinants optimal for protection against individual types of damage. JF - Journal of medicinal chemistry AU - Krishna, M C AU - DeGraff, W AU - Hankovszky, O H AU - Sár, C P AU - Kálai, T AU - Jeko, J AU - Russo, A AU - Mitchell, J B AU - Hideg, K AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/08/27/ PY - 1998 DA - 1998 Aug 27 SP - 3477 EP - 3492 VL - 41 IS - 18 SN - 0022-2623, 0022-2623 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Free Radicals KW - Oxidants KW - Radiation-Protective Agents KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Animals KW - Fibroblasts -- drug effects KW - Cricetulus KW - Fibroblasts -- metabolism KW - Structure-Activity Relationship KW - Oxidation-Reduction KW - Hydrogen Peroxide -- toxicity KW - Cell Survival -- drug effects KW - Oxidants -- toxicity KW - Fibroblasts -- radiation effects KW - Free Radicals -- chemistry KW - Cell Survival -- radiation effects KW - Free Radicals -- pharmacology KW - Cell Line KW - Cricetinae KW - Radiation-Protective Agents -- chemistry KW - Antioxidants -- pharmacology KW - Cyclic N-Oxides -- pharmacology KW - Radiation-Protective Agents -- pharmacology KW - Cyclic N-Oxides -- chemistry KW - Antioxidants -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73878217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Studies+of+structure-activity+relationship+of+nitroxide+free+radicals+and+their+precursors+as+modifiers+against+oxidative+damage.&rft.au=Krishna%2C+M+C%3BDeGraff%2C+W%3BHankovszky%2C+O+H%3BS%C3%A1r%2C+C+P%3BK%C3%A1lai%2C+T%3BJeko%2C+J%3BRusso%2C+A%3BMitchell%2C+J+B%3BHideg%2C+K&rft.aulast=Krishna&rft.aufirst=M&rft.date=1998-08-27&rft.volume=41&rft.issue=18&rft.spage=3477&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topography of the interaction of HPr(Ser) kinase with HPr. AN - 73879780; 9718298 AB - The phosphocarrier protein, HPr, from Gram-positive organisms and mycoplasmas is a substrate for an ATP-dependent kinase that phosphorylates serine 46. In Gram-negative organisms, the corresponding HPr is not phosphorylated on serine 46 and the ATP-dependent kinase is absent. To determine the specificity requirements for phosphorylation of Mycoplasma capricolum HPr, a chimera in which residues 43-57 were replaced by the Escherichia coli sequence was constructed. The chimeric protein folded properly, but was not phosphorylated on either serine 46 or histidine 15. A dissection of the region required for phosphorylation specificity was carried out by further mutagenesis. The deficiency in phosphorylation at histidine 15 was localized primarily to the region including residues 51-57. Activity studies revealed that residues 48, 49, and 51-53 are important for recognition of M. capricolum HPr by its cognate HPr(Ser) kinase. The characteristics of this region suggest that the kinase-HPr interaction occurs mainly through a hydrophobic region. Molecular modeling comparisons of M. capricolum HPr and the chimeric construct provided a basis for interpreting the results of the activity assays. JF - Biochemistry AU - Zhu, P P AU - Herzberg, O AU - Peterkofsky, A AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/08/25/ PY - 1998 DA - 1998 Aug 25 SP - 11762 EP - 11770 VL - 37 IS - 34 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Serine KW - 452VLY9402 KW - Histidine KW - 4QD397987E KW - Asparagine KW - 7006-34-0 KW - Protein Kinases KW - EC 2.7.- KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - phosphocarrier protein HPr KW - HPr kinase KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Models, Molecular KW - Asparagine -- metabolism KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Escherichia coli -- enzymology KW - Base Sequence KW - Sequence Alignment KW - Phosphorylation KW - Amino Acid Substitution -- genetics KW - Histidine -- genetics KW - Asparagine -- genetics KW - Mycoplasma -- enzymology KW - Molecular Sequence Data KW - Mycoplasma -- genetics KW - Binding Sites -- genetics KW - Sequence Homology, Amino Acid KW - Mutagenesis, Insertional KW - Histidine -- metabolism KW - Protein Kinases -- metabolism KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- genetics KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- chemistry KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - Serine -- metabolism KW - Serine -- genetics KW - Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73879780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topography+of+the+interaction+of+HPr%28Ser%29+kinase+with+HPr.&rft.au=Zhu%2C+P+P%3BHerzberg%2C+O%3BPeterkofsky%2C+A&rft.aulast=Zhu&rft.aufirst=P&rft.date=1998-08-25&rft.volume=37&rft.issue=34&rft.spage=11762&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-14 N1 - Date created - 1998-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A bivalent disulfide-stabilized Fv with improved antigen binding to erbB2. AN - 80068464; 9698563 AB - We have used protein engineering to generate a stable bivalent Fv molecule of the anti-erbB2 monoclonal antibody e23. The VH and VL domains of the Fv are linked to each other by a disulfide bond and the two Fvs are connected by a flexible 15 amino acid residue (Gly4-Ser)3 linker. The e23 (dsFv)2 molecule is fused to a truncated form of Pseudomonas exotoxin to generate a bivalent disulfide-stabilized, (dsFv)2, immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro and purified to about 95% purity. Binding studies demonstrated that the (dsFv)2 molecule has a much higher affinity for erbB2 than a monovalent dsFv molecule and a similar binding affinity as the parental antibody e23. The (dsFv)2 immunotoxin was 5 to 20-fold more cytotoxic to two e23 antigen-positive cell lines than the monovalent dsFv immunotoxin. The bivalent dsFv molecule is very stable, retaining 94% of its activity after a 24 hours incubation in human serum at 37 degreesC. Two other molecules with shorter linkers five and ten amino acid residues in length were produced and showed similar activities as the molecule containing a 15 amino acid residue linker. The bivalency, stability and the relative ease of purification makes these e23 (dsFv)2 molecules valuable reagents for cancer immunotherapy and diagnosis. Copyright 1998 Academic Press. JF - Journal of molecular biology AU - Bera, T K AU - Onda, M AU - Brinkmann, U AU - Pastan, I AD - National Cancer Institute, National Institutes of Health, Building 37, Bethesda, MD, 20892-4255, USA. Y1 - 1998/08/21/ PY - 1998 DA - 1998 Aug 21 SP - 475 EP - 483 VL - 281 IS - 3 SN - 0022-2836, 0022-2836 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - Serum Albumin 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 - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Models, Molecular KW - Plasmids -- genetics KW - Humans KW - Inclusion Bodies KW - Antibodies, Monoclonal -- chemistry KW - Antibody Affinity KW - Disulfides -- chemistry KW - Recombinant Proteins -- metabolism KW - Binding, Competitive KW - Protein Folding KW - Recombinant Proteins -- chemistry KW - Binding Sites, Antibody KW - Cell Line KW - Immunotoxins -- toxicity KW - Receptor, ErbB-2 -- metabolism KW - Immunoglobulin Fragments -- genetics KW - Exotoxins -- chemistry KW - Exotoxins -- isolation & purification KW - Immunoglobulin Fragments -- chemistry KW - Immunotoxins -- chemistry KW - Immunoglobulin Fragments -- metabolism KW - Exotoxins -- toxicity KW - Immunotoxins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80068464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+bivalent+disulfide-stabilized+Fv+with+improved+antigen+binding+to+erbB2.&rft.au=Bera%2C+T+K%3BOnda%2C+M%3BBrinkmann%2C+U%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-08-21&rft.volume=281&rft.issue=3&rft.spage=475&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase. AN - 73930290; 9744796 AB - An active sulfotransferase (ST, residues 558-882) domain of the human heparan sulfate N-deacetylase/N-sulfotransferase (hHSNST) has been identified by aligning the amino acid sequence of hHSNST to that of mouse estrogen sulfotransferase (EST). The bacterially expressed ST domain transfers the 5'-sulfuryl group of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to only deacetylated heparin with an efficiency similar to that previously reported for the purified rat HSNST. Moreover, the K(m,PAPS) (2.1 microM) of the ST domain is also similar to that of the rat enzyme. Lys48 is a key residue in mEST catalysis. The residue corresponding to Lys48 is conserved in all known heparan sulfate sulfotransferases (Lys614 in the ST domain of hHSNST). Mutation of Lys614 to Ala abolishes N-sulfotransferase activity, indicating an important catalytic role of Lys614 in the ST domain. Crystals of the ST domain have been grown (orthorhombic space group P2(1)2(1)2) with diffraction to 2.5 A resolution. JF - FEBS letters AU - Sueyoshi, T AU - Kakuta, Y AU - Pedersen, L C AU - Wall, F E AU - Pedersen, L G 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, NC 27709, USA. Y1 - 1998/08/21/ PY - 1998 DA - 1998 Aug 21 SP - 211 EP - 214 VL - 433 IS - 3 SN - 0014-5793, 0014-5793 KW - Recombinant Proteins KW - 0 KW - Sulfotransferases KW - EC 2.8.2.- KW - heparitin sulfotransferase KW - EC 2.8.2.8 KW - Amidohydrolases KW - EC 3.5.- KW - Lysine KW - K3Z4F929H6 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Rats KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Amidohydrolases -- metabolism KW - Sulfotransferases -- metabolism KW - Sulfotransferases -- chemistry KW - Amidohydrolases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73930290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+role+of+Lys614+in+the+sulfotransferase+activity+of+human+heparan+sulfate+N-deacetylase%2FN-sulfotransferase.&rft.au=Sueyoshi%2C+T%3BKakuta%2C+Y%3BPedersen%2C+L+C%3BWall%2C+F+E%3BPedersen%2C+L+G%3BNegishi%2C+M&rft.aulast=Sueyoshi&rft.aufirst=T&rft.date=1998-08-21&rft.volume=433&rft.issue=3&rft.spage=211&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 - 1998-10-08 N1 - Date created - 1998-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asparagine-linked oligosaccharides are localized to a luminal hydrophilic loop in human glucose-6-phosphatase. AN - 73872232; 9705299 AB - Deficiency of glucose-6-phosphatase (G6Pase), an endoplasmic reticulum transmembrane glycoprotein, causes glycogen storage disease type 1a. We have recently shown that human G6Pase contains an odd number of transmembrane segments, supporting a nine-transmembrane helical model for this enzyme. Sequence analysis predicts the presence of three potential asparagine (N)-linked glycosylation sites, N96TS, N203AS, and N276SS, conserved among mammalian G6Pases. According to this model, Asn96, located in a 37-residue luminal loop, is a potential acceptor for oligosaccharides, whereas Asn203 and Asn276, located in a 12-residue cytoplasmic loop and helix 7, respectively, would not be utilized for this purpose. We therefore characterized mutant G6Pases lacking one, two, or all three potential N-linked glycosylation sites. Western blot and in vitro translation studies showed that G6Pase is glycosylated only at Asn96, further validating the nine-transmembrane topology model. Substituting Asn96 with an Ala (N96A) moderately reduced enzymatic activity and had no effect on G6Pase synthesis or degradation, suggesting that oligosaccharide chains do not play a major role in protecting the enzyme from proteolytic degradation. In contrast, mutation of Asn276 to an Ala (N276A) destabilized the enzyme and markedly reduced enzymatic activity. We present additional evidence suggesting that the integrity of transmembrane helices is essential for G6Pase stability and catalytic activity. JF - The Journal of biological chemistry AU - Pan, C J AU - Lei, K J AU - Chou, J Y AD - Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-1830, USA. Y1 - 1998/08/21/ PY - 1998 DA - 1998 Aug 21 SP - 21658 EP - 21662 VL - 273 IS - 34 SN - 0021-9258, 0021-9258 KW - Oligosaccharides KW - 0 KW - Asparagine KW - 7006-34-0 KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary KW - Blotting, Western KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Glycosylation KW - Cell Line KW - Structure-Activity Relationship KW - Glucose-6-Phosphatase -- chemistry KW - Oligosaccharides -- chemistry KW - Asparagine -- chemistry KW - Glucose-6-Phosphatase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73872232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Asparagine-linked+oligosaccharides+are+localized+to+a+luminal+hydrophilic+loop+in+human+glucose-6-phosphatase.&rft.au=Pan%2C+C+J%3BLei%2C+K+J%3BChou%2C+J+Y&rft.aulast=Pan&rft.aufirst=C&rft.date=1998-08-21&rft.volume=273&rft.issue=34&rft.spage=21658&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation. AN - 73833464; 9705287 AB - We studied arachidonic acid metabolism and the expression of cyclooxygenase (Cox) and 15-lipoxygenase (15-LO) in the human colorectal carcinoma cell line, Caco-2, which undergo apoptosis and cell differentiation in the presence of sodium butyrate (NaBT). Caco-2 cells expressed very low levels of Cox-1 but highly expressed Cox-2. NaBT treatment shifted the arachidonic acid metabolites by cell lysates from prostaglandins to 15-hydroxyeicosatetraenoic acid, indicating the presence of a 15-LO. Linoleic acid, an excellent substrate for 15-LO, was metabolized poorly by the Caco-2 cells, but NaBT treatment shifted metabolism to 15-LO metabolite, 13(S)-hydroxyoctadecadienoic acid. Caco-2 cells expressed a 15-LO but only after treatment with NaBT, as determined by Northern blotting. Immunoblotting with anti-human 15-LO antibody detected a 72-kDa band in NaBT-treated Caco-2 cells. Expression of 15-LO mRNA was dependent on the duration of NaBT treatment, with the highest expression observed between 10 and 24 h. Results from expression and metabolism studies with arachidonic and linoleic acid cells indicated Cox-2 was responsible for the lipid metabolism in control cells, whereas 15-LO was the major enzyme responsible after NaBT induction of apoptosis and cell differentiation. The 15-LO in Caco-2 cells was characterized as human reticulocyte 15-LO by reverse transcription-polymerase chain reaction and restriction enzyme analysis. The expression of 15-LO and 15-hydroxyeicosatetraenoic acid or 13(S)-hydroxyoctadecadienoic acid formation correlates with cell differentiation or apoptosis in Caco-2 cells induced by NaBT. The addition of nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly increased NaBT-induced apoptosis, whereas the addition of indomethacin did not alter NaBT-induced apoptosis in the Caco-2 cells. However, indomethacin treatment decreased the expression of Cox-2 in NaBT-treated cells and significantly increased the expression of 15-LO during NaBT treatment. These studies suggest a role for 15-LO, in addition to Cox-2, in modulating NaBT-induced apoptosis and cell differentiation in human colorectal carcinoma cells. JF - The Journal of biological chemistry AU - Kamitani, H AU - Geller, M AU - Eling, T AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/08/21/ PY - 1998 DA - 1998 Aug 21 SP - 21569 EP - 21577 VL - 273 IS - 34 SN - 0021-9258, 0021-9258 KW - Butyrates KW - 0 KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Lipoxygenase Inhibitors KW - Membrane Proteins KW - Butyric Acid KW - 107-92-6 KW - Masoprocol KW - 7BO8G1BYQU KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 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 - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Butyrates -- pharmacology KW - Humans KW - Cell Differentiation KW - Caco-2 Cells KW - Isoenzymes -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Indomethacin -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Lipoxygenase Inhibitors -- pharmacology KW - Masoprocol -- pharmacology KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Apoptosis KW - Colorectal Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73833464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+15-lipoxygenase+by+human+colorectal+carcinoma+Caco-2+cells+during+apoptosis+and+cell+differentiation.&rft.au=Kamitani%2C+H%3BGeller%2C+M%3BEling%2C+T&rft.aulast=Kamitani&rft.aufirst=H&rft.date=1998-08-21&rft.volume=273&rft.issue=34&rft.spage=21569&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer risk in women exposed to diethylstilbestrol in utero AN - 16560426; 4393138 AB - Context. - The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero. Objective. - To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. Design. - A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. Participants. - A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. Main Outcome Measures. - Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. Results. - To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. Conclusions. - Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years. JF - Journal of the American Medical Association AU - Hatch, EE AU - Palmer, J R AU - Titus-Ernstoff, L AU - Noller, K L AU - Kaufman, R H AU - Mittendorf, R AU - Robboy, S J AU - Hyer, M AU - Cowan, C M AU - Adam, E AU - Colton, T AU - Hartge, P AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6130 Executive Blvd., MSC7362, Bethesda, MD 20892-7362, USA Y1 - 1998/08/19/ PY - 1998 DA - 1998 Aug 19 SP - 630 EP - 634 VL - 280 IS - 7 SN - 0098-7484, 0098-7484 KW - diethylstilbestrol KW - man KW - Toxicology Abstracts; Risk Abstracts KW - Risk assessment KW - Historical account KW - Prenatal experience KW - Intrauterine exposure KW - Cancer KW - Pregnancy KW - Public health KW - Females KW - Adenocarcinoma KW - R2 23060:Medical and environmental health KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16560426?accountid=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+American+Medical+Association&rft.atitle=Cancer+risk+in+women+exposed+to+diethylstilbestrol+in+utero&rft.au=Hatch%2C+EE%3BPalmer%2C+J+R%3BTitus-Ernstoff%2C+L%3BNoller%2C+K+L%3BKaufman%2C+R+H%3BMittendorf%2C+R%3BRobboy%2C+S+J%3BHyer%2C+M%3BCowan%2C+C+M%3BAdam%2C+E%3BColton%2C+T%3BHartge%2C+P%3BHoover%2C+R+N&rft.aulast=Hatch&rft.aufirst=EE&rft.date=1998-08-19&rft.volume=280&rft.issue=7&rft.spage=630&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 - Risk assessment; Public health; Pregnancy; Historical account; Females; Cancer; Prenatal experience; Intrauterine exposure; Adenocarcinoma ER - TY - JOUR T1 - Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. AN - 73862957; 9707417 AB - The solution structure of the ectodomain of simian immunodeficiency virus (SIV) gp41 (e-gp41), consisting of residues 27-149, has been determined by multidimensional heteronuclear NMR spectroscopy. SIV e-gp41 is a symmetric 44 kDa trimer with each subunit consisting of antiparallel N-terminal (residues 30-80) and C-terminal (residues 107-147) helices connected by a 26 residue loop (residues 81-106). The N-terminal helices of each subunit form a parallel coiled-coil structure in the interior of the complex which is surrounded by the C-terminal helices located on the exterior of the complex. The loop region is ordered and displays numerous intermolecular and non-sequential intramolecular contacts. The helical core of SIV e-gp41 is similar to recent X-ray structures of truncated constructs of the helical core of HIV-1 e-gp41. The present structure establishes unambiguously the connectivity of the N- and C-terminal helices in the trimer, and characterizes the conformation of the intervening loop, which has been implicated by mutagenesis and antibody epitope mapping to play a key role in gp120 association. In conjunction with previous studies, the solution structure of the SIV e-gp41 ectodomain provides insight into the binding site of gp120 and the mechanism of cell fusion. The present structure of SIV e-gp41 represents one of the largest protein structures determined by NMR to date. JF - The EMBO journal AU - Caffrey, M AU - Cai, M AU - Kaufman, J AU - Stahl, S J AU - Wingfield, P T AU - Covell, D G 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, Bethesda, MD 20892-0520, USA. Y1 - 1998/08/17/ PY - 1998 DA - 1998 Aug 17 SP - 4572 EP - 4584 VL - 17 IS - 16 SN - 0261-4189, 0261-4189 KW - HIV Envelope Protein gp120 KW - 0 KW - HIV Envelope Protein gp41 KW - Hemagglutinin Glycoproteins, Influenza Virus KW - Membrane Glycoproteins KW - Retroviridae Proteins KW - SIV envelope protein gp41 KW - Solutions KW - Index Medicus KW - AIDS/HIV KW - Protein Structure, Secondary KW - Models, Molecular KW - HIV Envelope Protein gp120 -- chemistry KW - Amino Acid Sequence KW - Binding Sites KW - Magnetic Resonance Spectroscopy KW - Static Electricity KW - Mutagenesis, Site-Directed KW - Cell Fusion KW - HIV Envelope Protein gp41 -- genetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Hemagglutinin Glycoproteins, Influenza Virus -- chemistry KW - HIV Envelope Protein gp41 -- chemistry KW - Membrane Glycoproteins -- chemistry KW - Retroviridae Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73862957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three-dimensional+solution+structure+of+the+44+kDa+ectodomain+of+SIV+gp41.&rft.au=Caffrey%2C+M%3BCai%2C+M%3BKaufman%2C+J%3BStahl%2C+S+J%3BWingfield%2C+P+T%3BCovell%2C+D+G%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Caffrey&rft.aufirst=M&rft.date=1998-08-17&rft.volume=17&rft.issue=16&rft.spage=4572&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 - 1998-10-07 N1 - Date created - 1998-10-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1986 Jul 4;46(1):1-4 [3013415] Biochemistry. 1996 Nov 12;35(45):14381-94 [8916925] Cell. 1987 Jul 31;50(3):327-8 [3496970] Annu Rev Biochem. 1987;56:365-94 [3304138] FEBS Lett. 1988 Mar 14;229(2):317-24 [3345845] J Mol Biol. 1990 Apr 20;212(4):737-61 [2329580] J Virol. 1991 Apr;65(4):2119-23 [2002555] J Virol. 1991 May;65(5):2682-5 [2016774] Science. 1991 Jun 7;252(5011):1390-9 [2047852] J Virol. 1991 Sep;65(9):4832-8 [1714520] Proteins. 1991;11(4):281-96 [1758883] Virology. 1992 Mar;187(1):377-82 [1736542] J Virol. 1992 Jul;66(7):4532-5 [1602558] Cell. 1997 Apr 18;89(2):263-73 [9108481] Nature. 1997 May 22;387(6631):426-30 [9163431] Protein Sci. 1997 Jun;6(6):1179-89 [9194178] J Biomol NMR. 1997 Apr;9(3):323-8 [9204558] Protein Sci. 1997 Aug;6(8):1653-60 [9260278] Curr Opin Immunol. 1997 Aug;9(4):551-62 [9287172] J Mol Biol. 1997 Sep 5;271(5):819-26 [9299329] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8 [9356444] J Mol Biol. 1997 Oct 17;273(1):122-49 [9367752] J Magn Reson. 1997 Jan;124(1):154-64 [9424305] J Cell Biol. 1998 Jan 26;140(2):315-23 [9442107] Trends Biotechnol. 1998 Jan;16(1):22-34 [9470228] Cell. 1998 Mar 20;92(6):759-72 [9529252] J Magn Reson. 1997 Mar;125(1):171-7 [9245376] Nat Struct Biol. 1998 Apr;5(4):276-9 [9546217] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10537-41 [1438243] AIDS Res Hum Retroviruses. 1992 Sep;8(9):1571-80 [1457203] J Virol. 1993 May;67(5):2747-55 [8474172] Cell. 1993 May 21;73(4):823-32 [8500173] J Virol. 1993 Nov;67(11):6642-7 [7692082] J Virol. 1993 Dec;67(12):7383-93 [7693970] Proteins. 1993 Nov;17(3):297-309 [8272427] J Virol. 1994 Mar;68(3):2002-10 [7509005] J Magn Reson B. 1994 May;104(1):99-103 [8025816] Protein Sci. 1994 May;3(5):717-29 [8061602] Nature. 1981 Jan 29;289(5796):366-73 [7464906] Proc Natl Acad Sci U S A. 1982 Feb;79(4):968-72 [6951181] Nature. 1994 Sep 1;371(6492):37-43 [8072525] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9770-4 [7937889] Methods Enzymol. 1994;239:79-105 [7830604] Virology. 1995 Jan 10;206(1):713-7 [7530400] J Magn Reson B. 1995 Jan;106(1):92-6 [7850178] Protein Sci. 1994 Nov;3(11):2064-72 [7703852] J Biol Chem. 1995 Oct 13;270(41):23883-6 [7592573] Biochemistry. 1995 Nov 21;34(46):14955-62 [7578108] J Biomol NMR. 1995 Nov;6(3):277-93 [8520220] Nat Struct Biol. 1995 Dec;2(12):1075-82 [8846219] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):13-20 [8552589] EMBO J. 1996 Apr 1;15(7):1507-14 [8612573] J Mol Graph. 1996 Feb;14(1):51-5, 29-32 [8744573] Protein Sci. 1996 Jun;5(6):1067-80 [8762138] Cold Spring Harb Symp Quant Biol. 1995;60:573-80 [8824430] Biochemistry. 1996 Nov 5;35(44):13922-8 [8909289] Cell. 1987 Jun 5;49(5):659-68 [3107838] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No association between Alzheimer plaques and decreased levels of cytochrome oxidase subunit mRNA, a marker of neuronal energy metabolism. AN - 73867817; 9729244 AB - It has been proposed that neuritic plaques or toxic substances diffusing from them contribute to neurodegeneration in Alzheimer disease. We examined this hypothesis by looking for evidence of decreased neuronal energy metabolism in the proximity of neuritic plaques. Levels of mitochondrial DNA-encoded mRNA for subunit III of cytochrome oxidase, a marker of neuronal energy metabolism, were determined in post mortem brain samples. Consistent with earlier results, overall cytochrome oxidase subunit III mRNA levels were decreased in Alzheimer midtemporal cortex compared with controls. However, this reduction did not correlate with plaque density. In Alzheimer brains, cytochrome oxidase subunit III mRNA levels in neurons bearing neurofibrillary tangles were lower than in tangle-free neurons. However, neuronal cell bodies in close proximity of neuritic plaques showed no decrease in cytochrome oxidase subunit III mRNA or total polyadenylated mRNA compared with more distant neurons. Cytochrome oxidase enzyme activity in neuronal processes also showed no local reduction around neuritic plaques. These results suggest that neuritic plaques do not contribute to reduced neuronal energy metabolism in Alzheimer disease. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Hatanpää, K AU - Chandrasekaran, K AU - Brady, D R AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA. hatanpaa@helix.nih.gov Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 13 EP - 21 VL - 59 IS - 1 SN - 0169-328X, 0169-328X KW - RNA, Messenger KW - 0 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - In Situ Hybridization KW - Cell Count KW - Aged, 80 and over KW - Humans KW - Aged KW - Temporal Lobe -- enzymology KW - Immunohistochemistry KW - Male KW - Female KW - Motor Cortex -- enzymology KW - Electron Transport Complex IV -- genetics KW - Plaque, Amyloid -- pathology KW - Neurons -- enzymology KW - Energy Metabolism KW - Electron Transport Complex IV -- metabolism KW - Alzheimer Disease -- enzymology KW - RNA, Messenger -- biosynthesis KW - Neurons -- pathology KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73867817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=No+association+between+Alzheimer+plaques+and+decreased+levels+of+cytochrome+oxidase+subunit+mRNA%2C+a+marker+of+neuronal+energy+metabolism.&rft.au=Hatanp%C3%A4%C3%A4%2C+K%3BChandrasekaran%2C+K%3BBrady%2C+D+R%3BRapoport%2C+S+I&rft.aulast=Hatanp%C3%A4%C3%A4&rft.aufirst=K&rft.date=1998-08-15&rft.volume=59&rft.issue=1&rft.spage=13&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 - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of N-acetylation polymorphisms in smoking-associated bladder cancer: evidence of a gene-gene-exposure three-way interaction. AN - 73855596; 9721868 AB - Arylamines are known bladder carcinogens and are an important constituent of tobacco smoke. The handling of arylamines in the body is complex and includes metabolism by NAT1 and NAT2, enzymes that play a role in both activation and detoxification of arylamines and their congeners. Both NAT1 and NAT2 are polymorphic, with alleles that have been shown to correlate with higher or lower enzyme activity. To explore the combined role of these genes and exposure on bladder cancer risk, we examined the NAT1 and NAT2 genotype in a case-control study of bladder cancer in which detailed exposure histories were available on all 230 cases and 203 frequency-matched controls. Using PCR-RFLP genotyping, we determined NAT2 genotype for the five most common alleles, NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14 (frequently referred to as WT, M1, M2, M3, and M4, respectively). Similarly, the NAT1 genotype was determined for the four most common alleles NAT1*3, NAT1*4, and NAT1*11, and the putative high-activity allele, NAT1*10. No association between NAT2 genotype and bladder cancer risk was found whether genotype was considered alone or in combination with smoking, in either stratified or logistic regression analysis that adjusted for age, sex, and race. Stratified and logistic regression analysis both demonstrated an increased risk for individuals carrying the NAT1*10 allele among smokers. There was evidence of a gene-dosage effect, such that those who were homozygous for the NAT1*10 allele had the highest risks. There was also evidence of a statistically significant gene-environment interaction, such that bladder cancer risk depends on both NAT1 genotype and smoking exposure. Interestingly, although NAT2 genotype did not influence risk either alone or in combination with smoking exposure, there was evidence of a statistically significant gene-gene-environment three-way interaction. Bladder cancer risk from smoking exposure is particularly high in those who inherit NAT2 slow alleles in combination with one or two copies of the NAT1*10 allele. A biological mechanism for this finding is suggested. JF - Cancer research AU - Taylor, J A AU - Umbach, D M AU - Stephens, E AU - Castranio, T AU - Paulson, D AU - Robertson, C AU - Mohler, J L AU - Bell, D A AD - Epidemiology Branch, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. taylor@niehs.nih.gov Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 3603 EP - 3610 VL - 58 IS - 16 SN - 0008-5472, 0008-5472 KW - Isoenzymes KW - 0 KW - Neoplasm Proteins KW - Acetyltransferases KW - EC 2.3.1.- KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Index Medicus KW - Genotype KW - Acetylation KW - African Continental Ancestry Group -- genetics KW - Logistic Models KW - Humans KW - Aged KW - Middle Aged KW - Occupations KW - European Continental Ancestry Group -- genetics KW - Male KW - Female KW - Alleles KW - Acetyltransferases -- metabolism KW - Polymorphism, Genetic -- genetics KW - Urinary Bladder Neoplasms -- genetics KW - Neoplasm Proteins -- genetics KW - Smoking -- metabolism KW - Urinary Bladder Neoplasms -- enzymology KW - Smoking -- adverse effects KW - Acetyltransferases -- genetics KW - Neoplasm Proteins -- metabolism KW - Arylamine N-Acetyltransferase -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73855596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+N-acetylation+polymorphisms+in+smoking-associated+bladder+cancer%3A+evidence+of+a+gene-gene-exposure+three-way+interaction.&rft.au=Taylor%2C+J+A%3BUmbach%2C+D+M%3BStephens%2C+E%3BCastranio%2C+T%3BPaulson%2C+D%3BRobertson%2C+C%3BMohler%2C+J+L%3BBell%2C+D+A&rft.aulast=Taylor&rft.aufirst=J&rft.date=1998-08-15&rft.volume=58&rft.issue=16&rft.spage=3603&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in the safety of high dose bolus interleukin-2 administration in patients with metastatic cancer. AN - 73853191; 9708948 AB - Administration of recombinant high dose interleukin-2 (IL-2) can mediate tumor regression in patients with metastatic melanoma and renal carcinoma. Significant trends in the safety of high dose IL-2 administration at a single institution over a 12-year study period were reviewed. A consecutive series of 1241 metastatic cancer patients treated with intravenous bolus infusions of IL-2 (720,000 IU/kg every 8 hours) were evaluated for the incidence of specific treatment-related toxicities, the maximum number of administered IL-2 doses, and objective response rates. Significant decreases in the incidence of Grade 3 and/or Grade 4 toxicities were found when the initial group of 155 patients was compared with the final group: Grade 3/4 line sepsis (18% vs. 4%), Grade 3/4 diarrhea (92% vs. 12%), Grade 4 neuropsychiatric toxicity (19% vs. 8%), pulmonary intubations (12% vs. 3%), Grade 3/4 hypotension (81% vs. 31%), and Grade 4 cardiac ischemia (3% vs. 0%). No treatment-related deaths were noted in the final 809 patients. Laboratory abnormalities, such as increased creatinine, hyperbilirubinemia, and thrombocytopenia, were less severe, whereas percent weight gain remained stable over the 12-year period. The maximum number of administered IL-2 doses during the first cycle of therapy decreased from an initial median of 13 doses to 7 doses per first treatment cycle. No significant differences in overall and ongoing complete response rates to high dose bolus IL-2 were observed for melanoma patients (two-tailed P value = 0.40 and 1.0, respectively), or renal carcinoma patients (two-tailed P value = 0.92 and 0.89, respectively) over the study period. Progressive reduction in morbidity and mortality was found with the systemic administration of high dose IL-2-based therapies over the 12-year study period. The improvement in safety most likely reflects the development of strategies to screen eligible patients, optimize therapeutic conditions, and judiciously terminate dosing when significant toxicities are noted. Despite these interventions, the overall and ongoing complete response rates for melanoma and renal carcinoma have not shown significant compromise. These trends suggest that high dose IL-2 can be safely administered to metastatic cancer patients under the current treatment guidelines and result in durable responses in a small subset of patients. JF - Cancer AU - Kammula, U S AU - White, D E AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 797 EP - 805 VL - 83 IS - 4 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Interleukin-2 KW - Abridged Index Medicus KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Clinical Trials as Topic KW - Aged KW - Middle Aged KW - Infusions, Intravenous -- trends KW - Adolescent KW - Male KW - Infusions, Intravenous -- adverse effects KW - Female KW - Neoplasms -- drug therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Neoplasms -- pathology KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73853191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Trends+in+the+safety+of+high+dose+bolus+interleukin-2+administration+in+patients+with+metastatic+cancer.&rft.au=Kammula%2C+U+S%3BWhite%2C+D+E%3BRosenberg%2C+S+A&rft.aulast=Kammula&rft.aufirst=U&rft.date=1998-08-15&rft.volume=83&rft.issue=4&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-28 N1 - Date created - 1998-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. AN - 73852478; 9715354 AB - Impulsive violence, suicide, and depression are strongly associated with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA). Increased suicide and trauma reported in some cholesterol-lowering trials may be related to altered concentrations of polyunsaturated fatty acids rather than cholesterol, a possible surrogate marker. CSF 5-HIAA and homovanillic acid (HVA), total cholesterol, and plasma fatty acid concentrations were examined in 176 subjects, including 49 healthy volunteers, and 88 early- and 39 late-onset alcoholics. Among each group, polyunsaturated fatty acids predicted both CSF 5-HIAA and CSF HVA concentrations, but total cholesterol was unrelated to either neurotransmitter metabolite. The relationships between plasma 22: 6n3 and CSF 5-HIAA were significantly different when healthy volunteers (r = .35) were compared to early-onset alcoholics (r = -.38) (p < .0002). Dietary studies are indicated to determine if essential fatty acid supplementation can influence central nervous system serotonin and dopamine metabolism and modify impulsive behaviors related to these neurotransmitters. JF - Biological psychiatry AU - Hibbeln, J R AU - Linnoila, M AU - Umhau, J C AU - Rawlings, R AU - George, D T AU - Salem, N AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 235 EP - 242 VL - 44 IS - 4 SN - 0006-3223, 0006-3223 KW - Biomarkers KW - 0 KW - Fatty Acids, Unsaturated KW - Docosahexaenoic Acids KW - 25167-62-8 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Cholesterol KW - 97C5T2UQ7J KW - Dopamine KW - VTD58H1Z2X KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Regression Analysis KW - Age of Onset KW - Humans KW - Biomarkers -- cerebrospinal fluid KW - Cholesterol -- blood KW - Cross-Sectional Studies KW - Docosahexaenoic Acids -- blood KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Biomarkers -- blood KW - Statistics, Nonparametric KW - Female KW - Male KW - Homovanillic Acid -- cerebrospinal fluid KW - Alcoholism -- classification KW - Alcoholism -- cerebrospinal fluid KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Dopamine -- metabolism KW - Alcoholism -- metabolism KW - Serotonin -- metabolism KW - Fatty Acids, Unsaturated -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73852478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Essential+fatty+acids+predict+metabolites+of+serotonin+and+dopamine+in+cerebrospinal+fluid+among+healthy+control+subjects%2C+and+early-+and+late-onset+alcoholics.&rft.au=Hibbeln%2C+J+R%3BLinnoila%2C+M%3BUmhau%2C+J+C%3BRawlings%2C+R%3BGeorge%2C+D+T%3BSalem%2C+N&rft.aulast=Hibbeln&rft.aufirst=J&rft.date=1998-08-15&rft.volume=44&rft.issue=4&rft.spage=235&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidermal growth factor and transforming growth factor-alpha-associated overexpression of cyclin D1, Cdk4, and c-Myc during hepatocarcinogenesis in Helicobacter hepaticus-infected A/JCr mice. AN - 73850197; 9721866 AB - Helicobacter hepaticus is a new bacterial species that is homologous to Helicobacter pylori, a human gastric carcinogen. H. hepaticus causes chronic active hepatitis, with progression to hepatocellular tumors. We hypothesized that chronic up-regulation of epidermal growth factor (EGF), transforming growth factor-alpha, and nuclear oncogenes (cyclin D1 and c-Myc), all known to transform by overexpression, might contribute to tumorigenesis. Livers from mice that were 6-18 months old were analyzed, including nonneoplastic and preneoplastic tissues and tumors, along with age-matched controls, by immunohistochemistry and immunoblotting. EGF and transforming growth factor-alpha were increased at the earliest stage, with a further increase in EGF in tumors. Cyclin D1, cyclin-dependent kinase 4, and c-Myc were strongly increased in all infected livers, with even greater increases in tumors. An increase in cyclin D1/cyclin-dependent kinase 4 complex was also demonstrated in tumors, and its functionality was confirmed by an increase in the hyperphosphorylated:hypophosphorylated retinoblastoma protein ratio. Our findings suggest a possible cooperation of growth factors, cell cycle proteins, and transcription factors during the development of H. hepaticus-associated liver tumors and may have relevance to human cancers associated with bacterial, viral, or parasitic infections. JF - Cancer research AU - Ramljak, D AU - Jones, A B AU - Diwan, B A AU - Perantoni, A O AU - Hochadel, J F AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. ramljak@mail.ncifcrf.gov Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 3590 EP - 3597 VL - 58 IS - 16 SN - 0008-5472, 0008-5472 KW - Neoplasm Proteins KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - Retinoblastoma Protein KW - Transforming Growth Factor alpha KW - Cyclin D1 KW - 136601-57-5 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Cdk4 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Hepatitis, Animal -- complications KW - Mice, Inbred A KW - Hepatitis, Animal -- metabolism KW - Animals KW - Phosphorylation KW - Hepatitis, Animal -- microbiology KW - Retinoblastoma Protein -- metabolism KW - Mice KW - Male KW - Cyclin-Dependent Kinases -- metabolism KW - Cyclin D1 -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- microbiology KW - Liver Neoplasms, Experimental -- metabolism KW - Helicobacter Infections -- microbiology KW - Helicobacter Infections -- complications KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Neoplasm Proteins -- metabolism KW - Epidermal Growth Factor -- metabolism KW - Helicobacter Infections -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73850197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Epidermal+growth+factor+and+transforming+growth+factor-alpha-associated+overexpression+of+cyclin+D1%2C+Cdk4%2C+and+c-Myc+during+hepatocarcinogenesis+in+Helicobacter+hepaticus-infected+A%2FJCr+mice.&rft.au=Ramljak%2C+D%3BJones%2C+A+B%3BDiwan%2C+B+A%3BPerantoni%2C+A+O%3BHochadel%2C+J+F%3BAnderson%2C+L+M&rft.aulast=Ramljak&rft.aufirst=D&rft.date=1998-08-15&rft.volume=58&rft.issue=16&rft.spage=3590&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a mobile Stat6 activation motif in the human IL-4 receptor. AN - 73848783; 9712048 AB - The IL-4R induces proliferation and gene expression through the use of conserved tyrosine residues located in growth and gene regulation domains, respectively. We demonstrate that residues surrounding these conserved tyrosines (juxtatyrosine residues) are essential for the proper activation of the signaling molecules IRS-2 and Stat6, as well as for IL-4-induced gene expression. Further, we found that the IL-4R gene regulation domain (amino acids 557-657) contains a tyrosine-based sequence (EAGYKAF) that can convey Stat6 DNA binding and gene expression activities to a minimally active IL-4R mutant, delta 557. Thus, this tyrosine-based sequence can function as a mobile Stat6 activation cassette. However, mutants bearing this sequence induced CD23 expression much less efficiently than did wild-type IL-4R, requiring 150-fold more IL-4 to reach maximal CD23 expression. Our results indicate the importance of juxtatyrosine residues in IL-4R signaling and argue for an essential role of extended domain structure in the recognition and function of juxtatyrosine sequences. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ryan, J J AU - McReynolds, L J AU - Huang, H AU - Nelms, K AU - Paul, W E AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 1811 EP - 1821 VL - 161 IS - 4 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Amino Acids KW - Peptide Fragments KW - Receptors, IgE KW - Receptors, Interleukin-4 KW - STAT6 Transcription Factor KW - STAT6 protein, human KW - Stat6 protein, mouse KW - Trans-Activators KW - Interleukin-4 KW - 207137-56-2 KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Abridged Index Medicus KW - Index Medicus KW - Phosphotyrosine -- genetics KW - Animals KW - Adjuvants, Immunologic -- physiology KW - Gene Expression Regulation -- immunology KW - Humans KW - Interleukin-4 -- pharmacology KW - Phosphotyrosine -- metabolism KW - Mice KW - Protein Binding -- immunology KW - Peptide Fragments -- physiology KW - Receptors, IgE -- biosynthesis KW - Gene Expression Regulation -- genetics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Sequence Deletion -- immunology KW - Dose-Response Relationship, Immunologic KW - Receptors, IgE -- antagonists & inhibitors KW - Molecular Sequence Data KW - Tyrosine -- genetics KW - Protein Binding -- genetics KW - Tyrosine -- metabolism KW - Amino Acids -- physiology KW - Trans-Activators -- metabolism KW - Receptors, Interleukin-4 -- chemistry KW - Receptors, Interleukin-4 -- metabolism KW - Trans-Activators -- genetics KW - Trans-Activators -- chemistry KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - Trans-Activators -- antagonists & inhibitors KW - Receptors, Interleukin-4 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73848783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+a+mobile+Stat6+activation+motif+in+the+human+IL-4+receptor.&rft.au=Ryan%2C+J+J%3BMcReynolds%2C+L+J%3BHuang%2C+H%3BNelms%2C+K%3BPaul%2C+W+E&rft.aulast=Ryan&rft.aufirst=J&rft.date=1998-08-15&rft.volume=161&rft.issue=4&rft.spage=1811&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 - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assembly of MHC Class I Molecules with Biosynthesized Endoplasmic Reticulum-Targeted Peptides Is Inefficient in Insect Cells and Can Be Enhanced by Protease Inhibitors AN - 16526342; 4368426 AB - To study the requirements for assembly of MHC class I molecules with antigenic peptides in the endoplasmic reticulum (ER), we studied Ag processing in insect cells. Insects lack a class I recognition system, and their cells therefore provide a and blank slate and for identifying the proteins that have evolved to facilitate assembly of class I molecules in vertebrate cells. H-2K super(b) heavy chain, mouse beta sub(2)-microglobulin, and an ER- targeted version of a peptide corresponding to Ova sub(257-264) were expressed in insect cells using recombinant vaccinia viruses. Cell surface expression of K super(b)-OVA sub(257-264) complexes was quantitated using a recently described complex- specific mAb (25-D1.16). Relative to TAP-deficient human cells, insect cells expressed comparable levels of native, peptide-receptive cell surface K super(b) molecules, but generated cell surface K super(b)-OVA sub(257-264) complexes at least 20-fold less efficiently from ER-targeted peptides. The inefficient assembly of K super(b)-OVA sub(257-264) complexes in the ER of insect cells cannot be attributed solely to a requirement for human tapasin, since first, human cells lacking tapasin expressed endogenously synthesized K super(b)- OVA sub(257-264) complexes at levels comparable to tapasin-expressing cells, and second, vaccinia virus-mediated expression of human tapasin in insect cells did not detectably enhance the expression of K super(b)- VA sub(257-264) complexes. The assembly of K super(b)-OVA sub(257-264) complexes could be greatly enhanced in insect but not human cells by a nonproteasomal protease inhibitor. These findings indicate that insect cells lack one or more factors required for the efficient assembly of class I-peptide complexes in vertebrate cells and are consistent with the idea that the missing component acts to protect antigenic peptides or their immediate precursors from degradation. JF - Journal of Immunology AU - Deng, Y AU - Gibbs, J AU - Bacik, I AU - Porgador, A AU - Copeman, J AU - Lehner, P AU - Ortmann, B AU - Cresswell, P AU - Bennink, J R AU - Yewdell, J W AD - Room 213, Building 4, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA, jyewdell@nih.gov Y1 - 1998/08/15/ PY - 1998 DA - 1998 Aug 15 SP - 1677 EP - 1685 VL - 161 IS - 4 SN - 0022-1767, 0022-1767 KW - class I molecules KW - insect cells KW - proteinase inhibitors KW - synthetic peptides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews KW - F 06823:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16526342?accountid=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=Assembly+of+MHC+Class+I+Molecules+with+Biosynthesized+Endoplasmic+Reticulum-Targeted+Peptides+Is+Inefficient+in+Insect+Cells+and+Can+Be+Enhanced+by+Protease+Inhibitors&rft.au=Deng%2C+Y%3BGibbs%2C+J%3BBacik%2C+I%3BPorgador%2C+A%3BCopeman%2C+J%3BLehner%2C+P%3BOrtmann%2C+B%3BCresswell%2C+P%3BBennink%2C+J+R%3BYewdell%2C+J+W&rft.aulast=Deng&rft.aufirst=Y&rft.date=1998-08-15&rft.volume=161&rft.issue=4&rft.spage=1677&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 ER - TY - JOUR T1 - Effects of arfaptin 1 on guanine nucleotide-dependent activation of phospholipase D and cholera toxin by ADP-ribosylation factor. AN - 80057688; 9694811 AB - Arfaptin 1, a approximately 39-kDa protein based on the deduced amino acid sequence, had been initially identified in a yeast two-hybrid screen using dominant active ARF3 (Q71L) as bait with an HL-60 cDNA library. It was suggested that arfaptin 1 may be involved in Golgi functions, since the FLAG-tagged protein was associated with Golgi membranes when expressed in COS-7 cells and could be bound to Golgi in vitro in an ADP-ribosylation factor (ARF)- and GTPgammaS-dependent, brefeldin A-inhibited fashion. Arfaptin 2, found in the same two-hybrid screen as arfaptin 1, is 60% identical in amino acid sequence and may or may not have an analogous function. We now report some effects of arfaptin 1 on ARF activation of phospholipase D and cholera toxin ADP-ribosyltransferase. Arfaptin 1 inhibited activation of both enzymes in a concentration-dependent manner and was without effect in the absence of ARF. Two ARF1 mutants that activated the toxin, one lacking 13 N-terminal amino acids and the other, in which 73 residues at the N terminus were replaced with the analogous sequence from ARL1, were not inhibited by arfaptin, consistent with the conclusion that arfaptin interaction requires the N terminus of ARF. This region has also been implicated in phospholipase D activation, but whether the two proteins interact with the same structural elements in ARF remains to be determined. Arfaptin inhibition of the action of ARF5 and ARF6 was less than that of ARF1 and ARF3; its effects were less on nonmyristoylated than myristoylated ARFs. Arfaptin effects on guanine nucleotide binding by ARFs were minimal whether or not a purified ARF guanine nucleotide-exchange protein was present. These findings indicate that arfaptin acts as an inhibitor of ARF actions in vitro, raising the possibility that it has a similar role in vivo. JF - The Journal of biological chemistry AU - Tsai, S C AU - Adamik, R AU - Hong, J X AU - Moss, J AU - Vaughan, M AU - Kanoh, H AU - Exton, J H AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1590, USA. Y1 - 1998/08/14/ PY - 1998 DA - 1998 Aug 14 SP - 20697 EP - 20701 VL - 273 IS - 33 SN - 0021-9258, 0021-9258 KW - ARFIP1 protein, human KW - 0 KW - Adaptor Proteins, Signal Transducing KW - Carrier Proteins KW - Guanine Nucleotides KW - Recombinant Proteins KW - Magnesium Chloride KW - 02F3473H9O KW - Tritium KW - 10028-17-8 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Phospholipase D KW - EC 3.1.4.4 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Recombinant Proteins -- metabolism KW - HL-60 Cells KW - Enzyme Activation KW - Humans KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Phospholipase D -- metabolism KW - Carrier Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Carrier Proteins -- pharmacology KW - Guanine Nucleotides -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80057688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+arfaptin+1+on+guanine+nucleotide-dependent+activation+of+phospholipase+D+and+cholera+toxin+by+ADP-ribosylation+factor.&rft.au=Tsai%2C+S+C%3BAdamik%2C+R%3BHong%2C+J+X%3BMoss%2C+J%3BVaughan%2C+M%3BKanoh%2C+H%3BExton%2C+J+H&rft.aulast=Tsai&rft.aufirst=S&rft.date=1998-08-14&rft.volume=273&rft.issue=33&rft.spage=20697&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 - 1998-09-14 N1 - Date created - 1998-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The biosynthesis of mycolic acids in Mycobacterium tuberculosis: Enzymatic methyl(ene) transfer to acyl carrier protein bound meromycolic acid in vitro AN - 16544948; 4353440 AB - A closely related family of enzymes from Mycobacterium tuberculosis has been shown by heterologous expression to catalyze the modification of mycolic acids through the addition of a methyl (or methylene) group derived from S-adenosyl-L-methionine (SAM). Overproduction of all six of these enzymes in Escherichia coli and subsequent in vitro reactions with heat- inactivated acceptor fractions derived from Mycobacterium smegmatis in the presence of [methyl- super(3)H]SAM demonstrated that the immediate substrate to which methyl group addition occurs was a family of very long-chain fatty acids. Inhibitors of methyl transfer such as S-adenosyl-L-homocysteine and sinefungin, were shown to inhibit this reaction but had no effect on whole cells of either M. smegmatis or M. tuberculosis. Purified mycolic acids from M. tuberculosis were pyrolyzed, and the resulting meroaldehyde was oxidized and methylated to produce full-length methyl meromycolates. These esters were shown to comigrate with a fraction of the acceptor from the in vitro reactions, suggesting that methyl group addition occurs up to the level of the meromycolate. Protease and other treatments destroyed the activity of the acceptor fraction, which was also found to be extremely sensitive to basic pH. Antibody to the acyl carrier protein AcpM, which has recently been shown to be the carrier of full-length meromycolate produced by a unique type II fatty acid synthase system, inhibited the cell-free methyl(en)ation of these acids. These results suggest that mycolate modification reactions occur parallel with the synthesis of the AcpM-bound meromycolate chain. JF - Journal of Biological Chemistry AU - Yuan, Y AU - Mead, D AU - Schroeder, B G AU - Zhu, Y AU - Barry, CE AD - Tuberculosis Research Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840 Y1 - 1998/08/14/ PY - 1998 DA - 1998 Aug 14 SP - 21282 EP - 21290 VL - 273 IS - 33 SN - 0021-9258, 0021-9258 KW - acyl carrier protein KW - mycolic acids KW - Microbiology Abstracts B: Bacteriology KW - Fatty acids KW - Mycobacterium tuberculosis KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16544948?accountid=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=The+biosynthesis+of+mycolic+acids+in+Mycobacterium+tuberculosis%3A+Enzymatic+methyl%28ene%29+transfer+to+acyl+carrier+protein+bound+meromycolic+acid+in+vitro&rft.au=Yuan%2C+Y%3BMead%2C+D%3BSchroeder%2C+B+G%3BZhu%2C+Y%3BBarry%2C+CE&rft.aulast=Yuan&rft.aufirst=Y&rft.date=1998-08-14&rft.volume=273&rft.issue=33&rft.spage=21282&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 - Mycobacterium tuberculosis; Fatty acids ER - TY - JOUR T1 - Required buried alpha-helical structure in the bilirubin UDP-glucuronosyltransferase, UGT1A1, contains a nonreplaceable phenylalanine. AN - 80049575; 9692996 AB - A conserved hydrophobic region in the bilirubin-type UDP-glucuronosyltransferase isozyme was first uncovered as a consequence of a deleterious mutation in the UGT1A1 (HUG-Br1) isozyme of a Crigler-Najjar (CN) Type I patient. According to analysis by the RAOARGOS computer program, this hydrophobic region in UGT1A1 is located between residues 159-177 and defines a buried helix centered over position 169-172 with a positive factor of 1.22. Further analysis showed that the planar phenol-type UGT1A6 (HLUG P1) isoform, unlike the steroid-type UGT2B7 (UDPGTh2) isozyme, has a similar conserved hydrophobic region and that the positive factor for its buried helix is 1.14 compared to the threshold of 1.13 for such a structure. The analysis detected the typical membrane-insertion-signal sequence and a membrane-anchoring domain in each isoform. The different amino acid sequence patterns between positions 168-172 for the three types of isoforms and the deleterious mutations in this microregion (MRA) of UGT1A1 in CN-I patients are evidence of a critical and descriminating role for MRA. With the recombinant UGT1A1 enzyme and its mutants, P167G, F170del, F170L, F170I, F170V, F170A, F170Y, F170E, F171L, F171I, F171V, F171A, F171Y, or L175Q, expressed in COS-1 cells, bilirubin glucuronidating activity at both pH 6.4 and 7.6 demonstrated that Phe-170 is not replaceable, whereas Phe-171 can be replaced by Leu without any loss of activity. The less hydrophobic buried helix in the phenolic-type UGT1A6 has a Tyr/Leu at position 170/171; this isoform glucuronidated bilirubin at 1/10 the level of that by UGT1A1 with a Km (bilirubin) of 25 microM compared to that for UGT1A1 of 5. 0 microM. JF - Biochemistry AU - Ciotti, M AU - Cho, J W AU - George, J AU - Owens, I S AD - Human Genetics Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1998/08/04/ PY - 1998 DA - 1998 Aug 04 SP - 11018 EP - 11025 VL - 37 IS - 31 SN - 0006-2960, 0006-2960 KW - Isoenzymes KW - 0 KW - Phenylalanine KW - 47E5O17Y3R KW - UDP-glucuronosyltransferase, UGT1A6 KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - bilirubin glucuronoside glucuronosyltransferase KW - EC 2.4.1.95 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Isoenzymes -- chemistry KW - Software KW - Animals KW - Conserved Sequence KW - Humans KW - Molecular Sequence Data KW - Rabbits KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Isoenzymes -- genetics KW - Structure-Activity Relationship KW - Phenylalanine -- chemistry KW - Protein Structure, Secondary KW - Glucuronosyltransferase -- genetics KW - Phenylalanine -- genetics KW - Glucuronosyltransferase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80049575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Required+buried+alpha-helical+structure+in+the+bilirubin+UDP-glucuronosyltransferase%2C+UGT1A1%2C+contains+a+nonreplaceable+phenylalanine.&rft.au=Ciotti%2C+M%3BCho%2C+J+W%3BGeorge%2C+J%3BOwens%2C+I+S&rft.aulast=Ciotti&rft.aufirst=M&rft.date=1998-08-04&rft.volume=37&rft.issue=31&rft.spage=11018&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of the polo-box disrupts localization and mitotic functions of the mammalian polo kinase Plk. AN - 80045763; 9689075 AB - Members of the polo subfamily of protein kinases play pivotal roles in cell proliferation. In addition to the kinase domain, polo kinases have a strikingly conserved sequence in the noncatalytic domain, termed the polo-box. The function of the polo-box is currently undefined. The mammalian polo-like kinase Plk is a functional homologue of Saccharomyces cerevisiae Cdc5. Here, we show that Plk localizes at the spindle poles and cytokinetic neck filaments. Without impairing kinase activity, a conservative mutation in the polo-box disrupts the capacity of Plk to complement the defect associated with a cdc5-1 temperature-sensitive mutation and to localize to these subcellular structures. Our data provide evidence that the polo-box plays a critical role in Plk function, likely by directing its subcellular localization. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lee, K S AU - Grenfell, T Z AU - Yarm, F R AU - Erikson, R L AD - Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. kyunglee@pop.nci.nih.gov Y1 - 1998/08/04/ PY - 1998 DA - 1998 Aug 04 SP - 9301 EP - 9306 VL - 95 IS - 16 SN - 0027-8424, 0027-8424 KW - CEF1 protein, S cerevisiae KW - 0 KW - Cell Cycle Proteins KW - Fungal Proteins KW - Proto-Oncogene Proteins KW - RNA-Binding Proteins KW - Saccharomyces cerevisiae Proteins KW - Protein Kinases KW - EC 2.7.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - polo-like kinase 1 KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Mice KW - Fungal Proteins -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Cell Cycle Proteins -- genetics KW - Genetic Complementation Test KW - Molecular Sequence Data KW - Spindle Apparatus KW - Catalysis KW - Protein Kinases -- metabolism KW - Mitosis -- genetics KW - Protein Kinases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80045763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+of+the+polo-box+disrupts+localization+and+mitotic+functions+of+the+mammalian+polo+kinase+Plk.&rft.au=Lee%2C+K+S%3BGrenfell%2C+T+Z%3BYarm%2C+F+R%3BErikson%2C+R+L&rft.aulast=Lee&rft.aufirst=K&rft.date=1998-08-04&rft.volume=95&rft.issue=16&rft.spage=9301&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 - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1996 Jan 26;84(2):187-90 [8565063] Mol Cell Biol. 1995 Dec;15(12):7143-51 [8524282] Science. 1996 Sep 6;273(5280):1377-80 [8703070] J Cell Biol. 1996 Dec;135(6 Pt 2):1681-4 [8991082] J Cell Biol. 1996 Dec;135(6 Pt 2):1701-13 [8991084] Proc Natl Acad Sci U S A. 1997 May 13;94(10):4817-20 [9144146] Mol Cell Biol. 1997 Jun;17(6):3408-17 [9154840] Cell. 1997 Sep 19;90(6):1097-106 [9323137] Biochem Biophys Res Commun. 1997 Oct 20;239(2):377-85 [9344838] EMBO J. 1998 Mar 2;17(5):1328-35 [9482730] EMBO J. 1998 Mar 2;17(5):1336-49 [9482731] Mol Cell. 1998 Feb;1(3):371-80 [9660921] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] J Theor Biol. 1983 Mar 21;101(2):289-316 [6683772] Cell. 1984 Jul;37(3):969-78 [6378388] Int Rev Cytol. 1986;105:245-81 [3539854] J Cell Biol. 1989 Nov;109(5):2225-32 [2808526] Genes Dev. 1991 Dec;5(12A):2153-65 [1660828] Curr Opin Cell Biol. 1992 Feb;4(1):43-52 [1313686] Mol Cell Biol. 1992 Sep;12(9):4164-9 [1508211] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4882-6 [8099445] Mol Cell Biol. 1993 Jul;13(7):4445-57 [8321244] Mol Cell Biol. 1993 Dec;13(12):7793-801 [7902533] Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1736-40 [8127874] Cell Growth Differ. 1994 Mar;5(3):249-57 [8018557] J Cell Sci. 1994 Jun;107 ( Pt 6):1509-17 [7962193] J Biol Chem. 1995 Apr 28;270(17):10351-7 [7730342] Genes Dev. 1995 May 1;9(9):1059-73 [7744248] J Cell Biol. 1995 Jun;129(6):1617-28 [7790358] J Biol Chem. 1996 Aug 9;271(32):19402-8 [8702627] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autoregulation of the Raf-1 serine/threonine kinase. AN - 80044387; 9689060 AB - The Raf-1 serine/threonine kinase is a key protein involved in the transmission of many growth and developmental signals. In this report, we show that autoinhibition mediated by the noncatalytic, N-terminal regulatory region of Raf-1 is an important mechanism regulating Raf-1 function. The inhibition of the regulatory region occurs, at least in part, through binding interactions involving the cysteine-rich domain. Events that disrupt this autoinhibition, such as mutation of the cysteine-rich domain or a mutation mimicking an activating phosphorylation event (Y340D), alleviate the repression of the regulatory region and increase Raf-1 activity. Based on the striking similarites between the autoregulation of the serine/threonine kinases protein kinase C, Byr2, and Raf-1, we propose that relief of autorepression and activation at the plasma membrane is an evolutionarily conserved mechanism of kinase regulation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Cutler, R E AU - Stephens, R M AU - Saracino, M R AU - Morrison, D K AD - Molecular Basis of Carcinogenesis Laboratory, Advanced BioSciences Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1998/08/04/ PY - 1998 DA - 1998 Aug 04 SP - 9214 EP - 9219 VL - 95 IS - 16 SN - 0027-8424, 0027-8424 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Mutation KW - Catalysis KW - Proto-Oncogene Proteins c-raf -- chemistry KW - Proto-Oncogene Proteins c-raf -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80044387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autoregulation+of+the+Raf-1+serine%2Fthreonine+kinase.&rft.au=Cutler%2C+R+E%3BStephens%2C+R+M%3BSaracino%2C+M+R%3BMorrison%2C+D+K&rft.aulast=Cutler&rft.aufirst=R&rft.date=1998-08-04&rft.volume=95&rft.issue=16&rft.spage=9214&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 - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1997 Aug 22;272(34):20990-3 [9261098] Mol Cell Biol. 1997 Aug;17(8):4509-16 [9234708] Mol Cell Biol. 1990 Jun;10(6):2503-12 [2188091] Cancer Cells. 1990 Dec;2(12):377-82 [2150916] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Cell. 1993 Jul 16;74(1):205-14 [8334704] J Cell Biol. 1993 Aug;122(3):645-52 [8335690] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] J Biol Chem. 1993 Sep 25;268(27):20232-6 [8397201] Mol Cell Biol. 1993 Nov;13(11):7133-43 [8413302] J Biol Chem. 1994 Apr 1;269(13):10000-7 [8144497] Trends Genet. 1994 Feb;10(2):44-8 [8191584] Curr Opin Genet Dev. 1994 Feb;4(1):82-9 [8193545] EMBO J. 1994 Jun 1;13(11):2592-9 [8013459] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5982-6 [8016101] J Biol Chem. 1994 Sep 2;269(35):22340-6 [8071362] J Biol Chem. 1994 Dec 2;269(48):30105-8 [7982912] Cell. 1995 Jan 27;80(2):187-97 [7834739] J Biol Chem. 1995 Apr 28;270(17):9809-12 [7730360] Mol Cell Biol. 1995 Jun;15(6):3390-7 [7760835] Nature. 1995 Jun 15;375(6532):554-60 [7791872] EMBO J. 1995 Jul 3;14(13):3136-45 [7542586] J Biol Chem. 1995 Dec 22;270(51):30274-7 [8530446] J Biol Chem. 1996 Jan 5;271(1):233-7 [8550565] Cell. 1996 Mar 22;84(6):889-97 [8601312] Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218-22 [6308607] Proc Natl Acad Sci U S A. 1985 Sep;82(17):5641-5 [3862088] Proc Natl Acad Sci U S A. 1985 Sep;82(17):5954-8 [2994056] Nucleic Acids Res. 1986 Jan 24;14(2):1009-15 [3003687] Nucleic Acids Res. 1987 Jan 26;15(2):595-609 [3029685] Mol Cell Biol. 1987 Mar;7(3):1171-9 [3561413] Mol Cell Biol. 1987 Mar;7(3):1226-32 [3550433] Mol Cell Biol. 1988 Jun;8(6):2651-4 [3043188] Mol Cell Biol. 1989 Feb;9(2):639-47 [2710120] Oncogene. 1989 Apr;4(4):437-42 [2524024] Nat Struct Biol. 1996 Mar;3(3):244-51 [8605626] J Biol Chem. 1996 Apr 5;271(14):8472-80 [8626548] Oncogene. 1996 Feb 1;12(3):609-19 [8637718] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7 [8710867] Protein Sci. 1997 Feb;6(2):477-80 [9041654] Curr Opin Cell Biol. 1997 Apr;9(2):161-7 [9069266] Curr Opin Cell Biol. 1997 Apr;9(2):174-9 [9069260] EMBO J. 1997 Apr 15;16(8):1953-60 [9155021] Mol Cell Biol. 1997 Oct;17(10):5876-87 [9315645] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Classical conditioning increases membrane-bound protein kinase C in rabbit cerebellum. AN - 73860177; 9721953 AB - We examined membrane-bound protein kinase C (PKC) in the cerebellum of rabbits given paired presentations of a tone conditioned stimulus (CS) that co-terminated with a periocular electrical stimulation unconditioned stimulus (US) or unpaired presentations of the CS and US or restraint in the experimental context. PKC activation was measured by quantitative film autoradiography of [3H]phorbol 12,13-dibutyrate ([3H]PBt2) binding in the molecular and granule cells layers of lobule HVI, anterior vermis and Crus I, and in the dentate/interpositus nuclei. There was a statistically significant increase in [3H]PBt2 binding within the molecular layer of lobule HVI in rabbits given paired training relative to controls. The results indicate PKC activation in lobule HVI may be important in acquisition of conditioned eyeblink responses. JF - Neuroreport AU - Freeman, J H AU - Scharenberg, A M AU - Olds, J L AU - Schreurs, B G AD - Behavioral Neuroscience Unit, Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/08/03/ PY - 1998 DA - 1998 Aug 03 SP - 2669 EP - 2673 VL - 9 IS - 11 SN - 0959-4965, 0959-4965 KW - Enzyme Inhibitors KW - 0 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Membranes -- enzymology KW - Animals KW - Enzyme Inhibitors -- pharmacology KW - Rabbits KW - Autoradiography KW - Image Processing, Computer-Assisted KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Conditioning, Classical -- physiology KW - Cerebellum -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73860177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Classical+conditioning+increases+membrane-bound+protein+kinase+C+in+rabbit+cerebellum.&rft.au=Freeman%2C+J+H%3BScharenberg%2C+A+M%3BOlds%2C+J+L%3BSchreurs%2C+B+G&rft.aulast=Freeman&rft.aufirst=J&rft.date=1998-08-03&rft.volume=9&rft.issue=11&rft.spage=2669&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-18 N1 - Date created - 1998-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lingual action in normal sequential swallowing. AN - 85407461; pmid-9712125 AB - Current knowledge about the flexibility in lingual motor control and performance during swallowing is incomplete. The present study aimed at gaining a better understanding of the tongue's motor flexibility and at identifying variable versus invariant lingual motor program parameters in light of changing swallowing task demands (discrete vs. sequential). Specifically, the timing and patterns of tongue-palate contact and the associated changes in tongue shape and action were examined in 5 normal adults using simultaneous electropalatography and ultrasound. Tasks for discrete swallowing included 5 and 30 cc of water; tasks for sequential swallowing involved drinking 200 cc of water at normal and fast rates. Results showed little variation in propulsive contact pattern as a function of task or subject. However, the tongue demonstrated shorter movement duration and overlapping gestures during sequential swallowing. Thus, continuous drinking was performed without changes in motor strategies per se but with changes in the timing coordination of the "drink" and "swallow" action sequences. These findings support the theory that the deglutitive lingual motor program has both invariant and variant parameters, and that movement pattern and action sequence reflect fixed elements within the structure of the motor program, but movement timing can be modified according to the demands of the task at hand. JF - Journal of speech, language, and hearing research : JSLHR AU - Chi-Fishman, G AU - Stone, M AU - McCall, G N AD - Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA. gcf@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 771 EP - 785 VL - 41 IS - 4 SN - 1092-4388, 1092-4388 KW - Index Medicus KW - National Library of Medicine KW - Palate -- ultrasonography KW - Humans KW - Palate -- innervation KW - Adult KW - Middle Aged KW - Electric Stimulation KW - Time Factors KW - Female KW - Male KW - Deglutition -- physiology KW - Tongue -- ultrasonography KW - Movement -- physiology KW - Tongue -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85407461?accountid=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+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.atitle=Lingual+action+in+normal+sequential+swallowing.&rft.au=Chi-Fishman%2C+G%3BStone%2C+M%3BMcCall%2C+G+N&rft.aulast=Chi-Fishman&rft.aufirst=G&rft.date=1998-08-01&rft.volume=41&rft.issue=4&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Journal+of+speech%2C+language%2C+and+hearing+research+%3A+JSLHR&rft.issn=10924388&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Electromyography in near-total laryngectomy. AN - 85407218; pmid-9708709 AB - OBJECTIVE: To investigate the dynamics of speech shunt muscle in patients with Pearson near-total laryngectomy by needle electromyography and correlation of ability to activate shunt muscle with speech production. DESIGN AND SETTINGS: Prospective study of patients with near-total laryngectomy at 2 hospital-based academic tertiary care centers. PARTICIPANTS AND INTERVENTION: Fourteen patients with near-total laryngectomy were subjected to percutaneous needle electromyographic study of the shunt muscle. MAIN OUTCOME MEASURES: Speech ability, electromyographic evidence of viable muscle in shunt wall, and ability to activate shunt muscle were recorded. RESULTS: Twelve of 14 patients had good speech; 11 had evidence of viable shunt muscle; and 9 were able to activate muscle by phonation, swallowing, or deep breathing, indicating preserved innervation. Six of the 12 patients with speech ability and 1 of the 2 patients without speech ability were able to recruit motor units during attempted phonation. CONCLUSIONS: Electromyography demonstrated viable muscle with retained innervation in 64% of the patients with near-total laryngectomy, proving its "dynamic" nature. However, the usefulness of shunt muscle activation in speech and prevention of aspiration needs further confirmation. JF - Archives of otolaryngology--head & neck surgery AU - Arunodaya, G R AU - Shenoy, A M AU - Premalata, S AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 857 EP - 860 VL - 124 IS - 8 SN - 0886-4470, 0886-4470 KW - Abridged Index Medicus; Index Medicus KW - National Library of Medicine KW - Prospective Studies KW - Humans KW - Adult KW - Laryngeal Neoplasms -- surgery KW - Aged KW - Middle Aged KW - Female KW - Male KW - Laryngectomy -- methods KW - Electromyography KW - Speech -- physiology KW - Laryngeal Muscles -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85407218?accountid=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=Electromyography+in+near-total+laryngectomy.&rft.au=Arunodaya%2C+G+R%3BShenoy%2C+A+M%3BPremalata%2C+S&rft.aulast=Arunodaya&rft.aufirst=G&rft.date=1998-08-01&rft.volume=124&rft.issue=8&rft.spage=857&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 - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The preoccupation scale: its development and relationship with depression scales. AN - 85255924; pmid-9696114 AB - Self-focus has been thought to be an important factor in the development and maintenance of depression. The disposition to focus attention inward has been measured by the Private Self-Consciousness Scale (PSCS), which does not reflect the duration of self-focusing. Study 1 aimed to develop a Self-Preoccupation Scale (SPS) that would reflect both the degree and duration of self-focusing. In addition, a new concept, external-preoccupation-the maintenance of external-focus on a specific object-was proposed as a risk factor of depression. An External-Preoccupation Scale (EPS) was developed to measure this. Both the SPS and EPS showed excellent internal consistency and test-retest reliability. Study 2 aimed to examine the relationship between the SPS, EPS, and PSCS and depression. The EPS was not significantly correlated with depression scales. The moderate correlations of the SPS with the depression scales were significantly higher than the correlations of the PSCS with the depression scales. JF - Journal of Clinical Psychology AU - Sakamoto, S AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Chiba, Japan. PY - 1998 SP - 645 EP - 654 VL - 54 IS - 5 SN - 0021-9762, 0021-9762 KW - Depression KW - Reproducibility of Results KW - Human KW - Chi-Square Distribution KW - Adult KW - Obsessive Behavior KW - Narcissism KW - Attention KW - Psychometrics KW - Male KW - Female KW - Self Assessment (Psychology) KW - Psychiatric Status Rating Scales KW - Personality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85255924?accountid=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+Clinical+Psychology&rft.atitle=The+preoccupation+scale%3A+its+development+and+relationship+with+depression+scales.&rft.au=Sakamoto%2C+S&rft.aulast=Sakamoto&rft.aufirst=S&rft.date=1998-08-01&rft.volume=54&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Psychology&rft.issn=00219762&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Functional coupling and regional activation of human cortical motor areas during simple, internally paced and externally paced finger movements. AN - 85228564; pmid-9712013 AB - We studied the activation and interaction of cortical motor regions during simple, internally paced and externally paced right-hand finger extensions in healthy volunteers. We recorded EEGs from 28 scalp electrodes and analysed task-related coherence, task-related power and movement-related cortical potentials. Task-related coherence reflects inter-regional functional coupling of oscillatory neuronal activity, task-related power reflects regional oscillatory activity of neuronal assemblies and movement-related cortical potentials reflect summated potentials of apical dendrites of pyramidal cells. A combination of these three analytical techniques allows comprehensive evaluation of different aspects of information processing in neuronal assemblies. For both externally and internally paced finger extensions, movement-related regional activation was predominant over the contralateral premotor and primary sensorimotor cortex, and functional coupling occurred between the primary sensorimotor cortex of both hemispheres and between the primary sensorimotor cortex and the mesial premotor areas, probably including the supplementary motor area. The main difference between the different types of movement pacing was enhanced functional coupling of central motor areas during internally paced finger extensions, particularly inter-hemispherically between the left and right primary sensorimotor cortexes and between the contralateral primary sensorimotor cortex and the mesial premotor areas. Internally paced finger extensions were also associated with additional regional (premovement) activation over the mesial premotor areas. The maximal task-related coherence differences between internally and externally paced finger extensions occurred in the frequency range of 20-22 Hz rather than in the range of maximal task-related power differences (9-11 Hz). This suggests that important aspects of information processing in the human motor system could be based on network-like oscillatory cortical activity and might be modulated on at least two levels, which to some extent can operate independently from each other: (i) regional activation (task-related power) and (ii) inter-regional functional coupling. We propose that internal pacing of movement poses higher demands on the motor system than external pacing, and that the motor system responds not only by increasing regional activation of the mesial premotor system, including the supplementary motor area, but also by enhancing information flow between lateral and mesial premotor and sensorimotor areas of both hemispheres, even if the movements are simple and unimanual. JF - Brain AU - Gerloff, C AU - Richard, J AU - Hadley, J AU - Schulman, A E AU - Honda, M AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1513 EP - 1531 VL - 121 ( Pt 8) SN - 0006-8950, 0006-8950 KW - Human KW - Electroencephalography KW - Electromyography KW - Movement KW - Motor Cortex KW - Fingers KW - Brain Mapping KW - Evoked Potentials, Motor KW - Adult KW - Cues KW - Support, Non-U.S. Gov't KW - Middle Age KW - Periodicity KW - Male KW - Female KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85228564?accountid=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&rft.atitle=Functional+coupling+and+regional+activation+of+human+cortical+motor+areas+during+simple%2C+internally+paced+and+externally+paced+finger+movements.&rft.au=Gerloff%2C+C%3BRichard%2C+J%3BHadley%2C+J%3BSchulman%2C+A+E%3BHonda%2C+M%3BHallett%2C+M&rft.aulast=Gerloff&rft.aufirst=C&rft.date=1998-08-01&rft.volume=121+%28+Pt+8%29&rft.issue=&rft.spage=1513&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Calorie restriction reduces ulcerative dermatitis and infection-related mortality in p53-deficient and wild-type mice. AN - 80058233; 9699732 AB - In rodents calorie restriction (CR) reduces cancer incidence, improves health by delaying age-related declines in physiologic measures, and extends both median and maximal life span. The mechanisms underlying the various beneficial effects of CR remain undefined. In this study, heterozygous p53-deficient (p53(+/-)) mice (in which the inactivation of one allele of the p53 tumor suppressor gene increases susceptibility to spontaneous and carcinogen-induced tumor development) and wild-type (WT) litter mates were subjected to a two-stage skin carcinogenesis protocol with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Instead of skin carcinomas, however, the chemical treatment protocol caused ulcerous skin lesions, and 89% of mice fed ad libitum died from infection/septicemia. When WT mice were restricted to 60% of the average calorie intake of the respective ad libitum group, however, only 33% developed such lesions, and the CR mice survived twice as long on average as the ad libitum mice. CR also extended life span in p53(+/-) mice, but 50% of p53(+/-) mice subjected to CR still developed skin ulcers and mean life span was shorter than that seen in WT mice. Differences in response to CR between WT and p53(+/-) mice may be due to the reduction in p53 gene dosage, dissimilarity in the application of the CR treatment, or both. These results suggest that some of the beneficial effects of CR may need full expression of p53 for complete realization. JF - The Journal of investigative dermatology AU - Perkins, S N AU - Hursting, S D AU - Phang, J M AU - Haines, D C AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 292 EP - 296 VL - 111 IS - 2 SN - 0022-202X, 0022-202X KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Animals KW - Nitric Oxide Synthase -- physiology KW - Mice, Inbred C57BL KW - Sepsis -- mortality KW - Mice KW - Gene Dosage KW - Skin Neoplasms -- prevention & control KW - Male KW - Genes, p53 -- physiology KW - Skin Ulcer -- prevention & control KW - Diet, Reducing KW - Infection -- mortality KW - Energy Intake UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80058233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Calorie+restriction+reduces+ulcerative+dermatitis+and+infection-related+mortality+in+p53-deficient+and+wild-type+mice.&rft.au=Perkins%2C+S+N%3BHursting%2C+S+D%3BPhang%2C+J+M%3BHaines%2C+D+C&rft.aulast=Perkins&rft.aufirst=S&rft.date=1998-08-01&rft.volume=111&rft.issue=2&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-19 N1 - Date created - 1998-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. AN - 80058112; 9699688 AB - Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence. The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly. In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding. In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans. JF - The American journal of psychiatry AU - Heinz, A AU - Higley, J D AU - Gorey, J G AU - Saunders, R C AU - Jones, D W AU - Hommer, D AU - Zajicek, K AU - Suomi, S J AU - Lesch, K P AU - Weinberger, D R AU - Linnoila, M AD - Clinical Brain Disorders Branch, NIMH Neuroscience Center at St. Elizabeths Hospital, Washington, DC, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1023 EP - 1028 VL - 155 IS - 8 SN - 0002-953X, 0002-953X KW - Serotonin KW - 333DO1RDJY KW - 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane KW - 4H1Z7121WS KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Alcoholism -- etiology KW - Tomography, Emission-Computed, Single-Photon KW - Cocaine -- analogs & derivatives KW - Brain Stem -- metabolism KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Adult KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Brain Stem -- physiopathology KW - Male KW - Serotonin -- physiology KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Aggression -- physiology KW - Brain -- physiopathology KW - Alcoholic Intoxication -- physiopathology KW - Aggression -- psychology KW - Macaca mulatta -- metabolism KW - Behavior, Animal -- physiology KW - Macaca mulatta -- cerebrospinal fluid KW - Serotonin -- metabolism KW - Alcoholic Intoxication -- metabolism KW - Serotonin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80058112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+association+between+alcohol+intoxication%2C+aggression%2C+and+serotonin+transporter+availability+in+nonhuman+primates.&rft.au=Heinz%2C+A%3BHigley%2C+J+D%3BGorey%2C+J+G%3BSaunders%2C+R+C%3BJones%2C+D+W%3BHommer%2C+D%3BZajicek%2C+K%3BSuomi%2C+S+J%3BLesch%2C+K+P%3BWeinberger%2C+D+R%3BLinnoila%2C+M&rft.aulast=Heinz&rft.aufirst=A&rft.date=1998-08-01&rft.volume=155&rft.issue=8&rft.spage=1023&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 - 1998-08-17 N1 - Date created - 1998-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer. AN - 80057451; 9699666 AB - The 5-year survival rate for women with metastatic breast cancer is only 25-30%; thus, the need to improve treatment is apparent. Overexpression of insulin-like growth factor-I receptor (IGF-IR) correlates with poor prognosis and local recurrence. In this study, we addressed whether functional impairment of IGF-IR affects adhesion, invasion, and metastasis of breast cancer. Impairment of IGF-IR function was achieved by transfecting a dominant negative form of the receptor, termed 486stop, into MDA-MB-435 metastatic breast cancer cells. The protein product of 486stop is secreted extracellularly, resulting in a bystander effect. Cellular adhesion to laminin and collagen was inhibited 94 and 88%, respectively. Furthermore, 486stop inhibited insulin-like growth factor-I-stimulated invasion through collagen IV by 75%. The dominant negative receptor was secreted, as evidenced by the observation that MDA-MB-435 and MDA-MB-231 cells were prevented from binding to laminin by 90% when treated with conditioned medium (CM) from 486stop-transfected cells. CM also inhibited the invasion of MDA-MB-231 cells across collagen IV by 80%. Finally, CM made MDA-MB-231 cells 30% more sensitive to Taxol-induced cell death. Growth in soft agar was suppressed by 486stop, but growth in monolayer was unaffected. When injected into the mammary fat pad, 486stop did not significantly suppress growth of the primary tumor, but metastasis to the lungs, livers, lymph nodes, and lymph vessels was significantly decreased compared to the vector control. In conclusion, inhibition of IGF-IR resulted in suppression of adhesion, invasion, and metastasis, providing a mechanistic rationale for targeting IGF-IR in the treatment of metastatic breast cancer. JF - Cancer research AU - Dunn, S E AU - Ehrlich, M AU - Sharp, N J AU - Reiss, K AU - Solomon, G AU - Hawkins, R AU - Baserga, R AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 3353 EP - 3361 VL - 58 IS - 15 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Codon KW - Culture Media, Conditioned KW - Laminin KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Collagen KW - 9007-34-5 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Neoplasm Invasiveness KW - Insulin-Like Growth Factor I -- physiology KW - Laminin -- metabolism KW - Cell Adhesion -- physiology KW - Collagen -- metabolism KW - Humans KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Cell Division -- physiology KW - Paclitaxel -- pharmacology KW - Precipitin Tests KW - Signal Transduction -- physiology KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Point Mutation KW - Neoplasm Metastasis KW - Female KW - Breast Neoplasms -- genetics KW - Receptor, IGF Type 1 -- physiology KW - Breast Neoplasms -- pathology KW - Receptor, IGF Type 1 -- genetics KW - Breast Neoplasms -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80057451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dominant+negative+mutant+of+the+insulin-like+growth+factor-I+receptor+inhibits+the+adhesion%2C+invasion%2C+and+metastasis+of+breast+cancer.&rft.au=Dunn%2C+S+E%3BEhrlich%2C+M%3BSharp%2C+N+J%3BReiss%2C+K%3BSolomon%2C+G%3BHawkins%2C+R%3BBaserga%2C+R%3BBarrett%2C+J+C&rft.aulast=Dunn&rft.aufirst=S&rft.date=1998-08-01&rft.volume=58&rft.issue=15&rft.spage=3353&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 - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability. AN - 80055488; 9697699 AB - The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes. Deletion or inactivation of both RB alleles is an essential, rate-limiting step in the formation of retinoblastoma and osteosarcoma that arise in families that carry mutant RB (ref. 2). RB inactivation is also found in other human tumours. Whereas loss of RB function is associated with the loss of cellular proliferative control, introduction of a wild-type RB can suppress cell growth and tumorigenicity. Thus, identification of factors that interfere with and/or control the function of the RB protein is critical for understanding both cell-cycle control and oncogenesis. Here we describe a new gene, Bog (for B5T over-expressed gene), which was identified and shown to be overexpressed in several transformed rat liver epithelial (RLE) cell lines resistant to the growth-inhibitory effect of TGF-beta1, as well as in primary human liver tumours. The Bog protein shares homology with other retinoblastoma-binding proteins and contains the Rb-binding motif LXCXE. Using the yeast two-hybrid system and co-immunoprecipitation, we demonstrated that Bog binds to Rb. In vivo, Bog/Rb complexes do not contain E2F-1, and Bog can displace E2F-1 from E2F-1/Rb complexes in vitro. Overexpression of Bog in normal RLE cells conferred resistance to the growth-inhibitory effect of TGF-beta1. Furthermore, normal RLE cells are rapidly transformed when Bog is continuously overexpressed and form hepatoblastoma-like tumours when transplanted into nude mice. These data suggest that Bog may be important in the transformation process, in part due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta1 through interaction with Rb and the subsequent displacement of E2F-1. JF - Nature genetics AU - Woitach, J T AU - Zhang, M AU - Niu, C H AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 371 EP - 374 VL - 19 IS - 4 SN - 1061-4036, 1061-4036 KW - Arid4a protein, mouse KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - E2F1 Transcription Factor KW - E2F1 protein, human KW - E2f1 protein, mouse KW - E2f1 protein, rat KW - FFA-1 protein, Xenopus KW - Intracellular Signaling Peptides and Proteins KW - Neoplasm Proteins KW - RBBP9 protein, human KW - RNA, Messenger KW - RNA, Neoplasm KW - Rbbp9 protein, mouse KW - Rbbp9 protein, rat KW - Retinoblastoma Protein KW - Retinoblastoma-Binding Protein 1 KW - Transcription Factor DP1 KW - Transcription Factors KW - Transforming Growth Factor beta KW - Xenopus Proteins KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Liver -- cytology KW - Transcription Factors -- metabolism KW - Humans KW - Liver -- metabolism KW - Mice, Nude KW - RNA, Neoplasm -- analysis KW - Rats KW - Tumor Cells, Cultured KW - Carcinoma, Hepatocellular -- pathology KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Cell Division KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Mice KW - Organ Specificity KW - Cloning, Molecular KW - Epithelial Cells KW - Carcinoma, Hepatocellular -- chemistry KW - Cell Line KW - Carrier Proteins -- metabolism KW - Cell Cycle -- physiology KW - Carrier Proteins -- genetics KW - Retinoblastoma Protein -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- isolation & purification KW - Cell Transformation, Neoplastic KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80055488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+retinoblastoma-binding+protein+that+affects+cell-cycle+control+and+confers+transforming+ability.&rft.au=Woitach%2C+J+T%3BZhang%2C+M%3BNiu%2C+C+H%3BThorgeirsson%2C+S+S&rft.aulast=Woitach&rft.aufirst=J&rft.date=1998-08-01&rft.volume=19&rft.issue=4&rft.spage=371&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 - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF025819; GENBANK; AF039564 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of cyclin G1 during murine hepatic regeneration following Dipin-induced DNA damage. AN - 80053390; 9696022 AB - Cyclin G1 has been linked to both positive and negative growth regulation. The expression of cyclin G1 is induced by transforming growth factor beta1 and p53, as well as by multiple mitogenic stimuli in mammalian cells in culture. However, the physiological role of cyclin G1 remains unclear. To examine the cell-cycle regulation of cyclin G1 in vivo, two models of coordinated cell proliferation induced by partial hepatectomy (PH) in the presence or absence of DNA damage were used. To introduce DNA damage, mice were treated with the alkylating drug, 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin) 2 hours before PH. Cell-cycle progression was monitored by 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA, the frequency of mitoses, the expression of cell-cycle control genes, and by flow cytometry. Dipin treatment resulted in cell-cycle arrest at the G2/M boundary without affecting G0/G1 and G1/S transitions. While the hepatocytes progressively entered G2 phase arrest, the cyclin G1 mRNA and protein levels increased more than five- and eightfold, respectively. Cyclin G1 had a nuclear localization in all interphase cells with clear absence from nucleoli. In contrast, during mitosis, cyclin G1 was undetectable by immunohistochemistry. Taken together, our data provide evidence for a putative role of cyclin G1 in G2/M checkpoint control. JF - Hepatology (Baltimore, Md.) AU - Jensen, M R AU - Factor, V M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 537 EP - 546 VL - 28 IS - 2 SN - 0270-9139, 0270-9139 KW - Aziridines KW - 0 KW - Ccnb1 protein, mouse KW - Ccng1 protein, mouse KW - Cyclin A KW - Cyclin B KW - Cyclin B1 KW - Cyclin G KW - Cyclin G1 KW - Cyclins KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - dipin KW - L16KNK08VM KW - Index Medicus KW - Cyclin A -- metabolism KW - Mice, Inbred Strains KW - Animals KW - CDC2 Protein Kinase -- metabolism KW - Kinetics KW - Cyclin B -- metabolism KW - Mice KW - Tissue Distribution KW - Male KW - Liver -- cytology KW - Liver -- drug effects KW - DNA Damage KW - Liver -- metabolism KW - Cyclins -- metabolism KW - Liver Regeneration -- physiology KW - Aziridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80053390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+cyclin+G1+during+murine+hepatic+regeneration+following+Dipin-induced+DNA+damage.&rft.au=Jensen%2C+M+R%3BFactor%2C+V+M%3BThorgeirsson%2C+S+S&rft.aulast=Jensen&rft.aufirst=M&rft.date=1998-08-01&rft.volume=28&rft.issue=2&rft.spage=537&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis. AN - 80051134; 9687573 AB - The aryl hydrocarbon receptor (AHR) is believed to mediate many of the toxic, carcinogenic, and teratogenic effects of environmental contaminants such as dioxins, polycyclic aromatic hydrocarbons, and polyhalogenated biphenyls. Ligands for the AHR have been shown to influence cell proliferation, differentiation, and apoptosis, but the mechanism by which the AHR affects the cell cycle is not known. Increased levels of mature transforming growth factor-beta (TGFbeta) has been correlated with reduced cell proliferation and increased rates of apoptosis and fibrosis. Based on the increase in portal fibrosis and small liver size observed in AHR-null (Ahr-/-) mice, the relationship between TGFbeta expression and apoptosis in this mouse line was analyzed. Livers from Ahr-/- mice had marked increase in active TGFbeta1 and TGFbeta3 proteins and elevated numbers of hepatocytes undergoing apoptosis compared with wild-type mice. Furthermore, increases in TGFbeta and apoptotic cells were found in the portal areas of the liver, where fibrosis is found in the Ahr-/- mice. In vitro, primary hepatocyte cultures from Ahr-/- mice exhibited a high number of cells in later stages of apoptosis and an elevated secretion of active TGFbeta into the media compared with cultures from wild-type mice, which have previously been shown to secrete only latent forms of the molecule. Conditioned media from Ahr-/- hepatocytes stimulated apoptosis in cultured hepatocytes from wild-type mice. Taken together, these findings suggest that the phenotypic abnormalities in Ahr-/- mice could be mediated in part by abnormal levels of active TGFbeta and altered cell cycle control. JF - Molecular pharmacology AU - Zaher, H AU - Fernandez-Salguero, P M AU - Letterio, J AU - Sheikh, M S AU - Fornace, A J AU - Roberts, A B AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 313 EP - 321 VL - 54 IS - 2 SN - 0026-895X, 0026-895X KW - Culture Media, Conditioned KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Mink KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Mice KW - Liver -- pathology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Liver -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80051134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+involvement+of+aryl+hydrocarbon+receptor+in+the+activation+of+transforming+growth+factor-beta+and+apoptosis.&rft.au=Zaher%2C+H%3BFernandez-Salguero%2C+P+M%3BLetterio%2C+J%3BSheikh%2C+M+S%3BFornace%2C+A+J%3BRoberts%2C+A+B%3BGonzalez%2C+F+J&rft.aulast=Zaher&rft.aufirst=H&rft.date=1998-08-01&rft.volume=54&rft.issue=2&rft.spage=313&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Side effects of morphine administration in cancer patients. AN - 80043961; 9691512 AB - According to the World Health Organization (WHO) guidelines, oral morphine is the first choice drug for treating moderate to severe cancer-related pain. The fear of the side effects caused by this drug and the scarce information about prevention and management of these effects are the main reasons for the underuse of morphine. The aim of this paper is to provide a review of the literature on the side effects most frequently present both in the titration phase and during chronic administration of oral morphine and to describe the appropriate treatment. JF - Cancer nursing AU - Vanegas, G AU - Ripamonti, C AU - Sbanotto, A AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 289 EP - 297 VL - 21 IS - 4 SN - 0162-220X, 0162-220X KW - Analgesics, Opioid KW - 0 KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Nursing KW - Administration, Oral KW - Humans KW - Pain -- etiology KW - Pain -- drug therapy KW - Morphine -- therapeutic use KW - Neoplasms -- complications KW - Morphine -- adverse effects KW - Analgesics, Opioid -- therapeutic use KW - Analgesics, Opioid -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80043961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nursing&rft.atitle=Side+effects+of+morphine+administration+in+cancer+patients.&rft.au=Vanegas%2C+G%3BRipamonti%2C+C%3BSbanotto%2C+A%3BDe+Conno%2C+F&rft.aulast=Vanegas&rft.aufirst=G&rft.date=1998-08-01&rft.volume=21&rft.issue=4&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Cancer+nursing&rft.issn=0162220X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of interferon-alpha in melanoma therapy: results from a randomized controlled trial. AN - 80039014; 9690541 AB - The objective of this study was to evaluate the neurologic and quality of life impact of low dose adjuvant interferon (IFN)-alpha immunotherapy in patients with malignant melanoma metastatic to regional lymph nodes after radical surgery. One hundred and thirteen patients were randomized to receive IFN-alpha, 3 x 10(6) IU three times weekly by subcutaneous injection for 36 months or until melanoma recurrence (IFN group), or to act as controls (CTR group). Seventy-five of these patients (66%) entered the toxicity study and underwent formal neurologic, neuropsychologic, psychologic, and quality of life assessments. Patients were assessed at baseline and after 1, 3, 6, and 12 months of follow-up. For each variable, maximum worsening of symptoms from baseline was considered as a response variable. The differences between the two groups regarding this variable were evaluated by means of the Hodges-Lehmann median unbiased point estimates and their 95% confidence interval. A significant degree of action tremor was found in eight patients in the IFN group and in none of the controls. No differences were found during psychiatric evaluation and for cognitive tests. There was a greater increase in anxiety in the IFN group on both trait and state anxiety. With regard to quality of life the analysis showed a significant worsening of at most one level on only three questionnaire items and on the fatigue scale. Neurologic dysfunction associated with IFN therapy was mild. Psychiatric symptoms and neuropsychologic impairment were not found. Levels of fatigue and anxiety were increased in the IFN group but without a sizable impact on quality of life measures. JF - Cancer AU - Caraceni, A AU - Gangeri, L AU - Martini, C AU - Belli, F AU - Brunelli, C AU - Baldini, M AU - Mascheroni, L AU - Lenisa, L AU - Cascinelli, N AD - Pain Therapy and Palliative Care Division, National Cancer Institute of Milan, Italy. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 482 EP - 489 VL - 83 IS - 3 SN - 0008-543X, 0008-543X KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Abridged Index Medicus KW - Index Medicus KW - Cognition Disorders -- etiology KW - Prospective Studies KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Anxiety -- etiology KW - Interferon-alpha -- adverse effects KW - Melanoma -- psychology KW - Brain -- drug effects KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80039014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Neurotoxicity+of+interferon-alpha+in+melanoma+therapy%3A+results+from+a+randomized+controlled+trial.&rft.au=Caraceni%2C+A%3BGangeri%2C+L%3BMartini%2C+C%3BBelli%2C+F%3BBrunelli%2C+C%3BBaldini%2C+M%3BMascheroni%2C+L%3BLenisa%2C+L%3BCascinelli%2C+N&rft.aulast=Caraceni&rft.aufirst=A&rft.date=1998-08-01&rft.volume=83&rft.issue=3&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human LINE-1 reverse transcriptase:effect of deletions outside the common reverse transcriptase domain. AN - 80028967; 9671814 AB - Heterologous expression of human LINE-1 ORF2 in yeast yielded a single polypeptide (Mr145 000) which reacted with specific antibodies and co-purified with a reverse transcriptase activity not present in the host cells. Various deletion derivatives of the ORF2 polypeptide were also synthesized. Reverse transcriptase assays using synthetic polynucleotides as template and primer revealed that ORF2 protein missing a significant portion of the N-terminal endonuclease domain still retains some activity. Deletion of the C-terminal cysteine-rich motif reduces activity only a small amount. Three non-overlapping deletions spanning 144 amino acids just N-terminal to the common polymerase domain of the ORF2 protein were analyzed for their effect on reverse transcriptase activity; this region contains the previously-noted conserved Z motif. The two deletions most proximal to the polymerase domain eliminate activity while the third, most-distal deletion had no effect. An inactive enzyme was also produced by substitution of two different amino acids in a highly-conserved octapeptide sequence, Z8, located within the region removed to make the deletion most proximal to the polymerase domain; substitution of a third had no effect. We conclude that the octapeptide sequence and neighboring amino acids in the Z region are essential for reverse transcriptase activity, while the endonuclease and cysteine-rich domains are not absolutely required. JF - Nucleic acids research AU - Clements, A P AU - Singer, M F AD - Laboratory of Biochemistry, National Cancer Institute, Building 37, Room 4A-01, Bethesda, MD 20892, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 3528 EP - 3535 VL - 26 IS - 15 SN - 0305-1048, 0305-1048 KW - DNA-Binding Proteins KW - 0 KW - L1Hs-encoded protein p40, human KW - 148349-28-4 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Animals KW - Open Reading Frames KW - Humans KW - Gene Expression KW - Transcription, Genetic KW - Substrate Specificity KW - Sequence Deletion KW - Mutagenesis KW - Binding Sites KW - DNA-Binding Proteins -- genetics KW - RNA-Directed DNA Polymerase -- metabolism KW - RNA-Directed DNA Polymerase -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80028967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+human+LINE-1+reverse+transcriptase%3Aeffect+of+deletions+outside+the+common+reverse+transcriptase+domain.&rft.au=Clements%2C+A+P%3BSinger%2C+M+F&rft.aulast=Clements&rft.aufirst=A&rft.date=1998-08-01&rft.volume=26&rft.issue=15&rft.spage=3528&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 - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] EMBO J. 1998 Jan 15;17(2):590-7 [9430649] Nucleic Acids Res. 1987 Mar 11;15(5):2251-60 [3562227] Mol Cell Biol. 1988 Jan;8(1):114-23 [2447482] Nature. 1988 Mar 10;332(6160):164-6 [2831458] Mol Cell Biol. 1988 Apr;8(4):1385-97 [2454389] Mol Gen Genet. 1988 Nov;214(3):533-40 [2851098] Q Rev Biol. 1989 Mar;64(1):1-30 [2469098] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6990-4 [1698287] EMBO J. 1990 Oct;9(10):3353-62 [1698615] Mol Cell Biol. 1990 Dec;10(12):6718-29 [1701022] Science. 1991 Dec 20;254(5039):1805-8 [1662412] Science. 1991 Dec 20;254(5039):1808-10 [1722352] Cancer Res. 1992 Feb 1;52(3):643-5 [1310068] Mol Biol Evol. 1991 Nov;8(6):835-56 [1663570] Science. 1992 Jun 26;256(5065):1783-90 [1377403] Nucleic Acids Res. 1992 Jun 25;20(12):3139-45 [1320255] Cancer. 1993 Apr 1;71(7):2383-6 [8384068] Biochem Biophys Res Commun. 1993 Mar 15;191(2):625-32 [8384847] Mol Cell Biol. 1993 Sep;13(9):5383-92 [8395003] Gene. 1993 Nov 15;133(2):273-7 [7693554] Cell. 1993 Dec 17;75(6):1071-81 [7505202] Hum Mol Genet. 1993 Oct;2(10):1697-702 [8268924] Mol Gen Genet. 1994 Mar;242(6):658-65 [7512193] Mol Cell Biol. 1994 Jul;14(7):4485-92 [7516468] Nat Genet. 1994 Jun;7(2):143-8 [7920631] EMBO J. 1996 Feb 1;15(3):630-9 [8599946] Trends Biochem Sci. 1996 Aug;21(8):283-5 [8772379] Cell. 1996 Nov 29;87(5):905-16 [8945517] Cell. 1996 Nov 29;87(5):917-27 [8945518] Curr Opin Genet Dev. 1996 Dec;6(6):743-8 [8994846] Nat Genet. 1997 May;16(1):37-43 [9140393] Science. 1997 Aug 15;277(5328):955-9 [9252327] Cell. 1997 Aug 22;90(4):785-95 [9288757] J Mol Biol. 1997 Aug 8;271(1):7-12 [9300051] EMBO J. 1997 Oct 1;16(19):6034-43 [9312060] EMBO J. 1997 Nov 3;16(21):6590-602 [9351839] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3875-9 [3012536] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - POU transcription factors control expression of CNS stem cell-specific genes. AN - 80026120; 9671582 AB - Multipotential stem cells throughout the developing central nervous system have common properties. Among these is expression of the intermediate filament protein nestin and the brain fatty acid binding protein (B-FABP). To determine if common mechanisms control transcription in CNS stem cells, the regulatory elements of these two genes were mapped in transgenic mice. A 257 basepair enhancer of the rat nestin gene is sufficient for expression throughout the embryonic neuroepithelium. This enhancer contains two sites bound by the class III POU proteins Brn-1, Brn-2, Brn-4, and Tst-1. Only one of the two POU sites is required for CNS expression. An adjacent hormone response element is necessary for expression in the dorsal midbrain and forebrain. The regulatory sites of the B-FABP gene are strikingly similar to those of the nestin gene. A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2. This site is essential for expression in most of the CNS. In addition, a hormone response element is necessary for forebrain expression. Both the nestin and B-FABP genes therefore depend on POU binding sites for general CNS expression, with hormone response elements additionally required for activity in the anterior CNS. These data indicate that regulation by POU proteins and hormone receptors is a general mechanism for CNS stem cell-specific transcription. JF - Development (Cambridge, England) AU - Josephson, R AU - Müller, T AU - Pickel, J AU - Okabe, S AU - Reynolds, K AU - Turner, P A AU - Zimmer, A AU - McKay, R D AD - Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-4157, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 3087 EP - 3100 VL - 125 IS - 16 SN - 0950-1991, 0950-1991 KW - Carrier Proteins KW - 0 KW - Fabp5 protein, mouse KW - Fabp7 protein, mouse KW - Fabp7 protein, rat KW - Fatty Acid-Binding Protein 7 KW - Fatty Acid-Binding Proteins KW - Intermediate Filament Proteins KW - Myelin P2 Protein KW - Neoplasm Proteins KW - Nerve Tissue Proteins KW - Nes protein, mouse KW - Nes protein, rat KW - Nestin KW - Transcription Factors KW - Index Medicus KW - Animals KW - DNA Mutational Analysis KW - Mice KW - Mutagenesis -- genetics KW - Histocytochemistry KW - Nerve Tissue Proteins -- genetics KW - Mice, Transgenic KW - Base Sequence KW - DNA Footprinting KW - Molecular Sequence Data KW - Enhancer Elements, Genetic -- genetics KW - Genes, Reporter KW - Promoter Regions, Genetic -- genetics KW - Binding Sites -- genetics KW - Transcription Factors -- physiology KW - Intermediate Filament Proteins -- genetics KW - Central Nervous System -- growth & development KW - Gene Expression Regulation, Developmental -- genetics KW - Carrier Proteins -- genetics KW - Stem Cells -- physiology KW - Myelin P2 Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=POU+transcription+factors+control+expression+of+CNS+stem+cell-specific+genes.&rft.au=Josephson%2C+R%3BM%C3%BCller%2C+T%3BPickel%2C+J%3BOkabe%2C+S%3BReynolds%2C+K%3BTurner%2C+P+A%3BZimmer%2C+A%3BMcKay%2C+R+D&rft.aulast=Josephson&rft.aufirst=R&rft.date=1998-08-01&rft.volume=125&rft.issue=16&rft.spage=3087&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 - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Manganese: a transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of parkinsonism. AN - 80025620; 9681949 AB - It has been suggested that transition metals such as iron and manganese produce oxidative injury to the dopaminergic nigrostriatal system. which may play a critical role in the pathogenesis of Parkinson's disease. Intranigral infusion of ferrous citrate (0 to 8.4 nmol, i.n.) acutely increased lipid peroxidation in the substantia nigra and dopamine turnover in the caudate nucleus. Subsequently, it caused a severe depletion of dopamine levels in the rat caudate nucleus. In contrast to iron's pro-oxidant effect, manganese (up to 30 nmol, i.n.) causes neither lipid peroxidation nor nigral injury/dopamine depletion. Manganese (1.05 to 4.2 nmol, i.n.) dose-dependently protected nigral neurons from iron-induced oxidative injury and dopamine depletion. Manganese also suppressed acute increase in dopamine turnover and contralateral turning behaviour induced by iron. In brain homogenates manganese (0 to 10 microM) concentration-dependently inhibited propagation of lipid peroxidation caused by iron (0 to 5 microM). Without the contribution of manganese-superoxide dismutase manganese was still effective in sodium azide and/or heat-pretreated brain homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate that iron and manganese are two transition metals mediating opposite effects in the nigrostriatal system, as pro-oxidant and antioxidant, respectively. In conclusion, intranigral infusion of iron, but not manganese, provides an animal model for studying the pathophysiological role of oxidant and oxidative stress in nigrostriatal degeneration and Parkinsonism. The present results further suggest that the atypical antioxidative properties of manganese may protect substantia nigra compacta neurons from iron-induced oxidative stress. JF - Neuroscience AU - Sziráki, I AU - Mohanakumar, K P AU - Rauhala, P AU - Kim, H G AU - Yeh, K J AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD 20892-1264, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1101 EP - 1111 VL - 85 IS - 4 SN - 0306-4522, 0306-4522 KW - Neuroprotective Agents KW - 0 KW - Hydroxyl Radical KW - 3352-57-6 KW - Manganese KW - 42Z2K6ZL8P KW - Iron KW - E1UOL152H7 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Caudate Nucleus -- cytology KW - Hydroxyl Radical -- metabolism KW - Brain -- drug effects KW - Dopamine -- physiology KW - Lipid Peroxidation -- drug effects KW - Superoxide Dismutase -- metabolism KW - Caudate Nucleus -- drug effects KW - Dopamine -- metabolism KW - Stereotyped Behavior -- drug effects KW - Mesencephalon -- cytology KW - Rats KW - Brain -- enzymology KW - Mesencephalon -- drug effects KW - Rats, Sprague-Dawley KW - Male KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease, Secondary -- metabolism KW - Parkinson Disease, Secondary -- chemically induced KW - Manganese -- pharmacology KW - Neostriatum -- drug effects KW - Oxidative Stress -- drug effects KW - Substantia Nigra -- drug effects KW - Neostriatum -- cytology KW - Substantia Nigra -- cytology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80025620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Manganese%3A+a+transition+metal+protects+nigrostriatal+neurons+from+oxidative+stress+in+the+iron-induced+animal+model+of+parkinsonism.&rft.au=Szir%C3%A1ki%2C+I%3BMohanakumar%2C+K+P%3BRauhala%2C+P%3BKim%2C+H+G%3BYeh%2C+K+J%3BChiueh%2C+C+C&rft.aulast=Szir%C3%A1ki&rft.aufirst=I&rft.date=1998-08-01&rft.volume=85&rft.issue=4&rft.spage=1101&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-01 N1 - Date created - 1998-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of single benzo[a]pyrene diol epoxide-deoxyguanosine adducts on the action of DNA polymerases in vitro. AN - 80006274; 9664121 AB - Neither Sequenase 2.0 nor Klenow fragment were able to extend 12-mer primers using the eight templates (16-mers) derived by placing each of the four isomeric benzo[a]pyrene diol epoxide-deoxyguanosine adducts at the 13th nucleotide from the 3'-end of two different sequence contexts. Using an 11-mer primer to get a running start did not overcome the adduct induced block of primer extension except for the Klenow fragment and one of the two sequence contexts, indicating primer extension is dependent on both the polymerase and sequence context. In this case, purine nucleoside triphosphates (dATP>dGTP) were incorporated opposite each of the four adducts. JF - International journal of oncology AU - Lipinski, L J AU - Ross, H L AU - Zajc, B AU - Sayer, J M AU - Jerina, D M AU - Dipple, A AD - Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 269 EP - 273 VL - 13 IS - 2 SN - 1019-6439, 1019-6439 KW - DNA Adducts KW - 0 KW - Oligonucleotides KW - benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA Polymerase I KW - EC 2.7.7.- KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Templates, Genetic KW - Oligonucleotides -- metabolism KW - Mutation KW - DNA Replication KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - Deoxyguanosine -- metabolism KW - DNA Polymerase I -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80006274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Effect+of+single+benzo%5Ba%5Dpyrene+diol+epoxide-deoxyguanosine+adducts+on+the+action+of+DNA+polymerases+in+vitro.&rft.au=Lipinski%2C+L+J%3BRoss%2C+H+L%3BZajc%2C+B%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Lipinski&rft.aufirst=L&rft.date=1998-08-01&rft.volume=13&rft.issue=2&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization of endogenous ARF6 to sites of cortical actin rearrangement and involvement of ARF6 in cell spreading. AN - 80002693; 9664047 AB - To study the function of the endogenous ARF6 GTP binding protein in cells, we generated an antibody which specifically recognizes ARF6, and not the other ARF proteins. Using this antibody, ARF6 was detected in all mouse organs tested and in a variety of cultured cell lines including RBL, MDCK, NRK, BHK, COS, and HeLa cells. In NRK cells, by immunofluorescence, ARF6 localized to the plasma membrane, especially at regions exhibiting membrane ruffling, and was also concentrated in a fine punctate distribution in the juxtanuclear region. This pattern of localization of the endogenous protein was similar to the localization of ARF6 when overexpressed in NRK, or HeLa, cells. Treatments which perturb cortical actin in NRK cells, such as replating of cells after trypsinization or treatment with phorbol ester, resulted in the recruitment of endogenous ARF6 to the regions of cortical actin rearrangement. ARF6 activation and subsequent membrane recycling was required for cell spreading activity since expression of the dominant-negative, GTP-binding defective mutant of ARF6, T27N, previously shown to inhibit ARF6-regulated membrane recycling, inhibited cell attachment and spreading in HeLa cells. Furthermore, phorbol ester treatment enhanced the cell spreading activities in NRK cells, and in HeLa cells, but was not observed in cells expressing T27N. Taken together, these observations support a role for endogenous ARF6 in modeling the plasma membrane and cortical actin cytoskeleton. JF - Journal of cell science AU - Song, J AU - Khachikian, Z AU - Radhakrishna, H AU - Donaldson, J G AD - Laboratory of Cell Biology, NHLBI, Bld 3, Room B1-22, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2257 EP - 2267 VL - 111 ( Pt 15) SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Cytochalasin D KW - 22144-77-0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Adhesion -- physiology KW - Humans KW - Organ Specificity KW - Amino Acid Sequence KW - Mice KW - Antibody Specificity KW - Transfection KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- chemistry KW - Cytochalasin D -- pharmacology KW - Actin Cytoskeleton KW - Cell Line KW - Cell Size -- physiology KW - Actins -- metabolism KW - GTP-Binding Proteins -- physiology KW - GTP-Binding Proteins -- analysis KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Localization+of+endogenous+ARF6+to+sites+of+cortical+actin+rearrangement+and+involvement+of+ARF6+in+cell+spreading.&rft.au=Song%2C+J%3BKhachikian%2C+Z%3BRadhakrishna%2C+H%3BDonaldson%2C+J+G&rft.aulast=Song&rft.aufirst=J&rft.date=1998-08-01&rft.volume=111+%28+Pt+15%29&rft.issue=&rft.spage=2257&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Naturally occurring mutations define a novel function of the hepatitis B virus core promoter in core protein expression. AN - 79995196; 9658127 AB - Functional analysis of naturally occurring hepatitis B virus (HBV) mutations is crucial in understanding their impact on disease. We have recently identified two mutations in the HBV core promoter of an HBV strain associated with fulminant hepatitis leading to highly (15-fold) enhanced replication as a result of increased viral encapsidation of pregenomic RNA into the core particles (T. F. Baumert et al., J. Clin. Invest. 98:2268-2276, 1996). Functional studies in an encapsidation assay had demonstrated that the increase in encapsidation was largely independent of pregenomic RNA transcription. In this study, we define the molecular mechanism whereby the two core promoter mutations (C to T at nucleotide [nt] 1768 and T to A at nt 1770) result in enhanced viral encapsidation and replication. The effect of these mutations leading to increased encapsidation is mediated through enhanced core protein synthesis (15-fold) by the mutant virus. The marked increase in core protein synthesis is largely a result of posttranscriptional or translational effect of the mutations because the mutations resulted in only a twofold increase in pregenomic RNA transcription. In addition, this effect appears to be selective for core expression since reverse transcriptase-polymerase expression was increased only twofold. trans-complementation analyses of HBV replication demonstrated that enhanced replication occurred only when the mutations were provided together with the core protein in trans, confirming the functional association of the core promoter mutations and core protein expression. In addition, the effect of the mutations appears to be quantitatively dependent on the strain background to which the mutations were introduced. Our study suggests that the HBV core promoter regulates core protein expression at both transcriptional and posttranscriptional levels. JF - Journal of virology AU - Baumert, T F AU - Marrone, A AU - Vergalla, J AU - Liang, T J AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 6785 EP - 6795 VL - 72 IS - 8 SN - 0022-538X, 0022-538X KW - Hepatitis B Core Antigens KW - 0 KW - Protein Precursors KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - Virus Replication KW - RNA-Directed DNA Polymerase -- biosynthesis KW - Protein Precursors -- metabolism KW - Tumor Cells, Cultured KW - Open Reading Frames KW - Humans KW - Genes, Viral KW - Mutagenesis KW - Hepatitis B Core Antigens -- genetics KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Viral KW - Hepatitis B virus -- genetics KW - Hepatitis B virus -- physiology KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79995196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Naturally+occurring+mutations+define+a+novel+function+of+the+hepatitis+B+virus+core+promoter+in+core+protein+expression.&rft.au=Baumert%2C+T+F%3BMarrone%2C+A%3BVergalla%2C+J%3BLiang%2C+T+J&rft.aulast=Baumert&rft.aufirst=T&rft.date=1998-08-01&rft.volume=72&rft.issue=8&rft.spage=6785&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 - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1993 Dec;13(12):7476-86 [8246965] Cell. 1993 Nov 19;75(4):653-60 [8242741] J Virol. 1994 Sep;68(9):5579-87 [7520092] Ann Intern Med. 1995 Feb 15;122(4):241-8 [7825758] Annu Rev Immunol. 1995;13:29-60 [7612225] Virology. 1995 Aug 1;211(1):144-56 [7645207] RNA. 1995 Jul;1(5):453-65 [7489507] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1065-70 [8577715] Hepatology. 1996 Aug;24(2):300-6 [8690396] J Virol. 1996 Sep;70(9):5845-51 [8709203] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8253-7 [8710856] J Clin Invest. 1996 Nov 15;98(10):2268-76 [8941643] Virology. 1996 Dec 15;226(2):269-80 [8955047] J Virol. 1996 Dec;70(12):8318-31 [8970951] J Virol. 1997 Feb;71(2):1058-71 [8995626] Nature. 1997 Jan 23;385(6614):357-61 [9002523] J Virol. 1997 Mar;71(3):2192-201 [9032353] Hepatology. 1997 Jun;25(6):1507-15 [9185776] Virology. 1997 Jul 7;233(2):374-81 [9217060] J Virol. 1997 Dec;71(12):9366-74 [9371596] Anal Biochem. 1967 Jul;20(1):114-49 [6034985] Intervirology. 1977;8(6):336-50 [893038] Nature. 1979 Oct 25;281(5733):646-50 [399327] Cell. 1982 Jun;29(2):403-15 [6180831] Nucleic Acids Res. 1984 Jan 25;12(2):857-72 [6694911] Nature. 1985 Oct 10-16;317(6037):489-95 [2995835] J Virol. 1987 Mar;61(3):904-11 [3806799] Annu Rev Biochem. 1987;56:651-93 [3039907] Nature. 1990 Apr 5;344(6266):552-5 [1690862] EMBO J. 1990 Oct;9(10):3389-96 [2209549] Cell. 1990 Dec 21;63(6):1357-63 [2261646] J Virol. 1991 Apr;65(4):1836-42 [2002544] N Engl J Med. 1991 Jun 13;324(24):1705-9 [2034247] Cell. 1992 Jan 24;68(2):177-180 [1733496] J Virol. 1992 May;66(5):3086-92 [1560538] J Virol. 1992 Jul;66(7):4073-84 [1602534] EMBO J. 1992 Nov;11(11):4153-8 [1396596] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9612-6 [1384058] Virology. 1992 Nov;191(1):237-45 [1413504] Virology. 1993 May;194(1):263-76 [8480422] J Virol. 1993 Jun;67(6):3254-63 [7684464] J Virol. 1993 Jul;67(7):3756-62 [8510204] J Virol. 1994 Mar;68(3):1651-9 [8107226] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice. AN - 73983327; 9762524 AB - To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment. JF - Experimental gerontology AU - Shefer, V I AU - Talan, M I AD - Laboratory of Behavioral Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 467 EP - 476 VL - 33 IS - 5 SN - 0531-5565, 0531-5565 KW - Anesthetics KW - 0 KW - Neuromuscular Nondepolarizing Agents KW - Urethane KW - 3IN71E75Z5 KW - Vecuronium Bromide KW - 7E4PHP5N1D KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Oxygen Consumption -- drug effects KW - Anesthetics -- pharmacology KW - Body Temperature -- drug effects KW - Body Weight -- physiology KW - Mice KW - Vecuronium Bromide -- pharmacology KW - Oxygen Consumption -- physiology KW - Mice, Inbred C57BL KW - Body Temperature -- physiology KW - Urethane -- pharmacology KW - Neuromuscular Nondepolarizing Agents -- pharmacology KW - Male KW - Aging -- physiology KW - Physical Conditioning, Animal -- physiology KW - Body Temperature Regulation -- physiology KW - Cold Temperature KW - Shivering -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73983327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology&rft.atitle=The+effect+of+exercise+training+in+cold+on+shivering+and+nonshivering+thermogenesis+in+adult+and+aged+C57BL%2F6J+mice.&rft.au=Shefer%2C+V+I%3BTalan%2C+M+I&rft.aulast=Shefer&rft.aufirst=V&rft.date=1998-08-01&rft.volume=33&rft.issue=5&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Experimental+gerontology&rft.issn=05315565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The eosinophil ribonucleases. AN - 73970978; 9760988 AB - The eosinophil ribonucleases, eosinophilderived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3) are two closely related proteins with intriguing functional and evolutionary properties. While both EDN and ECP maintain the structural and catalytic residues typical of the RNase A superfamily, the role of ribonuclease activity in the physiologic function of these proteins remains unclear. The biochemistry and physiology of EDN, ECP and the recently discovered ribonuclease k6 (RNase 6) will be reviewed in this chapter. JF - Cellular and molecular life sciences : CMLS AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hr2k@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 795 EP - 803 VL - 54 IS - 8 SN - 1420-682X, 1420-682X KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - History of medicine KW - Phylogeny KW - Animals KW - History, 20th Century KW - Humans KW - Molecular Sequence Data KW - History, 19th Century KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Ribonucleases -- history KW - Ribonucleases -- physiology KW - Eosinophils -- enzymology KW - Ribonucleases -- chemistry KW - Eosinophils -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73970978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+eosinophil+ribonucleases.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-08-01&rft.volume=54&rft.issue=8&rft.spage=795&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine use early in treatment predicts outcome in a behavioral treatment program. AN - 73952175; 9735588 AB - In this evaluation of baseline drug use as a predictor of treatment outcome, cocaine use during a 5-week baseline was compared in methadone maintenance patients who had or = 5 (n = 9) weeks of abstinence during an experimental cocaine abstinence reinforcement treatment. Cocaine use was evaluated at the 1st and last visit and the 1st and last week of baseline and as a mean across the 5-week baseline treatment; response was calculated as a mean across 12 weeks of experimental treatment. Those who had successful outcomes (abstainers) used significantly less cocaine in the 5-week baseline than those with less successful outcomes (nonabstainers). Differences in cocaine use were not evident in the 1st baseline visit or week, but the abstainers used significantly less cocaine in the last visit and week of baseline compared with the nonabstainers. Cocaine use during baseline provided critical predictors of response to the experimental treatment. JF - Journal of consulting and clinical psychology AU - Preston, K L AU - Silverman, K AU - Higgins, S T AU - Brooner, R K AU - Montoya, I AU - Schuster, C R AU - Cone, E J AD - Intramural Research Program, National Institute on Drug Abuse (NIDA), Baltimore, Maryland 21224, USA. kpreston@intra.nida.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 691 EP - 696 VL - 66 IS - 4 SN - 0022-006X, 0022-006X KW - Narcotics KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Methadone -- therapeutic use KW - Forecasting -- methods KW - Humans KW - Adult KW - Treatment Outcome KW - Opioid-Related Disorders -- rehabilitation KW - Middle Aged KW - Longitudinal Studies KW - Male KW - Female KW - Narcotics -- adverse effects KW - Narcotics -- administration & dosage KW - Cocaine-Related Disorders -- therapy KW - Behavior Therapy -- methods KW - Cocaine-Related Disorders -- complications KW - Cocaine -- adverse effects KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73952175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+consulting+and+clinical+psychology&rft.atitle=Cocaine+use+early+in+treatment+predicts+outcome+in+a+behavioral+treatment+program.&rft.au=Preston%2C+K+L%3BSilverman%2C+K%3BHiggins%2C+S+T%3BBrooner%2C+R+K%3BMontoya%2C+I%3BSchuster%2C+C+R%3BCone%2C+E+J&rft.aulast=Preston&rft.aufirst=K&rft.date=1998-08-01&rft.volume=66&rft.issue=4&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Journal+of+consulting+and+clinical+psychology&rft.issn=0022006X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-09 N1 - Date created - 1998-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive effects of the aromatase inhibitor vorozole (R 83842) in the methylnitrosourea-induced mammary cancer model. AN - 73949832; 9744527 AB - The chemopreventive activity of the highly specific nonsteroidal aromatase inhibitor, vorozole, was examined in the methylnitrosourea (MNU)-induced rat model of mammary carcinogenesis. Various doses of vorozole (0.08-1.25 mg/kg body wt/day) were administered daily (by gavage) to female Sprague-Dawley rats starting at 43 days of age. Seven days later, the rats were given a single i.v. dose of MNU (50 mg/kg body wt). Rats were continually treated with vorozole until the end of the experiment (120 days post-MNU). Vorozole caused a dose dependent inhibition of mammary cancer multiplicity. The highest dose of vorozole (1.25 mg/kg body wt/day) decreased cancer multiplicity by approximately 90%, and simultaneously decreased cancer incidence from 100 to 44%. The next two highest doses of vorozole (0.63 and 0.31 mg/kg body wt/day) inhibited MNU-induced mammary cancer multiplicity by 70-80%. Even the two lowest doses of vorozole (0.16 and 0.08 mg/kg body wt/ day) decreased cancer multiplicity -50%. Serum level determinations were performed on a variety of endpoints at either 4 or 24 h following the last dose of vorozole. Insulin-like growth factor (IGF)-1 levels were slightly, but significantly, increased by vorozole treatment. Vorozole induced striking increases in serum testosterone levels at 4 h at all the dose levels employed. Testosterone levels were significantly elevated over controls at 24 h in rats given the lower doses of vorozole (0.08-0.31 mg/kg body wt/day), but were significantly lower than in rats administered the higher doses of vorozole (0.63 or 1.25 mg/kg body wt/ day). This result presumably reflects the limited half-life of vorozole in rats. In a second series of experiments, the effects of limited duration of dosing with vorozole (2.5 mg/kg body wt/day) or intermittent dosing with vorozole were determined. Treatment of rats with vorozole for limited time periods, from 3 days post-MNU administration until 30 or 60 days post-MNU treatment, resulted in significant delays in the time to appearance of palpable cancers. However, these limited treatments did not greatly affect the overall incidence or multiplicity of mammary cancers when compared with the MNU controls at the end of the study (150 days post-MNU). Finally, the effects of intermittent dosing with vorozole (2.5 mg/kg body wt/day) were examined. Rats were administered cycles of vorozole daily for a period of 3 weeks followed by treatment with the vorozole vehicle for the next 3 weeks (total of four cycles). Although this intermittent treatment did inhibit the appearance of new tumors during each of the periods that vorozole was administered, it did not cause regression of palpable cancers. JF - Carcinogenesis AU - Lubet, R A AU - Steele, V E AU - DeCoster, R AU - Bowden, C AU - You, M AU - Juliana, M M AU - Eto, I AU - Kelloff, G J AU - Grubbs, C J AD - NCI-DCP, Bethesda, MD 20892, USA. lubetr@dcpcepn.nci.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1345 EP - 1351 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - Aromatase Inhibitors KW - Carcinogens KW - Triazoles KW - vorozole KW - 1E2S9YXV2A KW - Testosterone KW - 3XMK78S47O KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Animals KW - Drug Screening Assays, Antitumor KW - Drug Administration Schedule KW - Genes, ras -- drug effects KW - Insulin-Like Growth Factor I -- metabolism KW - Estrus -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Estradiol -- blood KW - Testosterone -- blood KW - Body Weight -- drug effects KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Antineoplastic Agents -- administration & dosage KW - Triazoles -- therapeutic use KW - Mammary Neoplasms, Experimental -- prevention & control KW - Antineoplastic Agents -- therapeutic use KW - Mammary Neoplasms, Experimental -- blood KW - Triazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73949832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pigment+epithelium-derived+factor+%28PEDF%29+differentially+protects+immature+but+not+mature+cerebellar+granule+cells+against+apoptotic+cell+death.&rft.au=Araki%2C+T%3BTaniwaki%2C+T%3BBecerra%2C+S+P%3BChader%2C+G+J%3BSchwartz%2C+J+P&rft.aulast=Araki&rft.aufirst=T&rft.date=1998-07-01&rft.volume=53&rft.issue=1&rft.spage=7&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of 99mTc-mercaptoacetyltriglycine (MAG3)-biocytin hepatobiliary scintigraphy to study the protective effect of a synthetic enzyme inhibitor on acute hepatotoxicity in mice. AN - 73928830; 9751424 AB - Recent data suggest that inhibitors of ethanol-inducible cytochrome P450 (CYP2E1) can protect the liver from injury caused by various substrates of CYP2E1. In this study, we measured the protective effect of isopropyl-2-(1,3-dithioetane-2-ylidene)-2[N-(4-methylthiazol -2-yl)-carbamoyl]acetate (YH439), a transcriptional inhibitor of CYP2E1, against carbon tetrachloride (CCl4)-induced hepatotoxicity by using various conventional methods and dynamic scintigraphy with 99mTc-mercaptoacetyltriglycine (MAG3)-biocytin, a recently developed scintigraphic agent. Balb/c mice were pretreated with two doses of YH439 (50 or 150 mg/kg per day) at 48 h and 24 h and one dose of CCl4 (0.25 mL/kg) at 18 h before scintigraphy. The results were compared with those of two other groups, one that received CCl4 but not YH439, and the other that received neither (control). Scintigraphic images were acquired continuously at 15-sec intervals for 30 min. Pharmacokinetic parameters, such as peak liver/heart ratio (r(max)), peak liver uptake time (t(max)), and hepatic half-clearance time (HCT), were obtained from time-activity curves derived from regions-of-interest (ROI) over the liver and the heart. Acute administration of CCl4 alone caused centrilobular necrosis and serum transaminase levels to rise more than 5 times higher than those of the control group. Pharmacokinetic parameters also changed significantly from those of the control group. Administration of YH439 prevented centrilobular necrosis and significantly improved pharmacokinetic parameters. This study demonstrates for the first time that hepatobiliary scintigraphy can be used to study in vivo biochemistry of the CYP2E1 inhibitor (YH439) against liver toxicity. JF - Nuclear medicine and biology AU - Kim, M K AU - Song, B J AU - Seidel, J AU - Soh, Y AU - Jeong, K S AU - Kim, I S AU - Kobayashi, H AU - Green, M V AU - Carrasquillo, J A AU - Paik, C H AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 561 EP - 568 VL - 25 IS - 6 SN - 0969-8051, 0969-8051 KW - Cytochrome P-450 CYP2E1 Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Organotechnetium Compounds KW - Radiopharmaceuticals KW - Thiazoles KW - YH 439 KW - technetium Tc 99m MAG3-biocytin KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Necrosis KW - Drug Interactions KW - Chemical and Drug Induced Liver Injury KW - Carbon Tetrachloride -- antagonists & inhibitors KW - Mice KW - Mice, Inbred BALB C KW - Cytochrome P-450 CYP2E1 -- genetics KW - Carbon Tetrachloride -- toxicity KW - Female KW - Radionuclide Imaging KW - Liver -- pathology KW - Enzyme Inhibitors -- therapeutic use KW - Biliary Tract -- diagnostic imaging KW - Liver -- drug effects KW - Lysine -- analogs & derivatives KW - Liver Diseases -- diagnostic imaging KW - Liver Diseases -- prevention & control KW - Thiazoles -- therapeutic use KW - Liver -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73928830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nuclear+medicine+and+biology&rft.atitle=Use+of+99mTc-mercaptoacetyltriglycine+%28MAG3%29-biocytin+hepatobiliary+scintigraphy+to+study+the+protective+effect+of+a+synthetic+enzyme+inhibitor+on+acute+hepatotoxicity+in+mice.&rft.au=Kim%2C+M+K%3BSong%2C+B+J%3BSeidel%2C+J%3BSoh%2C+Y%3BJeong%2C+K+S%3BKim%2C+I+S%3BKobayashi%2C+H%3BGreen%2C+M+V%3BCarrasquillo%2C+J+A%3BPaik%2C+C+H&rft.aulast=Kim&rft.aufirst=M&rft.date=1998-08-01&rft.volume=25&rft.issue=6&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Nuclear+medicine+and+biology&rft.issn=09698051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-30 N1 - Date created - 1998-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Race/ethnicity differences in the prevalence of noise-induced hearing loss in a group of metal fabricating workers. AN - 73922006; 9729747 AB - The National Institute of Occupational Safety and Health rates noise-induced hearing loss as one of the top 10 work-related problems, involving at least 11 million workers. This retrospective study examines the differences between pure-tone hearing loss and race/ethnicity in 216 white and 70 non-white male metal fabricating workers. Significant variables upon univariate analysis found to be associated with race/ethnicity were mean years of employment and proportion of time worked without hearing protection. Among whites, the permanent threshold average for 1, 2, 3 and 5 kHz was 25.99 dB, compared with 17.71 dB in non-whites (P < 0.01). Backwards stepwise regression indicated that race/ethnicity, after being adjusted for years of employment, was the major-effect variable. The results of this study suggest that occupational noise exposure alone does not alone account for the racial hearing differences. JF - Journal of occupational and environmental medicine AU - Ishii, E K AU - Talbott, E O AD - Epidemiology, Statistics and Data System Branch, National Institute on Deafness and other Communication Disorders, National Institute of Health, Bethesda, Md., USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 661 EP - 666 VL - 40 IS - 8 SN - 1076-2752, 1076-2752 KW - Index Medicus KW - Regression Analysis KW - Age Factors KW - Audiometry, Pure-Tone KW - Humans KW - Chi-Square Distribution KW - Adult KW - Surveys and Questionnaires KW - Retrospective Studies KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Prevalence KW - Occupational Diseases -- ethnology KW - Hearing Loss, Noise-Induced -- ethnology KW - Metallurgy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73922006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+medicine&rft.atitle=Race%2Fethnicity+differences+in+the+prevalence+of+noise-induced+hearing+loss+in+a+group+of+metal+fabricating+workers.&rft.au=Ishii%2C+E+K%3BTalbott%2C+E+O&rft.aulast=Ishii&rft.aufirst=E&rft.date=1998-08-01&rft.volume=40&rft.issue=8&rft.spage=661&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-10 N1 - Date created - 1998-12-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in kinetics of induction and reversibility of TCDD-induced changes in cell proliferation and CYP1A1 expression in female Sprague-Dawley rat liver. AN - 73920008; 9744539 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent tumor promoter in two-stage initiation-promotion models and induces cell proliferation and development of enzyme-altered hepatic foci. It is believed that increased cell proliferation is a necessary step in carcinogenesis. Therefore, the analysis of the effect of TCDD on cell proliferation in rat liver may aid in the understanding of the mechanism of hepatocarcinogenesis induced by TCDD. The aim of this study was to investigate the time course and reversibility of cell proliferation in non-initiated and diethylnitrosamine-initiated female rats exposed biweekly to a daily averaged dose of 125 ng TCDD/kg/day for up to 60 weeks. In addition we evaluated the suitability of different dose metrics for the evaluation of TCDD-induced changes in cell proliferation and CYP1A1 enzyme induction. Cell proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into hepatocytes undergoing replicative DNA synthesis. Mean BrdU labeling indices in TCDD-treated animals were not increased over controls after 14 weeks exposure, but were increased 8- and 2-fold after 30 and 60 weeks' treatment respectively, despite similar liver levels of TCDD at all these times (23-30 p.p.b.). In comparison, CYP1A1 activity, as measured by ethoxyresorufin deethylase activity, was significantly induced at all times points analyzed. Sixteen weeks following cessation of TCDD treatment, labeling indices were still significantly elevated over controls, but after 30 weeks of withdrawal, labeling indices were no different from controls, indicating that TCDD-induced changes in cell proliferation were reversible. Dosimetric analysis indicated that rat liver tissue burden was suitable for prediction of CYP1A1 expression but not cell proliferation and that the area under the curve was unsuitable for prediction of both TCDD-induced changes in CYP1A1 expression and cell proliferation. JF - Carcinogenesis AU - Walker, N J AU - Miller, B D AU - Kohn, M C AU - Lucier, G W AU - Tritscher, A M AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. walker3@niehs.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1427 EP - 1435 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - ROC Curve KW - Cell Division -- drug effects KW - Enzyme Induction KW - Female KW - Organ Size -- drug effects KW - Bromodeoxyuridine -- metabolism KW - Liver -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Polychlorinated Dibenzodioxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73920008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+kinetics+of+induction+and+reversibility+of+TCDD-induced+changes+in+cell+proliferation+and+CYP1A1+expression+in+female+Sprague-Dawley+rat+liver.&rft.au=Walker%2C+N+J%3BMiller%2C+B+D%3BKohn%2C+M+C%3BLucier%2C+G+W%3BTritscher%2C+A+M&rft.aulast=Walker&rft.aufirst=N&rft.date=1998-08-01&rft.volume=19&rft.issue=8&rft.spage=1427&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of hepatic CYP1A in channel catfish increases binding of 2-aminoanthracene to DNA in vitro and in vivo. AN - 73914562; 9744548 AB - Data are presented from in vitro and in vivo studies that indicate cytochrome P4501A (CYP1A) in channel catfish (Ictalurus punctatus) hepatic tissue activates 2-amino-anthracene (AA) to a reactive metabolite that binds to DNA. Channel catfish were injected i.p. with vehicle or 10 mg/kg beta-naphthoflavone (betaNF) on two consecutive days. Two days after the final injection of vehicle or betaNF, vehicle or [3H]AA was injected i.p. at 10 mg/kg, creating four different treatments: vehicle only, betaNF only, [3H]AA only, and betaNF/[3H]AA. Hepatic tissue was examined for CYP1A-associated ethoxyresorufin-O-de-ethylase (EROD) activity, and for DNA adducts at 1, 2, 4 and 7 days following administration of vehicle or [3H]AA. Hepatic EROD activity in betaNF-treated fish was 17-fold higher at day 0 and remained significantly greater than untreated animals for the 7-day experiment. Hepatic DNA adducts, as measured by tritium-associated DNA, ranged from 4.8 to 8.6 pmol/mg DNA in vehicle-pretreated fish injected with [3H]AA, but ranged from 12.6 to 22.7 pmol/mg DNA in betaNF-pretreated fish injected with [3H]AA. Thus, pretreatment with betaNF significantly increased binding of [3H]AA to hepatic DNA in vivo at all four times. Analysis by 32P-post-labeling and thin layer chromatography of hepatic DNA from channel catfish treated with AA revealed two major and several minor spots, which are indicative of DNA adduct formation. Hepatic microsomes from betaNF-pretreated fish were more effective at catalysing the binding of [3H]AA to DNA in vitro than were microsomes from non-treated fish. In addition, binding was decreased by the CYP1A inhibitor 3,3',4,4'-tetrachlorobiphenyl. Collectively, these data demonstrate that CYP1A is involved in the activation of AA in channel catfish. JF - Carcinogenesis AU - Watson, D E AU - Reichert, W AU - Di Giulio, R T AD - Ecotoxicology Laboratory, Nicholas School of the Environment, Duke University, Durham, NC 27708-0328, USA. watson2@niehs.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1495 EP - 1501 VL - 19 IS - 8 SN - 0143-3334, 0143-3334 KW - Anthracenes KW - 0 KW - Carcinogens KW - DNA Adducts KW - Enzyme Inhibitors KW - beta-Naphthoflavone KW - 6051-87-2 KW - 2-anthramine KW - 8240818JGU KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Ictaluridae KW - Biotransformation KW - beta-Naphthoflavone -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Induction KW - Time Factors KW - DNA Adducts -- metabolism KW - Carcinogens -- metabolism KW - Anthracenes -- metabolism KW - Microsomes, Liver -- metabolism KW - DNA -- metabolism KW - Microsomes, Liver -- drug effects KW - Cytochrome P-450 CYP1A1 -- metabolism KW - DNA -- drug effects KW - Cytochrome P-450 CYP1A1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73914562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+hepatic+CYP1A+in+channel+catfish+increases+binding+of+2-aminoanthracene+to+DNA+in+vitro+and+in+vivo.&rft.au=Watson%2C+D+E%3BReichert%2C+W%3BDi+Giulio%2C+R+T&rft.aulast=Watson&rft.aufirst=D&rft.date=1998-08-01&rft.volume=19&rft.issue=8&rft.spage=1495&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pediatric psychopharmacology and the interaction between drugs and the developing brain. AN - 73909353; 9729684 AB - With increasing frequency, psychotropic medications are being prescribed to young children, often for long periods of time. The interaction between psychotropics and the developing brain has not been systematically investigated in humans. Data collected from animals suggest that developing neurotransmitter systems can be exquisitely sensitive to early inhibition or stimulation by pharmacological agents, which can lead to permanent changes in adult life. Most of these data are collected from rodents, and their extrapolation to humans is difficult. More relevant models could be developed for instance using primates. In humans, the focus of research has traditionally been on the possible teratogenic effects of prenatal drug exposure. Recently introduced quantitative imaging techniques can offer new approaches to studying the effects of psychotropics on the developing brain. This research has clear implications for the safety and efficacy of psychopharmacologic drug in children. JF - Canadian journal of psychiatry. Revue canadienne de psychiatrie AU - Vitiello, B AD - Child and Adolescent Treatment and Preventive Intervention Research Branch, National Institute of Mental Health, Rockville, MD 20857, USA. bvitiell@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 582 EP - 584 VL - 43 IS - 6 SN - 0706-7437, 0706-7437 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Animals KW - Age Factors KW - Pediatrics KW - Humans KW - Child KW - Neural Pathways -- growth & development KW - Child Psychiatry KW - Neural Pathways -- drug effects KW - Psychotropic Drugs -- pharmacology KW - Brain -- drug effects KW - Child Development -- drug effects KW - Brain -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73909353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.atitle=Pediatric+psychopharmacology+and+the+interaction+between+drugs+and+the+developing+brain.&rft.au=Vitiello%2C+B&rft.aulast=Vitiello&rft.aufirst=B&rft.date=1998-08-01&rft.volume=43&rft.issue=6&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Canadian+journal+of+psychiatry.+Revue+canadienne+de+psychiatrie&rft.issn=07067437&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-26 N1 - Date created - 1999-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age-related changes in activation of mitogen-activated protein kinase cascades by oxidative stress. AN - 73896140; 9732053 AB - Oxidative stress is thought to play a critical role in aging and the pathogenesis of human disease. Molecular studies of both the physiologic function of oxidants and the deleterious consequences of exposure to oxidative stress have suggested that signal transduction cascades may be targeted by oxidants. Here, we review recent studies from this laboratory examining the molecular basis for the activation of mitogen-activated protein kinases by oxidative stress and the influence of these pathways on cellular fate. We examine the association between constitutive activation of extracellular signal-regulated kinase (ERK) and cancer, and discuss how such mechanisms may contribute to oxidant-induced skin carcinogenesis. We also address the relationship between a decline in activation of this same pathway and the aged phenotype. In this regard, we review evidence that a decrease in activation of ERK by growth factor correlates with a reduced proliferative capacity in the isolated rat hepatocyte model, and we provide new data indicating that the activation of the ERK pathway in response to oxidant stimuli is also decreased with age. Further evidence demonstrates that this alteration is associated with both a reduced mitogenic response and a decline in hepatocyte cell survival in response to oxidative stress. Finally, we provide perspective on how modulations in ERK signaling may interplay with other changes in signal transduction cascades in the aging process. JF - The journal of investigative dermatology. Symposium proceedings AU - Guyton, K Z AU - Gorospe, M AU - Wang, X AU - Mock, Y D AU - Kokkonen, G C AU - Liu, Y AU - Roth, G S AU - Holbrook, N J AD - Section on Gene Expression and Aging, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 23 EP - 27 VL - 3 IS - 1 SN - 1087-0024, 1087-0024 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Rats KW - Animals KW - Enzyme Activation KW - Humans KW - Signal Transduction KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Aging -- metabolism KW - Oxidative Stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73896140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology.+Symposium+proceedings&rft.atitle=Age-related+changes+in+activation+of+mitogen-activated+protein+kinase+cascades+by+oxidative+stress.&rft.au=Guyton%2C+K+Z%3BGorospe%2C+M%3BWang%2C+X%3BMock%2C+Y+D%3BKokkonen%2C+G+C%3BLiu%2C+Y%3BRoth%2C+G+S%3BHolbrook%2C+N+J&rft.aulast=Guyton&rft.aufirst=K&rft.date=1998-08-01&rft.volume=3&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=The+journal+of+investigative+dermatology.+Symposium+proceedings&rft.issn=10870024&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Triazolam-induced changes in alcoholic thought processes. AN - 73893399; 9725753 AB - This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively un-impaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg p.o.), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers. JF - Psychopharmacology AU - Weingartner, H J AU - Rawlings, R AU - George, D T AU - Eckardt, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-1250, USA. HerbW@NIH.GOV Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 311 EP - 317 VL - 138 IS - 3-4 SN - 0033-3158, 0033-3158 KW - Hypnotics and Sedatives KW - 0 KW - Triazolam KW - 1HM943223R KW - Index Medicus KW - Analysis of Variance KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Neuropsychological Tests KW - Male KW - Female KW - Memory -- drug effects KW - Triazolam -- pharmacology KW - Alcoholism -- physiopathology KW - Thinking -- drug effects KW - Hypnotics and Sedatives -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73893399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Triazolam-induced+changes+in+alcoholic+thought+processes.&rft.au=Weingartner%2C+H+J%3BRawlings%2C+R%3BGeorge%2C+D+T%3BEckardt%2C+M&rft.aulast=Weingartner&rft.aufirst=H&rft.date=1998-08-01&rft.volume=138&rft.issue=3-4&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-04 N1 - Date created - 1998-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the human dihydropyrimidine dehydrogenase gene. AN - 73889291; 9721209 AB - Dihydropyrimidine dehydrogenase (DPD) catabolizes endogenous pyrimidines and pyrimidine-based antimetabolite drugs. A deficiency in human DPD is associated with congenital thymine-uraciluria in pediatric patients and severe 5-fluorouracil toxicity in cancer patients. The dihydropyrimidine dehydrogenase gene (DPYD) was isolated, and its physical map and exon-intron organization were determined by analysis of P1, PAC, BAC, and YAC clones. The DPYD gene was found to contain 23 exons ranging in size from 69 bp (exon 15) to 961 bp (exon 23). A physical map derived from a YAC clone indicated that DPYD is at least 950 kb in length with 3 kb of coding sequence and an average intron size of about 43 kb. The previously reported 5' donor splice site mutation present in pediatric thymine-uraciluria and cancer patients can now be assigned to exon 14. All 23 exons were sequenced from a series of human DNA samples, and three point mutations were identified in three racial groups as G1601A (exon 13, Ser534Asn), A1627G (exon 13, Ile543Val), and G2194A (exon 18, Val732Ile). These studies, which have established that the DPYD gene is unusually large, lay a framework for uncovering new mutations that are responsible for thymine-uraciluria and toxicity to fluoropyrimidine drugs. Copyright 1998 Academic Press. JF - Genomics AU - Wei, X AU - Elizondo, G AU - Sapone, A AU - McLeod, H L AU - Raunio, H AU - Fernandez-Salguero, P AU - Gonzalez, F J AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 391 EP - 400 VL - 51 IS - 3 SN - 0888-7543, 0888-7543 KW - Neoplasm Proteins KW - 0 KW - RNA, Messenger KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymine KW - QR26YLT7LT KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Point Mutation -- genetics KW - Thymine -- urine KW - Humans KW - RNA, Messenger -- genetics KW - Introns -- genetics KW - Cloning, Molecular KW - Exons -- genetics KW - Leukocytes -- enzymology KW - RNA Splicing -- genetics KW - Polymerase Chain Reaction KW - Alleles KW - Fluorouracil -- toxicity KW - Restriction Mapping KW - Neoplasm Proteins -- genetics KW - Gene Dosage KW - Uracil -- urine KW - Oxidoreductases -- genetics KW - Oxidoreductases -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73889291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+human+dihydropyrimidine+dehydrogenase+gene.&rft.au=Wei%2C+X%3BElizondo%2C+G%3BSapone%2C+A%3BMcLeod%2C+H+L%3BRaunio%2C+H%3BFernandez-Salguero%2C+P%3BGonzalez%2C+F+J&rft.aulast=Wei&rft.aufirst=X&rft.date=1998-08-01&rft.volume=51&rft.issue=3&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pertussis toxin modification of PC12 cells lowers cytoskeletal F-actin and enhances norepinephrine secretion: involvement of protein kinase C and protein phosphatases. AN - 73885460; 9711351 AB - We have investigated the relationship between norepinephrine secretion and cytoskeletal F-actin in rat phaeochromocytoma PC12 cells. Stimulation of PC12 cells with extracellular ATP or high K+ caused both the release of norepinephrine and a decrease in F-actin. The stimulation of secretion and the decrease in F-actin were dependent on extracellular Ca2+. The addition of Ca2+ to digitonin-permeabilized PC12 cells also stimulated norepinephrine release and decreased F-actin. Modification of PC12 cells with pertussis toxin caused a 35% decrease in F-actin, and it enhanced ATP-stimulated and K+ stimulated norepinephrine secretion from intact cells and Ca(2+)-dependent norepinephrine secretion from permeabilized cells. After down regulation of protein kinase C, pertussis toxin still enhanced secretion, but it had no effect on F-actin indicating that the effect of pertussis toxin on F-actin was dependent on protein kinase C activity. The addition of okadaic acid, an inhibitor of serine/threonine protein phosphatases, to PC12 cells caused a decrease F-actin, but it had no effect on ATP-stimulated or K(+)-stimulated norepinephrine secretion. After down regulation of protein kinase C, much higher concentrations of okadaic acid were need to decrease F-actin. The similarity between the effects of pertussis toxin and low concentrations of okadaic acid suggest that the effect of pertussis toxin on cytoskeletal F-actin in PC12 cells may result from an inhibition of protein phosphatase 2A. JF - Archives of physiology and biochemistry AU - Chen, F AU - Wagner, P D AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. f.chen@ic.ac.uk Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 317 EP - 328 VL - 105 IS - 4 SN - 1381-3455, 1381-3455 KW - Actins KW - 0 KW - Virulence Factors, Bordetella KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - Potassium KW - RWP5GA015D KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Secretory Rate -- drug effects KW - Rats KW - Animals KW - Down-Regulation KW - Cell Membrane Permeability -- drug effects KW - Okadaic Acid -- pharmacology KW - Potassium -- pharmacology KW - Membrane Potentials -- drug effects KW - PC12 Cells KW - Adenosine Triphosphate -- pharmacology KW - Protein Kinase C -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Cytoskeleton -- metabolism KW - Phosphoprotein Phosphatases -- metabolism KW - Actins -- metabolism KW - Norepinephrine -- secretion KW - Cytoskeleton -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73885460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology+and+biochemistry&rft.atitle=Pertussis+toxin+modification+of+PC12+cells+lowers+cytoskeletal+F-actin+and+enhances+norepinephrine+secretion%3A+involvement+of+protein+kinase+C+and+protein+phosphatases.&rft.au=Chen%2C+F%3BWagner%2C+P+D&rft.aulast=Chen&rft.aufirst=F&rft.date=1998-08-01&rft.volume=105&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Archives+of+physiology+and+biochemistry&rft.issn=13813455&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-11-17 N1 - Date created - 1998-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Patterns of drug use among nonmetropolitan and rural adults. AN - 73884492; 9744844 AB - This article examines illegal drug use among adults living in nonmetropolitan and rural areas of the United States using data from the National Household Survey on Drug Abuse. Subjects were classified into three categories by residence: nonmetropolitan-urban, metropolitan-rural, and nonmetropolitan-rural. Respondents indicate about 10% of adults were current users of marijuana or other illegal drugs. Discriminant analysis was used to examine differences among groups of individuals classified as current users, past users, and nonusers. For both marijuana and other illegal drugs, the variables that accounted most for group differences were age, marital, status, employment status, occupation, and income. Only minor differences in drug use were exhibited across the three residential categories. It is recommended that future research on the rural and nonmetropolitan adult population incorporate both structural level measures of socioeconomic and demographic characteristics of localities, and individual level measures of peer influence, work stress, family factors, and psychosocial characteristics. JF - Substance use & misuse AU - Robertson, E AU - Donnermeyer, J F AD - Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2109 EP - 2129 VL - 33 IS - 10 SN - 1082-6084, 1082-6084 KW - Street Drugs KW - 0 KW - Index Medicus KW - Cross-Sectional Studies KW - Humans KW - Adult KW - Incidence KW - United States -- epidemiology KW - Male KW - Female KW - Population Surveillance KW - Rural Population -- statistics & numerical data KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73884492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+use+%26+misuse&rft.atitle=Patterns+of+drug+use+among+nonmetropolitan+and+rural+adults.&rft.au=Robertson%2C+E%3BDonnermeyer%2C+J+F&rft.aulast=Robertson&rft.aufirst=E&rft.date=1998-08-01&rft.volume=33&rft.issue=10&rft.spage=2109&rft.isbn=&rft.btitle=&rft.title=Substance+use+%26+misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-30 N1 - Date created - 1998-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms. AN - 73884157; 9707512 AB - Hepatocytes, as well as nonparenchymal cells, secrete proinflammatory cytokines and chemokines that are involved in the pathology of many liver diseases. In particular, tumor necrosis factor-alpha (TNFalpha), as well as members of the CXC family of chemokines, including interleukin (IL)-8 in humans and macrophage inflammatory protein (MIP)-2 in rodents, have been implicated in both damage and repair processes associated with various hepatotoxins. In the liver, cytokine secretion is usually associated with nonparenchymal cells, particularly Kupffer cells. In the present studies, cytokine gene expression and secretion were investigated in hepatocytes treated with cadmium chloride (CdCl2) or vanadium pentoxide (V2O5). Using human Hep G2 cells and freshly isolated rodent hepatocytes, it was demonstrated that metals increase gene expression and secretion of CXC chemokines and TNFalpha. IL-8 and MIP-2 secretion induced either by the metals or H2O2 were inhibited by antioxidants such as tetramethyl-thiourea and N-acetyl-cysteine. In vitro neutralization experiments with TNFalpha and in vivo studies with TNFalpha receptor knockout mice indicated that the metals directly stimulate CXC chemokine secretion without the need for TNFalpha. Taken together these studies indicate that, in addition to other inflammatory mediators and acute phase proteins, cytokines and chemokines are produced by hepatocytes, which may participate in hepatotoxic responses. The events responsible for their expression involve cellular redox changes. JF - Toxicology and applied pharmacology AU - Dong, W AU - Simeonova, P P AU - Gallucci, R AU - Matheson, J AU - Flood, L AU - Wang, S AU - Hubbs, A AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 359 EP - 366 VL - 151 IS - 2 SN - 0041-008X, 0041-008X KW - Antioxidants KW - 0 KW - Cytokines KW - Inflammation Mediators KW - Reactive Oxygen Species KW - Vanadium Compounds KW - vanadium pentoxide KW - BVG363OH7A KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Animals KW - L Cells (Cell Line) KW - Liver -- cytology KW - Humans KW - Mice KW - Neutrophils -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Antioxidants -- pharmacology KW - Cells, Cultured KW - Liver -- drug effects KW - Mice, Inbred C57BL KW - Chemotaxis -- drug effects KW - Cytokines -- biosynthesis KW - Vanadium Compounds -- toxicity KW - Oxidative Stress KW - Cytokines -- secretion KW - Cadmium Chloride -- toxicity KW - Inflammation Mediators -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73884157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxic+metals+stimulate+inflammatory+cytokines+in+hepatocytes+through+oxidative+stress+mechanisms.&rft.au=Dong%2C+W%3BSimeonova%2C+P+P%3BGallucci%2C+R%3BMatheson%2C+J%3BFlood%2C+L%3BWang%2C+S%3BHubbs%2C+A%3BLuster%2C+M+I&rft.aulast=Dong&rft.aufirst=W&rft.date=1998-08-01&rft.volume=151&rft.issue=2&rft.spage=359&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 - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase. AN - 73879313; 9725111 AB - A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse. JF - Experimental and clinical psychopharmacology AU - Carmona, G N AU - Schindler, C W AU - Shoaib, M AU - Jufer, R AU - Cone, E J AU - Goldberg, S R AU - Greig, N H AU - Yu, Q S AU - Gorelick, D A AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. gcarmona@intra.nida.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 274 EP - 279 VL - 6 IS - 3 SN - 1064-1297, 1064-1297 KW - Narcotics KW - 0 KW - Butyrylcholinesterase KW - EC 3.1.1.- KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Male KW - Butyrylcholinesterase -- pharmacology KW - Narcotics -- metabolism KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Cocaine -- metabolism KW - Narcotics -- pharmacology KW - Butyrylcholinesterase -- metabolism KW - Butyrylcholinesterase -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73879313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Attenuation+of+cocaine-induced+locomotor+activity+by+butyrylcholinesterase.&rft.au=Carmona%2C+G+N%3BSchindler%2C+C+W%3BShoaib%2C+M%3BJufer%2C+R%3BCone%2C+E+J%3BGoldberg%2C+S+R%3BGreig%2C+N+H%3BYu%2C+Q+S%3BGorelick%2C+D+A&rft.aulast=Carmona&rft.aufirst=G&rft.date=1998-08-01&rft.volume=6&rft.issue=3&rft.spage=274&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 - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of moderate alcohol consumption on the central nervous system. AN - 73879079; 9726269 AB - The concept of moderate consumption of ethanol (beverage alcohol) has evolved over time from considering this level of intake to be nonintoxicating and noninjurious, to encompassing levels defined as "statistically" normal in particular populations, and the public health-driven concepts that define moderate drinking as the level corresponding to the lowest overall rate of morbidity or mortality in a population. The various approaches to defining moderate consumption of ethanol provide for a range of intakes that can result in blood ethanol concentrations ranging from 5 to 6 mg/dl, to levels of over 90 mg/dl (i.e., approximately 20 mM). This review summarizes available information regarding the effects of moderate consumption of ethanol on the adult and the developing nervous systems. The metabolism of ethanol in the human is reviewed to allow for proper appreciation of the important variables that interact to influence the level of exposure of the brain to ethanol once ethanol is orally consumed. At the neurochemical level, the moderate consumption of ethanol selectively affects the function of GABA, glutamatergic, serotonergic, dopaminergic, cholinergic, and opioid neuronal systems. Ethanol can affect these systems directly, and/or the interactions between and among these systems become important in the expression of ethanol's actions. The behavioral consequences of ethanol's actions on brain neurochemistry, and the neurochemical effects themselves, are very much dose- and time-related, and the collage of ethanol's actions can change significantly even on the rising and falling phases of the blood ethanol curve. The behavioral effects of moderate ethanol intake can encompass events that the human or other animal can perceive as reinforcing through either positive (e.g., pleasurable, activating) or negative (e.g., anxiolysis, stress reduction) reinforcement mechanisms. Genetic factors and gender play an important role in the metabolism and behavioral actions of ethanol, and doses of ethanol producing pleasurable feelings, activation, and reduction of anxiety in some humans/animals can have aversive, sedative, or no effect in others. Research on the cognitive effects of acute and chronic moderate intake of ethanol is reviewed, and although a number of studies have noted a measurable diminution in neuropsychologic parameters in habitual consumers of moderate amounts of ethanol, others have not found such changes. Recent studies have also noted some positive effects of moderate ethanol consumption on cognitive performance in the aging human. The moderate consumption of ethanol by pregnant women can have significant consequences on the developing nervous system of the fetus. Consumption of ethanol during pregnancy at levels considered to be in the moderate range can generate fetal alcohol effects (behavioral, cognitive anomalies) in the offspring. A number of factors--including gestational period, the periodicity of the mother's drinking, genetic factors, etc.--play important roles in determining the effect of ethanol on the developing central nervous system. A series of recommendations for future research endeavors, at all levels, is included with this review as part of the assessment of the effects of moderate ethanol consumption on the central nervous system. JF - Alcoholism, clinical and experimental research AU - Eckardt, M J AU - File, S E AU - Gessa, G L AU - Grant, K A AU - Guerri, C AU - Hoffman, P L AU - Kalant, H AU - Koob, G F AU - Li, T K AU - Tabakoff, B AD - Office of Scientific Affairs, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 998 EP - 1040 VL - 22 IS - 5 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Central Nervous System -- metabolism KW - Animals KW - Ethanol -- pharmacokinetics KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Infant, Newborn KW - Central Nervous System -- drug effects KW - Fetal Alcohol Spectrum Disorders -- blood KW - Female KW - Pregnancy KW - Fetal Alcohol Spectrum Disorders -- diagnosis KW - Alcohol-Related Disorders -- diagnosis KW - Alcohol-Related Disorders -- blood KW - Alcohol Drinking -- adverse effects KW - Central Nervous System Diseases -- blood KW - Central Nervous System Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73879079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+moderate+alcohol+consumption+on+the+central+nervous+system.&rft.au=Eckardt%2C+M+J%3BFile%2C+S+E%3BGessa%2C+G+L%3BGrant%2C+K+A%3BGuerri%2C+C%3BHoffman%2C+P+L%3BKalant%2C+H%3BKoob%2C+G+F%3BLi%2C+T+K%3BTabakoff%2C+B&rft.aulast=Eckardt&rft.aufirst=M&rft.date=1998-08-01&rft.volume=22&rft.issue=5&rft.spage=998&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 - 1998-12-15 N1 - Date created - 1998-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiotoxicity of iodine-125-labeled oligodeoxyribonucleotides in mammalian cells. AN - 73877494; 9708519 AB - We investigated the distribution, stability and radiotoxicity of 125I-oligodeoxyribonucleotides (125I-ODN) in human fibrosarcoma HT-1080 cells to study the radiotoxic effects of the Auger electron emitter 125I delivered to the cells by ODN. We delivered 125I-ODN into the cells via complexing with a liposomal delivery system. To assess the intracellular distribution and stability of 125I-ODN delivered by the liposomal delivery system, we used autoradiography, fluorescent and confocal microscopy and electrophoresis. To study the radiotoxicity of the unbound 125I-ODN, we used a clonogenic assay. The radiotoxicity of 125I-ODN delivered by the liposomal delivery system was compared with that of freely diffusible 125I-antipyrine, membrane-excluded 125I-bovine serum albumin and DNA incorporated 125I-deoxyuridine (125I-UdR). Oligodeoxyribonucleotides accumulated in the cell nucleus within a few hours of incubation. On the basis of the number of decays at 37% survival, 125I-ODN are 2 times more radiotoxic than 125I-antipyrine, which is freely diffusible into cells, and 8 times more radiotoxic than 125I-bovine serum albumin, which remains outside cells. However, the radiotoxicity of unbound 125I-ODN is almost 3 orders of magnitude lower than that of DNA-incorporated 125I-UdR. The 125I-ODN are not significantly degraded by intracellular nucleases during the time of uptake incubation. The dramatic difference in radiotoxicity between 125I-ODN and 125I-UdR confirms that, despite the nuclear localization, 125I-ODN are not bound to or incorporated within the genomic DNA. Our data demonstrate that the radiotoxicity of Auger electron emitters is determined by the radiation dose delivered to nuclear DNA, not necessarily to the nucleus. Therefore, relatively high intracellular concentrations of unbound 125I-ODN can be achieved without causing significant cell death. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Sedelnikova, O A AU - Panyutin, I G AU - Thierry, A R AU - Neumann, R D AD - Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1412 EP - 1418 VL - 39 IS - 8 SN - 0161-5505, 0161-5505 KW - Drug Carriers KW - 0 KW - Iodine Radioisotopes KW - Liposomes KW - Oligodeoxyribonucleotides KW - Radiopharmaceuticals KW - Serum Albumin, Radio-Iodinated KW - Antipyrine KW - T3CHA1B51H KW - Deoxyuridine KW - W78I7AY22C KW - Index Medicus KW - Animals KW - Cattle KW - Radiopharmaceuticals -- toxicity KW - Humans KW - Fibrosarcoma -- pathology KW - Antipyrine -- toxicity KW - Deoxyuridine -- toxicity KW - Tumor Stem Cell Assay KW - Serum Albumin, Radio-Iodinated -- toxicity KW - Oligodeoxyribonucleotides -- toxicity KW - Iodine Radioisotopes -- toxicity KW - Tumor Cells, Cultured -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73877494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Radiotoxicity+of+iodine-125-labeled+oligodeoxyribonucleotides+in+mammalian+cells.&rft.au=Sedelnikova%2C+O+A%3BPanyutin%2C+I+G%3BThierry%2C+A+R%3BNeumann%2C+R+D&rft.aulast=Sedelnikova&rft.aufirst=O&rft.date=1998-08-01&rft.volume=39&rft.issue=8&rft.spage=1412&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-04 N1 - Date created - 1998-09-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Nucl Med. 1999 Sep;40(9):1582 [10492382] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines. AN - 73866309; 9715255 AB - Anthralin is the most common therapeutic agent among a small number of pro-oxidant, 9-anthrones effective in the topical treatment of psoriasis. However, the usefulness of this drug is diminished by toxic side effects, including skin irritation and inflammation. The activities of anthralin are believed to be mediated by the generation of reactive oxygen intermediates and anthrone radicals produced in the skin. In this study, the dermal inflammatory response to anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by anthralin coincided with the elevation of cytokine mRNA expression in the skin, including interleukin-6, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, and tumor necrosis factor alpha at 24 h post challenge. The role of free radical generation in ear swelling and cytokine modulation were examined by systemic administration of cell permeable and impermeable antioxidants before anthralin challenge. Superoxide dismutase and alpha-tocopherol acetate, but not the glutathione precursor N-acetyl cysteine, were effective inhibitors of anthralin-induced ear swelling and cytokine elevation. Maximum inflammatory cell infiltration occurred 72-96 h post anthralin challenge and was also reduced by antioxidants. These data suggest that oxidative stress, generated at the site of anthralin treatment, alters the expression of dermal chemokines and other cytokines resulting in the recruitment of inflammatory cells. Systemic antioxidant administration may provide opportunities for therapeutic intervention against anthralin-associated toxicities. JF - Journal of leukocyte biology AU - Lange, R W AU - Germolec, D R AU - Foley, J F AU - Luster, M I AD - Environmental Immunology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. lange@vms.cis.pitt.edu Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 170 EP - 176 VL - 64 IS - 2 SN - 0741-5400, 0741-5400 KW - Anti-Inflammatory Agents KW - 0 KW - Antioxidants KW - Chemokine CXCL2 KW - Chemotactic Factors KW - Cytokines KW - Free Radical Scavengers KW - Free Radicals KW - Interleukin-6 KW - Irritants KW - Monokines KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Vitamin E KW - 1406-18-4 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Anthralin KW - U8CJK0JH5M KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Chemotactic Factors -- immunology KW - Animals KW - Tumor Necrosis Factor-alpha -- immunology KW - Ear KW - Mice, Inbred BALB C KW - Tumor Necrosis Factor-alpha -- genetics KW - Chemotactic Factors -- genetics KW - Gene Expression -- immunology KW - Superoxide Dismutase -- pharmacology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - Interleukin-6 -- genetics KW - Interleukin-6 -- immunology KW - Free Radical Scavengers -- pharmacology KW - Administration, Topical KW - Granulocyte-Macrophage Colony-Stimulating Factor -- immunology KW - Monokines -- immunology KW - RNA, Messenger -- analysis KW - Monokines -- genetics KW - Acetylcysteine -- pharmacology KW - Mice KW - Free Radicals -- immunology KW - Vitamin E -- pharmacology KW - Female KW - Dermatitis -- immunology KW - Antioxidants -- pharmacology KW - Skin -- immunology KW - Cytokines -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73866309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+leukocyte+biology&rft.atitle=Antioxidants+attenuate+anthralin-induced+skin+inflammation+in+BALB%2Fc+mice%3A+role+of+specific+proinflammatory+cytokines.&rft.au=Lange%2C+R+W%3BGermolec%2C+D+R%3BFoley%2C+J+F%3BLuster%2C+M+I&rft.aulast=Lange&rft.aufirst=R&rft.date=1998-08-01&rft.volume=64&rft.issue=2&rft.spage=170&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-04 N1 - Date created - 1998-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is St. John's wort (Hypericum perforatum) an effective antidepressant? AN - 73858526; 9717868 AB - SJW is a remarkably safe antidepressant with an apparently unique mode of action. Although it has demonstrated efficacy in mild and moderate depression when compared with placebo or tricyclic antidepressants, several research areas beg to be explored. Its effects should be compared with serotonin reuptake inhibitors. Studies in severely depressed patients are lacking, as are studies on its utility as a therapeutic adjunct to standard antidepressants. JF - The Journal of nervous and mental disease AU - Cott, J M AU - Fugh-Berman, A AD - Adult Psychopharmacology Program, National Institute of Mental Health, Rockville, Maryland 20857, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 500 EP - 501 VL - 186 IS - 8 SN - 0022-3018, 0022-3018 KW - Antidepressive Agents KW - 0 KW - Nonprescription Drugs KW - Plant Extracts KW - Xanthenes KW - Perylene KW - 5QD5427UN7 KW - hypericin KW - 7V2F1075HD KW - Quercetin KW - 9IKM0I5T1E KW - Protein Kinase C KW - EC 2.7.11.13 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Perylene -- analogs & derivatives KW - Phytotherapy KW - Animals KW - Xanthenes -- therapeutic use KW - Perylene -- therapeutic use KW - Plants, Medicinal KW - Nonprescription Drugs -- therapeutic use KW - Humans KW - Quercetin -- therapeutic use KW - Hypericum KW - Quercetin -- analogs & derivatives KW - Protein Kinase C -- antagonists & inhibitors KW - Plant Extracts -- therapeutic use KW - Plant Extracts -- toxicity KW - Depressive Disorder -- drug therapy KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects KW - Plant Extracts -- adverse effects KW - Antidepressive Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73858526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nervous+and+mental+disease&rft.atitle=Is+St.+John%27s+wort+%28Hypericum+perforatum%29+an+effective+antidepressant%3F&rft.au=Cott%2C+J+M%3BFugh-Berman%2C+A&rft.aulast=Cott&rft.aufirst=J&rft.date=1998-08-01&rft.volume=186&rft.issue=8&rft.spage=500&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nervous+and+mental+disease&rft.issn=00223018&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human brain capillary endothelium: modulation of K+ efflux and K+, Ca2+ uptake by endothelin. AN - 73855964; 9704603 AB - This report describes K+ efflux, K+ and Ca2+ uptake responses to endothelins (ET-1 and ET-3) in cultured endothelium derived from capillaries of human brain (HBEC). ET-1 dose dependently increased K+ efflux, K+ and Ca2+ uptake in these cells. ET-1 stimulated K+ efflux occurred prior to that of K+ uptake. ET-3 was ineffective. The main contributor to the ET-1 induced K+ uptake was ouabain but not bumetanide-sensitive (Na+-K+-ATPase and Na+-K+-Cl- cotransport activity, respectively). All tested paradigms of ET-1 effects in HBEC were inhibited by selective antagonist of ET(A) but not ET(B) receptors and inhibitors of phospholipase C and receptor-operated Ca2+ channels. Activation of protein kinase C (PKC) decreased whereas inhibition of PKC increased the ET-1 stimulated K+ efflux, K+ and Ca2+ uptake in HBEC. The results indicate that ET-1 affects the HBEC ionic transport systems through activation of ET(A) receptors linked to PLC and modulated by intracellular Ca2+ mobilization and PKC. JF - Neurochemical research AU - Spatz, M AU - Kawai, N AU - Bembry, J AU - Lenz, F AU - McCarron, R M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4128, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1125 EP - 1132 VL - 23 IS - 8 SN - 0364-3190, 0364-3190 KW - Calcium Channel Blockers KW - 0 KW - Endothelin-1 KW - Endothelin-3 KW - Endothelins KW - Indoles KW - Maleimides KW - Protein Kinase C KW - EC 2.7.11.13 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - bisindolylmaleimide KW - MBK3OO5K8T KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Type C Phospholipases -- antagonists & inhibitors KW - Ion Transport -- drug effects KW - Brain -- cytology KW - Endothelin-3 -- pharmacology KW - Dose-Response Relationship, Drug KW - Brain -- blood supply KW - Humans KW - Capillaries -- cytology KW - Protein Kinase C -- antagonists & inhibitors KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Calcium Channel Blockers -- pharmacology KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Endothelin-1 -- pharmacology KW - Maleimides -- pharmacology KW - Calcium -- metabolism KW - Endothelins -- pharmacology KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- enzymology KW - Endothelium, Vascular -- cytology KW - Potassium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73855964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemical+research&rft.atitle=Human+brain+capillary+endothelium%3A+modulation+of+K%2B+efflux+and+K%2B%2C+Ca2%2B+uptake+by+endothelin.&rft.au=Spatz%2C+M%3BKawai%2C+N%3BBembry%2C+J%3BLenz%2C+F%3BMcCarron%2C+R+M&rft.aulast=Spatz&rft.aufirst=M&rft.date=1998-08-01&rft.volume=23&rft.issue=8&rft.spage=1125&rft.isbn=&rft.btitle=&rft.title=Neurochemical+research&rft.issn=03643190&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 - Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells. AN - 73853517; 9715265 AB - Cytokines, IL-2, IL-4, IL-6, IL-7, IL-12, and IL-15 are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear. Recent studies reveal that a family of transcription factors, signal transducers and activators of transcription (STATs) directly mediate many cytokine signals. We analyzed the activation of STATs in primary human T and NK cells by a variety of specific cytokines. We demonstrate that IL-12 induces STAT4 only in freshly isolated primary NK cells, but not in primary T cells, consistent with the lack of the IL-12 receptor in resting T cells. In contrast, IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells. Moreover, IL-4 costimulation with IL-2 or IL-12 does not alter their own preferential GAS-like DNA binding patterns when C epsilon-, Fc gamma RI-, and SIE GAS motif containing oligonucleotide probes are compared, suggesting that induction of GAS-like DNA-protein binding complexes by IL-2, IL-4, and IL-12 is highly selective and represents one important factor in determining specific gene activation. In addition, IL-6 and IL-2 synergistically induce homo- and heterodimerized STAT1 alpha and STAT3 in both NK and T cells, consistent with their reported synergism in modulating perforin gene expression. We further demonstrated that IL-2, -7, and -15 induce multiple STAT proteins, including STAT5a, STAT5b, STAT1 alpha, STAT3, and another unidentified Fc gamma RI GAS DNA-binding protein. Finally, we observed that activated STAT5a and STAT5b proteins form distinct Fc gamma RI GAS binding patterns in T and NK cells, suggesting that they might have different roles in gene regulation. Our data provide evidence that the differential responses in gene expression and cell activation seen in primary NK and T cells on direct stimulation with different cytokines may be a direct result of distinct activation of STAT transcription factors. JF - Journal of leukocyte biology AU - Yu, C R AU - Young, H A AU - Ortaldo, J R AD - Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 245 EP - 258 VL - 64 IS - 2 SN - 0741-5400, 0741-5400 KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - Interleukin-15 KW - Interleukin-2 KW - Interleukin-6 KW - Interleukin-7 KW - Milk Proteins KW - Receptors, IgG KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - STAT5 Transcription Factor KW - STAT5A protein, human KW - STAT5B protein, human KW - Trans-Activators KW - Tumor Suppressor Proteins KW - Interleukin-12 KW - 187348-17-0 KW - Interleukin-4 KW - 207137-56-2 KW - Interferons KW - 9008-11-1 KW - Index Medicus KW - Gene Expression -- drug effects KW - Interleukin-2 -- pharmacology KW - Promoter Regions, Genetic -- immunology KW - Humans KW - Receptors, IgG -- metabolism KW - Interleukin-4 -- pharmacology KW - Interleukin-6 -- pharmacology KW - Interleukin-7 -- pharmacology KW - Gene Expression -- immunology KW - Interferons -- pharmacology KW - Interleukin-15 -- pharmacology KW - Interleukin-12 -- pharmacology KW - Drug Synergism KW - Trans-Activators -- metabolism KW - T-Lymphocytes -- metabolism KW - Cytokines -- pharmacology KW - Trans-Activators -- genetics KW - T-Lymphocytes -- chemistry KW - DNA-Binding Proteins -- genetics KW - Trans-Activators -- immunology KW - Killer Cells, Natural -- chemistry KW - Killer Cells, Natural -- metabolism KW - DNA-Binding Proteins -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73853517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+leukocyte+biology&rft.atitle=Characterization+of+cytokine+differential+induction+of+STAT+complexes+in+primary+human+T+and+NK+cells.&rft.au=Yu%2C+C+R%3BYoung%2C+H+A%3BOrtaldo%2C+J+R&rft.aulast=Yu&rft.aufirst=C&rft.date=1998-08-01&rft.volume=64&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-04 N1 - Date created - 1998-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single nucleotide substitution in the transcription start signal of the M2 gene of respiratory syncytial virus vaccine candidate cpts248/404 is the major determinant of the temperature-sensitive and attenuation phenotypes. AN - 73840130; 9705916 AB - Respiratory syncytial virus (RSV) cpts248/404 is a live-attenuated, temperature-sensitive (ts) vaccine candidate derived from cole-passaged cpRSV by two rounds of chemical mutagenesis and biological selection. Previous sequence analysis showed that these two steps introduced three single nucleotide substitutions into the cpRSV parent. Two of these occurred with the coding sequence for the L protein, and each resulted in a single amino acid substitution: Gin-831-Leu (248 mutation) and Asp-1183-Glu (404-L mutation). The third mutation resulted in a nucleotide substitution at position 9 of the c/s-acting gene start signal of the M2 gene (404-M2 mutation). In the present study, the genetic basis of attenuation of cpts248/404 was defined by the introduction of each of these mutations (singly or in combination) into a full-length cDNA clone of cpRSV. Recombinant RSV derived from each mutant cDNA was analyzed to determine the contribution of each mutation to the ts and attenuation phenotypes of the virus. This analysis showed that the 248 mutation specifies a significant reduction of plaque formation at 38 degrees and is responsible for an intermediate level of attenuation in mice. In contrast, the 404-L mutation did not contribute to the ts or attenuation phenotype alone or in combination with other mutations and is thus an incidental change. unexpectedly, the 404-M2 mutation alone specified complete restriction of plaque formation at 37 degrees C an a high level of attenuation in mice. This indicates that the level of temperature sensitivity and attenuation of cpts248/404 can be attributed primarily to the 404-M2 mutation. Thus the cpts248/404 virus contains a set of ts and non-ts attenuating mutations, which likely accounts for its genetic stability. The recombinant version of this virus, rA2cp248/404, was phenotypically indistinguishable from cpts248/404 and represents a background into which additional mutations can be introduced as needed to obtain the desired level of attenuation for successful immunization of the very young human infant. JF - Virology AU - Whitehead, S S AU - Firestone, C Y AU - Collins, P L AU - Murphy, B R AD - Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0720, USA. sswhitehead@nih.gov Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 232 EP - 239 VL - 247 IS - 2 SN - 0042-6822, 0042-6822 KW - Antigens, Viral KW - 0 KW - DNA, Complementary KW - HN Protein 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 - Humans KW - Temperature KW - Mice KW - Mice, Inbred BALB C KW - Phenotype KW - Chickens KW - Vaccines, Attenuated -- immunology KW - Vaccines, Attenuated -- genetics KW - Cell Line KW - Viral Proteins -- genetics KW - Respiratory Syncytial Viruses -- immunology KW - Respiratory Syncytial Viruses -- genetics KW - Respiratory Syncytial Viruses -- physiology KW - Antigens, Viral -- immunology KW - Viral Vaccines -- genetics KW - Point Mutation KW - Viral Vaccines -- immunology KW - Antigens, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73840130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+single+nucleotide+substitution+in+the+transcription+start+signal+of+the+M2+gene+of+respiratory+syncytial+virus+vaccine+candidate+cpts248%2F404+is+the+major+determinant+of+the+temperature-sensitive+and+attenuation+phenotypes.&rft.au=Whitehead%2C+S+S%3BFirestone%2C+C+Y%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Whitehead&rft.aufirst=S&rft.date=1998-08-01&rft.volume=247&rft.issue=2&rft.spage=232&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of nitric oxide in cardiovascular disease: focus on the endothelium. AN - 73836613; 9702990 AB - Nitric oxide is a soluble gas continuously synthesized by the endothelium. This substance has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood. A growing list of conditions, including those commonly associated as risk factors for atherosclerosis such as hypertension and hypercholesterolemia, are associated with diminished release of nitric oxide into the arterial wall either because of impaired synthesis or excessive oxidative degradation. Diminished nitric oxide bioactivity may cause constriction of coronary arteries during exercise or during mental stress and contribute to provocation of myocardial ischemia in patients with coronary artery disease. Additionally, diminished nitric oxide bioactivity may facilitate vascular inflammation that could lead to oxidation of lipoproteins and foam cell formation, the precursor of the atherosclerotic plaque. Numerous therapies have been investigated to assess the possibility of reversing endothelial dysfunction by enhancing the release of nitric oxide from the endothelium, either through stimulation of nitric oxide synthesis or protection of nitric oxide from oxidative inactivation and conversion to toxic molecules such as peroxynitrite. Accordingly, causal relationships between improved endothelial function and reduction in myocardial ischemia and acute coronary events can now be investigated. JF - Clinical chemistry AU - Cannon, R O AD - Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. cannonr@gwgate.nhlbi.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 1809 EP - 1819 VL - 44 IS - 8 Pt 2 SN - 0009-9147, 0009-9147 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Hypertension -- physiopathology KW - Humans KW - Hypercholesterolemia -- physiopathology KW - Vasomotor System -- physiopathology KW - Myocardial Ischemia -- physiopathology KW - Stress, Physiological -- physiopathology KW - Arteriosclerosis -- physiopathology KW - Endothelium, Vascular -- metabolism KW - Nitric Oxide -- physiology KW - Cardiovascular Diseases -- physiopathology KW - Endothelium, Vascular -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73836613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemistry&rft.atitle=Role+of+nitric+oxide+in+cardiovascular+disease%3A+focus+on+the+endothelium.&rft.au=Cannon%2C+R+O&rft.aulast=Cannon&rft.aufirst=R&rft.date=1998-08-01&rft.volume=44&rft.issue=8+Pt+2&rft.spage=1809&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Clin Chem 1998 Sep;44(9):2070 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer. AN - 73818230; 9704728 AB - We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Curti, B D AU - Ochoa, A C AU - Powers, G C AU - Kopp, W C AU - Alvord, W G AU - Janik, J E AU - Gause, B L AU - Dunn, B AU - Kopreski, M S AU - Fenton, R AU - Zea, A AU - Dansky-Ullmann, C AU - Strobl, S AU - Harvey, L AU - Nelson, E AU - Sznol, M AU - Longo, D L AD - Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD, USA. bcurti@psghs.edu Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2752 EP - 2760 VL - 16 IS - 8 SN - 0732-183X, 0732-183X KW - Antigens, CD3 KW - 0 KW - Antineoplastic Agents KW - Indium Radioisotopes KW - Interleukin-2 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Leukapheresis KW - Infusions, Intravenous KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Lymphocyte Activation KW - Cyclophosphamide -- administration & dosage KW - Antigens, CD3 -- immunology KW - Interleukin-2 -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Immunotherapy, Adoptive KW - CD4-Positive T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73818230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Familial+Mediterranean+fever+at+the+millennium.+Clinical+spectrum%2C+ancient+mutations%2C+and+a+survey+of+100+American+referrals+to+the+National+Institutes+of+Health.&rft.au=Samuels%2C+J%3BAksentijevich%2C+I%3BTorosyan%2C+Y%3BCentola%2C+M%3BDeng%2C+Z%3BSood%2C+R%3BKastner%2C+D+L&rft.aulast=Samuels&rft.aufirst=J&rft.date=1998-07-01&rft.volume=77&rft.issue=4&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Medicine&rft.issn=00257974&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agricultural use of DDT and risk of non-Hodgkin's lymphoma: pooled analysis of three case-control studies in the United States. AN - 70117388; 9849538 AB - The objective of this pooled analysis was to examine whether exposure to DDT was associated with the risk of non-Hodgkin's lymphoma among male farmers. Data from three case-control studies from four midwestern states in the United States (Nebraska, Iowa, Minnesota, Kansas) were pooled to carry out analyses of 993 cases and 2918 controls. Information on use of agricultural pesticides and other risk factors was based on interviews. Non-farmers (people who had never lived or worked on a farm) were used as a reference category. There were 161 cases and 340 controls who reported use of DDT on animals or crops, or on both, yielding an odds ratio (OR) of 1.2 (95% confidence intervals (95% CI) 1.0 to 1.6). Farmers who had used DDT for > or = 15 years had an OR of 1.5 (95% CI 1.0 to 2.3). Adjustment for respondent status and use of other pesticides resulted in slightly reduced ORs. Analyses by the number of days of use a year was limited to the Nebraska data. The most notable increase was found among farmers who used DDT for > or = 5 days a year (OR 2.6, 95% CI 1.1 to 5.9); however, additional adjustment for use of organophosphates, phenoxyacetic acids, and the individual pesticides lindane, malathion, and atrazine reduced the ORs to 1.0, 0.9, 1.1, 1.6, and 1.9 respectively. No strong consistent evidence was found for an association between exposure to DDT and risk of non-Hodgkin's lymphoma. It seems that the excess risk initially found may be explained by use of other pesticides. JF - Occupational and environmental medicine AU - Baris, D AU - Zahm, S H AU - Cantor, K P AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7364, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 522 EP - 527 VL - 55 IS - 8 SN - 1351-0711, 1351-0711 KW - Insecticides KW - 0 KW - Pesticides KW - DDT KW - CIW5S16655 KW - Index Medicus KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Time Factors KW - Pesticides -- adverse effects KW - Male KW - Insecticides -- adverse effects KW - Agricultural Workers' Diseases -- chemically induced KW - DDT -- adverse effects KW - Lymphoma, Non-Hodgkin -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70117388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Agricultural+use+of+DDT+and+risk+of+non-Hodgkin%27s+lymphoma%3A+pooled+analysis+of+three+case-control+studies+in+the+United+States.&rft.au=Baris%2C+D%3BZahm%2C+S+H%3BCantor%2C+K+P%3BBlair%2C+A&rft.aulast=Baris&rft.aufirst=D&rft.date=1998-08-01&rft.volume=55&rft.issue=8&rft.spage=522&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 completed - 1998-12-18 N1 - Date created - 1998-12-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lancet. 1997 Jul 26;350(9073):240-4 [9242800] Cancer Res. 1994 May 1;54(9):2386-9 [8162585] N Engl J Med. 1976 Mar 25;294(13):687-90 [55969] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] Am J Epidemiol. 1985 Jan;121(1):131-9 [3964988] Environ Health Perspect. 1985 May;60:115-20 [2411534] JAMA. 1986 Sep 5;256(9):1141-7 [3801091] J Natl Cancer Inst. 1987 Apr;78(4):675-8 [3470542] J Natl Cancer Inst. 1987 May;78(5):899-910 [3471999] Rev Environ Contam Toxicol. 1991;120:1-82 [1899728] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Occup Med. 1991 Jul-Sep;6(3):335-54 [1835166] Cancer Res. 1992 May 1;52(9):2447-55 [1568215] Am J Epidemiol. 1992 May 1;135(9):1019-28 [1595688] Cancer Res. 1993 May 15;53(10 Suppl):2421 [8329071] Scand J Work Environ Health. 1993 Apr;19(2):108-14 [8316777] Am J Ind Med. 1998 Jan;33(1):82-7 [9408531] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo use of adenoviral vectors: effects on salivary gland structure. AN - 70074103; 9825894 AB - Recently there has been considerable progress in the development of in vivo gene transfer technology. By this means, new genetic information may be introduced directly to cells, while the cells remain in their natural milieu. The ability to express exogenous proteins makes it possible to explore the functions of native or altered proteins and thereby develop new insights into cell function and dysfunction. We have demonstrated that the major salivary glands are efficiently infected by recombinant adenovirus vectors. These vectors are capable of expressing transgenes in both acinar and ductal cell types. Recently, we have developed vectors that contain cell-specific promoters so that proteins may be expressed in selected subpopulations of salivary cells. Early generations of adenoviral vectors elicited potent immune responses in vivo. However, modified vectors and adjunctive measures have improved the safety of gene transfer to salivary glands. Future studies will aim to increase the duration of adenovirus-based gene expression and to produce vector systems that are not toxic to the host. JF - European journal of morphology AU - O'Connell, B C AU - Redman, R S AU - Zheng, C AD - Gene Transfer Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-1190, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 55 EP - 60 VL - 36 Suppl SN - 0924-3860, 0924-3860 KW - Index Medicus KW - Rats KW - Animals KW - Gene Expression Regulation, Viral KW - Rats, Wistar KW - Transgenes -- physiology KW - Microscopy, Electron KW - Male KW - Adenoviridae KW - Submandibular Gland -- virology KW - Parotid Gland -- physiology KW - Gene Transfer Techniques KW - Parotid Gland -- ultrastructure KW - Submandibular Gland -- ultrastructure KW - Submandibular Gland -- physiology KW - Parotid Gland -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70074103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Evidence+of+past+recombination+events+among+the+genes+encoding+the+Erp+antigens+of+Borrelia+burgdorferi&rft.au=Stevenson%2C+B%3BCasjens%2C+S%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=144&rft.issue=7&rft.spage=1869&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-15 N1 - Date created - 1999-01-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PACAP activates calcium influx-dependent and -independent pathways to couple met-enkephalin secretion and biosynthesis in chromaffin cells. AN - 70065864; 9826785 AB - Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) caused a dose-dependent increase in met-enkephalin secretion and increased production of met-enkephalin peptide and proenkephalin A (PEnk) mRNA in bovine chromaffin cells, at concentrations as low as 300 pM. PACAP-38 was less potent than PACAP-27, but had similar effects. Vasoactive intestinal polypeptide (VIP) (1-100 nM) was without appreciable effect on either enkephalin secretion or biosynthesis, implicating PACAP type I receptors in PACAP-stimulated enkephalin secretion and synthesis. PACAP type I receptors can activate adenylate cyclase and stimulate phospholipase C through heterotrimeric G protein interactions, leading to increased intracellular cyclic AMP (cAMP), inositol triphosphate (IP3)-mediated calcium mobilization, and calcium- and diacylglycerol (DAG)-mediated protein kinase C (PKC) activation. Enkephalin secretion evoked by 10-100 nM PACAP-27 was not inhibited by 1 microM (-)-202-791, an L-type specific dihydropyridine calcium channel blocker, but was inhibited 65-80% by the arylalkylamine calcium channel blocker D600. Forty mM potassium-evoked secretion was inhibited > 90% by both D600 and (-)-202-791, 25 microM forskolin-induced secretion was blocked < 50% by D600 and was unaffected by (-)-202-791, and 100 nM phorbol myristate acetate (PMA)-induced secretion was unaffected by either D600 or (-)-202-791. Enkephalin biosynthesis was increased by 10 nM PACAP-27, as measured by increased met-enkephalin pentapeptide content and PEnk A mRNA levels. PACAP-, forskolin-, and PMA-stimulated enkephalin synthesis were not blocked by D600 or (-)-202-791. Elevated potassium-induced enkephalin biosynthesis upregulation was completely blocked by either D600 or (-)-202-791 at the same concentrations. PACAP acting through type I PACAP receptors couples calcium influx-dependent enkephalin secretion and calcium influx-independent enkephalin biosynthesis in chromaffin cells. Restriction of the effects of enhanced calcium influx to stimulation of secretion, but not of biosynthesis, is unique to PACAP. By contrast, potassium-induced enkephalin biosynthesis upregulation is completely calcium influx dependent, specifically via calcium influx through L-type calcium channels. We propose that subpopulations of voltage-dependent calcium channels are differentially linked to intracellular signal transduction pathways that control neuropeptide gene expression and secretion in chromaffin cells. JF - Journal of molecular neuroscience : MN AU - Hahm, S H AU - Hsu, C M AU - Eiden, L E AD - Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-4090, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 43 EP - 56 VL - 11 IS - 1 SN - 0895-8696, 0895-8696 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels KW - Calcium Channels, L-Type KW - Enkephalins KW - Neuropeptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Protein Precursors KW - proenkephalin KW - Colforsin KW - 1F7A44V6OU KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Enkephalin, Methionine KW - 58569-55-4 KW - Cyclic AMP KW - E0399OZS9N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Vasoactive Intestinal Peptide -- pharmacology KW - Animals KW - Calcium Channels -- physiology KW - Enkephalins -- genetics KW - Adrenal Glands -- cytology KW - Protein Precursors -- genetics KW - Cyclic AMP -- physiology KW - Radioimmunoassay KW - Models, Biological KW - Cattle KW - Colforsin -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Potassium -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Male KW - Neuropeptides -- pharmacology KW - Calcium Signaling -- drug effects KW - Enkephalin, Methionine -- secretion KW - Enkephalin, Methionine -- genetics KW - Chromaffin Cells -- metabolism KW - Enkephalin, Methionine -- metabolism KW - Chromaffin Cells -- drug effects KW - Enkephalin, Methionine -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70065864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuroscience+%3A+MN&rft.atitle=PACAP+activates+calcium+influx-dependent+and+-independent+pathways+to+couple+met-enkephalin+secretion+and+biosynthesis+in+chromaffin+cells.&rft.au=Hahm%2C+S+H%3BHsu%2C+C+M%3BEiden%2C+L+E&rft.aulast=Hahm&rft.aufirst=S&rft.date=1998-08-01&rft.volume=11&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+neuroscience+%3A+MN&rft.issn=08958696&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-27 N1 - Date created - 1999-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiation dependency of eicosanoid enzyme expression in human tracheobronchial cells. AN - 70058863; 9820673 AB - The expression of 15-lipoxygenase (15-LO) and prostaglandin H synthase-2 (PGHS-2) was studied in retinoic acid (RA) sufficient and RA-deficient normal human tracheobronchial epithelial (NHTBE) cell cultures. In the absence of RA, in which the cultures became squamous metaplastic, neither 15-LO nor PGHS-2 were expressed. In RA-sufficient cultures, which differentiated into a mucociliary epithelium, both enzymes were expressed: PGHS-2 during early phases and 15-LO during late stages of differentiation. Depending on the stage of differentiation, the RA-sufficient cultures produced PGE, and in the presence of exogenous linoleic acid (LA) 13-HODE. Experiments are underway to examine the effects of inflammatory cytokines on eicosanoid metabolism and the role these metabolites play in airway diseases. JF - Toxicology letters AU - Hill, E M AU - Eling, T AU - Nettesheim, P AD - Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, NC, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 239 EP - 244 VL - 96-97 SN - 0378-4274, 0378-4274 KW - Hydroxyeicosatetraenoic Acids KW - 0 KW - Isoenzymes KW - Linoleic Acids KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - Tretinoin KW - 5688UTC01R KW - 15-hydroxy-5,8,11,13-eicosatetraenoic acid KW - 73945-47-8 KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Phospholipases A KW - EC 3.1.1.32 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Tretinoin -- pharmacology KW - Hydroxyeicosatetraenoic Acids -- biosynthesis KW - Dinoprostone -- biosynthesis KW - Cytosol -- enzymology KW - Humans KW - Isoenzymes -- metabolism KW - Epithelial Cells -- cytology KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Isoenzymes -- biosynthesis KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Tretinoin -- metabolism KW - Linoleic Acids -- biosynthesis KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Arachidonate 15-Lipoxygenase -- metabolism KW - Bronchi -- cytology KW - Arachidonate 15-Lipoxygenase -- biosynthesis KW - Phospholipases A -- biosynthesis KW - Bronchi -- enzymology KW - Trachea -- cytology KW - Trachea -- enzymology KW - Phospholipases A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70058863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+letters&rft.atitle=Differentiation+dependency+of+eicosanoid+enzyme+expression+in+human+tracheobronchial+cells.&rft.au=Hill%2C+E+M%3BEling%2C+T%3BNettesheim%2C+P&rft.aulast=Hill&rft.aufirst=E&rft.date=1998-08-01&rft.volume=96-97&rft.issue=&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-01 N1 - Date created - 1998-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum concentrations of organochlorine compounds and endometrial cancer risk (United States). AN - 70005476; 9794174 AB - Endogenous and exogenous estrogens are important in the development of endometrial cancer. Several organochlorine compounds, such as o,p'-DDT, have estrogenic properties. The objective of this case-control analysis was to examine serum concentrations of organochlorine compounds and risk of endometrial cancer. Analyses were based on a sample of 90 endometrial cancer cases and 90 individually matched community controls from a multicenter case-control study in five geographic regions of the United States. Information on potential confounders, including menstrual and reproductive factors, cigarette smoking, diet, and weight, was obtained by interview. The adjusted relative risk of endometrial cancer in the highest quartile of exposure compared with women in the lowest quartile was 0.7 (95 percent confidence interval [CI] = 0.2-2.0) for p,p'-DDE, and 0.9 for total polychlorinated biphenyls (PCBs) (CI = 0.4-2.5). These findings do not support the hypothesis that organochlorine compounds are linked to the development of endometrial cancer. JF - Cancer causes & control : CCC AU - Sturgeon, S R AU - Brock, J W AU - Potischman, N AU - Needham, L L AU - Rothman, N AU - Brinton, L A AU - Hoover, R N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 417 EP - 424 VL - 9 IS - 4 SN - 0957-5243, 0957-5243 KW - Hydrocarbons, Chlorinated KW - 0 KW - Insecticides KW - Index Medicus KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Incidence KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Risk Assessment KW - Endometrial Neoplasms -- epidemiology KW - Carcinoma -- epidemiology KW - Endometrial Neoplasms -- blood KW - Carcinoma -- blood KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70005476?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+concentrations+of+organochlorine+compounds+and+endometrial+cancer+risk+%28United+States%29.&rft.au=Sturgeon%2C+S+R%3BBrock%2C+J+W%3BPotischman%2C+N%3BNeedham%2C+L+L%3BRothman%2C+N%3BBrinton%2C+L+A%3BHoover%2C+R+N&rft.aulast=Sturgeon&rft.aufirst=S&rft.date=1998-08-01&rft.volume=9&rft.issue=4&rft.spage=417&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Skin tumor risk among atomic-bomb survivors in Japan. AN - 69997741; 9794171 AB - Elevated risks of skin cancer following high doses of ionizing radiation have long been known. Recent reports on atomic-bomb survivors indicate that nonmelanoma skin cancer can be induced at low to medium doses. We studied atomic-bomb survivors to determine the effects of radiation on specific histologic types of skin cancer and to describe the dose-response relationship. Cases of melanoma, nonmelanoma skin cancers, and Bowen's disease were ascertained between 1958 and 1987 for the 80,000 cohort members through the population-based Hiroshima and Nagasaki (Japan) tumor registries augmented by searches of other records. An excess of basal cell carcinoma (n = 80), with some suggestion of a non-linear dose-response, was observed. The excess risk decreased markedly as age at exposure increased, and there was no evidence for an interaction between ionizing and ultraviolet radiation. No dose-response was found for squamous cell carcinoma (n = 69). The excess relative risk point-estimates were large, but statistically nonsignificant for both melanoma (n = 10) and Bowen's disease (n = 26). The basal layer of the epidermis appears to be quite sensitive to radiation carcinogenesis, particularly at a young age. The suprabasal layer seems to be more resistant, as shown by the lack of an association for squamous cell carcinomas. JF - Cancer causes & control : CCC AU - Ron, E AU - Preston, D L AU - Kishikawa, M AU - Kobuke, T AU - Iseki, M AU - Tokuoka, S AU - Tokunaga, M AU - Mabuchi, K AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 393 EP - 401 VL - 9 IS - 4 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Bowen's Disease -- etiology KW - Melanoma -- etiology KW - Humans KW - Aged KW - Child KW - Poisson Distribution KW - Dose-Response Relationship, Radiation KW - Melanoma -- epidemiology KW - Child, Preschool KW - Registries KW - Japan -- epidemiology KW - Bowen's Disease -- epidemiology KW - Risk Factors KW - Adult KW - Cohort Studies KW - Incidence KW - Confidence Intervals KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Survivors -- statistics & numerical data KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- epidemiology KW - Carcinoma, Basal Cell -- etiology KW - Skin Neoplasms -- etiology KW - Nuclear Warfare KW - Skin Neoplasms -- epidemiology KW - Carcinoma, Basal Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69997741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Skin+tumor+risk+among+atomic-bomb+survivors+in+Japan.&rft.au=Ron%2C+E%3BPreston%2C+D+L%3BKishikawa%2C+M%3BKobuke%2C+T%3BIseki%2C+M%3BTokuoka%2C+S%3BTokunaga%2C+M%3BMabuchi%2C+K&rft.aulast=Ron&rft.aufirst=JPM&rft.date=1998-07-01&rft.volume=29&rft.issue=1&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene disruption to evaluate the role of fungal candidate virulence genes. AN - 69187707; 10066511 AB - Gene disruption is a powerful genetic tool that can define pathogenic or virulence factors. In the past two years gene disruption approaches have been used to identify fungal virulence genes. The capsule genes, an alpha subunit of G protein and certain kinases of Cryptococcus neoformans have clearly been demonstrated to be associated with pathogenicity. In Candida albicans at least four genes involved in hyphal formation have been disrupted and tested for virulence. In other fungi, such as Histoplasma capsulatum, however, more efficient gene disruption methods need to be developed before such approaches can be regularly used for identifying virulence genes. JF - Current opinion in microbiology AU - Kwon-Chung, K AD - Molecular Microbiology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Building 10, 11C304, National Institutes of Health, Bethesda MD 20892, USA. June_Kwon-Chung@nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 381 EP - 389 VL - 1 IS - 4 SN - 1369-5274, 1369-5274 KW - Index Medicus KW - Virulence -- genetics KW - Gene Deletion KW - Candida -- genetics KW - Genes, Fungal KW - Cryptococcus neoformans -- genetics KW - Candida -- pathogenicity KW - Cryptococcus neoformans -- pathogenicity KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69187707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Gene+disruption+to+evaluate+the+role+of+fungal+candidate+virulence+genes.&rft.au=Kwon-Chung%2C+K&rft.aulast=Kwon-Chung&rft.aufirst=K&rft.date=1998-08-01&rft.volume=1&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+microbiology&rft.issn=13695274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-05 N1 - Date created - 1999-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potentiometric study of resting potential, contributing K+ channels and the onset of Na+ channel excitability in embryonic rat cortical cells. AN - 69176600; 9767384 AB - Resting membrane potential (RMP), K+ channel contribution to RMP and the development of excitability were investigated in the entire population of acutely dissociated embryonic (E) rat cortical cells over E11-22 using a voltage-sensitive fluorescent indicator dye and flow cytometry. During the period of intense proliferation (E11-13), two cell subpopulations with distinct estimated RMPs were recorded: one polarized at approximately -70 mV and the other relatively less-polarized at approximately -40 mV. Ca2+o was critical in sustaining the RMP of the majority of less-polarized cells, while the well-polarized cells were characterized by membrane potentials exhibiting a approximately Nernstian relationship between RMP and [K+]o. Analysis of these two subpopulations revealed that > 80% of less-polarized cells were proliferative, while > 90% of well-polarized cells were postmitotic. Throughout embryonic development, the disappearance of Ca2+o-sensitive, less-polarized cells correlated with the disappearance of the proliferating population, while the appearance of the K+o-sensitive, well-polarized population correlated with the appearance of terminally postmitotic neurons, immuno-identified as BrdU-, tetanus toxin+ cells. Differentiating neurons were estimated to contain increased K+i relative to less-polarized cells, coinciding with the developmental expression of Cs+/Ba2+-sensitive and Ca2+-dependent K+ channels. Both K+ channels contributed to the RMP of well-polarized cells, which became more negative toward the end of neurogenesis. Depolarizing effects of veratridine, first observed at E11, progressively changed from Ca2+o-dependent and tetrodotoxin-insensitive to Na+o-dependent and tetrodotoxin-sensitive response by E18. The results reveal a dynamic development of RMP, contributing K+ channels and voltage-dependent Na+ channels in the developing cortex as it transforms from proliferative to primarily differentiating tissue. JF - The European journal of neuroscience AU - Maric, D AU - Maric, I AU - Smith, S V AU - Serafini, R AU - Hu, Q AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. dragan@codon.nih.gov Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 2532 EP - 2546 VL - 10 IS - 8 SN - 0953-816X, 0953-816X KW - Potassium Channels KW - 0 KW - Sodium Channel Agonists KW - Sodium Channel Blockers KW - Sodium Channels KW - Cesium KW - 1KSV9V4Y4I KW - Barium KW - 24GP945V5T KW - Tetrodotoxin KW - 4368-28-9 KW - Veratridine KW - 71-62-5 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Cesium -- pharmacology KW - Animals KW - Intracellular Fluid -- metabolism KW - Potassium -- metabolism KW - Rats KW - Calcium -- metabolism KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Cells, Cultured KW - In Vitro Techniques KW - Flow Cytometry KW - Tetrodotoxin -- pharmacology KW - Veratridine -- pharmacology KW - Time Factors KW - Embryo, Mammalian KW - Barium -- pharmacology KW - Bromodeoxyuridine -- metabolism KW - Cell Division KW - Cerebral Cortex -- physiology KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- embryology KW - Membrane Potentials -- physiology KW - Sodium Channels -- physiology KW - Potassium Channels -- physiology KW - Membrane Potentials -- drug effects KW - Potassium Channels -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69176600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Potentiometric+study+of+resting+potential%2C+contributing+K%2B+channels+and+the+onset+of+Na%2B+channel+excitability+in+embryonic+rat+cortical+cells.&rft.au=Maric%2C+D%3BMaric%2C+I%3BSmith%2C+S+V%3BSerafini%2C+R%3BHu%2C+Q%3BBarker%2C+J+L&rft.aulast=Maric&rft.aufirst=D&rft.date=1998-08-01&rft.volume=10&rft.issue=8&rft.spage=2532&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 - 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 - Indications for, and use of, cytotoxic agents in SLE. AN - 69136810; 9890110 AB - Over the past decade, cytotoxic drugs have come to assume an increasingly important role in the management of systemic lupus erythematosus. Intravenous cyclophosphamide has become the standard treatment for lupus affecting major organs, in particular lupus nephritis. Cytotoxics with less potential for adverse side effects such as azathioprine and methotrexate are widely used in the management of non-major organ lupus and as an adjunct to reduce corticosteroid requirements. Recent clinical experience in lupus with newer cytotoxic drugs such as cyclosporin A, adenosine analogues, and mycophenolate mofetil appear promising and may offer improvements in lupus management in the future. JF - Bailliere's clinical rheumatology AU - Klippel, J H AD - Clinical Investigations Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1828, USA. Y1 - 1998/08// PY - 1998 DA - August 1998 SP - 511 EP - 527 VL - 12 IS - 3 SN - 0950-3579, 0950-3579 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Azathioprine -- toxicity KW - Humans KW - Azathioprine -- administration & dosage KW - Methotrexate -- administration & dosage KW - Methotrexate -- toxicity KW - Cyclophosphamide -- administration & dosage KW - Lupus Erythematosus, Systemic -- drug therapy KW - Immunosuppressive Agents -- toxicity KW - Cyclophosphamide -- toxicity KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69136810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+rheumatology&rft.atitle=Indications+for%2C+and+use+of%2C+cytotoxic+agents+in+SLE.&rft.au=Klippel%2C+J+H&rft.aulast=Klippel&rft.aufirst=J&rft.date=1998-08-01&rft.volume=12&rft.issue=3&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+rheumatology&rft.issn=09503579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Molecular aspects of neoplasia of Syrian hamster cells transformed in vitro by chemical carcinogens AN - 17266850; 4557625 AB - The addition of environmental agents (carcinogens) induces transformation that can be quantitated. Its frequency follows a linear relationship with dose and is consistent with a 'one hit' phenomenon. Transformed colonies produce transformed lines with attributes of neoplastic cells including production of tumors. The results parallel in vivo activity. Although, molecular analysis of most animal assay indicate the presence of activated oncogenes belonging to the ras family, ras activation is a low frequency event in the neoplastic conversion of Syrian hamster cells just as is found with human malignancies. In our analysis of 22 independently derived lines N-ras activation was found only with sodium bisulfite transformed lines. A novel oncogene named carcinogenesis promotion hamster (cph) because its association with the carcinogenic process has been identified. This resulted from focusing on Syrian hamster cells transformed with a single dose of 3-methylcholanthrene (MCA) and cosmid-rescue-techniques from a third-cycle NIH3T3 transformant obtained by sequential transfections of genomic DNA from MCA-initiated hamster fetal cells. cph transforms NIH3T3 cells and acts synergistically with Ha-ras to transform murine fibroblasts. Gene expression analysis using cph genomic fragments from normal and neoplastic cells identifies a number of transcripts including a major mRNA of 2.5kb as well as several larger transcripts. cph is actively transcribed in different tissues and different species. In the hamster it is a single copy gene localized by FISH to the euchromatic short arm of the X chromosome, at region Xpa7. cph does not have any significant global homology to sequences deposited in date banks, confirming that it is a novel gene. The transforming gene codes for a truncated 246 amino acids whereas the normal cph has a residue of 469 amino acids. In conclusion cph oncogene is activated by a single point-mutation; its activation appears an important mechanism for the conversion of carcinogen treated hamster cells to malignancy and because homologous sequences occur in human DNA it may also be important to the neoplastic conversion of human cells. JF - Toxicology Letters AU - Notario, V AU - DiPaolo, JA Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 221 EP - 230 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 96-97 IS - 1-3 KW - Syrian hamster cells KW - Toxicology Abstracts KW - Transformation KW - Carcinogens KW - Xenobiotics KW - Toxicity testing KW - Neoplasia KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17266850?accountid=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+Letters&rft.atitle=Molecular+aspects+of+neoplasia+of+Syrian+hamster+cells+transformed+in+vitro+by+chemical+carcinogens&rft.au=Notario%2C+V%3BDiPaolo%2C+JA&rft.aulast=Notario&rft.aufirst=V&rft.date=1998-08-01&rft.volume=96-97&rft.issue=1-3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&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 - Development of a Retrovirus-based Complementary DNA Expression System for the Cloning of Tumor Antigens AN - 17203392; 4495642 AB - A new retroviral system has been developed for the generation of a cDNA library and the functional cloning of tumor antigens. These retroviral vectors contain a cytomegalovirus promoter in the 5 theta long terminal repeat, an extended packaging signal for rapid production of high-titer retroviral particles, and many convenient cloning sites for cDNA library construction. The vesicular stomatitis virus G protein has been used to generate pseudotype retroviral particles to enable efficient viral infection. Using this system, viral titers in the range of 10 super(6) colony-forming units/ml could be generated routinely, and a high transduction efficiency in human primary cells, including fibroblasts, was achieved. In addition, a new procedure has been devised for screening a retrovirus-based cDNA library without a functional selection. The utility of this system was demonstrated by constructing a retrovirus-based cDNA library and re-isolating the NY-ESO-1 tumor antigen from a cDNA library using an antigenspecific CTL. This approach can facilitate the identification of novel tumor antigens recognized by T cells without knowledge of MHC class I restriction elements and is generally applicable for the isolation of any gene as long as a biological assay is available. JF - Cancer Research AU - Wang, R-F AU - Wang, X AU - Johnston, S L AU - Zeng, G AU - Robbins, P F AU - Rosenberg, SA AD - Surgery Branch, Building 10, 2B42, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892-1502, USA, rongfu@pop.nci.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 3519 EP - 3525 VL - 58 IS - 16 SN - 0008-5472, 0008-5472 KW - Retrovirus KW - cDNA KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Cloning vectors KW - Tumors KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17203392?accountid=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=Development+of+a+Retrovirus-based+Complementary+DNA+Expression+System+for+the+Cloning+of+Tumor+Antigens&rft.au=Wang%2C+R-F%3BWang%2C+X%3BJohnston%2C+S+L%3BZeng%2C+G%3BRobbins%2C+P+F%3BRosenberg%2C+SA&rft.aulast=Wang&rft.aufirst=R-F&rft.date=1998-08-01&rft.volume=58&rft.issue=16&rft.spage=3519&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; Cloning vectors; Antigen (tumor-associated); Tumors; Lymphocytes T ER - TY - JOUR T1 - Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus AN - 17159566; 4456819 AB - The activity of three human immunodeficiency virus (HIV) protease inhibitors was investigated in human primary monocytes/macrophages (M/M) chronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhibited the replication of HIV-1 in vitro, with EC sub(50)s of approximately 0.5-3.3 mu M. However, only partial inhibition was achievable, even at the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was approximately 7- to 26-fold lower than in acutely infected M/M and approximately 2- to 10-fold lower than in chronically infected H9 lymphocytes. When protease inhibitors were removed from cultures of chronically infected M/M, production of virus rapidly returned to the levels found in untreated M/M. Therefore, relatively high concentrations of protease inhibitors are required to suppress HIV-1 production in chronically infected macrophages, and such cells may be a vulnerable point for the escape of virus in patients taking these drugs. JF - Journal of Infectious Diseases AU - Perno, C-F AU - Newcomb, F M AU - Davis, DA AU - Aquaro, S AU - Humphrey, R W AU - Calio, R AU - Yarchoan, R AD - Bldg. 10, Rm. 12N226, 10 Center Dr., MSC 1906, Bethesda, MD 20892-1906, USA, yarchoan@helix.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 413 EP - 422 VL - 178 IS - 2 SN - 0022-1899, 0022-1899 KW - KNI-272 KW - Proteinase KW - Ritonavir KW - Saquinavir KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Macrophages KW - Cell culture KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Inhibitors KW - Monocytes KW - A 01068:Antiviral & viricidal KW - V 22003:AIDS: Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17159566?accountid=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+Infectious+Diseases&rft.atitle=Relative+potency+of+protease+inhibitors+in+monocytes%2Fmacrophages+acutely+and+chronically+infected+with+human+immunodeficiency+virus&rft.au=Perno%2C+C-F%3BNewcomb%2C+F+M%3BDavis%2C+DA%3BAquaro%2C+S%3BHumphrey%2C+R+W%3BCalio%2C+R%3BYarchoan%2C+R&rft.aulast=Perno&rft.aufirst=C-F&rft.date=1998-08-01&rft.volume=178&rft.issue=2&rft.spage=413&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 - Human immunodeficiency virus 1; Cell culture; Inhibitors; Macrophages; Antiviral agents; Monocytes ER - TY - JOUR T1 - Novel Benztropine [3 alpha -(Diphenylmethoxy)tropane] Analogs as Probes for the Dopamine Transporter AN - 17113571; 4422834 AB - The design, synthesis and pharmacological evaluation of novel dopamine transporter ligands, based on Benztropine [3 alpha -(diphenylmethoxy) tropane], has been a focus of our research efforts toward the development of novel cocaine-abuse pharmacotherapeutics. Structure-activity relationships at the dopamine transporter, for this series of compounds, have been derived and compared to those of cocaine and GBR 12909. These studies suggest that structurally diverse dopamine uptake inhibitors may access different binding domains on the dopamine transporter. The distinctive behavioral profile displayed in this series of compounds, as compared to cocaine and other dopamine uptake inhibitors, is of particular interest and is proposed to be relevant to the pharmacodynamic and pharmacokinetic properties of this class of tropane-based molecules. JF - Current Medicinal Chemistry AU - Newman, AH AU - Agoston, GE AD - Psychobiology Section, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 305 EP - 319 VL - 5 IS - 4 SN - 0929-8673, 0929-8673 KW - 3 alpha -( double prime Diphenylmethoxy)tropane KW - benztropine KW - benztropine [3 alpha -(diphenylmethoxy) tropane] KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Dopamine transporter KW - Dopamine KW - Reviews KW - Cocaine KW - Structure-activity relationships KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17113571?accountid=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+Medicinal+Chemistry&rft.atitle=Novel+Benztropine+%5B3+alpha+-%28Diphenylmethoxy%29tropane%5D+Analogs+as+Probes+for+the+Dopamine+Transporter&rft.au=Newman%2C+AH%3BAgoston%2C+GE&rft.aulast=Newman&rft.aufirst=AH&rft.date=1998-08-01&rft.volume=5&rft.issue=4&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Current+Medicinal+Chemistry&rft.issn=09298673&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 - Dopamine; Structure-activity relationships; Reviews; Dopamine transporter; Cocaine ER - TY - JOUR T1 - Mating patterns and gene dynamics of a population isolate of Native Americans AN - 17100853; 4411764 AB - Mating structure can have important effects on population genetic phenomena, including inbreeding and genetic drift. However, data necessary to test predictions based on mathematical models or identify sensitivity to simplifying assumptions are difficult to collect. We used two sources of such data, pedigrees and genotypes, collected in a human-population isolate. The population studied was Native American and located in New Mexico. It was founded in the mid-19th century by ca. 30 individuals, primarily of Navajo origin, and its size increased steadily thereafter. A complete tribal pedigree spanning ca. 100 years (up to 1948) was collected by anthropologists starting in the 1920s. Probabilities of allelic identity by descent (IBD) within and among individuals were calculated for all generations directly from the pedigree. Wright's F-statistics were calculated from the IBD probabilities, and N sub(e) was obtained from the statistic F sub(ST). Genetic typings were performed on blood samples collected from the population between 1991-1993. A second set of F-statistics were calculated from genetic typings. Genetic kinship between individuals (F sub(ST)) and average inbreeding within individuals (F sub(IT)) stabilized after the first two generations. However, F sub(ST) was always greater than F sub(IT) of the next generation, suggesting that the net effect of social practices was inbreeding avoidance. In contrast to general expectations for growing populations, N sub(e) increased over generations due to immigration. F-statistics estimated from the genetic typings were remarkably close to pedigree estimates, suggesting a drift-migration steady state. JF - Journal of Mammalogy AU - Long, J C AU - Romero, F C AU - Urbanek, M AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Park V Building, Room 451, MSC 8110, 12420 Parklawn Drive, Bethesda, MD 20892-8110, USA Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 681 EP - 691 VL - 79 IS - 3 SN - 0022-2372, 0022-2372 KW - Native American KW - USA, New Mexico KW - inbreeding KW - man KW - models KW - pedigree KW - Genetics Abstracts; Ecology Abstracts KW - Human ecology KW - Mating KW - Population genetics KW - Genetic drift KW - D 04690:Human ecology KW - G 07434:Population studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17100853?accountid=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+Mammalogy&rft.atitle=Mating+patterns+and+gene+dynamics+of+a+population+isolate+of+Native+Americans&rft.au=Long%2C+J+C%3BRomero%2C+F+C%3BUrbanek%2C+M%3BGoldman%2C+D&rft.aulast=Long&rft.aufirst=J&rft.date=1998-08-01&rft.volume=79&rft.issue=3&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Journal+of+Mammalogy&rft.issn=00222372&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 ecology; Population genetics; Mating; Genetic drift ER - TY - JOUR T1 - Early child care and self-control, compliance, and problem behavior at twenty-four and thirty-six months AN - 1667354554; 4658772 AB - To evaluate child-care effects on young children's self-control, compliance, and problem behavior, children enrolled in the NICHD Study of Early Child Care were tested and observed in the laboratory and in child care at 24 and 36 months, and mothers and caregivers completed questionnaires. Indicators of child-care quantity, quality, stability, type, and age of entry, along with measures of family background, mothering, and child characteristics obtained through the first 3 years of life were used to predict 2 and 3 year child functioning. Results revealed (1) mothering to be a stronger and more consistent predictor of child outcomes than child care; (2) little evidence that early, extensive, and continuous care was related to problematic child behavior, in contrast to results from earlier work; (3) that among the child-care predictors, child-care quality was the most consistent predictor of child functioning, although limited variance could be explained by any (or all) child-care variables; and (4) that virtually none of the anticipated interactions among child-care factors or between them and family or child measures proved significant. Reprinted by permission of the University of Chicago Press. © All rights reserved JF - Child development Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 1145 EP - 1170 VL - 69 IS - 4 SN - 0009-3920, 0009-3920 KW - Economics KW - Questionnaires KW - Family KW - Children KW - Child development KW - Child care KW - Motherhood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1667354554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+development&rft.atitle=Early+child+care+and+self-control%2C+compliance%2C+and+problem+behavior+at+twenty-four+and+thirty-six+months&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1998-08-01&rft.volume=69&rft.issue=4&rft.spage=1145&rft.isbn=&rft.btitle=&rft.title=Child+development&rft.issn=00093920&rft_id=info:doi/10.1111%2Fj.1467-8624.1998.tb06165.x LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2015-03-30 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - 2192; 8316; 4748; 10541; 2212; 2197 2212 6075 3483 DO - http://dx.doi.org/10.1111/j.1467-8624.1998.tb06165.x ER - TY - JOUR T1 - Harnessing research to control AIDS AN - 16560163; 4400065 AB - The Office of AIDS Research, a relatively small but influential unit within the US National Institutes of Health, is responsible for "coordinating the scientific, budgetary, legislative, and policy elements of the NIH AIDS research program". Here the new director, Neal Nathanson, presents his vision of how the nations $1.7 billion AIDS research effort should be used to respond to the challenge of AIDS. JF - Nature Medicine AU - Nathanson, N AD - Office of AIDS Research, NIH, US DHHS Bldg. 31 4C02, 9000 Rockville Pike, Bethesda, MD 20892-2340, USA, nathansn@od.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 879 EP - 881 VL - 4 IS - 8 SN - 1078-8956, 1078-8956 KW - HIV KW - man KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Disease control KW - Human immunodeficiency virus KW - Economics KW - Diseases KW - Research programs KW - V 22006:AIDS: Other aspects KW - H 12000:Epidemiology and Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16560163?accountid=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=Nature+Medicine&rft.atitle=Harnessing+research+to+control+AIDS&rft.au=Nathanson%2C+N&rft.aulast=Nathanson&rft.aufirst=N&rft.date=1998-08-01&rft.volume=4&rft.issue=8&rft.spage=879&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; Economics; Disease control; Research programs; Diseases; Acquired immune deficiency syndrome ER - TY - JOUR T1 - DNA immunization protects nonhuman primates against rabies virus AN - 16506514; 4400083 AB - More than 40,000 people die annually from rabies worldwide. Most of these fatalities occur in developing countries, where rabies is endemic, public health resources are inadequate and there is limited access to preventive treatment. Because of the high cost of vaccines derived from cell culture, many countries still use vaccines produced in sheep, goat or suckling mouse brain. The stability and low cost for mass production of DNA vaccines would make them ideal for use in developing countries. To investigate the potential of DNA vaccines for rabies immunization in humans, we vaccinated Macaca fascicularis (Cynomolgus) monkeys with DNA encoding the glycoprotein of the challenge virus standard rabies virus, or with a human diploid cell vaccine (HDCV). The monkeys then were challenged with a non-passaged rabies virus. DNA or HDCV vaccination elicited comparable primary and anamnestic neutralizing antibody responses. All ten vaccinated monkeys (DNA or HDCV) survived a rabies virus challenge, whereas monkeys vaccinated with only the DNA vector developed rabies. Furthermore, serum samples from DNA- or HDCV-vaccinated monkeys neutralized a global spectrum of rabies virus variants in vitro. This study shows that DNA immunization elicits protective immunity in nonhuman primates against lethal challenge with a human viral pathogen of the central nervous system. Our findings indicate that DNA vaccines may have a promising future in human rabies immunization. JF - Nature Medicine AU - Lodmell, D L AU - Ray, N B AU - Parnell, MJ AU - Ewalt, L C AU - Hanlon, CA AU - Shaddock, J H AU - Sanderlin, D S AU - Rupprecht, CE AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA, dlodmell@atlas.niaid.nih.gov Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 949 EP - 952 VL - 4 IS - 8 SN - 1078-8956, 1078-8956 KW - DNA vaccines KW - Macaca fascicularis KW - monkeys KW - primates KW - rabies virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06807:Active immunization KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16506514?accountid=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=DNA+immunization+protects+nonhuman+primates+against+rabies+virus&rft.au=Lodmell%2C+D+L%3BRay%2C+N+B%3BParnell%2C+MJ%3BEwalt%2C+L+C%3BHanlon%2C+CA%3BShaddock%2C+J+H%3BSanderlin%2C+D+S%3BRupprecht%2C+CE&rft.aulast=Lodmell&rft.aufirst=D&rft.date=1998-08-01&rft.volume=4&rft.issue=8&rft.spage=949&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 ER - TY - JOUR T1 - Growth Inhibition of Chronic Myelogenous Leukemia Cells by ODN-1, an Aptameric Inhibitor of p210 super(bcr-abl) Tyrosine Kinase Activity AN - 16497269; 4402691 AB - p210 super(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210 super(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67% plus or minus 19% (mean plus or minus SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also shown to decrease the number of more primitive cobblestone area-forming cells (CAFC) by 35%-87%. In contrast, there was little suppressive effect by the combination of electroporation and ODN-1 on either CFU-GM or CAFC numbers from normal donor bone marrow. These studies suggest that inhibition of p210 super(bcr-abl) protein-tyrosine kinase (PTK) activity by ODN-1 is associated with some degree of selective growth inhibition of p210 super(bcr-abl)-transformed cells. p210 super(bcr-abl) kinase inhibitory agents may be useful for the ex vivo purging of bone marrow or peripheral blood progenitor/stem cells in the setting of autologous transplantation for CML. JF - Antisense and Nucleic Acid Drug Development AU - Schwartz, G N AU - Liu, Yue-Qin AU - Tisdale, J AU - Walshe, K AU - Fowler, D AU - Gress, R AU - Bergan, R C AD - Building 10, Room 12N226, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20897, USA Y1 - 1998/08// PY - 1998 DA - Aug 1998 SP - 329 EP - 339 VL - 8 IS - 4 SN - 1087-2906, 1087-2906 KW - Abl gene KW - BCR gene KW - ODN-1 KW - aptamers KW - man KW - oligonucleotides KW - p210 protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids 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/16497269?accountid=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+Chronic+Myelogenous+Leukemia+Cells+by+ODN-1%2C+an+Aptameric+Inhibitor+of+p210+super%28bcr-abl%29+Tyrosine+Kinase+Activity&rft.au=Schwartz%2C+G+N%3BLiu%2C+Yue-Qin%3BTisdale%2C+J%3BWalshe%2C+K%3BFowler%2C+D%3BGress%2C+R%3BBergan%2C+R+C&rft.aulast=Schwartz&rft.aufirst=G&rft.date=1998-08-01&rft.volume=8&rft.issue=4&rft.spage=329&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 ER - TY - JOUR T1 - Serum cotinine concentration and self-reported smoking during pregnancy AN - 16491097; 4366504 AB - Although during pregnancy there is a better correlation between maternal serum cotinine concentration and adverse outcome than between self-reported smoking and such an outcome, few studies of pregnancy have measured cotinine concentration to determine how much a woman smokes. This study assessed the accuracy of self-reported smoking during pregnancy by performing serum cotinine assays on 448 women registered in the Collaborative Perinatal Project (1959-1966). Based on the assumption that a serum cotinine concentration of >10 ng/ml represented active smoking, 94.9% of women who denied smoking and 87.0% of women who stated that they smoked (kappa = 0.83) reported their status accurately. Among smokers, the correlation coefficient between cotinine concentration and number of cigarettes smoked per day was 0.44. Serum cotinine concentration correlated more strongly than self-reported smoking with infant birth weight (r = 0.246 vs. 0.200). In conclusion, this study showed that pregnant women accurately reported whether they smoked, but cotinine concentration was a better measure than self-report of the actual tobacco dose received. JF - American Journal of Epidemiology AU - Klebanoff, MA AU - Levine, R J AU - Clemens, J D AU - DerSimonian, R AU - Wilkins, D G AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, 6100 Building, Room 7B03, Bethesda, MD 20892-7510, USA Y1 - 1998/08/01/ PY - 1998 DA - 1998 Aug 01 SP - 259 EP - 262 VL - 148 IS - 3 SN - 0002-9262, 0002-9262 KW - cotinine KW - man KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16491097?accountid=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+Epidemiology&rft.atitle=Serum+cotinine+concentration+and+self-reported+smoking+during+pregnancy&rft.au=Klebanoff%2C+MA%3BLevine%2C+R+J%3BClemens%2C+J+D%3BDerSimonian%2C+R%3BWilkins%2C+D+G&rft.aulast=Klebanoff&rft.aufirst=MA&rft.date=1998-08-01&rft.volume=148&rft.issue=3&rft.spage=259&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 ER - TY - JOUR T1 - Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma. AN - 73853948; 9704014 AB - Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection. JF - Biochemical and biophysical research communications AU - Bera, T K AU - Tsukamoto, T AU - Panda, D K AU - Huang, T AU - Guzman, R C AU - Hwang, S I AU - Nandi, S AD - Cancer Research Laboratory, University of California at Berkeley 94720, USA. tkbera@helix.nih.gov Y1 - 1998/07/30/ PY - 1998 DA - 1998 Jul 30 SP - 835 EP - 840 VL - 248 IS - 3 SN - 0006-291X, 0006-291X KW - Recombinant Proteins KW - 0 KW - Methylnitrosourea KW - 684-93-5 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - AIDS/HIV KW - 3T3 Cells KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Exons KW - Mice KW - Rats KW - Base Sequence KW - Transfection KW - Genes, env KW - Introns KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Female KW - Genes, ras KW - Mammary Neoplasms, Experimental -- chemically induced KW - Promoter Regions, Genetic KW - Defective Viruses -- genetics KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Retroviridae -- physiology KW - Mammary Neoplasms, Experimental -- genetics KW - Retroviridae -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Defective Viruses -- physiology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73853948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Defective+retrovirus+insertion+activates+c-Ha-ras+protooncogene+in+an+MNU-induced+rat+mammary+carcinoma.&rft.au=Bera%2C+T+K%3BTsukamoto%2C+T%3BPanda%2C+D+K%3BHuang%2C+T%3BGuzman%2C+R+C%3BHwang%2C+S+I%3BNandi%2C+S&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-07-30&rft.volume=248&rft.issue=3&rft.spage=835&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 - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cryocrystallography and microspectrophotometry of a mutant (alpha D60N) tryptophan synthase alpha 2 beta 2 complex reveals allosteric roles of alpha Asp60. AN - 73845262; 9692955 AB - We have investigated the role of Asp60 of the alpha-subunit in allosteric communication between the tryptophan synthase alpha- and beta-subunits. Crystallographic and microspectrophotometric studies have been carried out on a mutant (alpha D60N) tryptophan synthase alpha 2 beta 2 complex which has no observable alpha-activity, but has substantial beta-activity. Single-crystal polarized absorption spectra indicate that the external aldimine is the predominant L-serine intermediate and that the amount of the intermediate formed is independent of pH, monovalent cations, and allosteric effectors. The three-dimensional structure is reported for this mutant enzyme complexed with indole 3-propanol phosphate bound to the alpha-site and L-serine bound to the beta-site (alpha D60N-IPP-Ser), and this structure is compared with that of the unliganded mutant enzyme (alpha D60N). In the complex, L-serine forms a stable external aldimine with the pyridoxal phosphate coenzyme at the active site of the beta-subunit. The conformation of the unliganded mutant is almost identical to that of the wild type enzyme. However, the structure of the mutant complexed with IPP and serine exhibits ligand-induced conformational changes much smaller than those observed previously for another mutant enzyme in the presence of the same ligands (beta K87T-IPP-Ser) [Rhee, S., Parris, K. D., Hyde, C. C., Ahmed, S. A., Miles, E. W., and Davies, D. R. (1997) Biochemistry 36, 7664-7680]. The alpha D60N-IPP-Ser alpha 2 beta 2 complex does not undergo the following ligand-induced conformational changes: (1) the closure of the alpha-subunit loop 6 (residues 178-191), (2) the movement of the mobile subdomain (residues 93-189) of the beta-subunit, and (3) the rotation of the alpha-subunit relative to the beta-subunit. These observations show that alpha Asp60 plays important roles in the closure of loop 6 and in allosteric communication between the alpha- and beta-subunits. JF - Biochemistry AU - Rhee, S AU - Miles, E W AU - Mozzarelli, A AU - Davies, D R AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1998/07/28/ PY - 1998 DA - 1998 Jul 28 SP - 10653 EP - 10659 VL - 37 IS - 30 SN - 0006-2960, 0006-2960 KW - Imines KW - 0 KW - Indoles KW - Aspartic Acid KW - 30KYC7MIAI KW - indolepropanol phosphate KW - 40716-80-1 KW - Serine KW - 452VLY9402 KW - Asparagine KW - 7006-34-0 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Crystallization KW - Protein Structure, Secondary KW - Models, Molecular KW - Freezing KW - Amino Acid Sequence KW - Serine -- chemistry KW - Mutagenesis KW - Microspectrophotometry KW - Allosteric Regulation -- genetics KW - Amino Acid Substitution -- genetics KW - Molecular Sequence Data KW - Indoles -- metabolism KW - Protein Binding -- genetics KW - Crystallography, X-Ray KW - Imines -- metabolism KW - Catalysis KW - Aspartic Acid -- metabolism KW - Aspartic Acid -- genetics KW - Tryptophan Synthase -- chemistry KW - Asparagine -- genetics KW - Tryptophan Synthase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73845262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cryocrystallography+and+microspectrophotometry+of+a+mutant+%28alpha+D60N%29+tryptophan+synthase+alpha+2+beta+2+complex+reveals+allosteric+roles+of+alpha+Asp60.&rft.au=Rhee%2C+S%3BMiles%2C+E+W%3BMozzarelli%2C+A%3BDavies%2C+D+R&rft.aulast=Rhee&rft.aufirst=S&rft.date=1998-07-28&rft.volume=37&rft.issue=30&rft.spage=10653&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1A5A; PDB; 1BEU N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-narcotic analgesics: renal and gastrointestinal considerations. Introduction. AN - 73861271; 9715827 JF - The American journal of medicine AU - Hamilton, F A AD - National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-6600, USA. Y1 - 1998/07/27/ PY - 1998 DA - 1998 Jul 27 VL - 105 IS - 1B SN - 0002-9343, 0002-9343 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Pain -- drug therapy KW - Humans KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Intestinal Diseases -- chemically induced KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine&rft.atitle=Non-narcotic+analgesics%3A+renal+and+gastrointestinal+considerations.+Introduction.&rft.au=Hamilton%2C+F+A&rft.aulast=Hamilton&rft.aufirst=F&rft.date=1998-07-27&rft.volume=105&rft.issue=1B&rft.spage=1S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On the origins of BSE AN - 17280103; 4480781 AB - The first recognised case of bovine spongiform encephalopathy (BSE) occurred in the UK in 1985, and it was followed by a rapidly developing epizootic that peaked in 1993, with close to 170 000 cattle dying of the disease and an unknown further number infected. A "new variant" of Creutzfelt-Jakob disease (Will-Ironside syndrome) appeared in the UK about 10 years after BSE first appeared. nvCJD (27 cases confirmed at the latest count) represents, on epidemiological and laboratory evidence, infection by the agent of BSE, presumably via beef contaminated with central-nervous-system tissue. JF - Lancet AU - Brown, P AD - Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/07/25/ PY - 1998 DA - 1998 Jul 25 SP - 252 EP - 253 VL - 352 IS - 9124 SN - 0099-5355, 0099-5355 KW - British Isles KW - bovine spongiform encephalopathy KW - epidemiology KW - man KW - transmissible spongiform encephalopathy KW - CSA Neurosciences Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Central nervous system KW - Food contamination KW - Epidemiology KW - Creutzfeldt-Jakob disease KW - N3 11130:Neurovirology KW - A 01017:Human foods KW - V 22130:Diseases associated with slow viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17280103?accountid=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=Lancet&rft.atitle=On+the+origins+of+BSE&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-07-25&rft.volume=352&rft.issue=9124&rft.spage=252&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 - Food contamination; Creutzfeldt-Jakob disease; Central nervous system; Epidemiology ER - TY - JOUR T1 - Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. AN - 80029816; 9671721 AB - Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are two related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequence homology of hanatoxin and grammotoxin, as well as their similar mechanism of action, raises the possibility that they interact with the same region of voltage-gated Ca2+ and K+ channels. Here, we show that each toxin can interact with both voltage-gated Ca2+ and K+ channels and modify channel gating. Moreover, mutagenesis of voltage-gated K+ channels suggests that hanatoxin and grammotoxin recognize the same structural motif. We propose that these toxins recognize a voltage-sensing domain or module present in voltage-gated ion channels and that this domain has a highly conserved three-dimensional structure. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Li-Smerin, Y AU - Swartz, K J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 8585 EP - 8589 VL - 95 IS - 15 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Peptides KW - Peptides, Cyclic KW - Potassium Channels KW - hanatoxin KW - omega-grammotoxin SIA KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Ion Channel Gating KW - Potassium Channels -- chemistry KW - Calcium Channels -- drug effects KW - Calcium Channels -- chemistry KW - Peptides -- chemistry KW - Peptides, Cyclic -- chemistry KW - Potassium Channels -- drug effects KW - Peptides, Cyclic -- pharmacology KW - Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gating+modifier+toxins+reveal+a+conserved+structural+motif+in+voltage-gated+Ca2%2B+and+K%2B+channels.&rft.au=Li-Smerin%2C+Y%3BSwartz%2C+K+J&rft.aulast=Li-Smerin&rft.aufirst=Y&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8585&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Physiol. 1975 Jan;244(2):511-34 [1079869] Mol Pharmacol. 1997 Dec;52(6):1095-104 [9415720] J Biol Chem. 1978 Oct 25;253(20):7393-6 [29897] J Gen Physiol. 1979 Sep;74(3):375-91 [479827] J Gen Physiol. 1985 Nov;86(5):739-62 [2415671] J Gen Physiol. 1987 Feb;89(2):253-74 [2435840] J Gen Physiol. 1988 Mar;91(3):335-49 [2454283] Science. 1988 Sep 23;241(4873):1661-4 [2458626] Nature. 1989 Aug 24;340(6235):642-5 [2770868] Science. 1989 Sep 22;245(4924):1382-5 [2476850] J Membr Biol. 1989 Aug;109(3):269-81 [2477548] Neuron. 1988 Dec;1(10):1003-6 [2483092] Neuron. 1988 Aug;1(6):449-61 [2856097] Nature. 1991 Apr 4;350(6317):398-402 [1849233] Mol Pharmacol. 1991 Oct;40(4):572-6 [1921987] FEBS Lett. 1991 Oct 21;291(2):253-8 [1657644] J Biol Chem. 1991 Nov 15;266(32):21943-7 [1718988] Proc Biol Sci. 1991 Aug 22;245(1313):101-7 [1682932] Neuron. 1992 Aug;9(2):307-13 [1379820] Biochemistry. 1993 Jul 13;32(27):6982-7 [7687466] Mol Pharmacol. 1993 Aug;44(2):451-60 [8394998] Neuron. 1995 Jun;14(6):1293-301 [7605638] Neuron. 1995 Jul;15(1):5-10 [7542463] Neuron. 1995 Oct;15(4):941-9 [7576642] J Gen Physiol. 1995 Oct;106(4):601-16 [8576699] Science. 1996 Jan 12;271(5246):213-6 [8539623] Neuron. 1996 Jan;16(1):113-22 [8562074] Neuron. 1996 Jun;16(6):1159-67 [8663992] Neuron. 1996 Jun;16(6):1169-77 [8663993] J Biol Chem. 1996 Jul 5;271(27):15950-62 [8663157] Neuron. 1996 Feb;16(2):387-97 [8789953] Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 [9019737] Biophys J. 1997 May;72(5):2117-28 [9129813] Neuron. 1997 Apr;18(4):665-73 [9136774] Neuron. 1997 Apr;18(4):675-82 [9136775] Biochemistry. 1997 Jun 10;36(23):6936-40 [9188688] Neuron. 1997 Nov;19(5):1127-40 [9390525] J Biol Chem. 1977 Dec 10;252(23):8660-8 [72754] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the native and recombinant catalytic subunit of human DNA polymerase gamma: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity. AN - 80028937; 9671525 AB - The human DNA polymerase gamma catalytic subunit was overexpressed in recombinant baculovirus-infected insect cells, and the 136 000 Da protein was purified to homogeneity. Application of the same purification protocol to HeLa mitochondrial lysates permitted isolation of native DNA polymerase gamma as a single subunit, allowing direct comparison of the native and recombinant enzymes without interference of other polypeptides. Both forms exhibited identical properties, and the DNA polymerase and 3' --> 5' exonuclease activities were shown unambiguously to reside in the catalytic polypeptide. The salt sensitivity and moderate processivity of the isolated catalytic subunit suggest other factors could be required to restore the salt tolerance and highly processive DNA synthesis typical of gamma polymerases. To facilitate our understanding of mitochondrial DNA replication and mutagenesis as well as cytotoxicity mediated by antiviral nucleotide analogues, we also constructed two site-directed mutant proteins of the human DNA polymerase gamma. Substituting alanine for two essential acidic residues in the exonuclease motif selectively eliminated the 3' --> 5' exonucleolytic function of the purified mutant polymerase gamma. Replacement of a tyrosine residue critical for sugar recognition with phenylalanine in polymerase motif B reduced dideoxynucleotide inhibition by a factor of 5000 with only minor effects on overall polymerase function. JF - Biochemistry AU - Longley, M J AU - Ropp, P A AU - Lim, S E AU - Copeland, W C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 10529 EP - 10539 VL - 37 IS - 29 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Deoxyribonucleotides KW - Peptide Fragments KW - Recombinant Proteins KW - DNA polymerase gamma KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Exonucleases KW - EC 3.1.- KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Peptide Fragments -- genetics KW - Humans KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Amino Acid Sequence KW - Substrate Specificity -- genetics KW - Catalysis KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- biosynthesis KW - Deoxyribonucleotides -- metabolism KW - Amino Acids -- metabolism KW - Recombinant Proteins -- chemistry KW - DNA-Directed DNA Polymerase -- genetics KW - Exonucleases -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80028937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+native+and+recombinant+catalytic+subunit+of+human+DNA+polymerase+gamma%3A+identification+of+residues+critical+for+exonuclease+activity+and+dideoxynucleotide+sensitivity.&rft.au=Longley%2C+M+J%3BRopp%2C+P+A%3BLim%2C+S+E%3BCopeland%2C+W+C&rft.aulast=Longley&rft.aufirst=M&rft.date=1998-07-21&rft.volume=37&rft.issue=29&rft.spage=10529&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice. AN - 80019505; 9671763 AB - High concentrations of nitric oxide (NO) cause DNA damage and apoptosis in many cell types. Thus, regulation of NO synthase (NOS) activity is essential for minimizing effects of cytotoxic and genotoxic nitrogen oxide species. We have shown previously that NO-induced p53 protein accumulation down-regulates basal and cytokine-modulated inducible NOS (NOS2) expression in human cells in vitro. To further characterize the feedback loop between NOS2 and p53, we have investigated NO production, i.e., urinary nitrate plus nitrite excretion, and NOS2 expression in homozygous p53 knockout (KO) mice. We report here that untreated p53 KO mice excreted 70% more nitrite plus nitrate than mice with wild-type (wt) p53. NOS2 protein expression was constitutively detected in the spleen of untreated p53 KO mice, whereas it was undetectable in the spleen of wt p53 controls. Upon treatment with heat-inactivated Corynebacterium parvum, urinary nitrite plus nitrate excretion of p53 KO mice exceeded that of wt controls by approximately 200%. C. parvum treatment also induced p53 accumulation in the liver. Splenectomy reduced the NO output of C. parvum-treated p53 KO mice but not of wt p53 controls. Although NO production and NOS2 protein expression were increased similarly in KO and wt p53 mice 10 days after injection of C. parvum, NOS2 expression returned to baseline levels only in wt p53 controls while remaining up-regulated in p53 KO mice. These genetic and functional data indicate that p53 is an important transrepressor of NOS2 expression in vivo and attenuates excessive NO production in a regulatory negative feedback loop. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Ambs, S AU - Ogunfusika, M O AU - Merriam, W G AU - Bennett, W P AU - Billiar, T R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/21/ PY - 1998 DA - 1998 Jul 21 SP - 8823 EP - 8828 VL - 95 IS - 15 SN - 0027-8424, 0027-8424 KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Index Medicus KW - Animals KW - Promoter Regions, Genetic KW - Mice, Inbred C57BL KW - Mice KW - Feedback KW - Nitric Oxide -- biosynthesis KW - Genetic Predisposition to Disease KW - Mice, Knockout KW - Gene Expression Regulation, Enzymologic KW - Nitric Oxide Synthase -- genetics KW - Neoplasms, Experimental -- genetics KW - Up-Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Up-regulation+of+inducible+nitric+oxide+synthase+expression+in+cancer-prone+p53+knockout+mice.&rft.au=Ambs%2C+S%3BOgunfusika%2C+M+O%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8823&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1987 Jul 15;139(2):518-25 [3110273] Cancer Res. 1998 Jan 15;58(2):334-41 [9443414] Biochem Biophys Res Commun. 1990 May 16;168(3):1034-40 [2346476] J Leukoc Biol. 1990 Dec;48(6):565-9 [2230601] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] J Exp Med. 1991 Oct 1;174(4):761-7 [1717630] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Science. 1991 Nov 15;254(5034):1001-3 [1948068] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10480-4 [1720542] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4 [1557408] J Exp Med. 1992 Jul 1;176(1):261-4 [1377225] J Biol Chem. 1992 Aug 25;267(24):16771-4 [1512218] J Biol Chem. 1992 Oct 25;267(30):21277-80 [1383221] J Physiol. 1992 Aug;454:451-65 [1282159] Science. 1993 Jan 1;259(5091):84-7 [8418500] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):522-6 [7678458] Nature. 1993 Apr 29;362(6423):847-9 [8479522] J Exp Med. 1993 Jun 1;177(6):1779-84 [7684434] Biochem Biophys Res Commun. 1993 Jun 30;193(3):1076-82 [8323533] J Exp Med. 1993 Aug 1;178(2):605-13 [7688028] Cell. 1993 Sep 24;74(6):957-67 [8402885] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730-4 [7692452] Cell. 1993 Nov 19;75(4):765-78 [8242748] Cell. 1993 Nov 19;75(4):817-25 [8242752] Cancer Res. 1994 Jun 15;54(12):3131-5 [8205530] Cell. 1994 Sep 23;78(6):915-8 [7522969] J Biol Chem. 1994 Oct 21;269(42):26066-75 [7929318] FEBS Lett. 1994 Nov 21;355(1):23-6 [7525358] Br J Pharmacol. 1995 Feb;114(3):689-93 [7537593] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4392-6 [7538668] J Immunol. 1995 Sep 15;155(6):2858-65 [7673702] Chem Res Toxicol. 1995 Apr-May;8(3):473-7 [7578935] J Biol Chem. 1995 Dec 8;270(49):29350-5 [7493969] Adv Pharmacol. 1995;34:17-43 [8562432] Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1054-9 [8577713] Hypertension. 1996 Mar;27(3 Pt 2):823-6 [8613247] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2442-7 [8637893] Curr Top Cell Regul. 1996;34:159-87 [8646847] Cancer Res. 1996 Feb 15;56(4):866-74 [8631026] Mol Carcinog. 1996 May;16(1):20-31 [8634091] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1776-80 [8700834] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 [8710843] Biochem J. 1996 Oct 1;319 ( Pt 1):299-305 [8870682] Biochim Biophys Acta. 1996 Oct 9;1288(2):F31-6 [8876631] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15102-7 [8986771] J Biol Chem. 1997 Jan 10;272(2):1402-11 [8995451] J Exp Med. 1997 Feb 17;185(4):601-7 [9034139] FASEB J. 1997 May;11(6):443-8 [9194524] Nature. 1997 Jul 31;388(6641):432-3 [9242400] Cancer Res. 1997 Aug 15;57(16):3365-9 [9269997] FASEB J. 1997 Sep;11(11):887-95 [9285487] J Biol Chem. 1997 Sep 26;272(39):24125-8 [9305857] J Biol Chem. 1997 Dec 5;272(49):31138-48 [9388267] Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5 [1689048] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replacement of tyrosine 1251 in the carboxyl terminus of the insulin-like growth factor-I receptor disrupts the actin cytoskeleton and inhibits proliferation and anchorage-independent growth. AN - 79999468; 9660809 AB - Insulin-like growth factor (IGF)-I signaling through the IGF-I receptor modulates cellular adhesion and proliferation and the transforming ability of cells overexpressing the IGF-I receptor. Tyrosine phosphorylation of intracellular proteins is essential for this transduction of the IGF-I-induced mitogenic and tumorigenic signals. IGF-I induces specific cytoskeletal structure and the phosphorylation of proteins in the associated focal adhesion complexes. The determination of the exact pathways emanating from the IGF-I receptor that are involved in mediating these signals will contribute greatly to the understanding of IGF-I action. We have previously shown that replacement of tyrosine residues 1250 and 1251 in the carboxyl terminus of the IGF-I receptor abrogates IGF-I-induced cellular proliferation and tumor formation in nude mice. In this study, replacement of either tyrosine 1250 or 1251 similarly reduces the cells ability to grow in an anchorage-independent manner. The actin cytoskeleton and cellular localization of vinculin are disrupted by replacement of tyrosine 1251. Tyrosine residues 1250 and 1251 are not essential for tyrosine phosphorylation of two known substrates; insulin receptor substrate-1 and SHC, nor association of known downstream adaptor proteins to these substrates. In addition, these mutant IGF-I receptors do not affect IGF-I-stimulated p42/p44 mitogen-activated protein kinase activation or phosphatidylinositol (PI) 3'-kinase activity. Thus, it appears that in fibroblasts expressing tyrosine 1250 and 1251 mutant IGF-I receptors, the signal transduction pathways impacting on mitogenesis and tumorigenesis do not occur exclusively through the PI 3'-kinase or mitogen-activated protein kinase pathways. JF - The Journal of biological chemistry AU - Blakesley, V A AU - Koval, A P AU - Stannard, B S AU - Scrimgeour, A AU - LeRoith, D AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1770, USA. Y1 - 1998/07/17/ PY - 1998 DA - 1998 Jul 17 SP - 18411 EP - 18422 VL - 273 IS - 29 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - IRS1 protein, human KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, mouse KW - Phosphoproteins KW - Vinculin KW - 125361-02-6 KW - Tyrosine KW - 42HK56048U KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Insulin-Like Growth Factor I -- pharmacology KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Vinculin -- metabolism KW - Phosphorylation KW - Cell Adhesion -- drug effects KW - Protein Conformation KW - Phosphoproteins -- metabolism KW - Cytoskeleton -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Actins -- metabolism KW - Tyrosine -- genetics KW - Receptor, IGF Type 1 -- genetics KW - Tyrosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79999468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Replacement+of+tyrosine+1251+in+the+carboxyl+terminus+of+the+insulin-like+growth+factor-I+receptor+disrupts+the+actin+cytoskeleton+and+inhibits+proliferation+and+anchorage-independent+growth.&rft.au=Blakesley%2C+V+A%3BKoval%2C+A+P%3BStannard%2C+B+S%3BScrimgeour%2C+A%3BLeRoith%2C+D&rft.aulast=Blakesley&rft.aufirst=V&rft.date=1998-07-17&rft.volume=273&rft.issue=29&rft.spage=18411&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complex formation by all five homologues of mammalian translation initiation factor 3 subunits from yeast Saccharomyces cerevisiae. AN - 79995283; 9660829 AB - The PRT1, TIF34, GCD10, and SUI1 proteins of Saccharomyces cerevisiae were found previously to copurify with eukaryotic translation initiation factor 3 (eIF3) activity. Although TIF32, NIP1, and TIF35 are homologous to subunits of human eIF3, they were not known to be components of the yeast factor. We detected interactions between PRT1, TIF34, and TIF35 by the yeast two-hybrid assay and in vitro binding assays. Discrete segments (70-150 amino acids) of PRT1 and TIF35 were found to be responsible for their binding to TIF34. Temperature-sensitive mutations mapping in WD-repeat domains of TIF34 were isolated that decreased binding between TIF34 and TIF35 in vitro. The lethal effect of these mutations was suppressed by increasing TIF35 gene dosage, suggesting that the TIF34-TIF35 interaction is important for TIF34 function in translation. Pairwise in vitro interactions were also detected between PRT1 and TIF32, TIF32 and NIP1, and NIP1 and SUI1. Furthermore, PRT1, NIP1, TIF34, TIF35, and a polypeptide with the size of TIF32 were specifically coimmunoprecipitated from the ribosomal salt wash fraction. We propose that all five yeast proteins homologous to human eIF3 subunits are components of a stable heteromeric complex in vivo and may comprise the conserved core of yeast eIF3. JF - The Journal of biological chemistry AU - Asano, K AU - Phan, L AU - Anderson, J AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/17/ PY - 1998 DA - 1998 Jul 17 SP - 18573 EP - 18585 VL - 273 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Eukaryotic Initiation Factor-3 KW - Fungal Proteins KW - NIP1 protein, S cerevisiae KW - Nuclear Proteins KW - Peptide Initiation Factors KW - Prt1 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - TIF34 protein, S cerevisiae KW - Transcription Factors KW - Index Medicus KW - Animals KW - Nuclear Proteins -- genetics KW - Transcription Factors -- metabolism KW - Humans KW - Temperature KW - Amino Acid Sequence KW - Transcription Factors -- genetics KW - Protein Binding KW - Saccharomyces cerevisiae KW - Mutagenesis, Site-Directed KW - Transcription Factors -- chemistry KW - Molecular Sequence Data KW - Point Mutation KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism KW - Protein Conformation KW - Fungal Proteins -- chemistry KW - Peptide Initiation Factors -- metabolism KW - Peptide Initiation Factors -- genetics KW - Fungal Proteins -- metabolism KW - DNA-Binding Proteins -- chemistry KW - DNA-Binding Proteins -- genetics KW - Peptide Initiation Factors -- chemistry KW - Fungal Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79995283?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Complex+formation+by+all+five+homologues+of+mammalian+translation+initiation+factor+3+subunits+from+yeast+Saccharomyces+cerevisiae.&rft.au=Asano%2C+K%3BPhan%2C+L%3BAnderson%2C+J%3BHinnebusch%2C+A+G&rft.aulast=Asano&rft.aufirst=K&rft.date=1998-07-17&rft.volume=273&rft.issue=29&rft.spage=18573&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. AN - 80057339; 9698073 AB - We examined the interaction of curcumin, a dietary constituent and chemopreventive compound, with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 mammary epithelial carcinoma cells. Curcumin caused a rapid accumulation of cytochrome P450 1A1 (CYP1A1) mRNA in a time- and concentration-dependent manner, and CYP1A1 monooxygenase activity increased as measured by ethoxyresorufin-O-deethylation. Curcumin activated the DNA-binding capacity of the AhR for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Curcumin was able to compete with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin for binding to the AhR in isolated MCF-7 cytosol, indicating that it interacts directly with the receptor. Although curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA-DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway. JF - Biochemical pharmacology AU - Ciolino, H P AU - Daschner, P J AU - Wang, T T AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, MD 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 197 EP - 206 VL - 56 IS - 2 SN - 0006-2952, 0006-2952 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - DNA-Binding Proteins KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Curcumin KW - IT942ZTH98 KW - Index Medicus KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacokinetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Biotransformation KW - Humans KW - Carcinogens -- pharmacokinetics KW - DNA-Binding Proteins -- genetics KW - RNA, Messenger -- genetics KW - Protein Binding KW - Polychlorinated Dibenzodioxins -- metabolism KW - Breast Neoplasms -- genetics KW - Cytochrome P-450 CYP1A1 -- genetics KW - Breast Neoplasms -- pathology KW - Anticarcinogenic Agents -- pharmacology KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Curcumin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80057339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+curcumin+on+the+aryl+hydrocarbon+receptor+and+cytochrome+P450+1A1+in+MCF-7+human+breast+carcinoma+cells.&rft.au=Ciolino%2C+H+P%3BDaschner%2C+P+J%3BWang%2C+T+T%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1998-07-15&rft.volume=56&rft.issue=2&rft.spage=197&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 - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-fluorouracil-mediated thymidylate synthase induction in malignant and nonmalignant human cells. AN - 80056309; 9698077 AB - Thymidylate synthase (TS, EC 2.1.1.45) is an important target enzyme for the fluoropyrimidines used in cancer chemotherapy. Studies have documented a 2- to 4-fold induction of TS protein following 5-fluorouracil (5-FU) treatment of malignant cells. We measured the effect that 5-FU exposure had on TS protein expression in nonmalignant human breast (MCF-10 and HBL-100), colorectal (ATCC Co18, Co112, and Co33), and bone marrow cells along with malignant breast (MCF-7) and colon (NCI-H630) cells. Twenty-four hours after plating, cells were treated with 0.01 to 10 microM of 5-FU for a period of 24 hr. TS was quantitated by Western immunoblot using monoclonal antibody TS106. Absolute levels of TS in nonmalignant cells were substantially lower than in the malignant lines, ranging from approximately 40% in HBL-100 cells to less than 10% in the colon lines. An approximately two-fold induction in the level of TS was found for all cell lines examined, and there was a strong dependence on 5-FU exposure concentration in free TS levels of MCF-WT, and total TS levels of H630-WT, normal bone marrow, and MCF-10 cells. The induction of TS following 5-FU exposure is a generally observed phenomenon in both malignant and nonmalignant cells, suggesting that a selective means for inhibiting this induction may be critical for the development of alternative therapeutic strategies using 5-FU and the antifolate TS inhibitors. JF - Biochemical pharmacology AU - Parr, A L AU - Drake, J C AU - Gress, R E AU - Schwartz, G AU - Steinberg, S M AU - Allegra, C J AD - National Cancer Institute, Medicine Branch, National Naval Medical Center, Bethesda, MD 20889-5101, USA. parra@navmed.nci.nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 231 EP - 235 VL - 56 IS - 2 SN - 0006-2952, 0006-2952 KW - Antimetabolites, Antineoplastic KW - 0 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Enzyme Induction KW - Cell Line KW - Fluorouracil -- pharmacology KW - Thymidylate Synthase -- biosynthesis KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80056309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=5-fluorouracil-mediated+thymidylate+synthase+induction+in+malignant+and+nonmalignant+human+cells.&rft.au=Parr%2C+A+L%3BDrake%2C+J+C%3BGress%2C+R+E%3BSchwartz%2C+G%3BSteinberg%2C+S+M%3BAllegra%2C+C+J&rft.aulast=Parr&rft.aufirst=A&rft.date=1998-07-15&rft.volume=56&rft.issue=2&rft.spage=231&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 - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a naturally occurring Pro15-Ser15 substitution in the serotonin5A receptor gene in alcoholics and healthy volunteers. AN - 80044174; 9685650 AB - We screened the serotonin5A receptor gene coding region in 186 unrelated alcoholic patients and 187 controls. A relatively abundant amino acid substitution and two synonymous DNA substitutions were detected. Two synonymous variants, A12T and C789T, had rarer-allele frequencies of 23% and 1%, respectively. The Pro15Ser substitution is located in the amino terminal, extracellular domain of the receptor adjacent to a putative phosphorylation site. Pro15Ser had rarer-allele frequencies of 8.1% and 5.9% in Finnish alcoholic patients and controls, respectively (p=n.s.). Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Brain research. Molecular brain research AU - Iwata, N AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Laboratory of Neurogenetics, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-8110, USA. nakao@box-n.nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 217 EP - 220 VL - 58 IS - 1-2 SN - 0169-328X, 0169-328X KW - DNA Primers KW - 0 KW - Receptors, Serotonin KW - serotonin 5 receptor KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Index Medicus KW - Polymerase Chain Reaction KW - Reference Values KW - Gene Frequency KW - Polymorphism, Restriction Fragment Length KW - Exons KW - Humans KW - Amino Acid Substitution KW - Receptors, Serotonin -- chemistry KW - Point Mutation KW - Alcoholism -- genetics KW - Receptors, Serotonin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80044174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+a+naturally+occurring+Pro15-Ser15+substitution+in+the+serotonin5A+receptor+gene+in+alcoholics+and+healthy+volunteers.&rft.au=Iwata%2C+N%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Iwata&rft.aufirst=N&rft.date=1998-07-15&rft.volume=58&rft.issue=1-2&rft.spage=217&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 - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single gene complementation of the hPMS2 defect in HEC-1-A endometrial carcinoma cells. AN - 80029972; 9679958 AB - Results from the analysis of human tumor cell lines with mutations in DNA mismatch repair genes have contributed to the understanding of the functions of these gene products in DNA mismatch repair, microsatellite instability, cell cycle checkpoint control, transcription-coupled nucleotide excision repair, and resistance to cytotoxic agents. However, complementation of human DNA mismatch repair defects by introduction of a single cloned gene or cDNA, which would serve to directly prove or disprove their involvement in these processes, has not been accomplished. Here, we introduce a wild-type copy of the hPMS2 cDNA by stable transfection into the PMS2 mutant HEC-1-A cell line. HEC-1-A cells expressing wild-type hPMS2 exhibit increased microsatellite stability, have a reduced mutation rate at the endogenous hypoxanthine phosphoribosyltransferase locus and extracts from these cells are able to perform strand-specific mismatch repair. These results demonstrate that the hPMS2 gene is integral to the maintenance of genome stability. JF - Cancer research AU - Risinger, J I AU - Umar, A AU - Glaab, W E AU - Tindall, K R AU - Kunkel, T A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 2978 EP - 2981 VL - 58 IS - 14 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Proteins KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - PMS2 protein, human KW - Mismatch Repair Endonuclease PMS2 KW - EC 3.6.1.3 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - HeLa Cells KW - Humans KW - Genetic Complementation Test KW - Mutation -- genetics KW - DNA, Neoplasm -- metabolism KW - Female KW - DNA Repair -- genetics KW - Neoplasm Proteins -- genetics KW - Endometrial Neoplasms -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics KW - Neoplasm Proteins -- metabolism KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=A+phase+II+study+of+bromocriptine+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Horti%2C+J%3BFigg%2C+W+D%3BWeinberger%2C+B%3BKohler%2C+D%3BSartor%2C+O&rft.aulast=Horti&rft.aufirst=J&rft.date=1998-07-01&rft.volume=5&rft.issue=4&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. AN - 80016190; 9670929 AB - Cytotoxicity of human NK cells is under negative control of killer cell Ig-like receptors (KIR) specific for HLA class I. To determine the specificity of five KIR containing two Ig domains (KIR2D), direct binding of soluble recombinant KIR2D to a panel of HLA class I transfectants was assayed. One soluble KIR2D, derived from an inhibitory receptor with a long cytoplasmic tail (KIR2DL1), bound to HLA-C allotypes containing asparagine 77 and lysine 80 in the heavy chain, as expected, since these allotypes inhibit lysis by NK cells expressing KIR2DL1. Surprisingly, another KIR2D (KIR2DL2), which inhibits NK lysis of cells expressing HLA-C molecules with serine 77 and asparagine 80, bound to HLA-C allotypes carrying either amino acid motif. Expression of the KIR2DL receptors in NK cells using recombinant vaccinia viruses confirmed these patterns of recognition, and identified KIR2DL3 as another KIR reacting with both groups of HLA-C allotypes. Mutagenesis of amino acid 44 in KIR2DL1 and KIR2DL2 suggested this residue controls the affinity of KIR for the 77/80 motif of HLA-C molecules. Two other soluble KIR2D, derived from noninhibitory receptors with short cytoplasmic tails (KIR2DS), did not bind to any of the HLA class I allotypes tested. One of these receptors (KIR2DS2) is closely related in sequence to KIR2DL2. Substitution of tyrosine 45 with the phenylalanine conserved in other KIR was sufficient to permit specific binding of KIR2DS2 to HLA-C. These results show that KIR2DL receptors are specific for HLA-C, but that recognition of HLA-C allotypes appears more permissive than indicated by previous functional experiments. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Winter, C C AU - Gumperz, J E AU - Parham, P AU - Long, E O AU - Wagtmann, N AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852-1727, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 571 EP - 577 VL - 161 IS - 2 SN - 0022-1767, 0022-1767 KW - HLA-C Antigens KW - 0 KW - KIR2DL2 protein, human KW - KIR2DL3 protein, human KW - Receptors, Immunologic KW - Receptors, KIR KW - Receptors, KIR2DL1 KW - Receptors, KIR2DL2 KW - Receptors, KIR2DL3 KW - Recombinant Fusion Proteins KW - Phenylalanine KW - 47E5O17Y3R KW - Abridged Index Medicus KW - Index Medicus KW - Transfection -- immunology KW - Solubility KW - Phenylalanine -- metabolism KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Protein Binding -- immunology KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Phenylalanine -- genetics KW - Protein Binding -- genetics KW - Receptors, Immunologic -- genetics KW - HLA-C Antigens -- metabolism KW - Alleles KW - Receptors, Immunologic -- physiology KW - Receptors, Immunologic -- metabolism KW - HLA-C Antigens -- immunology KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - HLA-C Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+binding+and+functional+transfer+of+NK+cell+inhibitory+receptors+reveal+novel+patterns+of+HLA-C+allotype+recognition.&rft.au=Winter%2C+C+C%3BGumperz%2C+J+E%3BParham%2C+P%3BLong%2C+E+O%3BWagtmann%2C+N&rft.aulast=Winter&rft.aufirst=C&rft.date=1998-07-15&rft.volume=161&rft.issue=2&rft.spage=571&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 - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical role of arg433 in rat transketolase activity as probed by site-directed mutagenesis. AN - 80004242; 9657977 AB - It has been shown that one arginine per monomer at an unknown position is essential for enzyme activity of the homodimeric transketolase (TK) [Kremer, Egan and Sable (1980) J. Biol. Chem. 255, 2405-2410]. To identify the critical arginine, four highly conserved arginine residues of rat TK (Arg102, Arg350, Arg433 and Arg506) were replaced with alanine by site-directed mutagenesis. Wild-type and mutant TK proteins were produced in Escherichia coli and characterized. The Arg102-->Ala mutant exhibited similar catalytic activity to the wild-type enzyme, whereas Arg350-->Ala, Arg506-->Ala and Arg433-->Ala mutants exhibited 36.7, 37.0 and 6.1% of the wild-type activity respectively. Three recombinant proteins (wild-type, Arg350-->Ala and Arg433-->Ala) were purified to apparent homogeneity using Ni2+-affinity chromatography and further characterized. All these proteins were able to form homodimers (148 kDa), as shown by immunoblot analysis subsequent to non-denaturing gel electrophoresis. The Arg433-->Ala mutant protein was less stable than the wild-type and Arg350-->Ala proteins at 55 degrees C. Kinetic analyses revealed that both Vmax and Km values were markedly affected in the Arg433-->Ala mutant. The Km values for two substrates xylulose 5-phosphate and ribose 5-phosphate were 11.5- and 24.3-fold higher respectively. The kcat/Km values of the Arg433-->Ala mutant for the two substrates were less than 1% of those of the wild-type protein. Molecular modelling of the rat TK revealed that Arg433 of one monomer has three potential hydrogen-bond interactions with the catalytically important highly conserved loop of the other monomer. Thus, our biochemical analyses and modelling data suggest the critical role of the previously uncharacterized Arg433 in TK activity. JF - The Biochemical journal AU - Soh, Y AU - Song, B J AU - Jeng, J AU - Kallarakal, A T AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12501 Washington Avenue, Rockville, MD 20852, USA. Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 367 EP - 372 VL - 333 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Arginine KW - 94ZLA3W45F KW - Transketolase KW - EC 2.2.1.1 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Kinetics KW - Enzyme Stability KW - Image Processing, Computer-Assisted KW - Structure-Activity Relationship KW - Protein Conformation KW - Catalysis KW - Transketolase -- metabolism KW - Arginine -- metabolism KW - Arginine -- genetics KW - Transketolase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Critical+role+of+arg433+in+rat+transketolase+activity+as+probed+by+site-directed+mutagenesis.&rft.au=Soh%2C+Y%3BSong%2C+B+J%3BJeng%2C+J%3BKallarakal%2C+A+T&rft.aulast=Soh&rft.aufirst=Y&rft.date=1998-07-15&rft.volume=333+%28+Pt+2%29&rft.issue=&rft.spage=367&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 - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1986 Jul;47(1):278-81 [3711903] Clin Chem. 1984 May;30(5):658-61 [6713626] Arch Neurol. 1988 Aug;45(8):841-5 [3395257] Gene. 1989 Apr 15;77(1):51-9 [2744487] Biochem Biophys Res Commun. 1990 Oct 30;172(2):396-401 [2241941] Biochemistry. 1992 Feb 18;31(6):1892-6 [1737042] Biochem Biophys Res Commun. 1992 Mar 31;183(3):1159-66 [1567394] EMBO J. 1992 Jul;11(7):2373-9 [1628611] J Mol Biol. 1992 Jul 20;226(2):507-33 [1640463] FEBS Lett. 1992 Nov 30;313(3):229-31 [1446740] J Biol Chem. 1993 Jan 15;268(2):1397-404 [8419340] Alcohol Clin Exp Res. 1993 Feb;17(1):31-7 [8452206] Eur J Biochem. 1993 Oct 1;217(1):487-92 [7916691] J Biol Chem. 1993 Nov 15;268(32):24346-52 [8226984] Alcohol Clin Exp Res. 1993 Oct;17(5):1084-8 [8279670] J Mol Biol. 1994 May 6;238(3):387-404 [8176731] J Biol Chem. 1994 Dec 23;269(51):32144-50 [7798210] Arch Biochem Biophys. 1996 Feb 1;326(1):137-44 [8579361] J Biol Chem. 1997 Jan 17;272(3):1864-9 [8999873] Eur J Biochem. 1997 Mar 1;244(2):646-52 [9119035] J Biol Chem. 1953 Dec;205(2):661-82 [13129245] J Clin Invest. 1968 Oct;47(10):2268-80 [5676522] Arch Biochem Biophys. 1975 Dec;171(2):527-32 [1106327] N Engl J Med. 1977 Dec 22;297(25):1367-70 [927453] J Biol Chem. 1980 Mar 25;255(6):2405-10 [7358678] J Biol Chem. 1981 May 25;256(10):4877-83 [7014563] Arch Biochem Biophys. 1983 Apr 15;222(2):489-96 [6847198] J Biol Chem. 1983 Oct 25;258(20):12405-8 [6355086] J Clin Invest. 1987 Apr;79(4):1039-43 [3558815] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity AN - 16532718; 4395030 AB - Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes. Although the physiologic function of eosinophils [and thus of the two eosinophil ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains controversial, we have recently shown that isolated human eosinophils promote ribonuclease-dependent toxicity toward extracellular virions of the single-stranded RNA virus, respiratory syncytial virus, group B (RSV-B). We have also shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease-dependent antiviral agent. In this work, we provide a biochemical characterization of recombinant human ECP (rhECP) prepared in baculovirus, and demonstrate that rhECP also promotes ribonuclease-dependent antiviral activity. The rhECP described here is N-glycosylated, as is native ECP, and has similar to 100-fold more ribonuclease activity than non-glycosylated rhECP prepared in bacteria. The enzymatic activity of rhECP was sensitive to inhibition by placental ribonuclease inhibitor (RI). Although rhECP was not as effective as rhEDN at reducing viral infectivity (500 nM rhECP reduced infectivity of RSV-B similar to 6 fold; 500 nM rhEDN, >50 fold), the antiviral activity appears to be unique to the eosinophil ribonucleases; no reduction in infectivity was promoted by bovine RNase A, by the amphibian ribonuclease, onconase, nor by the closely-related human ribonuclease, RNase k6. Interestingly, combinations of rhEDN and rhECP did not result in either a synergistic or even an additive antiviral effect. Taken together, these results suggest that that the interaction between the eosinophil ribonucleases and the extracellular virions of RSV-B may be specific and saturable. JF - Nucleic Acids Research AU - Domachowske, J B AU - Dyer, K D AU - Adams, A G AU - Leto, T L AU - Rosenberg, H F AD - Department of Pediatrics, State University of New York Health Science Center at Syracuse, Syracuse, NY 13210, USA, hr2k@nih.gov Y1 - 1998/07/15/ PY - 1998 DA - 1998 Jul 15 SP - 3358 EP - 3363 VL - 26 IS - 14 SN - 0305-1048, 0305-1048 KW - Eosinophil cationic protein KW - Eosinophil-derived neurotoxin KW - RNase A KW - Ribonuclease KW - Ribonuclease A KW - Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts A: Industrial & Applied Microbiology KW - N 14711:RNases KW - A 01068:Antiviral & viricidal KW - V 22100:Antiviral agents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16532718?accountid=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=Nucleic+Acids+Research&rft.atitle=Eosinophil+cationic+protein%2FRNase+3+is+another+RNase+A-family+ribonuclease+with+direct+antiviral+activity&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BAdams%2C+A+G%3BLeto%2C+T+L%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-07-15&rft.volume=26&rft.issue=14&rft.spage=3358&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 ER - TY - JOUR T1 - In vivo studies with [125I]5-I-A-85380, a nicotinic acetylcholine receptor radioligand. AN - 80048523; 9694220 AB - 5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([125I]5-I-A-85380) was evaluated in the mouse as a potential in vivo imaging ligand for central nicotinic acetylcholine receptors (nAChRs). After i.v. administration of [125I]5-I-A-85380, peak brain levels of radioactivity were measured within 1 h and declined slowly over 4 h. [125I]5-I-A-85380 binding was saturable, and both its pharmacology, based upon inhibition studies, and its pattern of accumulation in brain regions having high nAChR densities were consistent with an interaction at alpha4beta2 nAChR agonist binding sites. The thalamus:cerebellum radioactivity ratio, a measure of specific labeling, reached 37. Therefore, radiolabeled 5-I-A-85380 has excellent potential as an imaging radiotracer for nAChRs, particularly with single photon emission computed tomography, when 123I is incorporated into the molecule. JF - Neuroreport AU - Vaupel, D B AU - Mukhin, A G AU - Kimes, A S AU - Horti, A G AU - Koren, A O AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1998/07/13/ PY - 1998 DA - 1998 Jul 13 SP - 2311 EP - 2317 VL - 9 IS - 10 SN - 0959-4965, 0959-4965 KW - A 85380 KW - 0 KW - Azetidines KW - Cholinergic Antagonists KW - Iodine Radioisotopes KW - Ligands KW - Receptors, Nicotinic KW - Index Medicus KW - Seizures -- chemically induced KW - Behavior, Animal -- drug effects KW - Animals KW - Tomography, Emission-Computed, Single-Photon KW - Mice KW - Cholinergic Antagonists -- pharmacology KW - Brain -- metabolism KW - Tissue Distribution KW - Radioligand Assay KW - Autoradiography KW - Male KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- drug effects KW - Azetidines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80048523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+studies+with+%5B125I%5D5-I-A-85380%2C+a+nicotinic+acetylcholine+receptor+radioligand.&rft.au=Vaupel%2C+D+B%3BMukhin%2C+A+G%3BKimes%2C+A+S%3BHorti%2C+A+G%3BKoren%2C+A+O%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1998-07-13&rft.volume=9&rft.issue=10&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-14 N1 - Date created - 1998-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional characterization of a series of mutant G protein alphaq subunits displaying promiscuous receptor coupling properties. AN - 79985017; 9651394 AB - The N termini of two G protein alpha subunits, alphaq and alpha11, differ from those of other alpha subunits in that they display a unique, highly conserved six-amino acid extension (MTLESI(M)). We recently showed that an alphaq deletion mutant lacking these six amino acids (in contrast to wild type alphaq) was able to couple to several different Gs- and Gi/o-coupled receptors, apparently due to promiscuous receptor/G protein coupling (Kostenis, E., Degtyarev, M. Y., Conklin, B. R., and Wess, J. (1997) J. Biol. Chem. 272, 19107-19110). To study which specific amino acids within the N-terminal segment of alphaq/11 are critical for constraining the receptor coupling selectivity of these subunits, this region of alphaq was subjected to systematic deletion and alanine scanning mutagenesis. All mutant alphaq constructs (or wild type alphaq as a control) were coexpressed (in COS-7 cells) with the m2 muscarinic or the D2 dopamine receptors, two prototypical Gi/o-coupled receptors, and ligand-induced increases in inositol phosphate production were determined as a measure of G protein activation. Surprisingly, all 14 mutant G proteins studied (but not wild type alphaq) gained the ability to productively interact with the two Gi/o-linked receptors. Similar results were obtained when we examined the ability of selected mutant alphaq subunits to couple to the Gs-coupled beta2-adrenergic receptor. Additional experiments indicated that the functional promiscuity displayed by all investigated mutant alphaq constructs was not due to overexpression (as compared with wild type alphaq), lack of palmitoylation, or initiation of translation at a downstream ATG codon (codon seven). These data are consistent with the notion that the six-amino acid extension characteristic for alphaq/11 subunits forms a tightly folded protein subdomain that is critical for regulating the receptor coupling selectivity of these subunits. JF - The Journal of biological chemistry AU - Kostenis, E AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/10/ PY - 1998 DA - 1998 Jul 10 SP - 17886 EP - 17892 VL - 273 IS - 28 SN - 0021-9258, 0021-9258 KW - Receptors, Adrenergic, beta-2 KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Animals KW - COS Cells KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Sequence Deletion KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - GTP-Binding Proteins -- genetics KW - Receptors, Adrenergic, beta-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+characterization+of+a+series+of+mutant+G+protein+alphaq+subunits+displaying+promiscuous+receptor+coupling+properties.&rft.au=Kostenis%2C+E%3BZeng%2C+F+Y%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1998-07-10&rft.volume=273&rft.issue=28&rft.spage=17886&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of retinoic acid/retinoid receptors in the regulation of murine alphaB-crystallin/small heat shock protein gene expression in the lens. AN - 79983555; 9651402 AB - Crystallins are a diverse group of abundant soluble proteins that are responsible for the refractive properties of the transparent eye lens. We showed previously that Pax-6 can activate the alphaB-crystallin/small heat shock protein promoter via the lens-specific regulatory regions LSR1 (-147/-118) and LSR2 (-78/-46). Here we demonstrate that retinoic acid can induce the accumulation of alphaB-crystallin in N/N1003A lens cells and that retinoic acid receptor heterodimers (retinoic acid receptor/retinoid X receptor; RAR/RXR) can transactivate LSR1 and LSR2 in cotransfection experiments. DNase I footprinting experiments demonstrated that purified RAR/RXR heterodimers will occupy sequences resembling retinoic acid response elements within LSR1 and LSR2. Electrophoretic mobility shift assays using antibodies indicated that LSR1 and LSR2 can interact with endogenous RAR/RXR complexes in extracts of cultured lens cells. Pax-6 and RAR/RXR together had an additive effect on the activation of alphaB-promoter in the transfected lens cells. Thus, the alphaB-crystallin gene is activated by Pax-6 and retinoic acid receptors, making these transcription factors examples of proteins that have critical roles in early development as well as in the expression of proteins characterizing terminal differentiation. JF - The Journal of biological chemistry AU - Gopal-Srivastava, R AU - Cvekl, A AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, NEI, National Institutes of Health, Bethesda, Maryland 20892-2730, USA. Y1 - 1998/07/10/ PY - 1998 DA - 1998 Jul 10 SP - 17954 EP - 17961 VL - 273 IS - 28 SN - 0021-9258, 0021-9258 KW - Crystallins KW - 0 KW - DNA, Complementary KW - Heat-Shock Proteins KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Blotting, Western KW - Base Sequence KW - Blotting, Northern KW - Transfection KW - Molecular Sequence Data KW - Mice KW - RNA, Messenger -- genetics KW - Cell Line KW - Receptors, Retinoic Acid -- physiology KW - Gene Expression Regulation -- physiology KW - Lens, Crystalline -- metabolism KW - Tretinoin -- physiology KW - Crystallins -- genetics KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+retinoic+acid%2Fretinoid+receptors+in+the+regulation+of+murine+alphaB-crystallin%2Fsmall+heat+shock+protein+gene+expression+in+the+lens.&rft.au=Gopal-Srivastava%2C+R%3BCvekl%2C+A%3BPiatigorsky%2C+J&rft.aulast=Gopal-Srivastava&rft.aufirst=R&rft.date=1998-07-10&rft.volume=273&rft.issue=28&rft.spage=17954&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific interaction of conformational polypeptides derived from HIV gp120 with human T lymphocyte CD4 receptor AN - 16500241; 4385244 AB - Specifically cross-linked peptides (peptomers) have been prepared from the repeating sequences of the C4 domains of glycoproteins 120 present in different isolates of human immunodeficiency virus (HIV). In order to investigate if the HIV C4 peptomers could function as gp120 protein, we have used a novel protein-binding assay to examine if and which components of the peptomers could interact with CD4 receptor in vitro. Here, we demonstrate that all the polymeric components of the HIV-1 C4 peptomer could bind to recombinant soluble CD4 protein. A similar result was also obtained with HIV-2 C4 peptomer except that the binding occurred only in those of constituents having molecular weights higher than that of trimer. Remarkably, the CD4-binding was demonstrated to be specific to the HIV C4 peptomers as it did not occur with control peptomers such as Poly V3 MN and Poly NINA whose peptide sequences bore no homology to those of the HIV C4 peptomers. Furthermore, consistent with previous findings, no interaction of HIV-1 C4 monomeric peptide (419-436) with CD4 was detected under the same conditions. Since it is known that the HIV C4 peptomers have much higher contents of alpha -helical conformation than those of their monomeric peptides, we conclude that the secondary structure is a pivotal determinant for the successful CD4-binding by the peptomers. Our finding reveals a more defined molecular nature of the gp120-CD4 interaction and may be important for designing HIV vaccines and therapeutics which target the first step in the virus infection. JF - Immunology Letters AU - Liu, M AU - Zeng, J AU - Robey, F A AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 1998/07/08/ PY - 1998 DA - 1998 Jul 08 SP - 27 EP - 32 PB - Elsevier Science B.V. VL - 63 IS - 1 SN - 0165-2478, 0165-2478 KW - CD4 antigen KW - Cross-linked peptides KW - HIV-1 KW - binding KW - glycoprotein gp120 KW - human immunodeficiency virus KW - man KW - peptomers KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - W3 33340:Other proteins, peptides, amino acids KW - F 06840:Immunotherapy of immune diseases KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16500241?accountid=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+Letters&rft.atitle=Specific+interaction+of+conformational+polypeptides+derived+from+HIV+gp120+with+human+T+lymphocyte+CD4+receptor&rft.au=Liu%2C+M%3BZeng%2C+J%3BRobey%2C+F+A&rft.aulast=Liu&rft.aufirst=M&rft.date=1998-07-08&rft.volume=63&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Immunology+Letters&rft.issn=01652478&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 - Conformationally constrained analogues of diacylglycerol (DAG). 14. Dissection of the roles of the sn-1 and sn-2 carbonyls in DAG mimetics by isopharmacophore replacement. AN - 69115868; 9873429 AB - The replacement of the sn-1 and sn-2 carbonyl esters in DAG-surrogate lactones by sulfonate esters showed that their isosteric properties in protein kinase C binding are controlled by the location of the hydrophobic alkyl chain on the molecule. The CO and SO2 groups appear to be true isosteres only when they are adjacent to the alkyl chain, which is presumed to insert normal to the lipid bilayer. JF - Bioorganic & medicinal chemistry letters AU - Marquez, V E AU - Sharma, R AU - Wang, S AU - Lewin, N E AU - Blumberg, P M AU - Kim, I S AU - Lee, J AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07/07/ PY - 1998 DA - 1998 Jul 07 SP - 1757 EP - 1762 VL - 8 IS - 13 SN - 0960-894X, 0960-894X KW - Diglycerides KW - 0 KW - Lipid Bilayers KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Molecular Conformation KW - Diglycerides -- chemistry KW - Molecular Mimicry KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69115868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29.+14.+Dissection+of+the+roles+of+the+sn-1+and+sn-2+carbonyls+in+DAG+mimetics+by+isopharmacophore+replacement.&rft.au=Marquez%2C+V+E%3BSharma%2C+R%3BWang%2C+S%3BLewin%2C+N+E%3BBlumberg%2C+P+M%3BKim%2C+I+S%3BLee%2C+J&rft.aulast=Marquez&rft.aufirst=V&rft.date=1998-07-07&rft.volume=8&rft.issue=13&rft.spage=1757&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 - 1999-01-29 N1 - Date created - 1999-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus ORF61 deletion mutants replicate in cell culture, but a mutant with stop codons in ORF61 reverts to wild-type virus. AN - 80002413; 9657949 AB - Varicella-zoster virus (VZV) ORF61 encodes a phosphoprotein that transactivates VZV promoters. Transfection of cells with cosmid DNAs, including a cosmid with a large deletion in ORF61, resulted in a VZV ORF61 deletion mutant that was impaired for growth in vitro and could be partially complemented by growth in neuroblastoma or osteosarcoma cell lines. Cells infected with the VZV ORF61 deletion mutant expressed normal levels of an immediate-early VZV protein, but had reduced levels of a late protein and showed abnormal syncytia. Carboxy terminal truncation mutants of VZV ORF61 protein have a transrepressing phenotype and inhibit the infectivity of cotransfected wild-type viral DNA. Transfection of cells with cosmid DNAs, including a cosmid with stop codons that should result in an ORF61 truncation mutant expressing a transrepressing protein that retains the RING finger domain, resulted in a viral genome which reverted back to the wild-type sequence. BAL-31 exonuclease was used to produce deletions at the site of the stop codons in ORF61 of the cosmid, resulting in loss of the RING finger domain. Transfection of tissue culture cells with the ORF61 BAL-31 deletion mutants and other cosmid DNAs yielded viable viruses. Thus, while deletion mutants lacking the RING finger domain of ORF61 replicate in cell culture, a mutant with stop codons that retains this domain could not be propagated and reverted to wild-type virus. JF - Virology AU - Cohen, J I AU - Nguyen, H AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/07/05/ PY - 1998 DA - 1998 Jul 05 SP - 306 EP - 316 VL - 246 IS - 2 SN - 0042-6822, 0042-6822 KW - Codon, Terminator KW - 0 KW - Repressor Proteins KW - Viral Proteins KW - protein 61, Varicella-zoster virus KW - 106121-63-5 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Genes, Viral KW - Giant Cells KW - Sequence Deletion KW - Virus Replication KW - Herpesvirus 3, Human -- growth & development KW - Viral Proteins -- genetics KW - Repressor Proteins -- metabolism KW - Herpesvirus 3, Human -- metabolism KW - Repressor Proteins -- genetics KW - Viral Proteins -- physiology KW - Mutagenesis KW - Herpesvirus 3, Human -- genetics KW - Repressor Proteins -- physiology KW - Viral Proteins -- metabolism KW - Herpesvirus 3, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Varicella-zoster+virus+ORF61+deletion+mutants+replicate+in+cell+culture%2C+but+a+mutant+with+stop+codons+in+ORF61+reverts+to+wild-type+virus.&rft.au=Cohen%2C+J+I%3BNguyen%2C+H&rft.aulast=Cohen&rft.aufirst=J&rft.date=1998-07-05&rft.volume=246&rft.issue=2&rft.spage=306&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Five discrete cis-active domains direct cell type-specific transcription of the vasoactive intestinal peptide (VIP) gene. AN - 79972726; 9642274 AB - Vasoactive intestinal peptide (VIP) is a neuromodulator expressed with great anatomical specificity throughout the nervous system. Cell-specific expression of the VIP gene is mediated by a tissue specifier element (TSE) located within a 2.7-kilobase (kb) region between -5.2 and -2.5 kb upstream from the transcription start site, and requires an intact promoter proximal VIP-CRE (cyclic AMP-responsive element) (Hahm, S. H., and Eiden, L. E. (1997) J. Neurochem. 67, 1872-1881). We now report that the TSE comprises a 425-base pair domain located between -4.7 and -4.2 kb containing two AT-rich octamer-like sequences. The 425-base pair TSE is sufficient to provide full cell-specific regulation of the VIP gene, when fused to the 5' proximal 1.55 kb of the VIP gene. Mutational analysis and gel shift assays of these octamer-like sequences indicate that the binding of proteins related to the ubiquitously expressed POU-homeodomain proteins Oct-1 and/or Oct-2 to these octamer-like sequences plays a central role for the function of the TSE. The TSE interacts with three additional discrete domains besides the cAMP response element, which are located within the proximal 1.55 kb of the VIP gene, to provide cell-specific expression. An upstream domain from -1.55 to -1.37 kb contains E-boxes and MEF2-like motifs, and deletion of this domain results in complete abrogation of cell-specific transcriptional activity. The region from -1.37 to -1. 28 kb contains a STAT motif, and further removal of this domain allows the upstream TSE to act as an enhancer in both SH-EP and HeLa cells. The sequence from -1.28 to -0.9 kb containing a non-canonical AP-1 binding sequence (Symes, A., Gearan, T., Eby, J., and Fink, J. S. (1997) J. Biol. Chem. 272, 9648-9654), is absolutely required for TSE-dependent cellspecific expression of the VIP gene. Thus, five discrete domains of the VIP gene provide a combination of enhancer and repressor activities, each completely contingent on VIP gene context, that together result in cell-specific transcription of the VIP gene. JF - The Journal of biological chemistry AU - Hahm, S H AU - Eiden, L E AD - Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892-4090, USA. sungho@codon.nih.gov Y1 - 1998/07/03/ PY - 1998 DA - 1998 Jul 03 SP - 17086 EP - 17094 VL - 273 IS - 27 SN - 0021-9258, 0021-9258 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Genes, Reporter KW - Transcription, Genetic KW - Vasoactive Intestinal Peptide -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Five+discrete+cis-active+domains+direct+cell+type-specific+transcription+of+the+vasoactive+intestinal+peptide+%28VIP%29+gene.&rft.au=Hahm%2C+S+H%3BEiden%2C+L+E&rft.aulast=Hahm&rft.aufirst=S&rft.date=1998-07-03&rft.volume=273&rft.issue=27&rft.spage=17086&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-prostate immunotoxins: cytotoxicity of E4 antibody-Pseudomonas exotoxin constructs. AN - 79951741; 9639403 AB - E4 is a monoclonal antibody (MAb) that reacts with a surface antigen present on normal prostate and prostate cancers. Using this antibody, 2 immunotoxins were generated, one being a chemical conjugate with a mutant truncated form of Pseudomonas exotoxin A (PE), E4-PE35KDEL. The other is a recombinant single chain immunotoxin, E4(Fv)-PE38KDEL. The affinity of the conjugated immunotoxin was similar to the hybridoma-produced MAb E4, revealing that conjugation did not impair the binding ability. The affinity of the recombinant immunotoxin (10 nM) was 10-fold lower than that of the MAb, probably reflecting differences of bivalent (MAb) vs. monovalent (Fv) binding. Antigen positive prostate, breast and colon carcinoma cell lines showed cytotoxic response to the E4 immunotoxins while antigen negative cells were not affected. The IC50 value, representing a 50% inhibition of cellular protein synthesis, ranged from 0.3 to 20 ng/ml for E4-PE35KDEL and from 2 to 100 ng/ml for E4(Fv)-PE38KDEL. Therefore, the E4-derived immunotoxins may be useful for the treatment of prostate as well as breast and colon cancers. JF - International journal of cancer AU - Essand, M AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07/03/ PY - 1998 DA - 1998 Jul 03 SP - 123 EP - 127 VL - 77 IS - 1 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Antigens, Surface KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Recombinant Fusion 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 - Index Medicus KW - Humans KW - Amino Acid Sequence KW - Cell Death -- drug effects KW - Colonic Neoplasms -- immunology KW - Breast Neoplasms -- immunology KW - Tumor Cells, Cultured KW - Breast Neoplasms -- pathology KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- pharmacology KW - Colonic Neoplasms -- pathology KW - Female KW - Male KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- immunology KW - Prostate -- immunology KW - Carcinoma -- pathology KW - Exotoxins -- toxicity KW - Carcinoma -- immunology KW - Immunotoxins -- pharmacology KW - Antigens, Neoplasm -- immunology KW - Antigens, Surface -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-prostate+immunotoxins%3A+cytotoxicity+of+E4+antibody-Pseudomonas+exotoxin+constructs.&rft.au=Essand%2C+M%3BPastan%2C+I&rft.aulast=Essand&rft.aufirst=M&rft.date=1998-07-03&rft.volume=77&rft.issue=1&rft.spage=123&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 - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF025535; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor promoter induces high mobility group HMG-Y protein expression in transformation-sensitive but not -resistant cells. AN - 80043835; 9692546 AB - Elevated levels of high mobility group (HMG) nonhistone chromosomal proteins I and Y, alternatively spliced members of the HMG-I(Y) family of architectural transcription factors, have been linked with human cancer and with neo-plastic and metastatic phenotypes in model systems. To investigate whether HMG-I(Y) proteins may influence susceptibility to neoplastic transformation, HMG-I(Y) mRNA and protein levels were compared in the JB6 murine model of neoplastic progression. HMG-I(Y) mRNAs were expressed at very low levels in preneoplastic, transformation-resistant (P-) cell lines and were constitutively expressed at much higher levels in both transformation-sensitive (P +) and transformed (Tx) tumorigenic cell lines. HMG-I(Y) mRNAs were induced to higher levels by the tumor promoter 12-O-tetradecanoylphorbol acetate (TPA) and were sustained longer in P+ than in P- cells. Nevertheless, in both P- and P+ cells, primer extension analysis revealed that the same four major HMG-I(Y) gene transcription start sites were utilized with or without TPA treatment. RT-PCR revealed that there was always slightly more Y than I form mRNA present in all of the variant JB6 cell lines. Immunoblotting indicated that both HMG-I and -Y proteins increased in P + cells in response to TPA treatment. Remarkably, in P- cells treated with TPA, only HMG-I (and not HMG-Y) protein levels increased. This unique differential TPA-induction of the HMG-Y protein in JB6 variants suggests a role for HMG-Y in mediating tumor promoter-induced neoplastic transformation. Furthermore, these results demonstrate that HMG-I and Y protein translation and/or stability is differently regulated in JB6 P- cells and provide the first indication that I and Y proteins may have different functions. JF - Oncogene AU - Cmarik, J L AU - Li, Y AU - Ogram, S A AU - Min, H AU - Reeves, R AU - Colburn, N H AD - Laboratory of Biochemical Physiology, Frederick Cancer Research and Development Center, National Cancer Institute, Maryland 21702, USA. Y1 - 1998/07/02/ PY - 1998 DA - 1998 Jul 02 SP - 3387 EP - 3396 VL - 16 IS - 26 SN - 0950-9232, 0950-9232 KW - Carcinogens KW - 0 KW - High Mobility Group Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Transcription Factors KW - HMGA1a Protein KW - 124544-67-8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Polymerase Chain Reaction KW - Genetic Variation KW - Carcinogens -- pharmacology KW - Animals KW - Alternative Splicing KW - RNA, Messenger -- analysis KW - Transcription, Genetic KW - Mice KW - RNA, Neoplasm -- analysis KW - Gene Expression Regulation, Neoplastic KW - High Mobility Group Proteins -- biosynthesis KW - High Mobility Group Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Skin Neoplasms -- metabolism KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80043835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+promoter+induces+high+mobility+group+HMG-Y+protein+expression+in+transformation-sensitive+but+not+-resistant+cells.&rft.au=Cmarik%2C+J+L%3BLi%2C+Y%3BOgram%2C+S+A%3BMin%2C+H%3BReeves%2C+R%3BColburn%2C+N+H&rft.aulast=Cmarik&rft.aufirst=J&rft.date=1998-07-02&rft.volume=18&rft.issue=13&rft.spage=5078&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 - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Goal-directed and stimulus-driven attention in cross-dimensional texture segregation. AN - 85408498; pmid-9682607 AB - Goal-directed and stimulus-driven control of attention was examined in a visual texture segregation task. Recent published reports have debated the existence and efficiency of goal-directed guidance of attention. Some of this research has focused on the apparent stimulus-driven attentional priority given to salient distractors, even when they are known to be irrelevant to the task. In the present study, subjects searched a texture array for targets defined along one dimension. These displays also included distractors created by variation in an irrelevant dimension. Targets were of three different overall shapes. On each trial, distractors could be the same shape as the target or one of the other two shapes. In two experiments subjects were informed of the overall shape of the target prior to stimulus presentation. In these experiments, distractors that did not match the overall shape of the target caused less interference than distractors that matched the target's shape. In the third experiment, subjects were not informed of the overall shape of the target. In this experiment all distractors caused roughly equal interference. The results of these experiments demonstrate that if subjects are given information about the overall shape of the target, they are able to use this information to reduce interference from distractors that do not match the overall target shape. While acknowledging some stimulus-driven interference, this illustrates a previously unexplored source of goal-directed guidance that can reduce interfering effects of even salient distractors and argues against purely stimulus-driven control of attention. JF - Perception & psychophysics AU - Ghirardelli, T G AU - Egeth, H E AD - Johns Hopkins University, Baltimore, Maryland, USA. ghirardelli@nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 826 EP - 838 VL - 60 IS - 5 SN - 0031-5117, 0031-5117 KW - Index Medicus; Space life sciences KW - National Library of Medicine KW - Humans KW - Reaction Time KW - Visual Perception -- physiology KW - Goals KW - Attention -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85408498?accountid=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=Perception+%26+psychophysics&rft.atitle=Goal-directed+and+stimulus-driven+attention+in+cross-dimensional+texture+segregation.&rft.au=Ghirardelli%2C+T+G%3BEgeth%2C+H+E&rft.aulast=Ghirardelli&rft.aufirst=T&rft.date=1998-07-01&rft.volume=60&rft.issue=5&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=Perception+%26+psychophysics&rft.issn=00315117&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Case ascertainment uncertainties in prevalence surveys of Parkinson's disease. AN - 85407420; pmid-9686765 AB - Using unpublished data from five completed prevalence surveys of Parkinson's disease (PD), we investigated case ascertainment uncertainties that potentially have a direct effect on prevalence. These uncertainties arise from the choice of diagnostic criteria, the choice of screening method, and the amount of information lost because of nonresponse. The surveys were conducted in Argentina, India, China, Italy, and the Netherlands. Our analyses consisted of simple comparisons of prevalence results, positive predictive values (a screening measure), and nonresponse percentages. We found that (a) prevalence comparisons between surveys have diminished value if the surveys used different diagnostic criteria for PD; (b) screening performance may be affected adversely if symptom questions are answered by one family member for the entire family living together rather than by each family member individually; and (c) nonresponse from refusal or unavailability does not necessarily lead to bias, but special caution may be appropriate with prevalence results pertaining to elderly women. JF - Movement disorders : official journal of the Movement Disorder Society AU - Anderson, D W AU - Rocca, W A AU - de Rijk, M C AU - Grigoletto, F AU - Melcon, M O AU - Breteler, M M AU - Maraganore, D M AD - Biometry and Field Studies Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-9135, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 626 EP - 632 VL - 13 IS - 4 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Data Collection -- statistics & numerical data KW - Mass Screening -- statistics & numerical data KW - Humans KW - Cross-Cultural Comparison KW - Aged KW - Parkinson Disease -- diagnosis KW - Cross-Sectional Studies KW - Aged, 80 and over KW - Incidence KW - Bias (Epidemiology) KW - Male KW - Female KW - Parkinson Disease -- epidemiology KW - Health Surveys UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85407420?accountid=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=Case+ascertainment+uncertainties+in+prevalence+surveys+of+Parkinson%27s+disease.&rft.au=Anderson%2C+D+W%3BRocca%2C+W+A%3Bde+Rijk%2C+M+C%3BGrigoletto%2C+F%3BMelcon%2C+M+O%3BBreteler%2C+M+M%3BMaraganore%2C+D+M&rft.aulast=Anderson&rft.aufirst=D&rft.date=1998-07-01&rft.volume=13&rft.issue=4&rft.spage=626&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 - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Regional cerebral blood flow during auditory responsive naming: evidence for cross-modality neural activation. AN - 85280703; pmid-9694237 AB - One issue of continuing debate in language research concerns whether the brain holds separate representations for semantic information through the auditory vs visual modalities. Regardless of whether we hear, see or read meaningful information, our brains automatically activate both auditory and visual semantic associations to the sensory input. The prominent models for how the brain makes these cross-modality associations holds that semantic information conveyed through either sensory input modality is represented in a shared semantic system comprising the traditionally identified language areas in the brain. A few recent case reports as well as activation imaging studies, have challenged this notion by demonstrating category-specific organization within the semantic system in spatially discrete brain regions. Neither view posits a role for primary sensory cortices in semantic processing. We obtained positron emission tomographic (PET) images while subjects performed an auditory responsive naming task, an auditory analog to visual object naming. Subjects heard and responded to descriptions of concrete objects while blindfolded to prevent visual stimulation. Our results showed that, in addition to traditional language centers, auditory language input produced reciprocal activation in primary and secondary visual brain regions, just as if the language stimuli had entered in the visual modality. These findings provide evidence for a distributed semantic system in which sensory-specific semantic modules are mutually interactive, operating directly onto early sensory processing centers. JF - Neuroreport AU - Bookheimer, S Y AU - Zeffiro, T A AU - Blaxton, T A AU - Gaillard, W D AU - Malow, B AU - Theodore, W H AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 2409 EP - 2413 VL - 9 IS - 10 SN - 0959-4965, 0959-4965 KW - Auditory Cortex KW - Verbal Behavior KW - Human KW - Neurons KW - Adult KW - Tomography, Emission-Computed KW - Cerebrovascular Circulation KW - Female KW - Acoustic Stimulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85280703?accountid=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=Neuroreport&rft.atitle=Regional+cerebral+blood+flow+during+auditory+responsive+naming%3A+evidence+for+cross-modality+neural+activation.&rft.au=Bookheimer%2C+S+Y%3BZeffiro%2C+T+A%3BBlaxton%2C+T+A%3BGaillard%2C+W+D%3BMalow%2C+B%3BTheodore%2C+W+H&rft.aulast=Bookheimer&rft.aufirst=S&rft.date=1998-07-01&rft.volume=9&rft.issue=10&rft.spage=2409&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Rural-urban differences in depression treatment and suicidality. AN - 85264754; pmid-9674626 AB - OBJECTIVES: Because there are fewer per capita providers trained to deliver mental health services in rural areas, the authors hypothesized that depressed rural individuals would receive less outpatient treatment and report higher rates of hospital admittance and suicide attempts than their urban counterparts. METHODS: The authors recruited 74% of eligible participants (n = 470) from a 1992 telephone survey and followed up 95% of subjects for 1 year. The authors collected data from subjects on psychiatric problems and service use and from insurers/providers on treatment and expenditures. RESULTS: Although there were no rural-urban differences in the rate, type, or quality of outpatient depression treatment, rural subjects made significantly fewer specialty care visits for depression. Depressed rural individuals had 3.05 times the odds of being admitted to the hospital for physical problems (P = 0.02) and 3.06 times the odds of being admitted for mental health problems (P = 0.08) during the year. Elevated rates of hospital admittance disappear in models controlling for number of specialty care depression visits in the previous month. Rural subjects reported significantly more suicide attempts during the period of 1 year (P = 0.05). CONCLUSIONS: Additional work is warranted to determine how to alter barriers to outpatient specialty care if the rural health care delivery system is to provide cost-effective depression care. JF - Medical Care AU - Rost, K AU - Zhang, M AU - Fortney, J AU - Smith, J AU - Smith, G R AD - VAHSR&D Field Program for Mental Health and NIMH Center for Rural Mental Healthcare Research, Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, USA. PY - 1998 SP - 1098 EP - 1107 VL - 36 IS - 7 SN - 0025-7079, 0025-7079 KW - Odds Ratio KW - Support, U.S. Gov't, P.H.S. KW - Suicide, Attempted KW - Questionnaires KW - Patient Admission KW - Quality of Health Care KW - Human KW - Aged KW - Depressive Disorder KW - Health Services Accessibility KW - Ambulatory Care KW - Comparative Study KW - Health Care Surveys KW - Aged, 80 and over KW - Adult KW - Middle Age KW - Follow-Up Studies KW - Mental Health Services KW - Adolescent KW - Female KW - Arkansas KW - Male KW - Rural Population KW - Urban Population UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264754?accountid=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=Medical+Care&rft.atitle=Rural-urban+differences+in+depression+treatment+and+suicidality.&rft.au=Rost%2C+K%3BZhang%2C+M%3BFortney%2C+J%3BSmith%2C+J%3BSmith%2C+G+R&rft.aulast=Rost&rft.aufirst=K&rft.date=1998-07-01&rft.volume=36&rft.issue=7&rft.spage=1098&rft.isbn=&rft.btitle=&rft.title=Medical+Care&rft.issn=00257079&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Role of the M2 subunit of ribonucleotide reductase in regulation by hydroxyurea of the activity of the anti-HIV-1 agent 2',3'-dideoxyinosine. AN - 80055972; 9698094 AB - The ribonucleotide reductase inhibitor hydroxyurea exhibits potent synergism, even at low, non-cytotoxic concentrations, with the anti-HIV-1 dideoxynucleoside 2',3'-dideoxyinosine, bringing about failure of HIV DNA synthesis and, thus, of HIV replication. To elucidate the incompletely defined role of hydroxyurea in the hydroxyurea/dideoxyinosine interaction and, in particular, to identify the reasons for the unusual selective inhibitory action of the combination on retroviral rather than on cellular DNA synthesis, we prepared specific cDNA probes to determine the effects of low-level hydroxyurea on mammalian cell ribonucleotide reductase M1 and M2 subunit mRNA, while simultaneously quantitating the effects of the drug on cell cycle and on deoxynucleoside triphosphate pools. While dTTP, dCTP, and dGTP pools changed little or even increased in the presence of low-level hydroxyurea, there took place a rapid and specific inhibition of M2-subunit-catalyzed generation of dATP, with consequent slowing of cellular DNA synthesis and prolongation of S phase. However, the latter effect, in turn, resulted in increased M2 subunit mRNA transcription (a process blocked in Go/G1-phase cells, with full-length functional M2 transcripts being generated only during S phase) and, hence, in a return to normal levels of dATP and to a normal rate of cellular DNA synthesis. Because of this self-regulating mechanism, hydroxyurea-induced host-cell toxicity was obviated under conditions where HIV DNA synthesis, a process sensitive to both dATP depletion and the chain-terminating properties of the other inhibitory component of the combination (ddATP derived from dideoxyinosine), was unable to recover. JF - Biochemical pharmacology AU - Gao, W Y AU - Zhou, B S AU - Johns, D G AU - Mitsuya, H AU - Yen, Y AD - Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wygao@box-w.nih.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 105 EP - 112 VL - 56 IS - 1 SN - 0006-2952, 0006-2952 KW - Anti-HIV Agents KW - 0 KW - DNA Primers KW - Enzyme Inhibitors KW - RNA, Messenger KW - Reverse Transcriptase Inhibitors KW - Ribonucleotide Reductases KW - EC 1.17.4.- KW - Didanosine KW - K3GDH6OH08 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Humans KW - Cell Division -- drug effects KW - RNA, Messenger -- genetics KW - Drug Synergism KW - DNA Replication -- drug effects KW - Cell Line KW - Cell Cycle -- drug effects KW - Ribonucleotide Reductases -- genetics KW - Ribonucleotide Reductases -- metabolism KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Ribonucleotide Reductases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Hydroxyurea -- pharmacology KW - Didanosine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80055972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+M2+subunit+of+ribonucleotide+reductase+in+regulation+by+hydroxyurea+of+the+activity+of+the+anti-HIV-1+agent+2%27%2C3%27-dideoxyinosine.&rft.au=Gao%2C+W+Y%3BZhou%2C+B+S%3BJohns%2C+D+G%3BMitsuya%2C+H%3BYen%2C+Y&rft.aulast=Gao&rft.aufirst=W&rft.date=1998-07-01&rft.volume=56&rft.issue=1&rft.spage=105&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 - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I/II study of the protease inhibitor indinavir in children with HIV infection. AN - 80052713; 9651421 AB - Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine. JF - Pediatrics AU - Mueller, B U AU - Sleasman, J AU - Nelson, R P AU - Smith, S AU - Deutsch, P J AU - Ju, W AU - Steinberg, S M AU - Balis, F M AU - Jarosinski, P F AU - Brouwers, P AU - Mistry, G AU - Winchell, G AU - Zwerski, S AU - Sei, S AU - Wood, L V AU - Zeichner, S AU - Pizzo, P A AD - HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 101 EP - 109 VL - 102 IS - 1 Pt 1 SN - 0031-4005, 0031-4005 KW - Capsules KW - 0 KW - HIV Protease Inhibitors KW - Suspensions KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Indinavir KW - 5W6YA9PKKH KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - HIV -- drug effects KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Lamivudine -- adverse effects KW - Lamivudine -- therapeutic use KW - Child KW - CD4 Lymphocyte Count KW - Biological Availability KW - Child, Preschool KW - Viral Load KW - Infant KW - Drug Therapy, Combination KW - Zidovudine -- pharmacokinetics KW - Lamivudine -- pharmacokinetics KW - Zidovudine -- adverse effects KW - Virus Replication -- drug effects KW - Adult KW - Adolescent KW - Male KW - Female KW - HIV Infections -- virology KW - HIV Infections -- blood KW - HIV Infections -- drug therapy KW - Indinavir -- pharmacokinetics KW - Indinavir -- therapeutic use KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - Indinavir -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80052713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=A+phase+I%2FII+study+of+the+protease+inhibitor+indinavir+in+children+with+HIV+infection.&rft.au=Mueller%2C+B+U%3BSleasman%2C+J%3BNelson%2C+R+P%3BSmith%2C+S%3BDeutsch%2C+P+J%3BJu%2C+W%3BSteinberg%2C+S+M%3BBalis%2C+F+M%3BJarosinski%2C+P+F%3BBrouwers%2C+P%3BMistry%2C+G%3BWinchell%2C+G%3BZwerski%2C+S%3BSei%2C+S%3BWood%2C+L+V%3BZeichner%2C+S%3BPizzo%2C+P+A&rft.aulast=Mueller&rft.aufirst=B&rft.date=1998-07-01&rft.volume=102&rft.issue=1+Pt+1&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-14 N1 - Date created - 1998-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group. AN - 80039468; 9686552 AB - High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. A retrospective cohort study. Twenty-five clinics in the United States and 1 clinic in England. A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism. JF - JAMA AU - Ron, E AU - Doody, M M AU - Becker, D V AU - Brill, A B AU - Curtis, R E AU - Goldman, M B AU - Harris, B S AU - Hoffman, D A AU - McConahey, W M AU - Maxon, H R AU - Preston-Martin, S AU - Warshauer, M E AU - Wong, F L AU - Boice, J D AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 347 EP - 355 VL - 280 IS - 4 SN - 0098-7484, 0098-7484 KW - Iodine Radioisotopes KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Neoplasms, Radiation-Induced -- epidemiology KW - Humans KW - Adult KW - Retrospective Studies KW - Follow-Up Studies KW - Poisson Distribution KW - Likelihood Functions KW - Male KW - Female KW - Iodine Radioisotopes -- therapeutic use KW - Neoplasms -- complications KW - Neoplasms -- mortality KW - Iodine Radioisotopes -- adverse effects KW - Hyperthyroidism -- therapy KW - Hyperthyroidism -- complications KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80039468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer+mortality+following+treatment+for+adult+hyperthyroidism.+Cooperative+Thyrotoxicosis+Therapy+Follow-up+Study+Group.&rft.au=Ron%2C+E%3BDoody%2C+M+M%3BBecker%2C+D+V%3BBrill%2C+A+B%3BCurtis%2C+R+E%3BGoldman%2C+M+B%3BHarris%2C+B+S%3BHoffman%2C+D+A%3BMcConahey%2C+W+M%3BMaxon%2C+H+R%3BPreston-Martin%2C+S%3BWarshauer%2C+M+E%3BWong%2C+F+L%3BBoice%2C+J+D&rft.aulast=Ron&rft.aufirst=E&rft.date=1998-07-01&rft.volume=151&rft.issue=1&rft.spage=110&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1998 Jul 22-29;280(4):375-6 [9686558] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats. AN - 80035805; 9683040 AB - Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344 x NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P < .01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 micromol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH. JF - American journal of hypertension AU - Fedorova, O V AU - Anderson, D E AU - Bagrov, A Y AD - Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224, USA. fedorovo@grc.nia.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 796 EP - 802 VL - 11 IS - 7 SN - 0895-7061, 0895-7061 KW - Bufanolides KW - 0 KW - marinobufagenin KW - 470-42-8 KW - Ouabain KW - 5ACL011P69 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Sodium KW - 9NEZ333N27 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Animals KW - Erythrocytes -- drug effects KW - Hypertension -- blood KW - Sodium-Potassium-Exchanging ATPase -- drug effects KW - Rats KW - Erythrocytes -- enzymology KW - Heart Rate -- drug effects KW - Hypertension -- chemically induced KW - Rats, Inbred F344 KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Sarcolemma -- enzymology KW - Body Weight -- drug effects KW - Sodium -- blood KW - Blood Pressure -- drug effects KW - Systole KW - Sarcolemma -- drug effects KW - Male KW - Immunoassay KW - Ouabain -- blood KW - Bufanolides -- blood KW - Adrenocorticotropic Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80035805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Plasma+marinobufagenin-like+and+ouabain-like+immunoreactivity+in+adrenocorticotropin-treated+rats.&rft.au=Fedorova%2C+O+V%3BAnderson%2C+D+E%3BBagrov%2C+A+Y&rft.aulast=Fedorova&rft.aufirst=O&rft.date=1998-07-01&rft.volume=11&rft.issue=7&rft.spage=796&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 - 1998-11-06 N1 - Date created - 1998-11-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. AN - 80032196; 9683299 AB - Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers. JF - British journal of cancer AU - Ambs, S AU - Bennett, W P AU - Merriam, W G AU - Ogunfusika, M O AU - Oser, S M AU - Khan, M A AU - Jones, R T AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 233 EP - 239 VL - 78 IS - 2 SN - 0007-0920, 0007-0920 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Genes, ras KW - Humans KW - Carcinoma, Squamous Cell -- genetics KW - Mutation KW - Carcinoma, Squamous Cell -- chemistry KW - Carcinoma, Small Cell -- genetics KW - Carcinoma, Small Cell -- chemistry KW - Lung Neoplasms -- chemistry KW - Genes, p53 -- physiology KW - Endothelial Growth Factors -- analysis KW - Lung Neoplasms -- genetics KW - Lymphokines -- analysis KW - Nitric Oxide Synthase -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80032196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vascular+endothelial+growth+factor+and+nitric+oxide+synthase+expression+in+human+lung+cancer+and+the+relation+to+p53.&rft.au=Ambs%2C+S%3BBennett%2C+W+P%3BMerriam%2C+W+G%3BOgunfusika%2C+M+O%3BOser%2C+S+M%3BKhan%2C+M+A%3BJones%2C+R+T%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-01&rft.volume=78&rft.issue=2&rft.spage=233&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1991 Aug 1;51(15):4090-6 [1855224] Clin Cancer Res. 1997 Jun;3(6):861-5 [9815760] FEBS Lett. 1991 Oct 7;291(1):145-9 [1718778] Cancer Res. 1992 May 1;52(9 Suppl):2665s-2669s [1562997] Nature. 1992 Oct 29;359(6398):843-5 [1279431] Nature. 1993 Apr 29;362(6423):841-4 [7683111] Am J Respir Cell Mol Biol. 1993 Oct;9(4):371-7 [7691109] Cancer Res. 1993 Oct 1;53(19):4727-35 [8402650] Nature. 1994 Feb 10;367(6463):576-9 [8107827] Oncogene. 1994 Mar;9(3):963-9 [8108142] Cancer Res. 1994 Mar 1;54(5):1352-4 [7509718] Jpn J Cancer Res. 1994 Apr;85(4):331-4 [7515384] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Science. 1994 Sep 9;265(5178):1582-4 [7521539] Int J Cancer. 1994 Nov 15;59(4):520-9 [7525492] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4392-6 [7538668] Br J Cancer. 1995 Jul;72(1):41-4 [7541238] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7809-13 [7544004] Cancer Res. 1995 Sep 15;55(18):3964-8 [7664263] Cancer Res. 1995 Oct 15;55(20):4575-80 [7553632] J Exp Med. 1995 Dec 1;182(6):1683-93 [7500013] Cancer Res. 1995 Dec 15;55(24):6161-5 [8521408] Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):351-64 [8532063] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2442-7 [8637893] Cell. 1996 Aug 9;86(3):353-64 [8756718] Mol Cell Biol. 1996 Sep;16(9):4604-13 [8756616] Cancer Res. 1996 Aug 1;56(15):3436-40 [8758908] Cancer Res. 1996 Dec 1;56(23):5391-6 [8968091] Cancer Res. 1997 Mar 1;57(5):948-55 [9041200] Br J Cancer. 1997;75(9):1295-301 [9155049] J Clin Invest. 1997 Jun 1;99(11):2625-34 [9169492] Cancer Res. 1997 Aug 1;57(15):3300-4 [9242464] Int J Cancer. 1997 Oct 21;74(5):502-7 [9355971] Cancer Res. 1997 Oct 15;57(20):4474-7 [9377555] Oncogene. 1991 Oct;6(10):1775-8 [1656362] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deamination and Dimroth rearrangement of deoxyadenosine-styrene oxide adducts in DNA. AN - 80026980; 9671547 AB - In reactions between styrene oxide and the ring nitrogen at the 1-position of deoxyadenosine, the epoxide is opened at both the alpha- (benzylic) and beta-carbons. The 1-substituted nucleosides formed are unstable and subsequently undergo either Dimroth rearrangement to give N6-substituted deoxyadenosines or deamination to give 1-substituted deoxyinosines. alphaN6-Substituted compounds are also formed from direct reaction at the exocyclic nitrogen. Kinetic experiments revealed that relative rates of deamination of 1-substituted deoxyadenosine-styrene oxides and 1-substituted adenosine-styrene oxides were similar. However, the rate of Dimroth rearrangement in beta1-substituted adenosine-styrene oxides was approximately 2.3-fold greater than that of beta1-substituted deoxyadenosine-styrene oxides and approximately 1.5-fold greater in alpha1-substituted adenosine-styrene oxides relative to alpha1-substituted deoxyadenosine-styrene oxides. Analysis of the products formed from reactions of styrene oxide with [3H]deoxyadenosine and [3H]deoxyadenosine incorporated into native and denatured DNA showed that the double-helical DNA structure reduced the levels of adducts formed 5-fold relative to denatured DNA but did not present a complete barrier to formation of either N6-substituted deoxyadenosine- or 1-substituted deoxyinosine-styrene oxide adducts in native DNA. Additionally, in denatured and native DNA the product distributions were altered in favor of formation of beta1-substituted deoxyinosine-styrene oxide adducts with respect to reactions of the nucleoside. The ratio of retained to inverted configuration of alphaN6-substituted products was higher in DNA than in nucleoside reactions. These experiments indicate that in addition to the N6-position, the ring nitrogen at the 1-position of deoxyadenosine is available, to some extent, for reaction in native DNA. In styrene oxide-DNA reactions, formation of 1-substituted adenines can lead to deaminated products where both Watson-Crick hydrogen-bonding sites are disrupted. JF - Chemical research in toxicology AU - Barlow, T AU - Takeshita, J 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 - 1998/07// PY - 1998 DA - July 1998 SP - 838 EP - 845 VL - 11 IS - 7 SN - 0893-228X, 0893-228X KW - DNA Adducts KW - 0 KW - Deoxyadenosines KW - Epoxy Compounds KW - DNA KW - 9007-49-2 KW - styrene oxide KW - 9QH06NGT6O KW - Index Medicus KW - Stereoisomerism KW - Kinetics KW - Deamination KW - Spectrophotometry, Ultraviolet KW - Circular Dichroism KW - Chromatography, High Pressure Liquid KW - DNA Adducts -- chemistry KW - Epoxy Compounds -- chemistry KW - DNA -- chemistry KW - Deoxyadenosines -- chemistry KW - DNA Adducts -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deamination+and+Dimroth+rearrangement+of+deoxyadenosine-styrene+oxide+adducts+in+DNA.&rft.au=Barlow%2C+T%3BTakeshita%2C+J%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1998-07-01&rft.volume=11&rft.issue=7&rft.spage=838&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 - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease. AN - 80019795; 9674803 AB - This study assessed the effects of the N-methyl-D-aspartate (NMDA) antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's disease (PD). Recent experimental evidence suggests that increased synaptic efficacy of NMDA receptors expressed on basal ganglia neurons may play a role in the pathophysiology of levodopa-induced motor response complications. DM was given to six PD patients with motor fluctuations in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week study arm, patients received several brief i.v. levodopa infusions while parkinsonian symptoms and dyskinesias were frequently scored. Levodopa dose-response curves for antiparkinsonian and dyskinetic effects were then compared for each study arm. With DM, average and maximum dyskinesia scores improved by >50%, without compromising the antiparkinsonian response magnitude or duration of levodopa, although in some subjects the levodopa threshold dose was slightly higher with DM than with placebo. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptors can ameliorate levodopa-associated dyskinesias. JF - Neurology AU - Verhagen Metman, L AU - Del Dotto, P AU - Natté, R AU - van den Munckhof, P 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 - 1998/07// PY - 1998 DA - July 1998 SP - 203 EP - 206 VL - 51 IS - 1 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Antitussive Agents KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Levodopa KW - 46627O600J KW - Dextromethorphan KW - 7355X3ROTS KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Aged KW - Middle Aged KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Male KW - Antiparkinson Agents -- adverse effects KW - Dextromethorphan -- administration & dosage KW - Dyskinesia, Drug-Induced -- drug therapy KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy KW - Antitussive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dextromethorphan+improves+levodopa-induced+dyskinesias+in+Parkinson%27s+disease.&rft.au=Verhagen+Metman%2C+L%3BDel+Dotto%2C+P%3BNatt%C3%A9%2C+R%3Bvan+den+Munckhof%2C+P%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-07-01&rft.volume=51&rft.issue=1&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death. AN - 80019455; 9670988 AB - We have shown previously that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed "natural" apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum- and 25 mM KCl-containing medium to serum-free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine-protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis. JF - Journal of neuroscience research AU - Araki, T AU - Taniwaki, T AU - Becerra, S P AU - Chader, G J AU - Schwartz, J P AD - Molecular Genetics Section, Clinical Neuroscience Branch, NINDS, Bethesda, Maryland 20892-4126, USA. Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 7 EP - 15 VL - 53 IS - 1 SN - 0360-4012, 0360-4012 KW - Eye Proteins KW - 0 KW - Nerve Growth Factors KW - Neuroprotective Agents KW - Nucleosomes KW - Proteins KW - Serpins KW - Tetrazolium Salts KW - Thiazoles KW - pigment epithelium-derived factor KW - 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium KW - 138169-43-4 KW - Trypan Blue KW - I2ZWO3LS3M KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Count KW - Cells, Cultured KW - Nucleosomes -- metabolism KW - Potassium -- pharmacology KW - Proteins -- pharmacology KW - Cerebellum -- cytology KW - Serpins -- pharmacology KW - Cerebellum -- growth & development KW - Nerve Growth Factors -- pharmacology KW - Cerebellum -- drug effects KW - Apoptosis -- drug effects KW - Cytoprotection -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pigment+epithelium-derived+factor+%28PEDF%29+differentially+protects+immature+but+not+mature+cerebellar+granule+cells+against+apoptotic+cell+death.&rft.au=Araki%2C+T%3BTaniwaki%2C+T%3BBecerra%2C+S+P%3BChader%2C+G+J%3BSchwartz%2C+J+P&rft.aulast=Araki&rft.aufirst=T&rft.date=1998-07-01&rft.volume=53&rft.issue=1&rft.spage=7&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 - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New prospects in the treatment of indolent lymphomas with purine analogues. AN - 80019036; 9672772 AB - To review the activity of the purine analogues fludarabine, cladribine (2-chlorodeoxyadenosine [2-CdA]), and pentostatin (2'-deoxycoformycin) in the treatment of indolent lymphoid malignancies, including chronic lymphocytic leukemia, hairy cell leukemia, and indolent non-Hodgkin's lymphomas (NHLs). Patients with previously untreated, relapsed, or refractory indolent NHL and other indolent lymphoid malignancies who have been treated with purine analogues. Purine analogues have revolutionized the treatment of indolent lymphomas. Fludarabine induces responses in almost 50% of patients with relapsed or refractory indolent NHL and produces complete remissions (CRs) in 10% to 15% of patients. In patients receiving fludarabine as initial treatment, CRs are achieved in almost 40%, with an overall response rate of 70% and a median time to progression > 1 year. Response rates with 2-CdA in previously treated patients appear similar to those with fludarabine, although less durable. Fludarabine and 2-CdA achieve a higher number of durable responses in Waldenström's macroglobulinemia than are generally achieved with alkylating agents in this disease. Pentostatin appears to be less active in NHL. Newer purine analogues currently in clinical trials in lymphomas include gemcitabine and compound 506U. Promising activity has been reported with the combination of fludarabine, mitoxantrone, dexamethasone, and fludarabine plus cyclophosphamide. Combinations of 2-CdA with other agents are also in development. Toxicities associated with these purine analogues primarily include moderate myelosuppression, profound immunosuppression, neurotoxicity at higher than recommended doses, and a possible increase in secondary malignancies. The purine analogues should provide the basis for new treatment strategies with the goal of curing patients with indolent NHL. For progress to continue, patients must be referred to important and innovative clinical research trials. JF - The cancer journal from Scientific American AU - Cheson, B D AD - Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892-7436, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - S27 EP - S36 VL - 4 Suppl 2 SN - 1081-4442, 1081-4442 KW - Antineoplastic Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Pentostatin KW - 395575MZO7 KW - Cladribine KW - 47M74X9YT5 KW - gemcitabine KW - B76N6SBZ8R KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Humans KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- therapeutic use KW - Drug Resistance, Neoplasm KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Vidarabine -- analogs & derivatives KW - Cladribine -- adverse effects KW - Pentostatin -- adverse effects KW - Cladribine -- therapeutic use KW - Lymphoma -- drug therapy KW - Vidarabine -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Vidarabine -- adverse effects KW - Pentostatin -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80019036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+journal+from+Scientific+American&rft.atitle=New+prospects+in+the+treatment+of+indolent+lymphomas+with+purine+analogues.&rft.au=Cheson%2C+B+D&rft.aulast=Cheson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=4+Suppl+2&rft.issue=&rft.spage=S27&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS. AN - 80016863; 9674825 AB - Transforming growth factor (TGF)-beta2 is a pleiotropic cytokine associated with remissions in multiple sclerosis (MS) and amelioration of allergic encephalomyelitis. We assessed the safety of TGF-beta2 in an open-label trial of 11 patients with secondary progressive (SP) MS. Five patients had a reversible decline in the glomerular filtration rate. There was no change in expanded disability status scale or MRI lesions during treatment. Systemic TGF-beta2 may be associated with reversible nephrotoxicity, and further investigation of its therapeutic potential in MS should be performed with caution. JF - Neurology AU - Calabresi, P A AU - Fields, N S AU - Maloni, H W AU - Hanham, A AU - Carlino, J AU - Moore, J AU - Levin, M C AU - Dhib-Jalbut, S AU - Tranquill, L R AU - Austin, H AU - McFarland, H F AU - Racke, M K AD - Neuroimmunology Branch of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 289 EP - 292 VL - 51 IS - 1 SN - 0028-3878, 0028-3878 KW - Transforming Growth Factor beta KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Cerebrospinal Fluid -- cytology KW - Renal Circulation -- drug effects KW - Humans KW - Glomerular Filtration Rate -- drug effects KW - Adult KW - Middle Aged KW - Chronic Disease KW - Blood Urea Nitrogen KW - Male KW - Female KW - Transforming Growth Factor beta -- administration & dosage KW - Transforming Growth Factor beta -- toxicity KW - Multiple Sclerosis -- drug therapy KW - Transforming Growth Factor beta -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+1+trial+of+transforming+growth+factor+beta+2+in+chronic+progressive+MS.&rft.au=Calabresi%2C+P+A%3BFields%2C+N+S%3BMaloni%2C+H+W%3BHanham%2C+A%3BCarlino%2C+J%3BMoore%2C+J%3BLevin%2C+M+C%3BDhib-Jalbut%2C+S%3BTranquill%2C+L+R%3BAustin%2C+H%3BMcFarland%2C+H+F%3BRacke%2C+M+K&rft.aulast=Calabresi&rft.aufirst=P&rft.date=1998-07-01&rft.volume=51&rft.issue=1&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A tryptophan hydroxylase gene marker for suicidality and alcoholism. AN - 80015446; 9672049 AB - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control. Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs. The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002). The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin. JF - Archives of general psychiatry AU - Nielsen, D A AU - Virkkunen, M AU - Lappalainen, J AU - Eggert, M AU - Brown, G L AU - Long, J C AU - Goldman, D AU - Linnoila, M AD - Section of Molecular Genetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. nielsen@helix.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 593 EP - 602 VL - 55 IS - 7 SN - 0003-990X, 0003-990X KW - Genetic Markers KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Tryptophan Hydroxylase KW - EC 1.14.16.4 KW - Abridged Index Medicus KW - Index Medicus KW - Disruptive, Impulse Control, and Conduct Disorders -- genetics KW - Genetic Linkage KW - Regression Analysis KW - Genetic Variation KW - Polymorphism, Genetic KW - Humans KW - Personality -- genetics KW - Prisoners -- statistics & numerical data KW - Personality -- classification KW - Disruptive, Impulse Control, and Conduct Disorders -- epidemiology KW - Genotype KW - Models, Genetic KW - Adult KW - Introns KW - Family KW - Finland -- epidemiology KW - Serotonin -- genetics KW - Male KW - Tryptophan Hydroxylase -- genetics KW - Alcoholism -- epidemiology KW - Suicide, Attempted -- statistics & numerical data KW - Alcoholism -- diagnosis KW - Suicide, Attempted -- classification KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80015446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+studies+with+%5B125I%5D5-I-A-85380%2C+a+nicotinic+acetylcholine+receptor+radioligand.&rft.au=Vaupel%2C+D+B%3BMukhin%2C+A+G%3BKimes%2C+A+S%3BHorti%2C+A+G%3BKoren%2C+A+O%3BLondon%2C+E+D&rft.aulast=Vaupel&rft.aufirst=D&rft.date=1998-07-13&rft.volume=9&rft.issue=10&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solving the puzzle of follicular lymphoma. AN - 80014702; 9672768 JF - The cancer journal from Scientific American AU - Longo, D L AD - National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - S1 EP - S4 VL - 4 Suppl 2 SN - 1081-4442, 1081-4442 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Antineoplastic Agents KW - Immunotoxins KW - Interferon-alpha KW - Rituximab KW - 4F4X42SYQ6 KW - Index Medicus KW - Interferon-alpha -- therapeutic use KW - Disease-Free Survival KW - Lymphoma -- classification KW - Humans KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Remission Induction KW - Antibodies, Monoclonal -- therapeutic use KW - Lymphoma, Follicular -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80014702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+journal+from+Scientific+American&rft.atitle=Solving+the+puzzle+of+follicular+lymphoma.&rft.au=Longo%2C+D+L&rft.aulast=Longo&rft.aufirst=D&rft.date=1998-07-01&rft.volume=4+Suppl+2&rft.issue=&rft.spage=S1&rft.isbn=&rft.btitle=&rft.title=The+cancer+journal+from+Scientific+American&rft.issn=10814442&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. AN - 80006077; 9655900 AB - We have studied the neuroprotective actions of lithium against various insults in cultured cerebellar granule cells of rats. The anticonvulsants, phenytoin and carbamazepine, have been shown to induce apoptosis of cerebellar granule cells at high concentrations. Here we found that co-presence of LiCl (1-10 mM) dose-dependently protected against phenytoin (20 microM)- and carbamazepine (100 microM)-induced neuronal apoptosis as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide metabolism, morphological inspection, chromatin condensation and DNA fragmentation. These neuroprotective effects were not prevented by inclusion of myoinositol nor mimicked by a potent inositol monophosphatase inhibitor, suggestive of a mechanism independent of inositol monophosphatase blockade. Lithium also significantly protected against apoptosis of cerebellar granule cells induced by aging of the cultures. Additionally, lithium suppressed death of cerebellar granule cells exposed to a low concentration of extracellular potassium. In contrast, it had no protective effect on cell death induced by Ca++ ionophores, a Na+ channel opener, a protein kinase inhibitor, a nitric oxide donor or H2O2. Thus, lithium has robust neuroprotective effects against apoptotic cell death induced by multiple insults with limited selectivity. These actions provide a new avenue to study the molecular and cellular mechanisms of this drug. JF - The Journal of pharmacology and experimental therapeutics AU - Nonaka, S AU - Katsube, N AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 539 EP - 547 VL - 286 IS - 1 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Neuroprotective Agents KW - Carbamazepine KW - 33CM23913M KW - Inositol KW - 4L6452S749 KW - Phenytoin KW - 6158TKW0C5 KW - Lithium KW - 9FN79X2M3F KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - 5'-Nucleotidase KW - EC 3.1.3.5 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Phosphatidylinositol 3-Kinases -- physiology KW - Inositol -- pharmacology KW - 5'-Nucleotidase -- antagonists & inhibitors KW - Potassium -- pharmacology KW - Phenytoin -- toxicity KW - Cerebellum -- drug effects KW - Carbamazepine -- toxicity KW - Anticonvulsants -- toxicity KW - Neuroprotective Agents -- pharmacology KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80006077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lithium+protects+rat+cerebellar+granule+cells+against+apoptosis+induced+by+anticonvulsants%2C+phenytoin+and+carbamazepine.&rft.au=Nonaka%2C+S%3BKatsube%2C+N%3BChuang%2C+D+M&rft.aulast=Nonaka&rft.aufirst=S&rft.date=1998-07-01&rft.volume=286&rft.issue=1&rft.spage=539&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia. AN - 80002876; 9667245 AB - To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AU - Frame, J N AU - Vena, D AU - Quashu, N AU - Sorensen, J M AD - Cancer Therapy Evaluation Program, Division of Cancer Diagnosis and Treatment, National Cancer Institute, Bethesda, MD 20892, USA. chesonb@ctep.nci.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 2313 EP - 2320 VL - 16 IS - 7 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Severity of Illness Index KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Retrospective Studies KW - Incidence KW - Aged KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Vidarabine -- analogs & derivatives KW - Tumor Lysis Syndrome -- blood KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Leukemia, Lymphocytic, Chronic, B-Cell -- blood KW - Tumor Lysis Syndrome -- etiology KW - Tumor Lysis Syndrome -- therapy KW - Vidarabine -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+lysis+syndrome%3A+an+uncommon+complication+of+fludarabine+therapy+of+chronic+lymphocytic+leukemia.&rft.au=Cheson%2C+B+D%3BFrame%2C+J+N%3BVena%2C+D%3BQuashu%2C+N%3BSorensen%2C+J+M&rft.aulast=Cheson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=16&rft.issue=7&rft.spage=2313&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of v-Ha-ras transgene expression with development of erythroleukemia in Tg.AC transgenic mice. AN - 80002656; 9665485 AB - A transgenic mouse line (Tg.AC) carrying an activated v-Ha-ras oncogene fused to the embryonic zeta-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation and infiltration. In the peripheral blood, there is a marked increase in the number of metarubricytes and other less differentiated erythroid progenitor cells. Leukemic cells stain positively with an erythroid-associated nuclear transcription factor (GATA-1). Using a reverse transcription polymerase chain reaction assay, co-expression of GATA-1 and endogenous zeta-globin genes is detected in hematopoietic tissues of nonleukemic transgenic and nontransgenic mice. ras transgene expression is, however, detected only in normal bone marrow and leukemic tissues of transgenic mice, and 5' mapping experiments using S1 protection analysis of total RNA from leukemic tissue indicates that transcription of the transgene mRNA is initiated from the natural zeta-globin promoter start site, supporting the belief that the zeta-globin promoter directs v-Ha-ras expression in erythroid progenitor cells, ultimately leading to leukemic transformation. JF - The American journal of pathology AU - Trempus, C S AU - Ward, S AU - Farris, G AU - Malarkey, D AU - Faircloth, R S AU - Cannon, R E AU - Mahler, J F AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 247 EP - 254 VL - 153 IS - 1 SN - 0002-9440, 0002-9440 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - GATA1 Transcription Factor KW - Gata1 protein, mouse KW - Transcription Factors KW - Globins KW - 9004-22-2 KW - ras Proteins KW - EC 3.6.5.2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Transcription Factors -- metabolism KW - Spleen -- metabolism KW - Spleen -- pathology KW - Bone Marrow -- metabolism KW - Liver -- metabolism KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Organ Size KW - Blood Cell Count KW - Polymerase Chain Reaction KW - Blood Cells -- metabolism KW - ras Proteins -- metabolism KW - Globins -- metabolism KW - DNA-Binding Proteins -- metabolism KW - Genes, ras -- genetics KW - Leukemia, Erythroblastic, Acute -- genetics KW - Leukemia, Erythroblastic, Acute -- pathology KW - Leukemia, Erythroblastic, Acute -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+v-Ha-ras+transgene+expression+with+development+of+erythroleukemia+in+Tg.AC+transgenic+mice.&rft.au=Trempus%2C+C+S%3BWard%2C+S%3BFarris%2C+G%3BMalarkey%2C+D%3BFaircloth%2C+R+S%3BCannon%2C+R+E%3BMahler%2C+J+F&rft.aulast=Trempus&rft.aufirst=C&rft.date=1998-07-01&rft.volume=153&rft.issue=1&rft.spage=247&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1996 Sep;17(9):1825-33 [8824502] Leukemia. 1996 Jan;10(1):83-90 [8558943] Mol Carcinog. 1997 Sep;20(1):68-77 [9328437] Blood. 1985 Mar;65(3):705-12 [2982442] Mol Cell Biol. 1985 Apr;5(4):667-74 [2985965] Mol Cell Biol. 1985 May;5(5):1025-33 [4000117] Lab Invest. 1988 May;58(5):484-502 [3285096] Am J Pathol. 1989 Jul;135(1):39-61 [2672826] Leukemia. 1990 Mar;4(3):210-5 [2156115] Lab Anim Sci. 1990 Jul;40(4):418-9 [2166875] Cell. 1990 Nov 16;63(4):665-72 [2225071] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178-82 [2251261] Nature. 1991 Jan 17;349(6306):257-60 [1987478] Blood. 1992 Aug 1;80(3):575-81 [1638017] Am J Pathol. 1993 Apr;142(4):1199-207 [8475993] Nat Genet. 1992 May;1(2):92-8 [1302015] Carcinogenesis. 1993 Jul;14(7):1335-41 [8330346] Eur J Morphol. 1993 Mar-Jun;31(1-2):144-50 [8398549] Toxicol Pathol. 1993;21(2):206-18 [8210943] Mol Carcinog. 1994 Mar;9(3):143-54 [7908201] Br J Haematol. 1994 Feb;86(2):410-2 [8199039] Leukemia. 1994 Jun;8(6):1034-8 [8207977] Genes Dev. 1994 May 15;8(10):1184-97 [7926723] Oncogene. 1994 Dec;9(12):3527-33 [7970713] Development. 1995 Jan;121(1):163-72 [7867497] Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9623-7 [7568185] Nat Genet. 1995 Sep;11(1):9-11 [7550322] Toxicol Pathol. 1996 Nov-Dec;24(6):710-6 [8994298] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II and dose-escalation with or without granulocyte colony-stimulating factor study of 9-aminocamptothecin in relapsed and refractory lymphomas. AN - 80002040; 9667249 AB - To assess the efficacy and maximum dose-intensity of a new topoisomerase I (topo I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. Eligible patients had measurable disease and were considered incurable. 9-AC was infused over 72 hours at an initial dose rate of 40 microg/m2/h every 3 weeks with subsequent intrapatient escalations or reductions in 10-microg/m2/h increments based on toxicity. To assess the impact of granulocyte-colony stimulating factor (G-CSF) on dose-intensity, the first 16 patients received no G-CSF and the subsequent 29 patients received G-CSF on all cycles. Forty-five patients received a total of 142 cycles of 9-AC. The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggressive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respectively, and Hodgkin's lymphoma in 9%. Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy-sensitive disease. Of 40 assessable patients, 10 (25%) achieved a partial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a median follow-up duration of 35 months, the median event-free survival (EFS) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response was 5 months (range, 1 to 10). G-CSF significantly reduced the incidence of neutropenia and diarrhea, but did not permit a significant increase in dose-intensity. 9-AC had a reasonable response rate of 25% in heavily pretreated patients. The low response rate in patients with chemotherapy-resistant disease suggests that there is cross-resistance between 9-AC and standard chemotherapy. However, there was no association between 9-AC response and the number of prior regimens. Due to dose-limiting thrombocytopenia, G-CSF support did not increase dose-intensity, although individual patients benefited from the use of G-CSF. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Little, R AU - Pearson, D AU - Jaffe, E S AU - Steinberg, S M AU - Cheson, B D AU - Humphrey, R AU - Kohler, D R AU - Elwood, P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wilsonw@box-w.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 2345 EP - 2351 VL - 16 IS - 7 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Administration Schedule KW - Disease-Free Survival KW - Infusions, Intravenous KW - Maximum Allowable Concentration KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Recurrence KW - Male KW - Female KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Antineoplastic Agents -- administration & dosage KW - Camptothecin -- analogs & derivatives KW - Lymphoma -- drug therapy KW - Lymphoma -- pathology KW - Camptothecin -- adverse effects KW - Camptothecin -- administration & dosage KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single+gene+complementation+of+the+hPMS2+defect+in+HEC-1-A+endometrial+carcinoma+cells.&rft.au=Risinger%2C+J+I%3BUmar%2C+A%3BGlaab%2C+W+E%3BTindall%2C+K+R%3BKunkel%2C+T+A%3BBarrett%2C+J+C&rft.aulast=Risinger&rft.aufirst=J&rft.date=1998-07-15&rft.volume=58&rft.issue=14&rft.spage=2978&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Clin Oncol 1999 Jun;17(6):1964 J Clin Oncol 1998 Aug;16(8):2895 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis. AN - 79999386; 9649454 AB - We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late-stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy. JF - Gastroenterology AU - Cawley, H M AU - Meltzer, S J AU - De Benedetti, V M AU - Hollstein, M C AU - Muehlbauer, K R AU - Liang, L AU - Bennett, W P AU - Souza, R F AU - Greenwald, B D AU - Cottrell, J AU - Salabes, A AU - Bartsch, H AU - Trivers, G E AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 19 EP - 27 VL - 115 IS - 1 SN - 0016-5085, 0016-5085 KW - Antibodies KW - 0 KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Carcinoma, Squamous Cell -- immunology KW - Humans KW - Adult KW - DNA -- analysis KW - Aged KW - Middle Aged KW - Adenocarcinoma -- immunology KW - Mutation KW - Immunohistochemistry KW - Male KW - Barrett Esophagus -- immunology KW - Antibodies -- blood KW - Esophageal Neoplasms -- diagnosis KW - Tumor Suppressor Protein p53 -- immunology KW - Esophageal Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79999386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Eosinophil+cationic+protein%2FRNase+3+is+another+RNase+A-family+ribonuclease+with+direct+antiviral+activity&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BAdams%2C+A+G%3BLeto%2C+T+L%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-07-15&rft.volume=26&rft.issue=14&rft.spage=3358&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta1 is a new form of tumor suppressor with true haploid insufficiency. AN - 79998682; 9662371 AB - Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-betas themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1 gene express only 10-30% of wild-type TGF-beta1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta1 allele, indicating that the TGF-beta1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis. JF - Nature medicine AU - Tang, B AU - Böttinger, E P AU - Jakowlew, S B AU - Bagnall, K M AU - Mariano, J AU - Anver, M R AU - Letterio, J J AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis (formerly Laboratory of Chemoprevention), National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 802 EP - 807 VL - 4 IS - 7 SN - 1078-8956, 1078-8956 KW - Cell Cycle Proteins KW - 0 KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Liver -- cytology KW - Liver Neoplasms -- metabolism KW - Apoptosis KW - Neoplasms, Experimental -- metabolism KW - Mice KW - Neoplasms, Experimental -- pathology KW - Liver Neoplasms -- pathology KW - Cell Cycle Proteins -- genetics KW - Mice, Inbred C57BL KW - Carcinogenicity Tests KW - Gene Targeting KW - Male KW - Cell Division KW - Lung Neoplasms -- metabolism KW - Lung Neoplasms -- pathology KW - Genes, Tumor Suppressor KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79998682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+growth+factor-beta1+is+a+new+form+of+tumor+suppressor+with+true+haploid+insufficiency.&rft.au=Tang%2C+B%3BB%C3%B6ttinger%2C+E+P%3BJakowlew%2C+S+B%3BBagnall%2C+K+M%3BMariano%2C+J%3BAnver%2C+M+R%3BLetterio%2C+J+J%3BWakefield%2C+L+M&rft.aulast=Tang&rft.aufirst=B&rft.date=1998-07-01&rft.volume=4&rft.issue=7&rft.spage=802&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 - 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 - Mechanical stretch alters the actin cytoskeletal network and signal transduction in human trabecular meshwork cells. AN - 79993212; 9660484 AB - Human trabecular meshwork (HTM) cells were mechanically stretched in vitro as a potential model for the distension of this tissue that can occur in vivo in response to increased pressure gradients. Cell morphology and certain components of the signal transduction pathways, including the mitogen-activated protein kinase (MAPK) and c-Jun N-terminal protein kinase (JNK) pathways, were evaluated for stretch-induced alterations. Primary HTM cells grown in tissue culture were subjected to a mechanical stretch lasting from 10 seconds to 4 days. The actin cytoskeletal network was visualized by phalloidin staining. Proteins phosphorylated on their tyrosine residues were isolated using an immunoaffinity system and were analyzed by gel electrophoresis and immunostaining. Mitogen-activated protein kinase activity was evaluated using an in-gel assay system, and the mRNA levels of c-fos and c-jun were determined by quantitation of competitive reverse transcription-polymerase chain reaction. In addition, the amount of c-Fos protein was estimated by chemiluminescent immunoblot analysis. On stretching, the HTM cells elongated but regained their normal morphologic characteristics within 24 hours. Unstretched HTM cells displayed a diffuse F-actin microfilament network, whereas stretched cells exhibited complex geodesic patterns. Ten seconds after stretching began, the level of tyrosine phosphorylation on the six major phosphoproteins significantly decreased between 80% and 100%, whereas the level of paxillin tyrosine phosphorylation significantly increased 39%. Stretching caused MAPK activity and the amount of mRNA and protein of the immediate-early gene c-fos to decrease more than 60% within 2 minutes, but within 15 to 30 minutes they increased above or equivalent to normal levels. The level of c-jun mRNA was unchanged by stretching. In response to a mechanical stretch, major cytoskeletal alterations occur in HTM cells, which involve changes in the levels of tyrosine phosphorylation. Mechanotransduction (signal transduction by mechanical stimulation) through the MAPK signaling pathway was significantly depressed immediately after stretching; however, the JNK pathway appeared to be unaffected. The data suggest that HTM cells adapt to mechanical stress by altering the cytoskeletal network and signaling cascades. JF - Investigative ophthalmology & visual science AU - Tumminia, S J AU - Mitton, K P AU - Arora, J AU - Zelenka, P AU - Epstein, D L AU - Russell, P AD - Laboratory for Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2735, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1361 EP - 1371 VL - 39 IS - 8 SN - 0146-0404, 0146-0404 KW - Actins KW - 0 KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Phalloidine KW - 17466-45-4 KW - Tyrosine KW - 42HK56048U KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Space life sciences KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Aged KW - Proto-Oncogene Proteins c-jun -- metabolism KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - Proto-Oncogene Proteins c-fos -- genetics KW - Adult KW - Proto-Oncogene Proteins c-jun -- genetics KW - Middle Aged KW - Tyrosine -- metabolism KW - Adolescent KW - Trabecular Meshwork -- metabolism KW - Stress, Mechanical KW - Actin Cytoskeleton -- metabolism KW - Actins -- metabolism KW - Trabecular Meshwork -- cytology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79993212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanical+stretch+alters+the+actin+cytoskeletal+network+and+signal+transduction+in+human+trabecular+meshwork+cells.&rft.au=Tumminia%2C+S+J%3BMitton%2C+K+P%3BArora%2C+J%3BZelenka%2C+P%3BEpstein%2C+D+L%3BRussell%2C+P&rft.aulast=Tumminia&rft.aufirst=S&rft.date=1998-07-01&rft.volume=39&rft.issue=8&rft.spage=1361&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 - 1998-07-14 N1 - Date created - 1998-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1888-9 [10393068] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity. AN - 79992061; 9661887 AB - We investigated the effect of the chemopreventive compound diosmin and its aglycone form, diosmetin, on the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 human breast epithelial cancer cells. Treatment of the cells with diosmin caused a dose-dependent increase in the metabolism of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), as assessed by increased formation of DMBA-DNA adducts and by DMBA-induced cytotoxicity. In contrast, treatment of the cells with diosmetin decreased both parameters. Diosmetin, but not diosmin, directly inhibited cytochrome P450 1A1 (CYP1A1) activity in a noncompetitive manner in microsomes isolated from DMBA-treated cells, as assayed by ethyoxyresorufin-O-deethylase activity. Treatment of the cells with diosmin or diosmetin, on the other hand, caused a dose- and time-dependent increase in CYP1A1 activity in intact cells that was comparable to that induced by DMBA or by the aryl hydrocarbon benzo(a)pyrene. Both diosmin and diosmetin caused an increase in the transcription of the CYP1A1 gene, as measured by increased levels of CYP1A1 mRNA. Both compounds caused the activation of the DNA-binding capacity of the AhR for the xenobiotic-responsive element of CYP1A1. These results indicate that diosmin and diosmetin are natural dietary agonists of the AhR, causing a potent increase in CYP1A1 transcription and CYP1A1 activity; however, only diosmetin is capable of inhibiting CYP1A1 enzyme activity, thus inhibiting carcinogen activation. JF - Cancer research AU - Ciolino, H P AU - Wang, T T AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Maryland 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 2754 EP - 2760 VL - 58 IS - 13 SN - 0008-5472, 0008-5472 KW - 7,12-dimethylbenz(a)anthracene-DNA adduct KW - 0 KW - Carcinogens KW - DNA Adducts KW - Flavonoids KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Diosmin KW - 7QM776WJ5N KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - diosmetin KW - TWZ37241OT KW - Index Medicus KW - Carcinogens -- pharmacology KW - Carcinogens -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- analogs & derivatives KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - DNA Adducts -- metabolism KW - Diosmin -- pharmacology KW - Receptors, Aryl Hydrocarbon -- agonists KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Flavonoids -- pharmacology KW - Cytochrome P-450 CYP1A1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79992061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diosmin+and+diosmetin+are+agonists+of+the+aryl+hydrocarbon+receptor+that+differentially+affect+cytochrome+P450+1A1+activity.&rft.au=Ciolino%2C+H+P%3BWang%2C+T+T%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1998-07-01&rft.volume=58&rft.issue=13&rft.spage=2754&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 - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein-linked DNA strand breaks induced by NSC 314622, a novel noncamptothecin topoisomerase I poison. AN - 79991650; 9658189 AB - NSC 314622 was found to have a cytotoxicity profile comparable to the topoisomerase I (top1) inhibitors camptothecin (CPT) and saintopin in the National Cancer Institute In Vitro Anticancer Drug Discovery Screen using the COMPARE analysis. In vitro data showed that NSC 314622 induced DNA cleavage in the presence of top1 at micromolar concentrations. Cleavage specificity was different from CPT in that NSC 314622 did not cleave all sites induced by CPT whereas some sites were unique to the NSC 314622 treatment. Top1-induced DNA cleavage was also more stable than cleavage induced by CPT. NSC 314622 did not induce DNA cleavage in the presence of human topoisomerase II. High concentrations of NSC 314622 did not produce detectable DNA unwinding, which suggests that NSC 314622 is not a DNA intercalator. DNA damage analyzed in human breast carcinoma MCF7 cells by alkaline elution showed that NSC 314622 induced protein-linked DNA single-strand breaks that reversed more slowly than CPT-induced strand breaks. CEM/C2, a CPT-resistant cell line because of a top1 point mutation [Cancer Res 55:1339-1346 (1995)], was cross-resistant to NSC 314622. These results demonstrate that NSC 314622 is a novel top1-targeted drug with a unique chemical structure. JF - Molecular pharmacology AU - Kohlhagen, G AU - Paull, K D AU - Cushman, M AU - Nagafuji, P AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 50 EP - 58 VL - 54 IS - 1 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - DNA, Neoplasm KW - Indenes KW - Isoquinolines KW - NSC 314622 KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Camptothecin -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Carcinoma -- enzymology KW - Breast Neoplasms -- enzymology KW - Indenes -- chemical synthesis KW - DNA, Neoplasm -- drug effects KW - Isoquinolines -- pharmacology KW - Indenes -- pharmacology KW - DNA Damage KW - Isoquinolines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79991650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein-linked+DNA+strand+breaks+induced+by+NSC+314622%2C+a+novel+noncamptothecin+topoisomerase+I+poison.&rft.au=Kohlhagen%2C+G%3BPaull%2C+K+D%3BCushman%2C+M%3BNagafuji%2C+P%3BPommier%2C+Y&rft.aulast=Kohlhagen&rft.aufirst=G&rft.date=1998-07-01&rft.volume=54&rft.issue=1&rft.spage=50&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth. AN - 79991303; 9659587 AB - The effects of lipoxygenase inhibitors were investigated using human lung cancer cell lines and A/J mice. By RT-PCR, 5-, 12-, and 15-lipoxygenase mRNA was detected in NSCLC cells. NDGA inhibited 5-LO activity in adenocarcinoma cell line NCI-H1264. Using an MTT assay, NDGA, MK591 and AA861 inhibited the growth of NSCLC cell lines tested with IC50 values of 3, 2, and 7 microM, respectively. Using a clonogenic assay, 10 microM NDGA significantly reduced NSCLC colony number. NDGA significantly slowed NSCLC xenograft growth in nude mice. When the tumors were excised and analyzed, nude mice treated with NDGA had significantly more apoptotic figures than did untreated tumors. A/J mice treated with urethane developed adenomas after 4 months and NDGA administration significantly reduced lung adenoma number. These data indicate that lipoxygenase inhibitors inhibit lung cancer growth and prevent lung carcinogenesis. JF - Experimental lung research AU - Moody, T W AU - Leyton, J AU - Martinez, A AU - Hong, S AU - Malkinson, A AU - Mulshine, J L AD - Cell and Cancer Biology Department, National Cancer Institute, Rockville, Maryland, USA. moodyt@bprb.nci.nih.gov PY - 1998 SP - 617 EP - 628 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - Benzoquinones KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - Indoles KW - Lipoxygenase Inhibitors KW - Quinolines KW - RNA, Messenger KW - MK 0591 KW - 136668-42-3 KW - Masoprocol KW - 7BO8G1BYQU KW - 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone KW - 80809-81-0 KW - Lipoxygenase KW - EC 1.13.11.12 KW - Index Medicus KW - Animals KW - Lipoxygenase -- genetics KW - Humans KW - Mice, Nude KW - DNA, Neoplasm -- analysis KW - Mice KW - Mice, Inbred BALB C KW - RNA, Messenger -- biosynthesis KW - Neoplasm Transplantation KW - Mice, Inbred A KW - Quinolines -- pharmacology KW - Tumor Cells, Cultured KW - Benzoquinones -- pharmacology KW - Indoles -- pharmacology KW - Immunoenzyme Techniques KW - DNA Primers -- chemistry KW - Masoprocol -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- prevention & control KW - Adenocarcinoma -- enzymology KW - Lung Neoplasms -- enzymology KW - Lung Neoplasms -- prevention & control KW - Lipoxygenase Inhibitors -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Adenocarcinoma -- prevention & control KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79991303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Lipoxygenase+inhibitors+prevent+lung+carcinogenesis+and+inhibit+non-small+cell+lung+cancer+growth.&rft.au=Moody%2C+T+W%3BLeyton%2C+J%3BMartinez%2C+A%3BHong%2C+S%3BMalkinson%2C+A%3BMulshine%2C+J+L&rft.aulast=Moody&rft.aufirst=T&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta expression in mouse lung carcinogenesis. AN - 79990475; 9659584 AB - Transforming growth factor-beta (TGF-beta) is a multifunctional growth modulator that inhibits the proliferation of many epithelial cells while stimulating the proliferation of most fibroblasts. To examine the role of TGF-beta in mouse lung chemically induced tumorigenesis, expression of the TGF-beta 1, -beta 2, and -beta 3 proteins was examined in A/J mice treated with the carcinogen urethane to induce lung adenomas using immunohistochemical staining analysis. Immunostaining for the TGF-beta ligands was detected in the epithelium of the bronchioles of untreated A/J mice with immunostaining being more intense for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3; immunostaining for each TGF-beta ligand was also detected in the bronchiolar epithelium of urethane-treated A/J mice at levels similar to untreated mice. Immunostaining for the TGF-beta ligands was also detected in adenomas by 2 months; staining for TGF-beta 1, -beta 2, and -beta 3 in adenomas was detected at levels comparable with bronchioles. Following treatment with urethane for 8 months, immunostaining for TGF-beta s 1, 2, and 3 in bronchioles persisted at levels comparable to that in normal bronchioles and also persisted in adenomas, with staining for the TGF-beta ligands being very prominent on the edge of the tumor. Expression of TGF-beta 1 mRNA was examined in urethane-treated mouse lung tissue using Northern blot hybridization; here, expression of TGF-beta 1 mRNA increased 2-fold in 3-month urethane-treated lung tissue and an additional 2.5-fold by 8 months following urethane administration. Expression of TGF-beta 1 mRNA was also examined in nontumorigenic and tumorigenic mouse lung cells; in these cells, expression of TGF-beta 1 mRNA was higher in the tumorigenic cells than in the nontumorigenic cell line. These data show that there is an increase in expression of TGF-beta 1 during tumorigenesis and suggest that TGF-beta may play an important role in mouse lung carcinogenesis induced by urethane. JF - Experimental lung research AU - Jakowlew, S B AU - Moody, T W AU - You, L AU - Mariano, J M AD - National Cancer Institute, Medicine Branch, Rockville, Maryland, USA. PY - 1998 SP - 579 EP - 593 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - Carcinogens KW - 0 KW - DNA Primers KW - Ligands KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Urethane KW - 3IN71E75Z5 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Lung -- cytology KW - Carcinogens -- toxicity KW - Disease Progression KW - Mice KW - Lung -- metabolism KW - RNA, Messenger -- biosynthesis KW - Epithelial Cells -- metabolism KW - Polymerase Chain Reaction KW - Mice, Inbred A KW - Tumor Cells, Cultured KW - Bronchi -- cytology KW - Bronchi -- metabolism KW - Urethane -- toxicity KW - Female KW - Immunoenzyme Techniques KW - DNA Primers -- chemistry KW - Adenoma -- metabolism KW - Adenoma -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Transforming Growth Factor beta -- genetics KW - Adenoma -- pathology KW - Transforming Growth Factor beta -- metabolism KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79990475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Transforming+growth+factor-beta+expression+in+mouse+lung+carcinogenesis.&rft.au=Jakowlew%2C+S+B%3BMoody%2C+T+W%3BYou%2C+L%3BMariano%2C+J+M&rft.aulast=Jakowlew&rft.aufirst=S&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=579&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques. AN - 79988679; 9657528 AB - This study investigated the sources of quinolinic acid, a neurotoxic tryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, quinolinic acid concentrations in HIV-infected patients were elevated by > 300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (>98%) was synthesized locally within the brain. These results demonstrate a role for induction of indoleamine-2,3dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Heyes, M P AU - Saito, K AU - Lackner, A AU - Wiley, C A AU - Achim, C L AU - Markey, S P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 881 EP - 896 VL - 12 IS - 10 SN - 0892-6638, 0892-6638 KW - Kynurenine KW - 343-65-7 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Central Nervous System -- metabolism KW - Animals KW - Cerebral Cortex -- metabolism KW - Macaca KW - Humans KW - Kynurenine -- cerebrospinal fluid KW - Quinolinic Acid -- cerebrospinal fluid KW - Acquired Immunodeficiency Syndrome -- blood KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Brain -- pathology KW - Kynurenine -- metabolism KW - Retroviridae Infections -- cerebrospinal fluid KW - Brain -- metabolism KW - Retroviridae Infections -- metabolism KW - HIV-1 KW - Acquired Immunodeficiency Syndrome -- cerebrospinal fluid KW - Acquired Immunodeficiency Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79988679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.atitle=Sources+of+the+neurotoxin+quinolinic+acid+in+the+brain+of+HIV-1-infected+patients+and+retrovirus-infected+macaques.&rft.au=Heyes%2C+M+P%3BSaito%2C+K%3BLackner%2C+A%3BWiley%2C+C+A%3BAchim%2C+C+L%3BMarkey%2C+S+P&rft.aulast=Heyes&rft.aufirst=M&rft.date=1998-07-01&rft.volume=12&rft.issue=10&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=08926638&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of an unstable allele of the Arabidopsis HY4 locus. AN - 79985922; 9649544 AB - The Arabidopsis HY4 gene encodes the nonessential blue light photoreceptor CRY1. Loss-of-function hy4 mutants have an elongated hypocotyl phenotype after germination under blue light. We previously analyzed 20 independent hy4 alleles produced by fast neutron mutagenesis. These alleles were grouped into two classes based on their genetic behavior and corresponding deletion size: (1) null hy4 alleles that were semidominant over wild type and contained small or moderate-sized deletions at HY4 and (2) null hy4 alleles that were recessive lethal and contained large HY4 deletions. Here we describe one additional fast neutron hy4 mutant, B144, that did not fall into either of these two classes. Mutant B144 was isolated as a heterozygote with an intermediate hy4 phenotype. One allele from this mutant, hy4-B144(Delta), contains a large deletion at HY4 and is recessive lethal. The other allele from this mutant, HY4-B144*, appears to be intact and functional but is unstable and spontaneously converts to a nonfunctional hy4 allele. In addition, HY4-B144* is lethal in homozygotes and suppresses local recombination. We discuss genetic and epigenetic mechanisms that may account for the unusual behavior of the HY4-B144* allele. JF - Genetics AU - Bruggemann, E P AU - Doan, B AU - Handwerger, K AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1575 EP - 1585 VL - 149 IS - 3 SN - 0016-6731, 0016-6731 KW - Arabidopsis Proteins KW - 0 KW - CRY1 protein, Arabidopsis KW - CRY1 protein, human KW - Cryptochromes KW - Drosophila Proteins KW - Eye Proteins KW - Flavoproteins KW - Plant Proteins KW - Receptors, G-Protein-Coupled KW - cryptochrome protein, Drosophila KW - Index Medicus KW - Phenotype KW - Neutrons KW - Genotype KW - Alleles KW - Crosses, Genetic KW - Light KW - Mutagenesis KW - Plant Proteins -- biosynthesis KW - Arabidopsis -- genetics KW - Flavoproteins -- biosynthesis KW - Flavoproteins -- genetics KW - Plant Proteins -- genetics KW - Genes, Plant KW - Arabidopsis -- physiology KW - Photoreceptor Cells, Invertebrate KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Up-regulation+of+inducible+nitric+oxide+synthase+expression+in+cancer-prone+p53+knockout+mice.&rft.au=Ambs%2C+S%3BOgunfusika%2C+M+O%3BMerriam%2C+W+G%3BBennett%2C+W+P%3BBilliar%2C+T+R%3BHarris%2C+C+C&rft.aulast=Ambs&rft.aufirst=S&rft.date=1998-07-21&rft.volume=95&rft.issue=15&rft.spage=8823&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 - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Plant J. 1993 Aug;4(2):403-10 [8106085] Plant J. 1993 Mar;3(3):493-4 [8220456] Plant Cell. 1994 May;6(5):613-28 [8038602] Biochemistry. 1995 May 23;34(20):6892-9 [7756321] Science. 1995 Aug 18;269(5226):968-70 [7638620] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8423-7 [7667306] Planta. 1995;197(2):213-8 [8547813] Planta. 1995;197(2):233-9 [8547814] Plant J. 1996 May;9(5):755-65 [8653121] Plant J. 1996 Oct;10(4):755-60 [8893551] Plant J. 1996 Nov;10(5):893-902 [8953250] Nucleic Acids Res. 1986 May 27;14(10):4051-64 [3012462] Mol Cell Biol. 1988 May;8(5):1985-92 [3386631] Proc Natl Acad Sci U S A. 1988 Sep;85(18):6856-60 [2901107] Nature. 1993 Nov 11;366(6451):162-6 [8232555] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of quantitative trait loci to map murine lung tumor susceptibility genes. AN - 79985094; 9659574 AB - During the last decade new methods for mapping quantitative trait loci (QTLs) have helped geneticists uncover disease-associated genes. Genetic dissection of complex multigenic diseases such as cancer is being accomplished in part by mapping QTLs in experimental crosses of mice [1]. With the recent construction of dense genetic linkage maps for the mouse, mapping of quantitative trait loci has become practical [2]. Over 6000 polymorphic simple sequence length repeat markers (microsatellite markers) have been mapped in the mouse genome [3], and new analytical approaches to linkage analysis have made QTL mapping a powerful technique for identifying cancer genes [4-7]. In this overview we discuss the design of QTL mapping studies and some of the findings from studies on the mapping of murine lung tumor susceptibility loci. JF - Experimental lung research AU - Devereux, T R AU - Kaplan, N L AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. devereux@niehs.nih.gov PY - 1998 SP - 407 EP - 417 VL - 24 IS - 4 SN - 0190-2148, 0190-2148 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Quantitative Trait, Heritable KW - Genetic Linkage KW - Microsatellite Repeats KW - Mice, Inbred A KW - Animals KW - Mice, Inbred C57BL KW - Disease Models, Animal KW - Mice KW - Inbreeding KW - Genetic Predisposition to Disease KW - Gene Expression Regulation, Neoplastic KW - Lung Neoplasms -- genetics KW - DNA, Neoplasm -- analysis KW - Chromosome Mapping KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79985094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Use+of+quantitative+trait+loci+to+map+murine+lung+tumor+susceptibility+genes.&rft.au=Devereux%2C+T+R%3BKaplan%2C+N+L&rft.aulast=Devereux&rft.aufirst=T&rft.date=1998-07-01&rft.volume=24&rft.issue=4&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weight change and obesity after liver transplantation: incidence and risk factors. AN - 79983690; 9649642 AB - Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P < .05). Posttransplantation predictors of obesity included absence of acute cellular rejection, higher cumulative prednisone dose in the second year, and cyclosporine-based immunosuppression, although only rejection and prednisone dose remained predictors on multivariate analysis. Despite the marked weight gain after transplantation, prevalence of obesity at 2 years was only slightly greater than in the general US population. Obesity occurred commonly after liver transplantation, sometimes with a striking gain in weight. In addition to BMI at transplantation, donor BMI, marital status, occurrence of acute rejection, and prednisone dose affected the incidence of obesity. Copyright 1998 W.B. Saunders Company. JF - Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society AU - Everhart, J E AU - Lombardero, M AU - Lake, J R AU - Wiesner, R H AU - Zetterman, R K AU - Hoofnagle, J H AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 285 EP - 296 VL - 4 IS - 4 SN - 1074-3022, 1074-3022 KW - Glucocorticoids KW - 0 KW - Immunosuppressive Agents KW - Cyclosporine KW - 83HN0GTJ6D KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Humans KW - Aged KW - Glucocorticoids -- adverse effects KW - Body Mass Index KW - Graft Rejection -- complications KW - Cyclosporine -- adverse effects KW - Prednisone -- adverse effects KW - Risk Factors KW - Adult KW - Cohort Studies KW - Graft Rejection -- drug therapy KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Immunosuppressive Agents -- adverse effects KW - Obesity -- etiology KW - Weight Gain KW - Obesity -- epidemiology KW - Liver Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.atitle=Weight+change+and+obesity+after+liver+transplantation%3A+incidence+and+risk+factors.&rft.au=Everhart%2C+J+E%3BLombardero%2C+M%3BLake%2C+J+R%3BWiesner%2C+R+H%3BZetterman%2C+R+K%3BHoofnagle%2C+J+H&rft.aulast=Everhart&rft.aufirst=J&rft.date=1998-07-01&rft.volume=4&rft.issue=4&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Liver+transplantation+and+surgery+%3A+official+publication+of+the+American+Association+for+the+Study+of+Liver+Diseases+and+the+International+Liver+Transplantation+Society&rft.issn=10743022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-11 N1 - Date created - 1998-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concentrating defect in experimental nephrotic syndrone: altered expression of aquaporins and thick ascending limb Na+ transporters. AN - 79974596; 9648076 AB - Several pathophysiological states associated with deranged water balance are associated with altered expression and/or intracellular distribution of aquaporin water channels. The possible role of dysregulation of thick ascending limb NaCl transporters, which are responsible for countercurrent multiplication in the kidney, has not been evaluated. Semiquantitative immunoblotting and immunocytochemistry were carried out in the kidneys of rat with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats. Preliminary studies confirmed the presence of a severe concentrating defect. Semiquantitative immunoblotting of outer medullary homogenates demonstrated a marked decrease in the abundance of three thick ascending limb Na+ transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit of the Na-K-ATPase. These results are predictive of a decrease in the NaCl transport capacity of the medullary thick ascending limb and therefore a decrease in countercurrent multiplication. Immunocytochemistry of outer medullary thin sections demonstrated broad (but highly variable) suppression of BSC-1 expression in the outer medullas of adriamycin-nephrotic rats. There was also a large decrease in outer medullary expression of two collecting duct water channels (aquaporin-2 and -3) and the major water channel of the thin descending limb of Henle's loop (aquaporin-1). The concentrating defect in adriamycin-induced nephrotic syndrome in rats is a consequence of multiple defects in water and solute transporter expression, which would alter both the generation of medullary interstitial hypertonicity and osmotic equilibration in the collecting duct. Whether a similar widespread defect in transporter expression is present in idiopathic nephrotic syndrome is, at this point, untested. JF - Kidney international AU - Fernández-Llama, P AU - Andrews, P AU - Ecelbarger, C A AU - Nielsen, S AU - Knepper, M AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, Maryland, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 170 EP - 179 VL - 54 IS - 1 SN - 0085-2538, 0085-2538 KW - Antibiotics, Antineoplastic KW - 0 KW - Aqp1 protein, rat KW - Aqp2 protein, rat KW - Aqp3 protein, rat KW - Aquaporin 2 KW - Aquaporin 6 KW - Aquaporins KW - Carrier Proteins KW - Ion Channels KW - Membrane Proteins KW - Mucoproteins KW - Sodium-Hydrogen Antiporter KW - Sodium-Potassium-Chloride Symporters KW - Umod protein, rat KW - Uromodulin KW - Aquaporin 1 KW - 146410-94-8 KW - Aquaporin 3 KW - 158801-98-0 KW - Doxorubicin KW - 80168379AG KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Mucoproteins -- metabolism KW - Membrane Proteins -- metabolism KW - Disease Models, Animal KW - Rabbits KW - Loop of Henle -- chemistry KW - Membrane Proteins -- analysis KW - Osmosis KW - Kidney Concentrating Ability -- physiology KW - Rats KW - Rats, Sprague-Dawley KW - Loop of Henle -- enzymology KW - Immunohistochemistry KW - Male KW - Mucoproteins -- analysis KW - Sodium-Potassium-Exchanging ATPase -- analysis KW - Sodium-Hydrogen Antiporter -- analysis KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Nephrotic Syndrome -- physiopathology KW - Carrier Proteins -- metabolism KW - Sodium-Hydrogen Antiporter -- metabolism KW - Nephrotic Syndrome -- metabolism KW - Ion Channels -- analysis KW - Nephrotic Syndrome -- chemically induced KW - Carrier Proteins -- analysis KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79974596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Concentrating+defect+in+experimental+nephrotic+syndrone%3A+altered+expression+of+aquaporins+and+thick+ascending+limb+Na%2B+transporters.&rft.au=Fern%C3%A1ndez-Llama%2C+P%3BAndrews%2C+P%3BEcelbarger%2C+C+A%3BNielsen%2C+S%3BKnepper%2C+M&rft.aulast=Fern%C3%A1ndez-Llama&rft.aufirst=T&rft.date=1998-07-30&rft.volume=248&rft.issue=3&rft.spage=835&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and substance abuse. AN - 79973294; 9650635 AB - Association studies with the DRD2 Taq1A marker have been variable in implicating DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse. Given that the Taq1A marker is not functionally significant, second-generation studies on the DRD2 receptor to identify functional variants and evaluate their effect on the phenotype are the logical step towards confirming and extending the DRD2 hypothesis. This article discusses the implications and process of progress made in these directions. The new findings are the description of structural variants in the D2 receptor, the demonstration that one of these, Ser311Cys, largely prevents signal transduction following receptor activation and the use of Ser311Cys in a large association and sib-pair linkage anlysis in an American Indian isolate. In this particular population, the Cys311 variant is far more abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2 intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and 15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism, substance use disorders, or schizophrenia. The implication is that a DRD2 variant that dramatically impairs receptor function was not sufficient to significantly alter alcoholism vulnerability in a relatively large and also genetically and environmentally homogeneous sample. JF - Alcohol (Fayetteville, N.Y.) AU - Goldman, D AU - Urbanek, M AU - Guenther, D AU - Robin, R AU - Long, J C AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. dgneuro@box-d.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 47 EP - 52 VL - 16 IS - 1 SN - 0741-8329, 0741-8329 KW - Receptors, Dopamine D2 KW - 0 KW - Index Medicus KW - Humans KW - Amino Acid Sequence KW - Indians, North American -- genetics KW - Genetic Linkage KW - Genetic Variation -- genetics KW - Receptors, Dopamine D2 -- genetics KW - Alcoholism -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%28Fayetteville%2C+N.Y.%29&rft.atitle=A+functionally+deficient+DRD2+variant+%5BSer311Cys%5D+is+not+linked+to+alcoholism+and+substance+abuse.&rft.au=Goldman%2C+D%3BUrbanek%2C+M%3BGuenther%2C+D%3BRobin%2C+R%3BLong%2C+J+C&rft.aulast=Goldman&rft.aufirst=D&rft.date=1998-07-01&rft.volume=16&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-11 N1 - Date created - 1998-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoids increase vasopressin V1b receptor coupling to phospholipase C. AN - 79972523; 9645696 AB - Vasopressin (VP) stimulates pituitary ACTH secretion after binding to V1b VP receptors (V1b-R) coupled to phospholipase C (PLC). This effect of VP on ACTH secretion, unlike that of CRH, is resistant to glucocorticoid feedback. To determine whether changes in V1b-R expression or signaling mediate the refractoriness to glucocorticoids, the effects of glucocorticoids on pituitary VP binding, V1b-R messenger RNA (mRNA) and VP-stimulated inositol phosphate (IP) formation were studied in vivo and in vitro in the rat. Dexamethasone injection for 7 days decreased VP binding but increased V1b-R mRNA, indicating that mRNA levels do not reflect receptor number. In spite of the binding loss, VP-stimulated IP formation was enhanced in dexamethasone-treated rats, suggesting that glucocorticoids increase the coupling efficiency of the V1b receptor to phospholipase C. Pretreatment of pituitary cells in vitro with dexamethasone or corticosterone, also potentiated IP formation by low and high doses of VP, indicating that glucocorticoids act directly in the pituitary and not through changes in hypothalamic factors. The effect is mediated by glucocorticoid receptors because it was blocked by glucocorticoid but not mineralocorticoid antagonists. Dexamethasone potentiated the stimulation of IP by other PLC-dependent ligands (GnRH, TRH) but not that by the calcium ionophore, ionomycin, suggesting a site of action between the receptor and PLC. After treatment with dexamethasone, in vivo or in vitro, Western blot analysis revealed marked increases in the GTP binding protein, Galpha(q), which may account for the potentiating effect of glucocorticoid on ligand-stimulated IP. The data demonstrate that glucocorticoids increase coupling of the V1b-R with PLC thereby providing a mechanism by which VP facilitates corticotroph responsiveness in spite of elevated levels of plasma glucocorticoids during stress. JF - Endocrinology AU - Rabadan-Diehl, C AU - Aguilera, G AD - Section on Endocrine, Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. rabadanc@cc1.nichd.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3220 EP - 3226 VL - 139 IS - 7 SN - 0013-7227, 0013-7227 KW - Glucocorticoids KW - 0 KW - Inositol Phosphates KW - Receptors, Vasopressin KW - Vasopressins KW - 11000-17-2 KW - Dexamethasone KW - 7S5I7G3JQL KW - Type C Phospholipases KW - EC 3.1.4.- KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Inositol Phosphates -- biosynthesis KW - Pituitary Gland, Anterior -- metabolism KW - Cells, Cultured KW - Dexamethasone -- pharmacology KW - Vasopressins -- pharmacology KW - Pituitary Gland, Anterior -- cytology KW - Drug Synergism KW - Male KW - Receptors, Vasopressin -- metabolism KW - Glucocorticoids -- pharmacology KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoids+increase+vasopressin+V1b+receptor+coupling+to+phospholipase+C.&rft.au=Rabadan-Diehl%2C+C%3BAguilera%2C+G&rft.aulast=Rabadan-Diehl&rft.aufirst=C&rft.date=1998-07-01&rft.volume=139&rft.issue=7&rft.spage=3220&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-17 N1 - Date created - 1998-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Statistical modeling of carcinogenic risks in dogs that inhaled 238PuO2. AN - 79972034; 9650604 AB - Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets. JF - Radiation research AU - Gilbert, E S AU - Griffith, W C AU - Boecker, B B AU - Dagle, G E AU - Guilmette, R A AU - Hahn, F F AU - Muggenburg, B A AU - Park, J F AU - Watson, C R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 66 EP - 82 VL - 150 IS - 1 SN - 0033-7587, 0033-7587 KW - plutonium dioxide KW - 12059-95-9 KW - Plutonium KW - 53023GN24M KW - Index Medicus KW - Space life sciences KW - Bone Neoplasms -- etiology KW - Animals KW - Lung Neoplasms -- etiology KW - Liver Neoplasms, Experimental -- etiology KW - Risk Factors KW - Linear Models KW - Dogs KW - Data Interpretation, Statistical KW - Dose-Response Relationship, Radiation KW - Administration, Inhalation KW - Male KW - Female KW - Proportional Hazards Models KW - Neoplasms, Radiation-Induced -- etiology KW - Plutonium -- administration & dosage KW - Plutonium -- toxicity KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Statistical+modeling+of+carcinogenic+risks+in+dogs+that+inhaled+238PuO2.&rft.au=Gilbert%2C+E+S%3BGriffith%2C+W+C%3BBoecker%2C+B+B%3BDagle%2C+G+E%3BGuilmette%2C+R+A%3BHahn%2C+F+F%3BMuggenburg%2C+B+A%3BPark%2C+J+F%3BWatson%2C+C+R&rft.aulast=Gilbert&rft.aufirst=E&rft.date=1998-07-01&rft.volume=150&rft.issue=1&rft.spage=66&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study. AN - 79965231; 9637799 AB - To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases. JF - Environmental health perspectives AU - Alavanja, M C AU - Sandler, D P AU - McDonnell, C J AU - Lynch, C F AU - Pennybacker, M AU - Zahm, S H AU - Lubin, J AU - Mage, D AU - Steen, W C AU - Wintersteen, W AU - Blair, A AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 415 EP - 420 VL - 106 IS - 7 SN - 0091-6765, 0091-6765 KW - Pesticides KW - 0 KW - Index Medicus KW - Office Visits -- statistics & numerical data KW - Regression Analysis KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Iowa -- epidemiology KW - Female KW - Agricultural Workers' Diseases -- epidemiology KW - Agricultural Workers' Diseases -- chemically induced KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79965231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Factors+associated+with+self-reported%2C+pesticide-related+visits+to+health+care+providers+in+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+S+H%3BLubin%2C+J%3BMage%2C+D%3BSteen%2C+W+C%3BWintersteen%2C+W%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1998-07-01&rft.volume=106&rft.issue=7&rft.spage=415&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 - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Agric Food Chem. 1983 May-Jun;31(3):645-50 [6886220] Arch Toxicol. 1983 Dec;54(4):257-65 [6667116] Am Ind Hyg Assoc J. 1984 Jan;45(1):56-62 [6702600] Med Care. 1985 May;23(5):438-60 [4010347] Arch Environ Contam Toxicol. 1986 Nov;15(6):677-86 [3789810] Vet Hum Toxicol. 1987 Oct;29(5):391-7 [2961120] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] J Psychosom Res. 1990;34(5):525-34 [2231486] Am J Public Health. 1991 Jun;81(6):750-3 [2029045] J Occup Med. 1992 Apr;34(4):414-21 [1564580] Epidemiology. 1993 Jan;4(1):55-62 [8420582] Am Ind Hyg Assoc J. 1995 Sep;56(9):883-9 [7677069] Vet Hum Toxicol. 1988 Jun;30(3):246-54 [3291386] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sonography of gallbladder abnormalities in acromegaly patients following octreotide and ursodiol therapy: incidence and time course. AN - 79960468; 9641388 AB - We studied the effects of octreotide and ursodiol on the gallbladders of patients with acromegaly. We performed gallbladder sonography in patients with acromegaly at various intervals during treatment. Group I (18 patients) was treated with subcutaneous injections of the somatostatin analogue octreotide. Group II (10 patients) was treated with ursodiol while receiving octreotide therapy. Seventy-eight percent of patients receiving octreotide developed gallbladder abnormalities: sludge in 72% (13/18) and calculi in 39% (7/18). Ursodiol reversed the gallbladder abnormalities in 7 of 10 patients. A majority of patients receiving octreotide develop gallbladder abnormalities. Ursodiol appears to reverse the abnormalities in most cases. JF - Journal of clinical ultrasound : JCU AU - Avila, N A AU - Shawker, T H AU - Roach, P AU - Bradford, M H AU - Skarulis, M C AU - Eastman, R AD - Diagnostic Radiology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1182, USA. PY - 1998 SP - 289 EP - 294 VL - 26 IS - 6 SN - 0091-2751, 0091-2751 KW - Cholagogues and Choleretics KW - 0 KW - Hormones KW - Ursodeoxycholic Acid KW - 724L30Y2QR KW - Octreotide KW - RWM8CCW8GP KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Ultrasonography KW - Time Factors KW - Male KW - Female KW - Gallbladder -- diagnostic imaging KW - Cholagogues and Choleretics -- therapeutic use KW - Octreotide -- therapeutic use KW - Octreotide -- adverse effects KW - Ursodeoxycholic Acid -- therapeutic use KW - Gallbladder Diseases -- diagnostic imaging KW - Hormones -- therapeutic use KW - Acromegaly -- drug therapy KW - Gallbladder Diseases -- chemically induced KW - Hormones -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79960468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ultrasound+%3A+JCU&rft.atitle=Sonography+of+gallbladder+abnormalities+in+acromegaly+patients+following+octreotide+and+ursodiol+therapy%3A+incidence+and+time+course.&rft.au=Avila%2C+N+A%3BShawker%2C+T+H%3BRoach%2C+P%3BBradford%2C+M+H%3BSkarulis%2C+M+C%3BEastman%2C+R&rft.aulast=Avila&rft.aufirst=N&rft.date=1998-07-01&rft.volume=26&rft.issue=6&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+ultrasound+%3A+JCU&rft.issn=00912751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-21 N1 - Date created - 1998-08-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coadministration of galanin antagonist M40 with a muscarinic M1 agonist improves delayed nonmatching to position choice accuracy in rats with cholinergic lesions. AN - 79953989; 9634573 AB - The neuropeptide galanin is overexpressed in the basal forebrain in Alzheimer's disease (AD). In rats, galanin inhibits evoked hippocampal acetylcholine release and impairs performance on several memory tasks, including delayed nonmatching to position (DNMTP). Galanin(1-13)-Pro2-(Ala-Leu)2-Ala-NH2 (M40), a peptidergic galanin receptor ligand, has been shown to block galanin-induced impairment on DNMTP in rats. M40 injected alone, however, does not improve DNMTP choice accuracy deficits in rats with selective cholinergic immunotoxic lesions of the basal forebrain. The present experiments used a strategy of combining M40 with an M1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin 192IgG-saporin. Coadministration of intraventricular M40 with intraperitoneal 3-(3-S-n-pentyl-1,2,5-thiadiazol-4-yl)-1,2,5, 6-tetrahydro-1-methylpyridine (TZTP), an M1 agonist, improved choice accuracy significantly more than a threshold dose of TZTP alone. These results suggest that a galanin antagonist may enhance the efficacy of cholinergic treatments for the cognitive deficits of AD. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - McDonald, M P AU - Willard, L B AU - Wenk, G L AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland 20982, USA. Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 5078 EP - 5085 VL - 18 IS - 13 SN - 0270-6474, 0270-6474 KW - 192 IgG-saporin KW - 0 KW - Antibodies, Monoclonal KW - Cholinergic Agents KW - Immunotoxins KW - M40 KW - Muscarinic Agonists KW - Peptide Fragments KW - Pyridines KW - Receptor, Muscarinic M1 KW - Receptors, Muscarinic KW - Ribosome Inactivating Proteins, Type 1 KW - Thiadiazoles KW - Galanin KW - 88813-36-9 KW - xanomeline KW - 9ORI6L73CJ KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Memory -- drug effects KW - Dose-Response Relationship, Drug KW - Cholinergic Fibers -- physiology KW - Memory -- physiology KW - Disease Models, Animal KW - Thiadiazoles -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Rats KW - Cognition -- physiology KW - Acetylcholine -- metabolism KW - Rats, Sprague-Dawley KW - Cognition -- drug effects KW - Muscarinic Agonists -- pharmacology KW - Cholinergic Agents -- pharmacology KW - Cholinergic Fibers -- drug effects KW - Immunotoxins -- pharmacology KW - Pyridines -- pharmacology KW - Male KW - Behavior, Animal -- drug effects KW - Galanin -- pharmacology KW - Choice Behavior -- drug effects KW - Alzheimer Disease -- physiopathology KW - Peptide Fragments -- pharmacology KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79953989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coadministration+of+galanin+antagonist+M40+with+a+muscarinic+M1+agonist+improves+delayed+nonmatching+to+position+choice+accuracy+in+rats+with+cholinergic+lesions.&rft.au=McDonald%2C+M+P%3BWillard%2C+L+B%3BWenk%2C+G+L%3BCrawley%2C+J+N&rft.aulast=McDonald&rft.aufirst=M&rft.date=1998-07-01&rft.volume=18&rft.issue=13&rft.spage=5078&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of structural p53 mutants which show selective defects in apoptosis but not cell cycle arrest. AN - 79952028; 9632751 AB - Suppression of tumor cell growth by p53 results from the activation of both apoptosis and cell cycle arrest, functions which have been shown to be separable activities of p53. We have characterized a series of p53 mutants with amino acid substitutions at residue 175 and show that these mutants fall into one of three classes: class I, which is essentially wild type for apoptotic and cell cycle arrest functions; class II, which retains cell cycle arrest activity but is impaired in the induction of apoptosis; and class III, which is defective in both activities. Several residue 175 mutants which retain cell cycle arrest function have been detected in cancers, and we show that these have lost apoptotic function. Furthermore, several class II mutants have been found to be temperature sensitive for apoptotic activity while showing constitutive cell cycle arrest function. Taken together, these mutants comprise an excellent system with which to investigate the biochemical nature of p53-mediated apoptosis, the function of principal importance in tumor suppression. All of the mutants that showed loss of apoptotic function also showed defects in the activation of promoters from the potential apoptotic targets Bax and the insulin-like growth factor-binding protein 3 gene (IGF-BP3), and a correlation between full apoptotic activity and activation of both of these promoters was also seen with the temperature-sensitive mutants. However, a role for additional apoptotic activities of p53 was suggested by the observation that some mutants retained significant apoptotic function despite being impaired in the activation of Bax- and IGF-BP3-derived promoters. In contrast to the case of transcriptional activation, a perfect correlation between transcriptional repression of the c-fos promoter and the ability to induce apoptosis was seen, although the observation that Bax expression induced a similar repression of transcription from this promoter suggests that this may be a consequence, rather than a cause, of apoptotic death. JF - Molecular and cellular biology AU - Ryan, K M AU - Vousden, K H AD - ABL Basic Research Program, NCI-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3692 EP - 3698 VL - 18 IS - 7 SN - 0270-7306, 0270-7306 KW - BAX protein, human KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Insulin-Like Growth Factor Binding Protein 3 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-fos KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Index Medicus KW - Insulin-Like Growth Factor Binding Protein 3 -- genetics KW - Tumor Cells, Cultured KW - Proto-Oncogene Proteins c-fos -- genetics KW - Humans KW - Temperature KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Transcriptional Activation KW - Cyclins -- genetics KW - Mutagenesis, Site-Directed KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Tumor Suppressor Protein p53 -- genetics KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79952028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+structural+p53+mutants+which+show+selective+defects+in+apoptosis+but+not+cell+cycle+arrest.&rft.au=Ryan%2C+K+M%3BVousden%2C+K+H&rft.aulast=Ryan&rft.aufirst=K&rft.date=1998-07-01&rft.volume=18&rft.issue=7&rft.spage=3692&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1994 Aug 1;13(15):3496-504 [8062826] Nature. 1994 Jul 21;370(6486):220-3 [8028670] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8940-4 [8090749] Nucleic Acids Res. 1994 Sep;22(17):3551-5 [7937055] Genes Dev. 1994 Nov 1;8(21):2540-51 [7958916] Genes Dev. 1994 Dec 1;8(23):2817-30 [7995520] Cell. 1994 Dec 2;79(5):817-27 [8001119] Mol Cell Biol. 1995 Feb;15(2):1060-70 [7823921] Cell. 1995 Jan 27;80(2):293-9 [7834749] Genes Dev. 1995 Sep 1;9(17):2170-83 [7657168] Cell. 1995 Aug 25;82(4):675-84 [7664346] Science. 1995 Oct 6;270(5233):96-9 [7569956] Nature. 1995 Oct 12;377(6549):552-7 [7566157] Nature. 1995 Oct 19;377(6550):646-9 [7566179] Cancer Res. 1995 Nov 15;55(22):5187-90 [7585571] EMBO J. 1996 Feb 15;15(4):827-38 [8631304] Genes Dev. 1996 May 1;10(9):1054-72 [8654922] Genes Dev. 1996 Aug 1;10(15):1945-52 [8756351] Mol Cell Biol. 1996 Sep;16(9):4952-60 [8756654] Mol Cell Biol. 1996 Sep;16(9):4961-71 [8756655] Curr Opin Genet Dev. 1996 Feb;6(1):12-8 [8791489] Genes Dev. 1996 Oct 1;10(19):2438-51 [8843196] Genes Dev. 1996 Dec 1;10(23):2971-80 [8956998] Nature. 1997 Feb 13;385(6617):637-40 [9024662] Cell. 1997 Feb 7;88(3):323-31 [9039259] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2345-9 [9122197] Nature. 1997 May 15;387(6630):296-9 [9153395] Nature. 1997 May 15;387(6630):299-303 [9153396] Oncogene. 1997 May 8;14(18):2137-47 [9174049] Science. 1997 Jul 18;277(5324):370-2 [9219694] Oncogene. 1997 Aug 14;15(7):857-69 [9266973] Cell. 1986 Aug 15;46(4):567-74 [3524858] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979-83 [1946467] Nature. 1992 Jul 2;358(6381):15-6 [1614522] Cell. 1992 Jun 26;69(7):1237-45 [1535557] J Virol. 1992 Aug;66(8):4757-62 [1352831] Nature. 1993 May 20;363(6426):281-3 [8387645] EMBO J. 1993 Jul;12(7):2705-13 [8334989] Cell. 1993 Sep 24;74(6):957-67 [8402885] Oncogene. 1994 Apr;9(4):1225-30 [8134125] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):1998-2002 [8134338] Science. 1994 Jul 15;265(5170):346-55 [8023157] Cell. 1994 Aug 26;78(4):703-11 [8069917] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel assay of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity in cultured cells and its use for evaluation of cadmium(II) inhibition of this activity. AN - 79945687; 9628918 AB - 8-Oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a product of oxidative modification of dGTP, thatcan be misincorporated into DNA, causing AT-->CG mutations. Cells are protected against 8-oxo-dGTP by 8-oxo-dGTP 5'-pyrophosphohydrolases (8-oxo-dGTP-ases) that convert it to 8-oxo-dGMP. Thus, inhibition of 8-oxo-dGTPases may lead to cancer. To elucidate the involvement of 8-oxo-dGTPases in carcinogenesis, an assay of the 8-oxo-dGTPase activity is required. This paper presents such an assay developed for Chinese hamster ovary (CHO) cells that can be applied to any biological material. It includes: (i) a convenient method for preparing 8-oxo-2'-deoxyguanosine 5'-phosphates; (ii) an HPLC/UV quantification of 8-oxo-dGTP hydrolysis products and (iii) separation of 8-oxo-dGTPase activity from interfering 8-oxo-dGTP phosphatase(s). The 8-oxo-dGTPase activity of CHO cells depends on magnesium, has a pH optimum of 8.5, Km for 8-oxo-dGTP of 9.3 microM, and is inhibited by 8-oxo-dGDP, the product of interfering 8-oxo-dGTP phosphatases. The latter must be removed from the assayed samples by ultrafiltration through 30 kDa cut-off membranes. The method was used to test the inhibition by cadmium ions of the activity of 8-oxo-dGTPase in CHO cells. The cells cultured with 0.3-3 microM cadmium(II) acetate for up to 24 h had their 8-oxo-dGTPase activity suppressed in a Cd(II) concentration-dependent manner, down to 70% of the control value. JF - Nucleic acids research AU - Bialkowski, K AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-FCRDC, Building 538, Room 205E, Frederick, MD 21702, USA. karolb@mail.ncifcrf.gov Y1 - 1998/07/01/ PY - 1998 DA - 1998 Jul 01 SP - 3194 EP - 3201 VL - 26 IS - 13 SN - 0305-1048, 0305-1048 KW - Deoxyguanine Nucleotides KW - 0 KW - Enzyme Inhibitors KW - Cadmium KW - 00BH33GNGH 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 - Index Medicus KW - Evaluation Studies as Topic KW - Deoxyguanine Nucleotides -- biosynthesis KW - Animals KW - Reproducibility of Results KW - Chromatography, DEAE-Cellulose KW - Kinetics KW - CHO Cells KW - Hydrolysis KW - Cricetinae KW - Cadmium -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Phosphoric Monoester Hydrolases -- metabolism KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79945687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+rheumatology&rft.atitle=Indications+for%2C+and+use+of%2C+cytotoxic+agents+in+SLE.&rft.au=Klippel%2C+J+H&rft.aulast=Klippel&rft.aufirst=J&rft.date=1998-08-01&rft.volume=12&rft.issue=3&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+rheumatology&rft.issn=09503579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1994 Sep 25;22(19):3930-5 [7937115] Biochemistry. 1994 Apr 19;33(15):4695-701 [8161527] Mutat Res. 1995 May;336(3):257-67 [7739614] J Biol Chem. 1995 Jun 16;270(24):14659-65 [7782328] J Biol Chem. 1995 Oct 27;270(43):25942-8 [7592783] Carcinogenesis. 1995 Oct;16(10):2343-50 [7586133] J Biol Chem. 1996 Oct 11;271(41):25059-62 [8810257] Chem Res Toxicol. 1996 Dec;9(8):1360-7 [8951241] Chem Res Toxicol. 1996 Dec;9(8):1375-81 [8951243] J Biol Chem. 1997 Feb 28;272(9):5892-8 [9038207] Genes Cells. 1996 Feb;1(2):139-45 [9140059] Cancer Lett. 1997 May 19;115(2):141-8 [9149117] Science. 1997 Oct 3;278(5335):128-30 [9311918] Carcinogenesis. 1997 Sep;18(9):1785-91 [9328176] Proc Natl Acad Sci U S A. 1966 Feb;55(2):274-81 [5328724] Nucleic Acids Res. 1984 Feb 24;12(4):2137-45 [6701097] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] J Biol Chem. 1988 Jun 25;263(18):8953-7 [3288626] Proc Natl Acad Sci U S A. 1989 Jun;86(11):3949-52 [2657730] J Biol Chem. 1992 Jan 5;267(1):166-72 [1730583] Nature. 1992 Jan 16;355(6357):273-5 [1309939] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11021-5 [1332067] Nucleic Acids Res. 1993 Apr 11;21(7):1563-8 [8479906] Trends Genet. 1993 Jul;9(7):246-9 [8379000] J Biol Chem. 1993 Nov 5;268(31):23524-30 [8226881] Biochemistry. 1995 Jan 10;34(1):89-95 [7819228] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II study of bromocriptine in patients with androgen-independent prostate cancer. AN - 79938585; 9625840 AB - Prolactin is an important physiological regulator of prostate development and growth in preclinical models. In prostate cancer there is strong evidence that prolactin exerts a trophic effect independent of testosterone. In addition, patients with prostate cancer that have an elevated prolactin level correlated with a poorer prognosis. Based on these data, we evaluated the clinical effect of prolactin suppression using bromocriptine in patients with androgen-independent prostate cancer. We conducted an open-label phase II trial of bromocriptine in patients with progressive metastatic prostate cancer. Basal and thyrotropin releasing hormone (TRH)-stimulated prolactin levels were utilized as biological endpoints for determining the dose of bromocriptine. All patients continued to receive complete androgen blockade. Thirteen patients were enrolled (median age 69.5 years). There were no complete or partial responses associated with bromocriptine in 11 of the evaluable patients. The mean duration of bromocriptine treatment was 8.2 weeks (2-14 weeks). One patient had a clinically insignificant decrease in prostate-specific antigen (PSA) and another patient had a 19.9% decrease in PSA with progression of a soft tissue mass. The vast majority of patients (10 of 11) had suppression of prolactin with a bromocriptine dose of 2.5 mg three times a day. One patient required a dose adjustment due to inadequate suppression, with a final maintenance dose of bromocriptine 12.5 mg per day resulting in complete suppression. No serious treatment-related toxicities were observed. The most common complications noted were nausea, headaches, dizziness, and fatigue. Our data showed that 2.5 mg three times per day of bromocriptine suppressed prolactin in 90% of the patients. Furthermore, this dose appears to be well tolerated. JF - Oncology reports AU - Horti, J AU - Figg, W D AU - Weinberger, B AU - Kohler, D AU - Sartor, O AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 893 EP - 896 VL - 5 IS - 4 SN - 1021-335X, 1021-335X KW - Androgens KW - 0 KW - Antineoplastic Agents KW - Bromocriptine KW - 3A64E3G5ZO KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Follow-Up Studies KW - Male KW - Bromocriptine -- adverse effects KW - Bromocriptine -- therapeutic use KW - Androgens -- physiology KW - Adenocarcinoma -- secondary KW - Prostatic Neoplasms -- physiopathology KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79938585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=A+phase+II+study+of+bromocriptine+in+patients+with+androgen-independent+prostate+cancer.&rft.au=Horti%2C+J%3BFigg%2C+W+D%3BWeinberger%2C+B%3BKohler%2C+D%3BSartor%2C+O&rft.aulast=Horti&rft.aufirst=J&rft.date=1998-07-01&rft.volume=5&rft.issue=4&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression and activity of phosphatases and protein kinases in adriamycin sensitive and resistant human breast cancer MCF-7 cells. AN - 79936937; 9625806 AB - Multidrug resistance is one of the major obstacles in cancer chemotherapy. In tumor cells, overexpression of the transmembrane P-glycoprotein 170 (P-gp) is associated with the multidrug resistance phenotype and serves as a drug efflux pump. The activation of P-gp has been suggested to occur at the post-translational level. Protein kinase C mediated phosphorylation may be associated with the drug effux mechanism but the overall phosphorylation pathway has not been completely defined. we report the novel finding of an increase in phosphatase 1B (a tyrosine phosphatase) and a decrease in PP1 and PP2A (serine/threonine phosphatases) expression and activity in our series of early (R65) and late (R500) stage adriamycin resistant MCF-7 cells. In addition, we show a decrease in protein kinase A (PKA) activity and an increase in protein kinase C (PKC) in our drug resistant cells. Analyses of PKC isoforms alpha through epsilon revealed that PKCbeta was not expressed and that all other isoforms increased with increasing resistance, except PKCgamma which was detected only in R65 cells. Our findings suggest that in drug resistant cells, there is a pattern consistant with the maintenance of serine and threonine residues in a phosphorylated state. JF - International journal of oncology AU - Ratnasinghe, D AU - Phang, J M AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 79 EP - 84 VL - 13 IS - 1 SN - 1019-6439, 1019-6439 KW - Antibiotics, Antineoplastic KW - 0 KW - Isoenzymes KW - P-Glycoprotein KW - Doxorubicin KW - 80168379AG KW - Protein Kinases KW - EC 2.7.- KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - P-Glycoprotein -- metabolism KW - Humans KW - Drug Resistance, Neoplasm KW - Isoenzymes -- metabolism KW - Female KW - Drug Resistance, Multiple KW - Protein Kinases -- metabolism KW - Doxorubicin -- pharmacology KW - Antibiotics, Antineoplastic -- pharmacology KW - Breast Neoplasms -- enzymology KW - Phosphoric Monoester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79936937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology&rft.atitle=Differential+expression+and+activity+of+phosphatases+and+protein+kinases+in+adriamycin+sensitive+and+resistant+human+breast+cancer+MCF-7+cells.&rft.au=Ratnasinghe%2C+D%3BPhang%2C+J+M%3BYeh%2C+G+C&rft.aulast=Ratnasinghe&rft.aufirst=D&rft.date=1998-07-01&rft.volume=13&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-20 N1 - Date created - 1998-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the cytotoxicity of protein toxins by a novel plant metabolite, mansonone-D. AN - 79917980; 9618143 AB - We have studied the effect of several structurally related mansonones on the cytotoxicity of plant and bacterial toxins in Vero and BER-40, a brefeldin A-resistant mutant of Vero cells. Mansonone-D (MD), a sesquiterpenoid ortho-naphthoquinone, inhibited the cytotoxicity of ricin, modeccin, Pseudomonas toxin, and diphtheria toxin in Vero cells to different extents. The inhibition of ricin cytotoxicity was dose dependent and reversed upon removal of the drug. Protection of ricin cytotoxicity was also observed in the presence of cycloheximide, indicating that de novo protein synthesis is not required for the protective effect. Although MD inhibited the degradation and excretion of ricin, the binding and internalization of ricin was not affected. In contrast, MD strongly reduced the specific binding of diphtheria toxin in Vero cells. Fluorescence microscopic studies show that MD treatment dramatically alters the morphology of the Golgi apparatus in Vero cells. The kinetic studies reveal that the protection of ricin cytotoxicity is the consequence of decreased toxin translocation to the cytosol in MD-treated cells. The reactive ortho-quinone moiety of MD is important for the protective effect as thespesone, a para-naphthoquinone with a heterocyclic ring structure identical to that of MD, did not inhibit the cytotoxicity of toxins. Thespone, a dehydromansonone-D, lacking two hydrogens from the heterocyclic dihydrofuran ring of MD, inhibited the cytotoxicity of ricin, but was albeit less potent than MD. Neither mansonone-E nor mansonone-H with reactive ortho-quinone moiety, but with a different heterocyclic structure, had any effect on the cytotoxicity of ricin indicating that the protective effect of MD is specifically related to the overall structure of the metabolite. JF - Journal of cellular physiology AU - Nambiar, M P AU - Murugesan, R AU - Wu, H C AD - Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. gopi@helix.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 40 EP - 49 VL - 176 IS - 1 SN - 0021-9541, 0021-9541 KW - Antitoxins KW - 0 KW - Diphtheria Toxin KW - Naphthoquinones KW - Plant Extracts KW - Plant Lectins KW - Sesquiterpenes KW - Toxins, Biological KW - mansonone D KW - Ricin KW - 9009-86-3 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Molecular Structure KW - Animals KW - Golgi Apparatus -- drug effects KW - Diphtheria Toxin -- metabolism KW - Diphtheria Toxin -- antagonists & inhibitors KW - Microscopy, Fluorescence KW - Plants -- chemistry KW - Ricin -- antagonists & inhibitors KW - Ricin -- metabolism KW - Protein Binding -- drug effects KW - Cycloheximide -- pharmacology KW - Kinetics KW - Cercopithecus aethiops KW - Endocytosis -- drug effects KW - Vero Cells KW - Immunohistochemistry KW - Antitoxins -- pharmacology KW - Plant Extracts -- pharmacology KW - Toxins, Biological -- toxicity KW - Naphthoquinones -- pharmacology KW - Sesquiterpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79917980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+cytotoxicity+of+protein+toxins+by+a+novel+plant+metabolite%2C+mansonone-D.&rft.au=Nambiar%2C+M+P%3BMurugesan%2C+R%3BWu%2C+H+C&rft.aulast=Nambiar&rft.aufirst=M&rft.date=1998-07-01&rft.volume=176&rft.issue=1&rft.spage=40&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined nicotinic and muscarinic blockade in elderly normal volunteers: cognitive, behavioral, and physiologic responses. AN - 79911311; 9608577 AB - Establishing a pharmacologic model of the memory deficits of Alzheimer's disease could be an important tool in understanding how memory fails. We examined the combined effects of the muscarinic antagonist scopolamine and the nicotinic antagonist mecamylamine in eight normal elderly volunteers (age 61.9 +/- 8.3 yrs, SD). Each received four separate drug challenges (scopolamine (0.4 mg i.v.), mecamylamine (0.2 mg/kg up to 15 mg PO), mecamylamine + scopolamine, and placebo). There was a trend toward increased impairment in explicit memory for the mecamylamine + scopolamine condition as compared to scopolamine alone. Increased impairment was also seen for the mecamylamine + scopolamine condition as compared to scopolamine alone in selected behavioral ratings. Pupil size increased when mecamylamine was added to scopolamine, while systolic blood pressure and pulse changed in concordance with ganglionic blockade. These data together with previous brain-imaging results suggest that this muscarinic-nicotinic drug combination may better model Alzheimer's disease than either drug alone. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Little, J T AU - Johnson, D N AU - Minichiello, M AU - Weingartner, H AU - Sunderland, T AD - Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 60 EP - 69 VL - 19 IS - 1 SN - 0893-133X, 0893-133X KW - Muscarinic Antagonists KW - 0 KW - Nicotinic Antagonists KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Mecamylamine KW - 6EE945D3OK KW - Index Medicus KW - Reaction Time -- drug effects KW - Memory -- drug effects KW - Alzheimer Disease -- physiopathology KW - Humans KW - Aged KW - Learning -- drug effects KW - Brief Psychiatric Rating Scale KW - Heart Rate -- drug effects KW - Pupil -- drug effects KW - Middle Aged KW - Blood Pressure -- drug effects KW - Drug Synergism KW - Female KW - Male KW - Behavior -- drug effects KW - Scopolamine Hydrobromide -- pharmacology KW - Cognition -- drug effects KW - Muscarinic Antagonists -- pharmacology KW - Nicotinic Antagonists -- pharmacology KW - Mecamylamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Combined+nicotinic+and+muscarinic+blockade+in+elderly+normal+volunteers%3A+cognitive%2C+behavioral%2C+and+physiologic+responses.&rft.au=Little%2C+J+T%3BJohnson%2C+D+N%3BMinichiello%2C+M%3BWeingartner%2C+H%3BSunderland%2C+T&rft.aulast=Little&rft.aufirst=J&rft.date=1998-07-01&rft.volume=19&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cocaine-related environmental stimuli on the spontaneous electroencephalogram in polydrug abusers. AN - 79910064; 9608572 AB - Relationships between the spontaneous electroencephalogram (EEG), self-reports of cocaine craving, and cerebral glucose metabolism, determined using 2-[18F]fluoro-2-deoxy-D-glucose and positron emission tomography, were assessed during the presentation of either neutral or cocaine-related environmental stimuli. In cocaine users but not non-drug-abusing controls, EEG power in the alpha1 and alpha2 frequency bands was significantly lowered during presentation of the drug-related stimuli when compared with the neutral test session. Decreases in alpha1 power were negatively correlated with increases in global glucose metabolism but were not correlated with either the time course or the magnitude of craving throughout the 30-min test session. Although EEG desynchronization is related to global brain metabolism, the difference in the time courses between EEG power and craving suggests that self-reports of cue-elicited cocaine craving do not simply reflect increases in the state of cortical arousal. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Liu, X AU - Vaupel, D B AU - Grant, S AU - London, E D AD - Brain Imaging Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 10 EP - 17 VL - 19 IS - 1 SN - 0893-133X, 0893-133X KW - Blood Glucose KW - 0 KW - Radiopharmaceuticals KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Blood Glucose -- metabolism KW - Arousal KW - Humans KW - Glucose -- metabolism KW - Adult KW - Tomography, Emission-Computed KW - Brain -- metabolism KW - Time Factors KW - Male KW - Female KW - Electroencephalography KW - Cocaine-Related Disorders -- psychology KW - Cues KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- metabolism KW - Cocaine-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Effect+of+cocaine-related+environmental+stimuli+on+the+spontaneous+electroencephalogram+in+polydrug+abusers.&rft.au=Liu%2C+X%3BVaupel%2C+D+B%3BGrant%2C+S%3BLondon%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=1998-07-01&rft.volume=19&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic conversion of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) in the male F344/NCr Rat. AN - 79900162; 9601927 AB - 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) and 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene (DDE) levels were measured by capillary gas chromatography with electron capture detection in liver and blood serum of male F344/NCr rats exposed for 2 weeks to DDD at dietary concentrations ranging from 8.51 ppm to 2,000 ppm. DDD burdens in serum ranged from <0.006 microM (limit of detection) in control rats to 1.1 microM in the rats fed DDD at 2,000 ppm. The corresponding liver burdens in these animals ranged from <0.006 micromol/kg liver (controls) to 11 micromol/kg liver in rats fed DDD at 2,000 ppm. Levels of DDE in serum or liver were undetectable (<0. 006 microM in serum; <0.006 micromol/kg liver) in rats fed control diet or diet containing 8.51 or 25.5 ppm DDD. The liver and serum burdens of DDE increased with dietary DDD concentration, reaching a maximum of 0.53 microM in serum and 4.7 micromol/kg liver in rats fed 2,000 ppm DDD. As a percentage of total DDD equivalents detected in liver or serum, the DDE burdens increased to a maximum of 36% and 31% in the serum and liver, respectively, of rats fed 689 ppm DDD. The possibility that the DDE might have been generated artifactually in the diet prior to administration to the rats was ruled out by analysis with capillary gas chromatography of the diet containing 2, 000 ppm DDD. The identification of DDE as a metabolite in liver extracts of rats fed 2,000 ppm DDD was confirmed with GC-MS. The results confirmed the presence of DDE as a metabolite of DDD. JF - Archives of environmental contamination and toxicology AU - Fox, S D AU - Roman, J M AU - Issaq, H J AU - Nims, R W AD - Chemical Synthesis and Analysis Laboratory, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 104 EP - 108 VL - 35 IS - 1 SN - 0090-4341, 0090-4341 KW - Insecticides KW - 0 KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Dichlorodiphenyldichloroethane KW - V14159DF29 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Administration Schedule KW - Biotransformation KW - Gas Chromatography-Mass Spectrometry KW - Animal Feed -- analysis KW - Liver -- metabolism KW - Male KW - Dichlorodiphenyldichloroethane -- blood KW - Dichlorodiphenyl Dichloroethylene -- metabolism KW - Dichlorodiphenyl Dichloroethylene -- blood KW - Dichlorodiphenyldichloroethane -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+contamination+and+toxicology&rft.atitle=Metabolic+conversion+of+1%2C1-dichloro-2%2C2-bis%28p-chlorophenyl%29ethane+%28DDD%29+to+1%2C1-dichloro-2%2C2-bis%28p-chlorophenyl%29ethylene+%28DDE%29+in+the+male+F344%2FNCr+Rat.&rft.au=Fox%2C+S+D%3BRoman%2C+J+M%3BIssaq%2C+H+J%3BNims%2C+R+W&rft.aulast=Fox&rft.aufirst=S&rft.date=1998-07-01&rft.volume=35&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+contamination+and+toxicology&rft.issn=00904341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-15 N1 - Date created - 1998-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlorambucil-induced pulmonary disease: a case report and review of the literature. AN - 73961382; 9760160 AB - A 77-year-old man developed pneumonitis while on chlorambucil therapy for chronic lymphocytic leukemia, with a cumulative dose of 2700 mg. The condition improved promptly with the discontinuation of the drug and initiation of steroids. A case report and review of the literature are presented in this paper. JF - Annals of hematology AU - Khong, H T AU - McCarthy, J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. PY - 1998 SP - 85 EP - 87 VL - 77 IS - 1-2 SN - 0939-5555, 0939-5555 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Chlorambucil KW - 18D0SL7309 KW - Index Medicus KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Humans KW - Aged KW - Male KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Lung Diseases -- chemically induced KW - Chlorambucil -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73961382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Chlorambucil-induced+pulmonary+disease%3A+a+case+report+and+review+of+the+literature.&rft.au=Khong%2C+H+T%3BMcCarthy%2C+J&rft.aulast=Khong&rft.aufirst=H&rft.date=1998-07-01&rft.volume=77&rft.issue=1-2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Annals+of+hematology&rft.issn=09395555&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-16 N1 - Date created - 1998-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipid formulations of amphotericin B: clinical perspectives for the management of invasive fungal infections in children with cancer. AN - 73915317; 9743964 AB - During the past four decades, amphotericin B deoxycholate has been the cornerstone of systemic chemotherapy for life-threatening fungal infections. Despite a broad spectrum of antifungal activity, its utility is greatly hampered by renal toxicity and limited clinical efficacy, in particular in patients with profound and persistent neutropenia. The novel lipid formulations of amphotericin B have distinct physicochemical properties resulting in different distribution patterns. Nevertheless, they all share a considerable reduction of nephrotoxicity, which allows for the delivery of higher daily dosages of amphotericin B. Preliminary efficacy data indicate that these compounds are overall at least as effective as amphotericin B deoxycholate. However, information for children is limited, and comparative studies for their use as first line agents are only in their beginnings. In this article, we review the clinical pharmacokinetics, safety, and efficacy of the lipid formulations of amphotericin B with special emphasis on pediatric data, and we seek to provide a rational framework for the determination of their current role in patients with cancer and proven or suspected invasive fungal infections. JF - Klinische Padiatrie AU - Groll, A H AU - Müller, F M 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. PY - 1998 SP - 264 EP - 273 VL - 210 IS - 4 SN - 0300-8630, 0300-8630 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Treatment Outcome KW - Child KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Amphotericin B -- pharmacokinetics KW - Opportunistic Infections -- microbiology KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Mycoses -- microbiology KW - Mycoses -- drug therapy KW - Antifungal Agents -- administration & dosage KW - Neoplasms -- microbiology KW - Opportunistic Infections -- drug therapy KW - Neutropenia -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73915317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Klinische+Padiatrie&rft.atitle=Lipid+formulations+of+amphotericin+B%3A+clinical+perspectives+for+the+management+of+invasive+fungal+infections+in+children+with+cancer.&rft.au=Groll%2C+A+H%3BM%C3%BCller%2C+F+M%3BPiscitelli%2C+S+C%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=1998-07-01&rft.volume=210&rft.issue=4&rft.spage=264&rft.isbn=&rft.btitle=&rft.title=Klinische+Padiatrie&rft.issn=03008630&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-16 N1 - Date created - 1998-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The potential of genetically altered mice as animal models for carcinogen identification. AN - 73873031; 9715518 JF - Toxicologic pathology AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 579 EP - 581 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Mutagens -- toxicity KW - Disease Models, Animal KW - Mice KW - Carcinogenicity Tests -- trends KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73873031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+potential+of+genetically+altered+mice+as+animal+models+for+carcinogen+identification.&rft.au=Maronpot%2C+R+R&rft.aulast=Maronpot&rft.aufirst=R&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=579&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 - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Morphological characterization of spindle cell tumors induced in transgenic Tg.AC mouse skin. AN - 73867162; 9715510 AB - Transgenic Tg.AC mice carry a v-Ha-ras coding region flanked by a zeta-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiation were observed in these malignancies. One malignancy that developed at the site of the papillomas was composed of bundles of spindle cells. This lesion is difficult to distinguish from fibrosarcomas by light microscopy. We characterized 16 of these malignancies (tentatively classified as spindle cell tumors) to determine if they were of epithelial or mesenchymal origin. Papillomas were induced in Tg.AC mice by full thickness wounding, 12-O-tetradecanoyl-13-phorbol acetate treatment, or ultraviolet radiation. With time, some papillomas became broad-based, downwardly invading lesions. These lesions were examined by light microscopy with immunohistochemical analysis for cytokeratins and by electron microscopy. Immunohistochemical examination with a polyclonal anti-cytokeratin antibody demonstrated various degrees of keratin staining in all tumors examined. Attenuated desmosomes were also observed in these lesions by electron microscopy. These results indicate an epithelial origin for these malignancies; therefore, they should be classified as spindle cell carcinomas. JF - Toxicologic pathology AU - Asano, S AU - Trempus, C S AU - Spalding, J W AU - Tennant, R W AU - Battalora, M S AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 512 EP - 519 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Microscopy, Electron KW - Mice KW - Histiocytoma, Benign Fibrous -- pathology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Histiocytoma, Benign Fibrous -- chemically induced KW - Immunohistochemistry KW - Female KW - Carcinoma -- pathology KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- pathology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73867162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Morphological+characterization+of+spindle+cell+tumors+induced+in+transgenic+Tg.AC+mouse+skin.&rft.au=Asano%2C+S%3BTrempus%2C+C+S%3BSpalding%2C+J+W%3BTennant%2C+R+W%3BBattalora%2C+M+S&rft.aulast=Asano&rft.aufirst=S&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=512&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 - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. AN - 73862386; 9715731 AB - Regarded as the most common and best understood of the hereditary periodic fever syndromes, familial Mediterranean fever (FMF) is a recessively inherited disease of episodic fever with some combination of severe abdominal pain, pleurisy, arthritis, and a characteristic ankle rash. The flares typically last for up to 3 days at a time, and most patients are completely asymptomatic between attacks; if untreated with prophylactic colchicine, some patients later develop amyloidosis and renal failure. The recent cloning of the FMF gene on the short arm of chromosome 16p, and the subsequent finding that its tissue expression is limited to granulocytes, has helped to explain the dramatic accumulation of neutrophils at the symptomatic serosal sites; the wild-type gene likely acts as an upregulator of an anti-inflammatory molecule or as a downregulator of a pro-inflammatory molecule. For nearly half a century, FMF was thought to cluster primarily in non-Ashkenazi Jews, Arabs, Armenians, and Turks, although the screening of the 8 known mutations in an American cohort has identified substantial numbers of people from the Ashkenazi Jewish and Italian populations in the United States who also have this disease. Nevertheless, the symptoms often go unrecognized and patients remain undiagnosed for years, not receiving the highly efficacious colchicine therapy; their histories often include multiple laparotomies, laparoscopies, and psychiatric evaluations. The combinations of clinical manifestations among FMF patients are quite heterogeneous, but our American cohort did not establish any connections between individual mutations and specific clinical pictures--as is seen in other diseases like cystic fibrosis, in which distinct genotypes target certain organ systems. Specifically, the data from our American series are insufficient to evaluate the hypothesis that the M694V/M694V genotype confers a more severe phenotype, or increases the risk of amyloidosis; but both our data and the recent literature (160) indicate that amyloidosis can occur in FMF patients with only 1 copy, or no copies, of the M694V mutation. It appears that specific MEFV mutations are probably not the sole determinants of phenotype, and that unknown environmental factors or modifying genes act as accomplices in this disease. Although we hope the discovery of the FMF gene will allow the diagnosis of FMF to become genetically accurate, the reality is that both clinical and genetic tools must still be used together unless mutations are identified on both of a patient's chromosomes. Physicians should be careful not to rule out the diagnosis in patients of high-risk ethnic backgrounds just because of atypical clinical features, as our data indicate that MEFV mutations are sometimes demonstrable in such patients. At the same time, physicians cannot yet rely solely on a genetic diagnosis because we have not yet identified a sufficient spectrum of mutations, and it is not currently feasible to examine every patient's full DNA sequence for the entire gene; screening an ethnically consistent and clinically positive patient for the 8 known mutations frequently identifies a mutation on only 1 chromosome, and genetic analysis of other classic cases will often reveal none of the 8 mutations. Still, our data suggest that ethnic background is an important predictor of finding 1 of the presently known mutations, and the knowledge of ancestries atypical for FMF can suggest the diagnosis of other hereditary periodic fever syndromes. As the list of FMF-associated MEFV mutations is expanded, and/or new sequencing technologies permit more rapid screening, the value and interpretation of genetic testing for FMF will become more straightforward. Moreover, as the pathophysiology of this disorder becomes less of a hypothesis and more of an understood entity, it is likely that treatment options will broaden beyond the use of daily prophylactic colchicine. (ABSTRACT TRUNCATED) JF - Medicine AU - Samuels, J AU - Aksentijevich, I AU - Torosyan, Y AU - Centola, M AU - Deng, Z AU - Sood, R AU - Kastner, D L AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892-1820, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 268 EP - 297 VL - 77 IS - 4 SN - 0025-7974, 0025-7974 KW - Amino Acids KW - 0 KW - DNA, Complementary KW - Gout Suppressants KW - Colchicine KW - SML2Y3J35T KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Severity of Illness Index KW - Point Mutation -- genetics KW - Gout Suppressants -- adverse effects KW - Amyloidosis -- complications KW - Diagnosis, Differential KW - Humans KW - Amino Acids -- genetics KW - Referral and Consultation KW - Child, Preschool KW - Cloning, Molecular KW - Genotype KW - Haplotypes -- genetics KW - Kidney Diseases -- complications KW - National Institutes of Health (U.S.) KW - Health Surveys KW - Adult KW - Middle Aged KW - Colchicine -- adverse effects KW - Male KW - Female KW - Familial Mediterranean Fever -- drug therapy KW - Familial Mediterranean Fever -- epidemiology KW - Familial Mediterranean Fever -- genetics KW - Familial Mediterranean Fever -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73862386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Familial+Mediterranean+fever+at+the+millennium.+Clinical+spectrum%2C+ancient+mutations%2C+and+a+survey+of+100+American+referrals+to+the+National+Institutes+of+Health.&rft.au=Samuels%2C+J%3BAksentijevich%2C+I%3BTorosyan%2C+Y%3BCentola%2C+M%3BDeng%2C+Z%3BSood%2C+R%3BKastner%2C+D+L&rft.aulast=Samuels&rft.aufirst=J&rft.date=1998-07-01&rft.volume=77&rft.issue=4&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Medicine&rft.issn=00257974&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-24 N1 - Date created - 1998-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reproductive endpoints in general toxicity studies: are they predictive? AN - 73859304; 9717700 AB - The ability to use necropsy and in-life vaginal cytology data from 90-d general toxicity studies to predict the outcome of more definitive reproductive toxicity tests was evaluated using data from 18 compounds tested by the National Toxicology Program. Sperm motility and vaginal cytology evaluations (SMVCE) were performed at the end of 90-d toxicity studies. When these same compounds were tested in the definitive Reproductive Assessment by Continuous Breeding (RACB) design, 13 of the 18 compounds were classified the same way by both tests. The different conclusions for five compounds can be explained by differences in dose used or in endpoints evaluated. We conclude that reproductive-system necropsy data from general toxicity studies can provide a valuable preliminary indication of the likely reproductive toxicity of the compound under study. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Chapin, R E AU - Sloane, R A AU - Haseman, J K AD - Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chapin@niehs.nih.gov PY - 1998 SP - 489 EP - 494 VL - 12 IS - 4 SN - 0890-6238, 0890-6238 KW - Index Medicus KW - Vagina -- drug effects KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Vagina -- pathology KW - Mice KW - Sperm Motility -- drug effects KW - Male KW - Female KW - Reproduction -- drug effects KW - Toxicology -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73859304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Reproductive+endpoints+in+general+toxicity+studies%3A+are+they+predictive%3F&rft.au=Chapin%2C+R+E%3BSloane%2C+R+A%3BHaseman%2C+J+K&rft.aulast=Chapin&rft.aufirst=R&rft.date=1998-07-01&rft.volume=12&rft.issue=4&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The National Toxicology Program evaluation of genetically altered mice as predictive models for identifying carcinogens. AN - 73857119; 9715504 AB - National Institute of Environmental Health Sciences researchers are exploring the utility of genetically altered mice to study mechanisms of carcinogenesis. Two of these mouse models, the Tg.AC (carrier of an activated mouse H-ras oncogene) and the p53+/- (heterozygous for the wild-type tumor suppressor gene Trp53), have genetic alterations that appear to hasten their expression of chemically induced tumors. These 2 models have been proposed as a basis for new strategies for identifying chemical carcinogens and for assessing risk. The National Toxicology Program (NTP) is conducting a series of studies with these 2 genetically altered strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens. In this first evaluation, candidates for study were drawn from the NTP historical database of 2-yr rodent carcinogenicity studies and the open literature (primarily for drugs). Results with this first set of 11 chemicals tested in genetically altered mice, compared with previous findings in the traditional 2-yr rodent assays and literature on human tumor findings, appear to support the premise advanced by Tennant et al that these models have the potential to serve as more rapid and less expensive test systems to identify carcinogens. JF - Toxicologic pathology AU - Eastin, W C AU - Haseman, J K AU - Mahler, J F AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. Eastin@niehs.nih.gov PY - 1998 SP - 461 EP - 473 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- genetics KW - Genes, p53 -- genetics KW - Disease Models, Animal KW - Predictive Value of Tests KW - Mice KW - Neoplasms, Experimental -- pathology KW - Male KW - Female KW - Survival Analysis KW - Carcinogens -- administration & dosage KW - Mice, Transgenic -- physiology KW - Carcinogens -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73857119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+National+Toxicology+Program+evaluation+of+genetically+altered+mice+as+predictive+models+for+identifying+carcinogens.&rft.au=Eastin%2C+W+C%3BHaseman%2C+J+K%3BMahler%2C+J+F%3BBucher%2C+J+R&rft.aulast=Eastin&rft.aufirst=W&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=461&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 - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous and chemically induced proliferative lesions in Tg.AC transgenic and p53-heterozygous mice. AN - 73847883; 9715509 AB - Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology. JF - Toxicologic pathology AU - Mahler, J F AU - Flagler, N D AU - Malarkey, D E AU - Mann, P C AU - Haseman, J K AU - Eastin, W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 501 EP - 511 VL - 26 IS - 4 SN - 0192-6233, 0192-6233 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Heterozygote KW - Mice KW - Neoplasms, Experimental -- pathology KW - Mice, Transgenic -- physiology KW - Genes, p53 -- genetics KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spontaneous+and+chemically+induced+proliferative+lesions+in+Tg.AC+transgenic+and+p53-heterozygous+mice.&rft.au=Mahler%2C+J+F%3BFlagler%2C+N+D%3BMalarkey%2C+D+E%3BMann%2C+P+C%3BHaseman%2C+J+K%3BEastin%2C+W&rft.aulast=Mahler&rft.aufirst=J&rft.date=1998-07-01&rft.volume=26&rft.issue=4&rft.spage=501&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 - 1998-11-16 N1 - Date created - 1998-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human capsaicin model of allodynia and hyperalgesia: sources of variability and methods for reduction. AN - 73847515; 9707653 AB - Intradermal and topical application of capsaicin have been used to study mechanisms of mechanical allodynia (MA) and pinprick hyperalgesia (PPH) and the efficacy of drugs in relieving these symptoms. However, it is associated with significant inter- and intra-subject variability. In order to improve the model's sensitivity, we examined several potential sources of variability of capsaicin-evoked MA and PPH in healthy volunteers, including skin temperature fluctuations, method (intradermal vs. topical) and site (volar forearm vs. foot dorsum) of administration. In study I, 12 subjects received, in a 6-session, randomized, crossover trial, 1) 250 micrograms of intradermal (ID) CAP to the volar forearm with skin temperature fixed at 36 degrees C (36 ID). 2) 250 micrograms ID CAP with varying skin temperature (VT ID), or 3) 250 microliters of l% CAP patch placed on the skin at 36 degrees C. The resulting MA and PPH areas observed with each method were measured. In study II, a 4-session, randomized crossover trial, 12 subjects were given 100 micrograms ID CAP in the volar forearm or foot dorsum and subsequent areas of MA and PPH recorded. In study I, 5/12 subjects had small MA areas (< or = 5 cm2) and one subject had small PPH areas in at least 4/6 sessions. The most consistent intra-subject responses were seen with the 36 ID method. Correlation coefficients for the two sessions using the same method of administration were: MA; 36 ID r = 0.83, VT ID = 0.19. Topical r = 0.81; PPH: 36 ID r = 0.93; VT ID r = 0.38, Topical r = 0.78. In study II, 4/12 subjects had little MA for both forearm and foot though all subjects developed PPH. However, greater intra-subject consistency (MA: foot: r = 0.84; arm: r = 0.49; PPH: r = 0.87; r = 0.39) and significantly larger areas of MA (15.8 +/- 4.2 vs 9.1 +/- 2.5, p < 0.05) were seen with the foot. (PPH: foot: 28.9 +/- 6.7; arm: 21.6 +/- 4.2, NS). Large variability exists among subjects receiving CAP, with some developing minimal MA. However, these subjects may be screened out prior to entry, increasing the sensitivity of the model, which may be further improved by clamping the skin temperature. JF - Journal of pain and symptom management AU - Liu, M AU - Max, M B AU - Robinovitz, E AU - Gracely, R H AU - Bennett, G J AD - Neurobiology and Anesthesiology Branch, National Institute of Dental, Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 10 EP - 20 VL - 16 IS - 1 SN - 0885-3924, 0885-3924 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Male KW - Female KW - Pain Measurement -- methods KW - Pain Measurement -- drug effects KW - Hyperalgesia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pain+and+symptom+management&rft.atitle=The+human+capsaicin+model+of+allodynia+and+hyperalgesia%3A+sources+of+variability+and+methods+for+reduction.&rft.au=Liu%2C+M%3BMax%2C+M+B%3BRobinovitz%2C+E%3BGracely%2C+R+H%3BBennett%2C+G+J&rft.aulast=Liu&rft.aufirst=M&rft.date=1998-07-01&rft.volume=16&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Journal+of+pain+and+symptom+management&rft.issn=08853924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-10 N1 - Date created - 1998-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of pamidronate disodium in the treatment of metastatic bone disease. AN - 70069682; 9824995 AB - Bone metastases are a common feature of advanced neoplastic disease and are considered to be among the most frequent causes of pain and complications in oncologic patients. The main objective of the treatment of such patients is to control their symptoms and improve their quality of life. Pamidronate disodium is a second-generation bisphosphonate capable of inhibiting bone resorption (particularly osteoclast activity) without affecting bone remineralization. After a brief introduction concerning the pathophysiology of bone metastases and neoplastic bone pain, we herein present data on the clinical pharmacology and toxicity of bisphosphonates in general, and pamidronate in particular. We conclude by reviewing the literature on the use of pamidronate in phase II and III trials involving patients with metastatic bone disease. The paper is based on a review of articles published between 1984 and 1997 selected from the Cancerline and Medline databases. In the considered phase II and III studies involving patients with bone metastases (breast cancer and multiple myeloma in particular), pamidronate proved to be efficacious in reducing the incidence of pain and skeletal complications, decreasing the excretion of metabolic markers of bone resorption and improving the quality of life. Intravenous infusions of 60-90 mg over a period of 2 hr every 3-4 weeks did not cause any significant toxic effects and was easily managed. Pamidronate is a bisphosphonate that is efficacious in the treatment of symptomatic bone metastases and can be considered an important therapeutic option in association with systemic treatments, radiotherapy and normal supportive care, especially in patients with breast cancer and multiple myeloma. Further randomized studies are necessary to confirm the positive preliminary results in other neoplasms, analyze the cost/benefit ratio of the treatment, and verify the possibility that, in addition to being used for palliative purposes, pamidronate may also prevent or delay the appearance of bone metastases. JF - Tumori AU - Ripamonti, C AU - Fulfaro, F AU - Ticozzi, C AU - Casuccio, A AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. tdpint@tin.it PY - 1998 SP - 442 EP - 455 VL - 84 IS - 4 SN - 0300-8916, 0300-8916 KW - Antineoplastic Agents KW - 0 KW - Diphosphonates KW - pamidronate KW - OYY3447OMC KW - Index Medicus KW - Bone Resorption -- etiology KW - Bone Remodeling -- drug effects KW - Humans KW - Clinical Trials as Topic KW - Diphosphonates -- therapeutic use KW - Bone Neoplasms -- physiopathology KW - Bone Neoplasms -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Bone Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70069682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tumori&rft.atitle=Role+of+pamidronate+disodium+in+the+treatment+of+metastatic+bone+disease.&rft.au=Ripamonti%2C+C%3BFulfaro%2C+F%3BTicozzi%2C+C%3BCasuccio%2C+A%3BDe+Conno%2C+F&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1998-07-01&rft.volume=84&rft.issue=4&rft.spage=442&rft.isbn=&rft.btitle=&rft.title=Tumori&rft.issn=03008916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-09 N1 - Date created - 1998-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postscript: where do we go from here? AN - 70025073; 9798797 JF - Journal of psychoactive drugs AU - Sloboda, Z AU - Stephens, R C AU - Alemagno, S AD - Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, Maryland 20857, USA. PY - 1998 SP - 307 EP - 314 VL - 30 IS - 3 SN - 0279-1072, 0279-1072 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Sexual Behavior KW - Needle Sharing KW - Humans KW - National Institutes of Health (U.S.) KW - Research Support as Topic KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Risk-Taking KW - Health Promotion -- methods KW - HIV Infections -- prevention & control KW - HIV Infections -- etiology KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology KW - Acquired Immunodeficiency Syndrome -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychoactive+drugs&rft.atitle=Postscript%3A+where+do+we+go+from+here%3F&rft.au=Sloboda%2C+Z%3BStephens%2C+R+C%3BAlemagno%2C+S&rft.aulast=Sloboda&rft.aufirst=Z&rft.date=1998-07-01&rft.volume=58&rft.issue=16&rft.spage=3590&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 - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An overview of topoisomerase I-targeting agents. AN - 69976937; 9779876 AB - The camptothecins are a new class of antitumor agents that target topoisomerase I. Irinotecan and topotecan are the most widely used camptothecin analogs in clinical practice, with documented clinical activity in colorectal and ovarian cancer. Ongoing clinical trials with these agents are further characterizing their spectra of clinical activity and determining their optimal schedule of administration in combination with other anticancer agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. The successful development of the camptothecins as antitumor agents demonstrates the importance of topoisomerase 1 as a target for cancer chemotherapy. JF - Seminars in hematology AU - Arbuck, S G AU - Takimoto, C H AD - Division of Cancer Treatment, Diagnosis, and Centers, National Cancer Institute, Bethesda Naval Hospital, MD 20892, USA. Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 3 EP - 12 VL - 35 IS - 3 Suppl 4 SN - 0037-1963, 0037-1963 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Topoisomerase I Inhibitors KW - irinotecan KW - 0H43101T0J KW - Topotecan KW - 7M7YKX2N15 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Humans KW - Drug Resistance, Neoplasm KW - Neoplasms -- drug therapy KW - Enzyme Inhibitors -- therapeutic use KW - Neoplasms -- enzymology KW - Camptothecin -- pharmacology KW - Camptothecin -- therapeutic use KW - Topotecan -- therapeutic use KW - Topotecan -- pharmacology KW - DNA Topoisomerases, Type I -- physiology KW - Camptothecin -- analogs & derivatives KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=An+overview+of+topoisomerase+I-targeting+agents.&rft.au=Arbuck%2C+S+G%3BTakimoto%2C+C+H&rft.aulast=Arbuck&rft.aufirst=S&rft.date=1998-07-01&rft.volume=35&rft.issue=3+Suppl+4&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neural Networks for Braille Reading by the Blind AN - 58353712; 9900162 AB - To explore the neural networks used for Braille reading, we measured regional cerebral blood flow with PET during tactile tasks performed both by Braille readers blinded early in life & by sighted subjects. Eight proficient Braille readers were studied during Braille reading with both right & left index fingers. Eight-character, non-contrasted Braille-letter strings were used, & subjects were asked to discriminate between words & non-words. To compare the behavior of the brain of the blind & the sighted directly, non-Braille tactile tasks were performed by 6 different blind subjects & 10 sighted control subjects using the right index finger. The tasks included a nondiscrimination task & three discrimination tasks (angle, width & character). Irrespective of reading finger (right or left), Braille reading by the blind activated the inferior parietal lobule, primary visual cortex, superior occipital gyri, fusiform gyri, ventral premotor area, superior parietal lobule, cerebellum & primary sensorimotor area bilaterally, also the right dorsal premotor cortex, right middle occipital gyrus & right prefrontal area. During non-Braille discrimination tasks, in blind subjects, the ventral occipital regions, including the primary visual cortex & fusiform gyri bilaterally were activated while the secondary somatosensory area was deactivated. The reverse pattern was found in sighted subjects where the secondary somatosensory area was activated while the ventral occipital regions were suppressed. These findings suggest that the tactile processing pathways usually linked in the secondary somatosensory area are rerouted in blind subjects to the ventral & occipital cortical regions originally reserved for visual shape discrimination. 7 Tables, 6 Figures, 63 References. Adapted from the source document JF - Brain AU - Sadato, Norihiro AU - Pascual-Leone, Alvaro AU - Grafman, Jordan AU - Deiber, Marie-Pierre AU - Ibanez, Vicente AU - Hallett, Mark AD - c/o Hallett-National Instits Health, 10 Center Dr MSC 1428 Bethesda MD 20892-1428 hallett@codon.nih.gov Y1 - 1998/07// PY - 1998 DA - July 1998 SP - 1213 EP - 1229 VL - 121 IS - 7 SN - 0006-8950, 0006-8950 KW - Neural Networks (57240) KW - Reading Aids for the Blind (70700) KW - Brain (09350) KW - Vision Disorders (94350) KW - article KW - 4018: psycholinguistics; neurolinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58353712?accountid=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=Brain&rft.atitle=Neural+Networks+for+Braille+Reading+by+the+Blind&rft.au=Sadato%2C+Norihiro%3BPascual-Leone%2C+Alvaro%3BGrafman%2C+Jordan%3BDeiber%2C+Marie-Pierre%3BIbanez%2C+Vicente%3BHallett%2C+Mark&rft.aulast=Sadato&rft.aufirst=Norihiro&rft.date=1998-07-01&rft.volume=121&rft.issue=7&rft.spage=1213&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&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 - BRAIAK N1 - SubjectsTermNotLitGenreText - Vision Disorders (94350); Reading Aids for the Blind (70700); Neural Networks (57240); Brain (09350) ER - TY - JOUR T1 - Contribution of Proton Release to the B2 Photocurrent of Bacteriorhodopsin AN - 17282028; 4513894 AB - The contribution of proton release from the so-called proton release group to the microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in polyacrylamide gels was determined. The fraction of the B2 current due to proton release was resolved by titration of the proton release group in M. At pH values below the pK sub(a) of the proton release group in M, the proton release group cannot release its proton during the first half of the bacteriorhodopsin photocycle. At these pH values, the B2 photocurrent is due primarily to translocation of the Schiff base proton to Asp super(85). The B2 photocurrent was measured in wild-type bR gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area (proportional to the amount of charge moved) exhibits a pH dependence with a pK sub(a) of 6.1. This is suggested to be the pK sub(a) of the proton release group in M; the value obtained is in good agreement with previous results obtained by examining photocycle kinetics and pH-sensitive dye signals. In the mutant Glu super(204)Gln, the B2 photocurrent of the mutant membranes was pH independent between pH 4 and 7. Because the proton release group is incapacitated, and early proton release is eliminated in the Glu super(204)Gln mutant, this supports the idea that the pH dependence of the B2 photocurrent in the wild type reflects the titration of the proton release group. In wild-type bacteriorhodopsin, proton release contributes approximately half of the B2 area at pH 7.5. The B2 area in the Glu super(204)Gln mutant is similar to that in the wild type at pH 4.5; in both cases, the B2 current is likely due only to movement of the Schiff base proton to Asp super(85). JF - Biophysical Journal AU - Misra, S AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bldg. 5, Rm. 433, 5 Center Dr., Bethesda, MD 20892, USA, misra@mimsy.niddk.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 382 EP - 388 VL - 75 IS - 1 SN - 0006-3495, 0006-3495 KW - bacteria KW - bacteriorhodopsin KW - currents KW - Microbiology Abstracts B: Bacteriology KW - Photocycles KW - Protons KW - Gel electrophoresis KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282028?accountid=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=Biophysical+Journal&rft.atitle=Contribution+of+Proton+Release+to+the+B2+Photocurrent+of+Bacteriorhodopsin&rft.au=Misra%2C+S&rft.aulast=Misra&rft.aufirst=S&rft.date=1998-07-01&rft.volume=75&rft.issue=1&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Biophysical+Journal&rft.issn=00063495&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 - Photocycles; Gel electrophoresis; Protons ER - TY - JOUR T1 - Role of the Endogenous Production of Interleukin 12 in Immunotherapy AN - 17204719; 4492286 AB - Previous studies demonstrated that injecting mice with the cytokine interleukin 12 (IL-12) could significantly suppress the growth of a number of tumors, including murine B16 melanoma. In this report, the persistence of the antitumor effects of IL-12 is investigated. The i.p. injection of IL-12 (0.1 mu g) on days 14, 16, 18, 20, and 22 was found to significantly suppress the growth of s.c. inoculated B16 melanoma for up to 2 weeks after the last injection of IL-12. Interestingly, the IL-12 serum level 4 days after the last injection of IL-12 was significantly elevated in tumor-bearing mice compared with that of IL-12-treated normal mice. The in vivo depletion of either CD4 super(+) or CD8 super(+) T cells abrogated the antitumor activity of IL-12 and diminished the apparent autocrine stimulation of IL-12 release seen after IL-12 treatment. Resection of the tumor-draining lymph nodes (LNs) but not of the spleen abrogated the antitumor effect of IL-12 treatment as well as the elevation of serum IL-12. Expression of mRNA encoding IL-12 as well as CD40 ligand (CD40L) was detected in the tumor-draining LNs but not in the spleen of tumor-bearing mice after IL-12 treatment. Furthermore, the antitumor activity observed after IL-12 treatment was diminished by the in vivo administration of either anti-IL-12 or anti-CD40L monoclonal antibodies. Collectively, these results suggest that the endogenous production of IL-12 resulting from the CD40-CD40L interaction between antigen-presenting cells and CD4 super(+) T cells in the tumor-draining LNs may play a role in the persistence of the antitumor effects seen after IL-12 treatment. JF - Cancer Research AU - Harada, M AU - Tamada, K AU - Abe, K AU - Yasumoto, K AU - Kimura, G AU - Nomoto, K AD - Surgery Branch, National Cancer Institute, NIH, Building 10, Room 2B42, Bethesda, MD 20892, USA, haradam@pop.nci.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 3073 EP - 3077 VL - 58 IS - 14 SN - 0008-5472, 0008-5472 KW - CD4 antigen KW - CD40 antigen KW - CD40L protein KW - CD8 antigen KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Interleukin 12 KW - Immunotherapy KW - Lymphocytes T KW - Melanoma KW - W3 33150:Cytokine based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17204719?accountid=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=Role+of+the+Endogenous+Production+of+Interleukin+12+in+Immunotherapy&rft.au=Harada%2C+M%3BTamada%2C+K%3BAbe%2C+K%3BYasumoto%2C+K%3BKimura%2C+G%3BNomoto%2C+K&rft.aulast=Harada&rft.aufirst=M&rft.date=1998-07-01&rft.volume=58&rft.issue=14&rft.spage=3073&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 - Melanoma; Interleukin 12; Immunotherapy; Lymphocytes T ER - TY - JOUR T1 - Evidence of past recombination events among the genes encoding the Erp antigens of Borrelia burgdorferi AN - 17157149; 4442966 AB - A single Borrelia burgdorferi bacterium may contain six or more different 32 kb circular plasmids (cp32s). Although these plasmids are homologous throughout much of their sequences, two loci have been identified at which they can very significantly. The cp32 plasmids and their relatives each contain two adjacent genes, orfc and orf3, that vary in sequence between plasmids found within clones of individual bacteria. The orfC gene product is homologous to proteins involved in partitioning of bacterial plasmids, and the differences at this locus between plasmids may account for their compatibility. The orfC-orf3 loci are located approximately 5 kb from another variable locus called erp. The orfC-orf3 loci were used as physically linked markers to assess genetic rearrangements in the erp loci; this revealed examples of recombination involving both individual genes and entire erp loci. Recombination of the genes encoding the Erp antigens might contribute to the evasion of the mammalian immune response and could play roles in the establishment and persistence of B. burgdorferi infections in mammalian hosts. JF - Microbiology AU - Stevenson, B AU - Casjens, S AU - Rosa, P AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA, lkpsic00@pop.uky.edu Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1869 EP - 1879 VL - 144 IS - 7 SN - 1350-0872, 1350-0872 KW - Erp antigen KW - antigens KW - erp gene KW - nucleotide sequence KW - orf3 gene KW - orfc gene KW - partitioning KW - plasmid cp32 KW - plasmids KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Recombination KW - Borrelia burgdorferi KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17157149?accountid=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=Evidence+of+past+recombination+events+among+the+genes+encoding+the+Erp+antigens+of+Borrelia+burgdorferi&rft.au=Stevenson%2C+B%3BCasjens%2C+S%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-07-01&rft.volume=144&rft.issue=7&rft.spage=1869&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 - Borrelia burgdorferi; Recombination ER - TY - JOUR T1 - Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls II: Rates of metabolism AN - 17108571; 4422632 AB - Physiologically based pharmacokinetic (PBPK) models are useful in describing the distribution, metabolism, and fate of xenobiotics across multiple species. The eventual goal of the present research is to create PBPK models for all 209 polychlorinated biphenyls (PCBs). Key parameters in any PBPK model are the metabolic rates. Data on metabolic rates of PCBs were derived from in vitro experiments and from fitting of PBPK models to in vivo data. The rate of metabolism was assumed to be a linear function of PCB concentration. Structural descriptors suggested by the literature were used in a stepwise regression to find an expression for the metabolic rate of PCBs as a function of five structural descriptors related to the degree and pattern of chlorine substitution. R super(2) for the fit of the model to the data is 0.9606. JF - Toxicology and Applied Pharmacology AU - Parham, F M AU - Portier, C J AD - OAO/National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 110 EP - 116 VL - 151 IS - 1 SN - 0041-008X, 0041-008X KW - pharmacokinetics KW - polychlorinated biphenyls KW - structure-activity relationships KW - Toxicology Abstracts KW - PCB KW - Models KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17108571?accountid=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=Using+structural+information+to+create+physiologically+based+pharmacokinetic+models+for+all+polychlorinated+biphenyls+II%3A+Rates+of+metabolism&rft.au=Parham%2C+F+M%3BPortier%2C+C+J&rft.aulast=Parham&rft.aufirst=F&rft.date=1998-07-01&rft.volume=151&rft.issue=1&rft.spage=110&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 - Models; PCB ER - TY - JOUR T1 - Phase 1 evaluation of Vibrio cholerae O1, serotype Inaba, polysaccharide-cholera toxin conjugates in adult volunteers AN - 17107012; 4401440 AB - Conjugate vaccines were prepared by binding hydrazine-treated lipopolysaccharide (DeALPS) from Vibrio cholerae O1, serotype Inaba, to cholera toxin (CT) variants CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 mu g of DeALPS, alone or as a conjugate, or the licensed cellular vaccine containing 4 times 10 super(9) organisms each of serotypes Inaba and Ogawa per ml. No serious adverse reactions were observed. DeALPS alone did not elicit serum LPS or vibriocidal antibodies in mice and only low levels of immunoglobulin M (IgM) anti-LPS in the volunteers. Recipients of the cellular vaccine had the highest IgM anti-LPS levels, but the difference was not statistically significant from that elicited by the conjugates. The conjugates elicited the highest levels of IgG anti-LPS (DeALPS-CT-2 > DeALPS-CT-1 > cellular vaccine). Both conjugates and the cellular vaccine elicited vibriocidal antibodies: after 8 months, recipients of cellular vaccine had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and DeALPS-CT-1 (330). The correlation coefficient between IgG anti-LPS and 2-mercaptoethanol (2-ME)-resistant vibriocidal antibodies was 0.81 (P = 0.0004). Convalescent sera from cholera patients had a mean vibriocidal titer of 2,525 that was removed by treatment with 2-ME. The vibriocidal activities of sera from all vaccine groups and from the patients were absorbed (>75%) by LPS but not by either CT-1 or CT-2. Conjugate-induced IgG vibriocidal antibodies persisted longer than those elicited by the whole-cell vaccine. Both conjugates, but not the cellular vaccine, elicited IgG anti-CT. JF - Infection and Immunity AU - Gupta, R K AU - Taylor, D N AU - Bryla, DA AU - Robbins, J B AU - Szu, ShC AD - Building 6, Room 424, NIH, 8800 Rockville Pike, Bethesda, MD 20892, USA, scszu@Helix.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 3095 EP - 3099 VL - 66 IS - 7 SN - 0019-9567, 0019-9567 KW - 2-mercaptoethanol KW - Lipopolysaccharides KW - Vibrio cholerae KW - man KW - polysaccharides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Toxins KW - Cholera toxin KW - Immunogenicity KW - Cholera KW - Vaccines KW - Immunoglobulin M 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/17107012?accountid=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=Phase+1+evaluation+of+Vibrio+cholerae+O1%2C+serotype+Inaba%2C+polysaccharide-cholera+toxin+conjugates+in+adult+volunteers&rft.au=Gupta%2C+R+K%3BTaylor%2C+D+N%3BBryla%2C+DA%3BRobbins%2C+J+B%3BSzu%2C+ShC&rft.aulast=Gupta&rft.aufirst=R&rft.date=1998-07-01&rft.volume=66&rft.issue=7&rft.spage=3095&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 - Vibrio cholerae; Immunoglobulins; Vaccines; Toxins; Immunogenicity; Immunoglobulin M; Cholera toxin; Cholera ER - TY - JOUR T1 - The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited AN - 16556263; 4397851 AB - To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up. JF - Annals of Epidemiology AU - Sempos, C T AU - Durazo-Arvizu, R AU - McGee, D L AU - Cooper, R S AU - Prewitt, TE AD - Epidemiology and Biometry Program, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8150, Bethesda, Maryland 20892-7934, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 289 EP - 300 VL - 8 IS - 5 SN - 1047-2797, 1047-2797 KW - body weight KW - man KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Risk assessment KW - Mortality KW - Body weight KW - Cigarette smoking KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16556263?accountid=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=Annals+of+Epidemiology&rft.atitle=The+influence+of+cigarette+smoking+on+the+association+between+body+weight+and+mortality.+The+Framingham+Heart+Study+revisited&rft.au=Sempos%2C+C+T%3BDurazo-Arvizu%2C+R%3BMcGee%2C+D+L%3BCooper%2C+R+S%3BPrewitt%2C+TE&rft.aulast=Sempos&rft.aufirst=C&rft.date=1998-07-01&rft.volume=8&rft.issue=5&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&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 - Risk assessment; Mortality; Body weight; Cigarette smoking ER - TY - JOUR T1 - Proliferation, development and DNA adduct levels in the mammary gland of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and a high fat diet AN - 16549031; 4355896 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine derived from cooked meat that is a mammary gland carcinogen in rats. A carcinogenic dose-regimen of PhIP (75 mg/kg, p.o., 10 doses, once per day) was administered to 43-day old female Sprague-Dawley rats, and the rats were then placed on a defined high fat (23.5% corn oil) or low fat (5% corn oil) diet for up to 6 weeks. At various times after carcinogen and diet, and prior to carcinogenesis, we examined the percentage of proliferating cells in terminal end bud (TEB) epithelial structures of the rat mammary gland by proliferating cell nuclear antigen staining, mammary gland architecture by whole mounting, and PhIP-DNA adduct levels in mammary epithelial cells by the super(32)P-post-labeling assay. Immediately after dosing, the percentage of proliferating epithelial cells in TEBs was significantly higher in PhIP-treated rats than in control rats receiving vehicle only [7.5 plus or minus 0.9% (n = 99) versus 4.2 plus or minus 0.6% (n = 127), respectively]. The mammary glands of PhIP-treated rats showed a significantly lower density of alveolar buds (ABs) and a higher density of TEBs than control rats, which suggests that PhIP exposure partially inhibited the normal glandular differentiation of TEBs to ABs. After 6 weeks on the diet, proliferation in TEBs was statistically higher in rats given PhIP plus a high fat diet than in rats given vehicle plus a low fat diet. The mammary glands from rats on a high fat diet also showed a statistically higher density of TEBs when compared with rats on a low fat diet [2.08 plus or minus 0.34% versus 1.04 plus or minus 0.20%, respectively (n = 6)]. PhIP-DNA adduct levels were relatively high in mammary epithelial cells of treated rats. At 3 h after the last dose of PhIP, DNA adduct levels [relative adduct labeling (RAL) x 10 super(7), mean plus or minus SE] were 10.5 plus or minus 1.7 (n = 8) and 0.9 plus or minus 0.2 (n = 7) in epithelial cells isolated from mammary gland and in the liver, respectively. DNA adduct removal rates from the mammary gland were not different between rats on the high fat and low fat diets. Adducts were still detected after 6 weeks on either diet. Thus, events that occurred prior to neoplasia in the mammary glands of PhIP-treated rats include formation of PhIP-DNA adducts at relatively high levels, and enhanced proliferation in TEBs (putative sites of origin of mammary gland carcinomas) and partial inhibition of TEB differentiation. The high fat diet, a promoter of PhIP-induced mammary gland carcinogenesis, appeared to sustain the proliferative effect of PhIP in mammary gland TEBs at a time when PhIP-DNA adducts are still detectable. These early events may contribute to the targeting and carcinogenicity of PhIP to the mammary gland of rats. JF - Carcinogenesis AU - Snyderwine, E G AU - Davis, C D AU - Schut, HAJ AU - Roberts-Thomson, S J AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Building 37, Room 3C28, NIH, Bethesda, MD 20892-4255, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1209 EP - 1215 VL - 19 IS - 7 SN - 0143-3334, 0143-3334 KW - 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - rats KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA adducts KW - Heterocyclic amines KW - Mammary gland KW - Meat KW - High fat diet KW - Carcinogenicity KW - Cooking KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16549031?accountid=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=Proliferation%2C+development+and+DNA+adduct+levels+in+the+mammary+gland+of+rats+given+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+and+a+high+fat+diet&rft.au=Snyderwine%2C+E+G%3BDavis%2C+C+D%3BSchut%2C+HAJ%3BRoberts-Thomson%2C+S+J&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1998-07-01&rft.volume=19&rft.issue=7&rft.spage=1209&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; Mammary gland; Heterocyclic amines; High fat diet; Cooking; DNA adducts; Meat ER - TY - JOUR T1 - On the discrepancy between epidemiologic studies in individuals of lung cancer and residential radon and Cohen's ecologic regression AN - 16539807; 4347820 AB - There is still substantial confusion in the radiation effects community about the inherent limitations of ecologic analysis. As a result, inordinate attention has been given to the discrepant results of Cohen, in which a negative estimate is observed for the regression of county mortality rates for lung cancer on estimated county radon levels. This paper demonstrates that Cohen's ecologic analysis cannot produce valid inference on the exposure-response relationship for individuals unless lung cancer risk factors (smoking, age, occupation, etc.) for individuals are statistically uncorrelated with indoor radon level within counties or unless risk effects for radon and other factors are additive. Both of these assumptions are contradicted in the literature. Thus, contrary to common assumption, when a linear no-threshold model is the true model for radon risk for individuals, higher average radon concentration for a county does not necessarily imply a higher lung cancer rate for the county. In addition, valid inference from county-level ecologic analysis and the elimination of the ecologic bias cannot be achieved with the addition of county-wide summary variables (including "stratification" variables) to the regression equation. Using hypothetical data for smoking and radon and assuming a true positive association for radon and lung cancer for individuals, the analysis demonstrates that a negative county-level ecologic regression can be induced when correlation coefficients for smoking and radon within county are in the range -0.05 to 0.05. Since adverse effects for radon at low exposures are supported by analysis of miner data (all data and data restricted only to low cumulative exposures), a meta-analysis of indoor radon studies, and molecular and cellular studies, and since ecologic regressions are burdened by severe limitations, the negative results from Cohen's analysis are most likely due to bias and should be rejected. JF - Health Physics AU - Lubin, J H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza North, Rm 403, Bethesda, MD 20892, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 4 EP - 10 VL - 75 IS - 1 SN - 0017-9078, 0017-9078 KW - CohenOs analysis KW - epidemiology KW - man KW - statistical analysis KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Epidemiology KW - Risk assessment KW - Statistical analysis KW - Models KW - Ecology KW - Regression analysis KW - Lung cancer KW - Tobacco smoking KW - Houses KW - Radon KW - Cancer KW - Lung KW - H 8000:Radiation Safety/Electrical Safety KW - X 24210:Radiation & radioactive materials KW - P 8000:RADIATION 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/16539807?accountid=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=Health+Physics&rft.atitle=On+the+discrepancy+between+epidemiologic+studies+in+individuals+of+lung+cancer+and+residential+radon+and+Cohen%27s+ecologic+regression&rft.au=Lubin%2C+J+H&rft.aulast=Lubin&rft.aufirst=J&rft.date=1998-07-01&rft.volume=75&rft.issue=1&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&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 - Risk assessment; Lung cancer; Ecology; Lung; Statistical analysis; Cancer; Epidemiology; Radon; Houses; Regression analysis; Models; Tobacco smoking ER - TY - JOUR T1 - High-frequency DNA rearrangements in the chromosomes of clinically isolated Mycoplasma fermentans AN - 16529489; 4383426 AB - Mycoplasma fermentans is currently being examined as an agent potentially associated with human disease. Several strains of M. fermentans were isolated from patients with respiratory tract disease and AIDS. Two of these clinical strains, M64 and SK6, were triple-filter-cloned and designated as the parental clones in this study. Genomic DNA of randomly picked subclones in four and five subsequent generations passed from the parental M64 and SK6 clones were analyzed by using a radiolabeled M. fermentans-specific insertion sequence (IS)-like element as the probe. The hybridization patterns of DNA restriction fragments revealed high frequencies of chromosomal changes accompanied with excision or new insertion of the IS-like element in M. fermentans chromosome. The findings indicate M. fermentans has an effective mechanism(s) to produce a rapid gene rearrangement that may be mediated by one or more copies of the IS-like element. JF - Current Microbiology AU - Hu, Wensi S AU - Hayes, M M AU - Wang, RYuan-Hu AU - Shih, JWai-Kuo AU - Lo, Shyh-Ching AD - Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1 EP - 5 VL - 37 IS - 1 SN - 0343-8651, 0343-8651 KW - gene rearrangements KW - hybridization analysis KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16529489?accountid=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+Microbiology&rft.atitle=High-frequency+DNA+rearrangements+in+the+chromosomes+of+clinically+isolated+Mycoplasma+fermentans&rft.au=Hu%2C+Wensi+S%3BHayes%2C+M+M%3BWang%2C+RYuan-Hu%3BShih%2C+JWai-Kuo%3BLo%2C+Shyh-Ching&rft.aulast=Hu&rft.aufirst=Wensi&rft.date=1998-07-01&rft.volume=37&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Current+Microbiology&rft.issn=03438651&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 - Cell cycle arrest, apoptosis and p53 expression in nickel(II) acetate-treated Chinese hamster ovary cells AN - 16523041; 4355895 AB - Nickel(II) compounds are known human and animal carcinogens. In this study, the effects of nickel(II) acetate on cell cycle, apoptosis and p53 expression were investigated in order to unveil the elements of early cellular responses to the metal. Chinese hamster ovary (CHO) cells were grown for 72 h in Ham's F-12 medium containing 0, 40, 80, 160, 240, 320, 480 or 640 mu M nickel(II) acetate. DNA fragmentation, representative of apoptosis, was examined by agarose gel electrophoresis. The distribution of cells among various phases of cell cycle was determined by DNA flow cytometry. Expression of p53 protein was measured by the Western blotting technique. DNA fragmentation was detectable in cells treated with greater than or equal to 160 mu M nickel(II) and its intensity increased with increasing nickel(II) concentration. The proportion of cells at S phase declined in a nickel(II) concentration-dependent manner. The decline was accompanied by an increase of cell proportion in G sub(2)/M phase and the increase became statistically significant in cells exposed to at least 480 mu M nickel(II). Expression of p53 protein was not different from that in the control among samples treated with less than or equal to 480 mu M nickel(II). However, an extra fraction that migrated close to the p53 protein fraction was detected in cells treated with 640 mu M nickel(II). Our findings suggest that nickel(II) modulates cellular response through effectors involved in both G sub(2)/M arrest and apoptosis regulatory pathways. The proportion of cells arrested at G sub(2)/M phase or undergoing apoptosis depends directly on nickel(II) concentration. High concentration of nickel(II) appears to up-regulate protein(s) other than the common form of p53 protein. JF - Carcinogenesis AU - Shiao, Yih-Horng AU - Lee, Sang-Han AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, NCI-FCRDC, NIH, Frederick, MD 21702, USA, shiao@ncifcrf.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 1203 EP - 1207 VL - 19 IS - 7 SN - 0143-3334, 0143-3334 KW - CHO cells KW - hamsters KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - X 24165:Biochemistry KW - B 26405:p53 gene, anti-suppressor genes (K-rev/rap/rab/RSU-1) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16523041?accountid=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=Cell+cycle+arrest%2C+apoptosis+and+p53+expression+in+nickel%28II%29+acetate-treated+Chinese+hamster+ovary+cells&rft.au=Shiao%2C+Yih-Horng%3BLee%2C+Sang-Han%3BKasprzak%2C+K+S&rft.aulast=Shiao&rft.aufirst=Yih-Horng&rft.date=1998-07-01&rft.volume=19&rft.issue=7&rft.spage=1203&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 ER - TY - JOUR T1 - Pertussis toxin modification of PC12 cells inhibits a protein phosphatase 2A-like phosphatase AN - 16520973; 4365153 AB - We have found that modification of rat PC12 cells with pertussis toxin resulted in an similar to 50% inhibition of a protein phosphatase 2A-like phosphatase. Protein phosphatase 2A (PP2A) is a major cellular serine/threonine-specific protein phosphatase. Treatment of extracts from pertussis toxin-modified PC12 cells with either immobilized alkaline phosphatase or Ca super(2+) reversed this inhibition. Reactivation of the PP2A-like phosphatase in Ca super(2+) appears to result from the dephosphorylation of a protein by the Ca super(2+)/calmodulin-dependent protein phosphatase calcineurin. The PP2A-like phosphatase in extracts from pertussis toxin-modified PC12 cells eluted from a Mono Q column at a higher ionic strength than did the PP2A-like phosphatase in extracts from control cells. After incubation in Ca super(2+), the PP2A-like phosphatase in extracts from pertussis toxin-modified cells eluted from a Mono Q column at the same ionic strength as did the PP2A-like phosphatase in extracts from control cells. These results indicate that the effect of pertussis toxin on this PP2A-like activity results from the phosphorylation of either one of the subunits of the PP2A-like phosphatase or a protein that when phosphorylated binds to and inhibits this phosphatase. Pertussis toxin modification did not result in the phosphorylation of the catalytic subunit of PP2A. Because phosphorylation regulates the activities of many enzymes and cell surface receptors, a pertussis toxin-induced decrease in PP2A activity could alter signaling pathways and other cellular processes in which G proteins are not directly involved. JF - Journal of Neurochemistry AU - Chen, Fusheng AU - Vu, Ngoc-Diep AU - Wagner, P D AD - Bldg. 37, Rm. 4C24, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 248 EP - 257 VL - 71 IS - 1 SN - 0022-3042, 0022-3042 KW - Bordetella pertussis KW - pertussis toxin KW - pheochromocytoma cells KW - protein phosphatase 2A-like phosphatase KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; Calcium & Calcified Tissue Abstracts KW - N3 11104:Mammals (except primates) KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects KW - T 20019:Cellular calcium, channels and currents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16520973?accountid=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+%3A+CMLS&rft.atitle=The+eosinophil+ribonucleases.&rft.au=Rosenberg%2C+H+F&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1998-08-01&rft.volume=54&rft.issue=8&rft.spage=795&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Targeted Disruption of the Acid alpha -Glucosidase Gene in Mice Causes an Illness with Critical Features of Both Infantile and Adult Human Glycogen Storage Disease Type II AN - 16497823; 4396481 AB - We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha -glucosidase gene (6 super(neo)/6 super(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 ( Delta 6/ Delta 6), like the recently published acid alpha -glucosidase knockout with disruption of exon 13, have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models. JF - Journal of Biological Chemistry AU - Raben, N AU - Nagaraju, K AU - Lee, E AU - Kessler, P AU - Byrne, B AU - Lee, L AU - LaMarca, M AU - King, C AU - Ward, J AU - Sauer, B AU - Plotz, P AD - National Institutes of Health, Bldg. 10, Rm. 9N244, 9000 Rockville Pike, Bethesda, MD 20892, USA, rabenn@arb.niams.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 19086 EP - 19092 VL - 273 IS - 30 SN - 0021-9258, 0021-9258 KW - glycogen storage disease II KW - mice KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07397:Rodentia (mice) 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/16497823?accountid=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=Targeted+Disruption+of+the+Acid+alpha+-Glucosidase+Gene+in+Mice+Causes+an+Illness+with+Critical+Features+of+Both+Infantile+and+Adult+Human+Glycogen+Storage+Disease+Type+II&rft.au=Raben%2C+N%3BNagaraju%2C+K%3BLee%2C+E%3BKessler%2C+P%3BByrne%2C+B%3BLee%2C+L%3BLaMarca%2C+M%3BKing%2C+C%3BWard%2C+J%3BSauer%2C+B%3BPlotz%2C+P&rft.aulast=Raben&rft.aufirst=N&rft.date=1998-07-01&rft.volume=273&rft.issue=30&rft.spage=19086&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 ER - TY - JOUR T1 - Entry of OpaA super(+) gonococci into HEp-2 cells requires concerted action of glycosaminoglycans, fibronectin and integrin receptors AN - 16480102; 4356615 AB - Heparan sulphate proteoglycans are increasingly implicated as eukaryotic cell surface receptors for bacterial pathogens. Here, we report that Neisseria gonorrhoeae adheres to proteoglycan receptors on HEp-2 epithelial cells but that internalization of the bacterium by this cell type requires the serum glycoprotein fibronectin. Fibronectin was shown to bind specifically to gonococci producing the OpaA adhesin. Binding assays with fibronectin fragments located the bacterial binding site near the N-terminal end of the molecule. However, none of the tested fibronectin fragments supported gonococcal entry into the eukaryotic cells; a 120 kDa fragment carrying the cell adhesion domain with the amino acid sequence RGD even inhibited the fibronectin-mediated uptake of MS11-OpaA. This inhibition could be mimicked by an RGD-containing hexapeptide and by alpha 5 beta 1 integrin-specific antibodies, suggesting that interaction of the central region of fibronectin with integrin receptors facilitated bacterial uptake. Fibronectin was unable to promote gonococcal entry into HEp-2 cells that had been treated with the enzyme heparinase III, which degrades the glycosaminoglycan side-chains of proteoglycan receptors. On the basis of these results, we propose a novel cellular uptake pathway for bacteria, which involves the binding of the pathogen to glycosaminoglycans that, in turn, act as co-receptors facilitating fibronectin-mediated bacterial uptake through integrin receptors. In this scenario, fibronectin would act as a molecular bridge linking the Opa-proteoglycan complex with host cell integrin receptors. JF - Molecular Microbiology AU - Van Putten, JPM AU - Duensing, T D AU - Cole, R L AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA, jos_van_putten@nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 369 EP - 379 VL - 29 IS - 1 SN - 0950-382X, 0950-382X KW - HEp-2 cells KW - fibronectin KW - glycosaminoglycans KW - Microbiology Abstracts B: Bacteriology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16480102?accountid=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=Entry+of+OpaA+super%28%2B%29+gonococci+into+HEp-2+cells+requires+concerted+action+of+glycosaminoglycans%2C+fibronectin+and+integrin+receptors&rft.au=Van+Putten%2C+JPM%3BDuensing%2C+T+D%3BCole%2C+R+L&rft.aulast=Van+Putten&rft.aufirst=JPM&rft.date=1998-07-01&rft.volume=29&rft.issue=1&rft.spage=369&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 ER - TY - JOUR T1 - Tissue microarrays for high-throughput molecular profiling of tumor specimens AN - 16448184; 4347922 AB - Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors. JF - Nature Medicine AU - Kononen, J AU - Bubendorf, L AU - Kallioniemi, A AU - Baerlund, M AU - Schraml, P AU - Leighton, S AU - Torhorst, J AU - Mihatsch, MJ AU - Sauter, G AU - Kallioniemi, O-P AD - Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A24, Bethesda, MD 20892-4470, USA, okalli@nhgri.nih.gov Y1 - 1998/07// PY - 1998 DA - Jul 1998 SP - 844 EP - 847 VL - 4 IS - 7 SN - 1078-8956, 1078-8956 KW - high-throughput screening KW - tissue microarrays KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33135:Diagnosis: Other KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16448184?accountid=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=Tissue+microarrays+for+high-throughput+molecular+profiling+of+tumor+specimens&rft.au=Kononen%2C+J%3BBubendorf%2C+L%3BKallioniemi%2C+A%3BBaerlund%2C+M%3BSchraml%2C+P%3BLeighton%2C+S%3BTorhorst%2C+J%3BMihatsch%2C+MJ%3BSauter%2C+G%3BKallioniemi%2C+O-P&rft.aulast=Kononen&rft.aufirst=J&rft.date=1998-07-01&rft.volume=4&rft.issue=7&rft.spage=844&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 ER - TY - JOUR T1 - Stimulatory effect of endogenous tissue inhibitor of metalloproteinases-1 (TIMP-1) overexpression on type IV collagen and laminin gene expression in rat mammary carcinoma cells. AN - 79993781; 9647740 AB - We recently reported enhanced tumor growth and stimulation of vascular endothelial growth factor (VEGF) expression in rat mammary carcinoma cells transfected with a human tissue inhibitor of metalloproteinases-1 (hTIMP-1) cDNA (1). In the present study, we examined if the composition of the stroma was altered in the tumors with the highest hTIMP-1 production. Immunohistological examination revealed increased amounts of the basement membrane (BM) components, type IV collagen and laminin, in the hTIMP-1 overexpressing tumors compared to that of the control. In vitro studies also revealed upregulation of type IV collagen and laminin gene expression associated with the hTIMP-1 overexpression. Endogenous RNA levels of rat TIMP-1 and the rat matrix metalloproteinases (MMPs), MMP-2, MMP-3, and MMP-9, were not affected by the hTIMP-1 transfection, suggesting that the increase in BM deposition was not a result of decreased collagenolytic activity. This is the first report to show an association between overexpression of TIMP-1 and increased tumor BM matrix production through stimulation of type IV collagen and laminin gene expression. JF - Biochemical and biophysical research communications AU - Yoshiji, H AU - Buck, T B AU - Harris, S R AU - Ritter, L M AU - Lindsay, C K AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/29/ PY - 1998 DA - 1998 Jun 29 SP - 605 EP - 609 VL - 247 IS - 3 SN - 0006-291X, 0006-291X KW - Laminin KW - 0 KW - RNA, Messenger KW - Tissue Inhibitor of Metalloproteinase-1 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Up-Regulation -- physiology KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Basement Membrane -- metabolism KW - Humans KW - Transfection -- genetics KW - Neoplasms, Experimental -- metabolism KW - Neoplasms, Experimental -- pathology KW - Immunohistochemistry KW - Collagen -- genetics KW - Laminin -- genetics KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79993781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stimulatory+effect+of+endogenous+tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29+overexpression+on+type+IV+collagen+and+laminin+gene+expression+in+rat+mammary+carcinoma+cells.&rft.au=Yoshiji%2C+H%3BBuck%2C+T+B%3BHarris%2C+S+R%3BRitter%2C+L+M%3BLindsay%2C+C+K%3BThorgeirsson%2C+U+P&rft.aulast=Yoshiji&rft.aufirst=H&rft.date=1998-06-29&rft.volume=247&rft.issue=3&rft.spage=605&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 - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor. AN - 79951236; 9632639 AB - Three mammalian bombesin receptor subtypes have been characterized: the gastrin-releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype 3 (BRS-3). In a previous report we identified four amino acids that are critical for high affinity binding of bombesin and gastrin-releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all species variants of the GRP-R and NMB-R which bind bombesin with high affinity, but they are diverged in BRS-3, the bombesin receptor subtype that binds bombesin with much lower affinity. Substituting these four divergent amino acids in BRS-3 for the conserved amino acids in either GRP-R or NMB-R increased the affinity of the mutated BRS-3 (4DeltaBRS-3) for bombesin compared with wild-type BRS-3. We hypothesized that the same four amino acids might be critical for high affinity NMB binding to the NMB-R. In this study we confirm this hypothesis by showing that the affinity of NMB is increased in a mutant BRS-3 receptor (4DeltaBRS-3) that contains these four substitutions resulting in an affinity that is close to the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid substitutions in BRS-3 did not result in the formation of a high affinity binding site for the recently described non-peptide NMB-R antagonist PD168368. JF - The Journal of biological chemistry AU - Sainz, E AU - Akeson, M AU - Mantey, S A AU - Jensen, R T AU - Battey, J F AD - Laboratory of Molecular Biology, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/26/ PY - 1998 DA - 1998 Jun 26 SP - 15927 EP - 15932 VL - 273 IS - 26 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Receptors, Bombesin KW - bombesin receptor subtype 3 KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Protein Structure, Secondary KW - Sequence Alignment KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Amino Acids -- metabolism KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- antagonists & inhibitors KW - Neurokinin B -- metabolism KW - Neurokinin B -- analogs & derivatives KW - Neurokinin B -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Four+amino+acid+residues+are+critical+for+high+affinity+binding+of+neuromedin+B+to+the+neuromedin+B+receptor.&rft.au=Sainz%2C+E%3BAkeson%2C+M%3BMantey%2C+S+A%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Sainz&rft.aufirst=E&rft.date=1998-06-26&rft.volume=273&rft.issue=26&rft.spage=15927&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural basis of an embryonically lethal single Ala --> Thr mutation in the vnd/NK-2 homeodomain. AN - 79955099; 9636163 AB - The structural and DNA binding behavior is described for an analog of the vnd/NK-2 homeodomain, which contains a single amino acid residue alanine to threonine replacement in position 35 of the homeodomain. Multidimensional nuclear magnetic resonance, circular dichroism, and electrophoretic gel retardation assays were carried out on recombinant 80-aa residue proteins that encompass the wild-type and mutant homeodomains. The mutant A35T vnd/NK-2 homeodomain is unable to adopt a folded conformation free in solution at temperatures down to -5 degreesC in contrast to the behavior of the corresponding wild-type vnd/NK-2 homeodomain, which is folded into a functional three-dimensional structure below 25 degreesC. The A35T vnd/NK-2 binds specifically to the vnd/NK-2 target DNA sequence, but with an affinity that is 50-fold lower than that of the wild-type homeodomain. Although the three-dimensional structure of the mutant A35T vnd/NK-2 in the DNA bound state shows characteristic helix-turn-helix behavior similar to that of the wild-type homeodomain, a notable structural deviation in the mutant A35T analog is observed for the amide proton of leucine-40. The wild-type homeodomain forms an unusual i,i-5 hydrogen bond with the backbone amide oxygen of residue 35. In the A35T mutant this amide proton resonance is shifted upfield by 1.27 ppm relative to the resonance frequency for the wild-type analog, thereby indicating a significant alteration of this i,i-5 hydrogen bond. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Xiang, B AU - Weiler, S AU - Nirenberg, M AU - Ferretti, J A AD - Laboratory of Biophysical Chemistry, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/23/ PY - 1998 DA - 1998 Jun 23 SP - 7412 EP - 7416 VL - 95 IS - 13 SN - 0027-8424, 0027-8424 KW - Drosophila Proteins KW - 0 KW - Homeodomain Proteins KW - Transcription Factors KW - vnd protein, Drosophila KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Drosophila melanogaster -- embryology KW - Animals KW - Drosophila melanogaster -- genetics KW - DNA -- metabolism KW - Temperature KW - Circular Dichroism KW - Amino Acid Sequence KW - Magnetic Resonance Spectroscopy KW - Mutagenesis, Site-Directed KW - Protein Folding KW - Molecular Sequence Data KW - Genes, Lethal KW - Amino Acid Substitution KW - Protein Conformation KW - Homeodomain Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Mutation KW - Homeodomain Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79955099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+basis+of+an+embryonically+lethal+single+Ala+--%26gt%3B+Thr+mutation+in+the+vnd%2FNK-2+homeodomain.&rft.au=Xiang%2C+B%3BWeiler%2C+S%3BNirenberg%2C+M%3BFerretti%2C+J+A&rft.aulast=Xiang&rft.aufirst=B&rft.date=1998-06-23&rft.volume=95&rft.issue=13&rft.spage=7412&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 - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mech Dev. 1997 May;63(2):187-98 [9203141] Biochemistry. 1997 May 6;36(18):5372-80 [9154919] Neuron. 1997 Jul;19(1):27-37 [9247261] Hum Mutat. 1997;10(3):207-11 [9298820] J Biol Chem. 1998 May 1;273(18):10994-1000 [9556579] Genetics. 1983 Jul;104(3):433-48 [6411520] Cell. 1989 Nov 3;59(3):573-80 [2572329] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7716-20 [2573058] Neuron. 1990 Jul;5(1):81-9 [2114885] EMBO J. 1990 Oct;9(10):3085-92 [1976507] Cell. 1990 Nov 2;63(3):579-90 [1977522] Cell. 1991 Nov 1;67(3):517-28 [1682054] Methods Enzymol. 1991;208:103-17 [1779832] J Biomol NMR. 1993 Mar;3(2):185-204 [8477186] Development. 1994 Jun;120(6):1517-24 [8050360] Biochemistry. 1994 Dec 20;33(50):15053-60 [7999763] Ann N Y Acad Sci. 1995 Jun 30;758:224-42 [7625694] EMBO J. 1995 Jul 17;14(14):3487-95 [7628450] J Mol Biol. 1995 Aug 11;251(2):297-307 [7643404] Dev Biol. 1995 Oct;171(2):306-16 [7556915] Science. 1995 Oct 13;270(5234):262-9 [7569974] J Biomol NMR. 1995 Nov;6(3):277-93 [8520220] Nat Genet. 1996 Aug;13(4):417-21 [8696335] Nature. 1996 Nov 28;384(6607):327-33 [8934515] Hum Mol Genet. 1996 Dec;5(12):1915-20 [8968743] Nat Genet. 1997 Jan;15(1):106-10 [8988180] Hum Hered. 1997 Jan-Feb;47(1):38-41 [9017978] Nat Genet. 1997 Feb;15(2):179-80 [9020844] Genes Dev. 1997 Mar 15;11(6):726-37 [9087427] Genetics. 1997 Jul;146(3):939-49 [9215898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence context profoundly influences the mutagenic potency of trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-purine nucleoside adducts in site-specific mutation studies. AN - 79952792; 9636059 AB - The postoligomerization method was used to prepare oligonucleotide 16-mers that contained dAdo or dGuo adducts, derived from trans opening of each enantiomer of the two diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxides, in two sequence contexts. These 16 oligonucleotides, along with the four corresponding oligonucleotides containing unsubstituted purines, were ligated into single-stranded DNA from bacteriophage M13mp7L2 and transfected into Escherichia coli SMH77. The mutagenic effects of replication past these adducts were then evaluated. The various adduct isomers induced point mutations at different frequencies and with different distributions of mutation types, as was anticipated. However, sequence context had the most substantial effects on mutation frequency. A high frequency of deletions of a single guanine was found in a context where the dGuo adduct was at the 3'-end of a run of five guanines, whereas no single base deletion was found in the other context studied, 5'-CGA-3'. Mutation frequencies in constructs containing dAdo adducts were much higher in a 5'-TAG-3' context (37-58%, depending on the individual isomer) than in a 5'-GAT-3' context (5-20%), and for a given adduct, mutation frequency was up to 10-fold higher in the former sequence than in the latter. These findings indicate that sequence context effects need more thorough evaluation if the goal of understanding the mechanism through which DNA adducts lead to mutation is to be achieved. JF - Biochemistry AU - Page, J E AU - Zajc, B AU - Oh-hara, T AU - Lakshman, M K AU - Sayer, J M 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 - 1998/06/23/ PY - 1998 DA - 1998 Jun 23 SP - 9127 EP - 9137 VL - 37 IS - 25 SN - 0006-2960, 0006-2960 KW - DNA Adducts KW - 0 KW - Ligands KW - Mutagens KW - Oligonucleotides KW - Purine Nucleosides KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Index Medicus KW - Genetic Vectors -- chemistry KW - Stereoisomerism KW - Base Sequence KW - Transfection KW - Oligonucleotides -- chemistry KW - Oligonucleotides -- isolation & purification KW - Models, Chemical KW - Bacteriophage M13 -- genetics KW - Oligonucleotides -- genetics KW - Mutagenesis, Site-Directed KW - DNA Adducts -- genetics KW - Purine Nucleosides -- chemistry KW - DNA Adducts -- chemistry KW - Purine Nucleosides -- genetics KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Mutagens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79952792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+profoundly+influences+the+mutagenic+potency+of+trans-opened+benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide-purine+nucleoside+adducts+in+site-specific+mutation+studies.&rft.au=Page%2C+J+E%3BZajc%2C+B%3BOh-hara%2C+T%3BLakshman%2C+M+K%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=J&rft.date=1998-06-23&rft.volume=37&rft.issue=25&rft.spage=9127&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thermodynamics of a transition state analogue inhibitor binding to Escherichia coli chorismate mutase: probing the charge state of an active site residue and its role in inhibitor binding and catalysis. AN - 79951659; 9636050 AB - Electrostatic interactions play important roles in the catalysis of chorismate to prephenate by chorismate mutase. Mutation of Gln88 to glutamate in the monofunctional chorismate mutase from Escherichia coli results in an enzyme with a pH profile of activity significantly different from that of the wild type protein. To investigate whether the mutation alters the substrate binding process or the catalysis, we have directly determined the thermodynamic parameters of a transition state analogue inhibitor binding to the wild-type chorismate mutase and its Q88E mutant using isothermal titration calorimetry. The results demonstrate that solvent reorganization and hydrophobic interactions contribute the predominant free energy to inhibitor binding. The charge state of Glu88 in the Q88E mutant was experimentally determined and was shown to be protonated at pH 4.5 and ionized at pH 7.8, consistent with earlier hypotheses. Most surprisingly, inhibitor binding energetics do not exhibit significant pH dependency for both enzymes. Our findings indicate that the charge state of Glu88 has a small impact on inhibitor binding but plays an important role in the catalytic process. JF - Biochemistry AU - Lee, A Y AU - Zhang, S AU - Kongsaeree, P AU - Clardy, J AU - Ganem, B AU - Erickson, J W AU - Xie, D AD - Structural Biochemistry Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1998/06/23/ PY - 1998 DA - 1998 Jun 23 SP - 9052 EP - 9057 VL - 37 IS - 25 SN - 0006-2960, 0006-2960 KW - Enzyme Inhibitors KW - 0 KW - Protons KW - Glutamine KW - 0RH81L854J KW - Glutamic Acid KW - 3KX376GY7L KW - Chorismate Mutase KW - EC 5.4.99.5 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Hydrogen-Ion Concentration KW - Binding Sites -- drug effects KW - Catalysis -- drug effects KW - Calorimetry KW - Binding Sites -- genetics KW - Glutamic Acid -- genetics KW - Chorismate Mutase -- genetics KW - Chorismate Mutase -- antagonists & inhibitors KW - Thermodynamics KW - Enzyme Inhibitors -- chemistry KW - Glutamine -- genetics KW - Glutamine -- chemistry KW - Escherichia coli -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Escherichia coli -- enzymology KW - Chorismate Mutase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thermodynamics+of+a+transition+state+analogue+inhibitor+binding+to+Escherichia+coli+chorismate+mutase%3A+probing+the+charge+state+of+an+active+site+residue+and+its+role+in+inhibitor+binding+and+catalysis.&rft.au=Lee%2C+A+Y%3BZhang%2C+S%3BKongsaeree%2C+P%3BClardy%2C+J%3BGanem%2C+B%3BErickson%2C+J+W%3BXie%2C+D&rft.aulast=Lee&rft.aufirst=A&rft.date=1998-06-23&rft.volume=37&rft.issue=25&rft.spage=9052&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-20 N1 - Date created - 1998-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality in neonatal rats is increased by moderate prenatal exposure to some monoamine reuptake inhibitors. A brief review. AN - 80008978; 9668441 JF - Annals of the New York Academy of Sciences AU - Sparenborg, S AD - Pharmacology & Toxicology Branch, National Institutes of Health, Rockville, Maryland 20857, USA. ss292q@nih.gov Y1 - 1998/06/21/ PY - 1998 DA - 1998 Jun 21 SP - 423 EP - 426 VL - 846 SN - 0077-8923, 0077-8923 KW - Adrenergic Uptake Inhibitors KW - 0 KW - Dopamine Uptake Inhibitors KW - Serotonin Uptake Inhibitors KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Death KW - Norepinephrine -- metabolism KW - Female KW - Pregnancy KW - Dopamine Uptake Inhibitors -- toxicity KW - Adrenergic Uptake Inhibitors -- toxicity KW - Serotonin Uptake Inhibitors -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80008978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+in+neonatal+rats+is+increased+by+moderate+prenatal+exposure+to+some+monoamine+reuptake+inhibitors.+A+brief+review.&rft.au=Sparenborg%2C+S&rft.aulast=Sparenborg&rft.aufirst=S&rft.date=1998-06-21&rft.volume=846&rft.issue=&rft.spage=423&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 - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of redox homeostasis in the transforming growth factor-alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis. AN - 79940886; 9624185 AB - In previous studies we have demonstrated that transforming growth factor (TGF)-alpha/c-myc double transgenic mice exhibit an enhanced rate of cell proliferation, accumulate extensive DNA damage, and develop multiple liver tumors between 4 and 8 months of age. To clarify the biochemical events that may be responsible for the genotoxic and carcinogenic effects observed in this transgenic model, several parameters of redox homeostasis in the liver were examined prior to development of hepatic tumors. By 2 months of age, production of reactive oxygen species, determined by the peroxidation-sensitive fluorescent dye, 2',7'-dichlorofluorescin diacetate, was significantly elevated in TGF-alpha/c-myc transgenic hepatocytes versus either wild type or c-myc single transgenic cells, and occurred in parallel with an increase in lipid peroxidation. Concomitantly with a rise in oxidant levels, antioxidant defenses were decreased, including total glutathione content and the activity of glutathione peroxidase, whereas thioredoxin reductase activity was not changed. However, hepatic tumors which developed in TGF-alpha/c-myc mice exhibited an increase in thioredoxin reductase activity and a very low activity of glutathione peroxidase. Furthermore, specific deletions were detected in mtDNA as early as 5 weeks of age in the transgenic mice. These data provide experimental evidence that co-expression of TGF-alpha and c-myc transgenes in mouse liver promotes overproduction of reactive oxygen species and thus creates an oxidative stress environment. This phenomenon may account for the massive DNA damage and acceleration of hepatocarcinogenesis observed in the TGF-alpha/c-myc mouse model. JF - The Journal of biological chemistry AU - Factor, V M AU - Kiss, A AU - Woitach, J T AU - Wirth, P J AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15846 EP - 15853 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - DNA, Mitochondrial KW - 0 KW - Proto-Oncogene Proteins c-myc KW - Reactive Oxygen Species KW - Transforming Growth Factor alpha KW - Index Medicus KW - Phenotype KW - Oxidation-Reduction KW - Gene Expression Regulation, Neoplastic KW - Reactive Oxygen Species -- metabolism KW - Animals KW - DNA Damage KW - Transgenes KW - DNA, Mitochondrial -- metabolism KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Signal Transduction KW - Liver Neoplasms, Experimental -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Homeostasis -- genetics KW - Proto-Oncogene Proteins c-myc -- genetics KW - Liver Neoplasms, Experimental -- physiopathology KW - Oxidative Stress -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79940886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disruption+of+redox+homeostasis+in+the+transforming+growth+factor-alpha%2Fc-myc+transgenic+mouse+model+of+accelerated+hepatocarcinogenesis.&rft.au=Factor%2C+V+M%3BKiss%2C+A%3BWoitach%2C+J+T%3BWirth%2C+P+J%3BThorgeirsson%2C+S+S&rft.aulast=Factor&rft.aufirst=V&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15846&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of c-Raf1 kinase to a conserved acidic sequence within the carboxyl-terminal region of the HIV-1 Nef protein. AN - 79939175; 9624170 AB - Nef is a membrane-associated cytoplasmic phosphoprotein that is well conserved among the different human (HIV-1 and HIV-2) and simian immunodeficiency viruses and has important roles in down-regulating the CD4 receptor and modulating T-cell signaling pathways. The ability to modulate T-cell signaling pathways suggests that Nef may physically interact with T-cell signaling proteins. In order to identify Nef binding proteins and map their site(s) of interaction, we targeted a highly conserved acidic sequence at the carboxyl-terminal region of Nef sharing striking similarity with an acidic sequence at the c-Raf1-binding site within the Ras effector region. Here, we used deletion and site-specific mutagenesis to generate mutant Nef proteins fused to bacterial glutathione S-transferase in in vitro precipitation assays and immunoblot analysis to map the specific interaction between the HIV-1LAI Nef and c-Raf1 to a conserved acidic sequence motif containing the core sequence Asp-Asp-X-X-X-Glu (position 174-179). Significantly, we demonstrate that substitution of the nonpolar glycine residue for either or both of the conserved negatively charged aspartic acid residues at positions 174 and 175 in the full-length recombinant Nef protein background completely abrogated binding of c-Raf1 in vitro. In addition, lysates from a permanent CEM T-cell line constitutively expressing the native HIV-1 Nef protein was used to coimmunoprecipitate a stable Nef-c-Raf1 complex, suggesting that molecular interactions between Nef and c-Raf1, an important downstream transducer of cell signaling through the c-Raf1-MAP kinase pathway, occur in vivo. This interaction may account for the Nef-induced perturbations of T-cell signaling and activation pathways in vitro and in vivo. JF - The Journal of biological chemistry AU - Hodge, D R AU - Dunn, K J AU - Pei, G K AU - Chakrabarty, M K AU - Heidecker, G AU - Lautenberger, J A AU - Samuel, K P AD - Laboratory of Leukocyte Biology, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15727 EP - 15733 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - Gene Products, nef KW - 0 KW - nef Gene Products, Human Immunodeficiency Virus KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Peptide Mapping KW - Conserved Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Binding Sites -- genetics KW - Amino Acid Substitution KW - Gene Products, nef -- metabolism KW - Gene Products, nef -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79939175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Binding+of+c-Raf1+kinase+to+a+conserved+acidic+sequence+within+the+carboxyl-terminal+region+of+the+HIV-1+Nef+protein.&rft.au=Hodge%2C+D+R%3BDunn%2C+K+J%3BPei%2C+G+K%3BChakrabarty%2C+M+K%3BHeidecker%2C+G%3BLautenberger%2C+J+A%3BSamuel%2C+K+P&rft.aulast=Hodge&rft.aufirst=D&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15727&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phospholipid- and GTP-dependent activation of cholera toxin and phospholipase D by human ADP-ribosylation factor-like protein 1 (HARL1). AN - 79937821; 9624189 AB - ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins named for their ability to activate cholera toxin (CT) ADP-ribosyltransferase activity, have a critical role in vesicular transport and activate a phospholipase D (PLD) isoform. Although ARF-like (ARL) proteins are very similar in sequence to ARFs, they were initially believed not to activate CT or PLD. mRNA for human ARL1 (hARL1), which is 57% identical in amino acid sequence to hARF1, is present in all tissues, with the highest amounts in kidney and pancreas and barely detectable amounts in brain. Relative amounts of hARL1 protein were similar to mRNA levels. Purified hARL1 (rARL1) synthesized in Escherichia coli had less activity toward PLD than did rARF1, although PLD activation by both proteins was guanosine guanosine 5'-(gamma-thio)triphosphate (GTPgammaS)-dependent. ARL1 stimulation of CT-catalyzed ADP-ribosylation was considerably less than that by rARF1 and was phospholipid dependent. GTPgammaS-binding by rARL1 was also phospholipid- and detergent-dependent, and in assays containing phosphatidylserine, was greater than that by rARF1. In vitro, the activities of rARL1 and rARF1 are similar. Rather than being a member of a separate subfamily, hARL1, which activates PLD and CT in a phospholipiddependent manner, appears to be part of a continuum of ARF family proteins. JF - The Journal of biological chemistry AU - Hong, J X AU - Lee, F J AU - Patton, W A AU - Lin, C Y AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 15872 EP - 15876 VL - 273 IS - 25 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Phospholipids KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Phospholipase D KW - EC 3.1.4.4 KW - ADP-ribosylation factor related proteins KW - EC 3.6.1.- KW - GTP Phosphohydrolases KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Brain Chemistry KW - In Vitro Techniques KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Tissue Distribution KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Catalysis KW - Phospholipase D -- metabolism KW - Membrane Proteins -- metabolism KW - GTP Phosphohydrolases -- metabolism KW - Phospholipids -- metabolism KW - Adenosine Diphosphate Ribose -- metabolism KW - Guanosine Triphosphate -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79937821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phospholipid-+and+GTP-dependent+activation+of+cholera+toxin+and+phospholipase+D+by+human+ADP-ribosylation+factor-like+protein+1+%28HARL1%29.&rft.au=Hong%2C+J+X%3BLee%2C+F+J%3BPatton%2C+W+A%3BLin%2C+C+Y%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Hong&rft.aufirst=J&rft.date=1998-06-19&rft.volume=273&rft.issue=25&rft.spage=15872&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The NIMH multisite HIV prevention trial: Reducing HIV sexual risk behavior AN - 213554659; 9632382; 03783771 AB - The efficacy of a behavioral intervention to reduce human immunodeficiency virus (HIV) risk behaviors was tested in a randomized, controlled trial with three high-risk populations at 37 clinics from seven sites across the United States. Compared with the 1855 individuals in the control condition, the 1851 participants assigned to a small-group, seven-session HIV risk reduction program reported fewer unprotected sexual acts, had higher levels of condom use, and were more likely to use condoms consistently over a 12-month follow-up period. On the basis of clinical record review, no difference in overall sexually transmitted disease (STD) reinfection rate was found between intervention and control condition participants. However, among men recruited from STD clinics, those assigned to the intervention condition had a gonorrhea incidence rate one-half that of those in the control condition. Intervention condition participants also reported fewer STD symptoms over the 12-month follow-up period. Study outcomes suggest that behavioral interventions can reduce HIV-related sexual risk behavior among low-income women and men served in public health settings. Studies that test strategies for reducing sexual risk behavior over longer periods of time are needed, especially with populations that remain most vulnerable to HIV infection. JF - Science AU - The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group AD - The National Institute of Mental Health (NIMH) Multisite HIV Prevention Trial Group Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 1889 EP - 94 CY - Washington PB - The American Association for the Advancement of Science VL - 280 IS - 5371 SN - 00368075 KW - Technology: Comprehensive Works KW - Human immunodeficiency virus KW - HIV KW - Clinical trials KW - Medical research KW - Sexual behavior KW - Sex Behavior KW - HIV Infections -- prevention control KW - Health Behavior KW - Health Education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/213554659?accountid=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=Science&rft.atitle=The+NIMH+multisite+HIV+prevention+trial%3A+Reducing+HIV+sexual+risk+behavior&rft.au=The+National+Institute+of+Mental+Health+%28NIMH%29+Multisite+HIV+Prevention+Trial+Group&rft.aulast=The+National+Institute+of+Mental+Health+%28NIMH%29+Multisite+HIV+Prevention+Trial+Group&rft.aufirst=&rft.date=1998-06-19&rft.volume=280&rft.issue=5371&rft.spage=1889&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright American Association for the Advancement of Science Jun 19, 1998 N1 - Last updated - 2010-06-08 N1 - CODEN - SCIEAS ER - TY - JOUR T1 - Bloodstream- versus tick-associated variants of a relapsing fever bacterium AN - 16438974; 4333706 AB - The relapsing fever spirochete, Borrelia hermsii, alternates infections between a mammal and a tick vector. Whether the spirochete changes phenotypically in the different hosts was examined by allowing the tick vector Ornithodoros hermsi to feed on mice infected with serotype 7 or serotype 8 of B. hermisii. Upon infection of ticks, the spirochetal serotype-specific variable major proteins (Vmps) 7 and 8 became undetectable and were replaced by Vmp33. This swtich from a bloodstream- to tick-associated phenotype could be induced in culture by a decrease in temperature. After tick-bite transmission back to mice, the process was reversed and the spirochetes resumed expression of the same Vmp present in the previous infectious blood meal. JF - Science (Washington) AU - Schwan, T G AU - Hinnebusch, B J AD - Lab. Microb. Struct. and Function, Rocky Mt. Lab., Natl. Inst. Allergy and Infect. Dis., NIH, Hamilton, MT 59840, USA, tom_schwan@nih.gov Y1 - 1998/06/19/ PY - 1998 DA - 1998 Jun 19 SP - 1938 EP - 1940 PB - American Association for the Advancement of Science VL - 280 IS - 5371 SN - 0036-8075, 0036-8075 KW - Acari KW - Vmp33 protein KW - Vmp7 protein KW - Vmp8 protein KW - mice KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16438974?accountid=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=Experimental+and+clinical+psychopharmacology&rft.atitle=Attenuation+of+cocaine-induced+locomotor+activity+by+butyrylcholinesterase.&rft.au=Carmona%2C+G+N%3BSchindler%2C+C+W%3BShoaib%2C+M%3BJufer%2C+R%3BCone%2C+E+J%3BGoldberg%2C+S+R%3BGreig%2C+N+H%3BYu%2C+Q+S%3BGorelick%2C+D+A&rft.aulast=Carmona&rft.aufirst=G&rft.date=1998-08-01&rft.volume=6&rft.issue=3&rft.spage=274&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Complementation of mismatch repair gene defects by chromosome transfer. AN - 80032705; 9675233 AB - The study of the multiple functions of mismatch repair genes in humans is being facilitated by the use of human tumor cell lines carrying defined MMR gene mutations. Such cell lines have elevated spontaneous mutation rates and may accumulate mutations in other genes, some of which could be causally related to the phenotypes of these cells. One approach to establish a cause-effect relationship between a MMR gene defect and a phenotype is to determine if that phenotype is reversed when a normal chromosome carrying a wild-type MMR gene is introduced by microcell fusion. This approach has the advantage of presenting the gene in its natural chromosomal environment with normal regulatory controls and at a reasonable dosage. The approach also limits candidate genes to only those encoded by the introduced chromosome and not elsewhere in the genome. Here we review studies demonstrating that hMSH2, hMSH3, hMSH6 and hMLH1 gene defects can each be complemented by transferring human chromosome 2, 5, 2 or 3, respectively. These transfers restore MMR activity, sensitivity to killing by MNNG, stability to microsatellite sequences and low spontaneous HPRT gene mutation rates. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Tindall, K R AU - Glaab, W E AU - Umar, A AU - Risinger, J I AU - Koi, M AU - Barrett, J C AU - Kunkel, T A AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 15 EP - 22 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Nucleic Acid Heteroduplexes KW - 0 KW - Index Medicus KW - Cell Fusion KW - Humans KW - Hybrid Cells KW - Mutation KW - DNA Repair -- genetics KW - Chromosomes, Human KW - Genetic Complementation Test UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80032705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Federal+News+Service+-+Congressional+Hearing+Prepared+Testimonies&rft.atitle=PREPARED+STATEMENT+OF+THE+HONORABLE+CAROL+M.+BROWNER+ADMINISTRATOR+OF+THE+ENVIRONMENTAL+PROTECTION+AGENCY+BEFORE+THE+SENATE+COMMITTEE+ON+FINANCE+THURSDAY%2C+JANUARY+28%2C+1999&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1999-01-28&rft.volume=&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Federal+News+Service+-+Congressional+Hearing+Prepared+Testimonies&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of Escherichia coli dnaE antimutator mutants on mutagenesis by the base analog N4-aminocytidine. AN - 80028759; 9675236 AB - Previous studies in our laboratory have identified a set of mutations in the Escherichia coli dnaE gene that confer increased accuracy of DNA replication (antimutators). The dnaE gene encodes the polymerase subunit of DNA polymerase III holoenzyme that replicates the E. coli chromosome. Here, we have investigated their effect on mutagenesis by the base analog N4-aminocytidine (4AC). For three different mutational markers, rifampicin resistance, nalidixic acid resistance and lacI forward mutagenesis, the dnaE911 allele reduced 4AC-induced mutagenesis by approximately 2.5-fold, while the dnaE915 allele reduced it by 2.5-, 3.5- and 6.5-fold, respectively. We also investigated the dependence of 4AC mutagenesis on mutations in the MutHLS mismatch repair system and the UvrABC nucleotide excision repair system. The results show that mutagenesis by 4AC is unaffected by defects in either system. The combined results point to the critical role of the DNA polymerase in preventing mutations by base analogs. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Schaaper, R M AU - Dunn, R L AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. schaaper@niehs.nih.gov Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 23 EP - 28 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Antimutagenic Agents KW - 0 KW - Mutagens KW - N(4)-aminocytidine KW - 57294-74-3 KW - Cytidine KW - 5CSZ8459RP KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Index Medicus KW - Alleles KW - Dose-Response Relationship, Drug KW - Chromosomes, Bacterial KW - DNA Polymerase III -- genetics KW - Mutagens -- toxicity KW - Escherichia coli -- genetics KW - Cytidine -- toxicity KW - Mutation KW - Cytidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80028759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+Escherichia+coli+dnaE+antimutator+mutants+on+mutagenesis+by+the+base+analog+N4-aminocytidine.&rft.au=Schaaper%2C+R+M%3BDunn%2C+R+L&rft.aulast=Schaaper&rft.aufirst=R&rft.date=1998-06-18&rft.volume=402&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 - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antimutagenic and anticarcinogenic potentials of some Thai vegetables. AN - 80027814; 9675301 AB - Fifteen kinds of commonly consumed Thai vegetables were sequentially extracted with hexane, chloroform and methanol, and then tested for antimutagenic activities against direct-acting (AF-2 and NaN3) and indirect-acting (AFB1 and B(a)P) mutagens using Ames' Salmonella mutagenicity test with Salmonella typhimurium TA100 as tester strain. It was found that only the methanol extract of neem leaves contain weak antimutagen inhibiting the mutagenicities of both direct-acting mutagens. Interestingly, all vegetables studied were found to contain chemical compounds, mainly nonpolar ones, capable of inhibiting the mutagenicity of AFB1, while only some vegetables contain chemical compounds capable of inhibiting the mutagenicity of B(a)P, which is also an indirect-acting mutagen. Studies on anticarcinogenic potentials demonstrated that Thai bitter gourd fruits, but not sweet basil leaves, at the concentration of 6.25% and 12.5% in the diet, partially inhibited DMBA-induced mammary gland carcinogenesis in female Sprague-Dawley rats when fed to the animals 2 weeks prior to DMBA. Results in the present study therefore demonstrated that most Thai vegetables contain antimutagens inhibiting the mutagenicity of some indirect-acting mutagen, particularly AFB1. The mechanism of their antimutagenicity may probably be the inhibition of the activity of metabolic-activating enzymes in rat liver homogenates. Very interestingly, our results clearly reveal that Thai bitter gourd fruits, which possess Phase II enzymes inducing property, as well as the ability to reduce Phase I enzyme activities in rat liver, contain some anticarcinogens or chemopreventive agents. However, sweet basil leaves that possess both Phase I and Phase II enzyme-inducing properties may not contain any anticarcinogen, at least against DMBA-induced mammary gland carcinogenesis. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Kusamran, W R AU - Tepsuwan, A AU - Kupradinun, P AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Rama VI Road, Bangkok 10400, Thailand. waroran@health.moph.go.th Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 247 EP - 258 VL - 402 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Anticarcinogenic Agents KW - 0 KW - Antimutagenic Agents KW - Aniline Hydroxylase KW - EC 1.14.14.- KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Mutagenicity Tests KW - Liver -- enzymology KW - Liver -- drug effects KW - Thailand KW - Aminopyrine N-Demethylase -- antagonists & inhibitors KW - Mammary Neoplasms, Experimental -- prevention & control KW - Salmonella typhimurium -- genetics KW - Female KW - Aniline Hydroxylase -- antagonists & inhibitors KW - Anticarcinogenic Agents -- analysis KW - Vegetables -- chemistry KW - Antimutagenic Agents -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Antimutagenic Agents -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80027814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antimutagenic+and+anticarcinogenic+potentials+of+some+Thai+vegetables.&rft.au=Kusamran%2C+W+R%3BTepsuwan%2C+A%3BKupradinun%2C+P&rft.aulast=Kusamran&rft.aufirst=W&rft.date=1998-06-18&rft.volume=402&rft.issue=1-2&rft.spage=247&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 - 1998-09-01 N1 - Date created - 1998-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines. AN - 80009854; 9671393 AB - KAI1 is a metastasis suppressor gene on human chromosome 11p11.2 that encodes a glycoprotein of the transmembrane four superfamily. Reduced KAI1 expression associates with malignant progression of human prostatic, lung and pancreatic cancers, but the role of KAI1 protein in the malignant progression of other human cancers remains to be elucidated. We analysed KAI1 protein in normal and cancer cells of the prostate, ovary, bladder, endometrium, lung and melanocytes by Western blot to determine if KAI1 may be involved in multiple cancers. We also investigated the relationship of KAI1 expression and two other transmembrane four superfamily proteins, CD81 and CD9, in the cells. We found that KAI1 protein was downregulated in 31/42 of the cancer cell lines analysed. Alternatively, some ovarian, bladder and endometrial cells had distinct, heterogeneous KAI1 protein band patterns in Western blots that were due primarily to N-linked glycosylation. Most of the cancer cells expressed two other transmembrane four superfamily proteins, CD81 and CD9. Downregulation of KAI1 protein may be an indicator of metastatic potential in cancers of urogenital, gynecological, and pulmonary origin and in melanomas. KAI1 may also have post-translational modifications specific to tissue type or malignant progression. JF - Oncogene AU - White, A AU - Lamb, P W AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 3143 EP - 3149 VL - 16 IS - 24 SN - 0950-9232, 0950-9232 KW - Antigens, CD KW - 0 KW - Antigens, CD81 KW - Antigens, CD82 KW - Antigens, CD9 KW - CD81 protein, human KW - CD82 protein, human KW - CD9 protein, human KW - Membrane Glycoproteins KW - Membrane Proteins KW - Proto-Oncogene Proteins KW - Index Medicus KW - Humans KW - Prostate -- metabolism KW - Prognosis KW - Neoplasms -- genetics KW - Neoplasm Metastasis -- genetics KW - Neoplasms -- pathology KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Prostate -- cytology KW - Male KW - Neoplasms -- immunology KW - Down-Regulation KW - Antigens, CD -- metabolism KW - Antigens, CD -- genetics KW - Antigens, CD -- immunology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80009854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Frequent+downregulation+of+the+KAI1%28CD82%29+metastasis+suppressor+protein+in+human+cancer+cell+lines.&rft.au=White%2C+A%3BLamb%2C+P+W%3BBarrett%2C+J+C&rft.aulast=White&rft.aufirst=A&rft.date=1998-06-18&rft.volume=16&rft.issue=24&rft.spage=3143&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three-dimensional quantitative structure-activity relationship study of nonsteroidal estrogen receptor ligands using the comparative molecular field analysis/cross-validated r2-guided region selection approach. AN - 79948180; 9632359 AB - A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands. JF - Journal of medicinal chemistry AU - Sadler, B R AU - Cho, S J AU - Ishaq, K S AU - Chae, K AU - Korach, K S AD - Laboratory of Reproductive and Developmental Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06/18/ PY - 1998 DA - 1998 Jun 18 SP - 2261 EP - 2267 VL - 41 IS - 13 SN - 0022-2623, 0022-2623 KW - Estrogens, Non-Steroidal KW - 0 KW - Indenes KW - Ligands KW - Receptors, Estrogen KW - indenestrol KW - 4A464K3BSI KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Diethylstilbestrol -- metabolism KW - Diethylstilbestrol -- chemistry KW - Mice KW - Diethylstilbestrol -- analogs & derivatives KW - Molecular Conformation KW - Indenes -- chemistry KW - Indenes -- metabolism KW - Structure-Activity Relationship KW - Models, Molecular KW - Estrogens, Non-Steroidal -- chemistry KW - Receptors, Estrogen -- metabolism KW - Estrogens, Non-Steroidal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79948180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three-dimensional+quantitative+structure-activity+relationship+study+of+nonsteroidal+estrogen+receptor+ligands+using+the+comparative+molecular+field+analysis%2Fcross-validated+r2-guided+region+selection+approach.&rft.au=Sadler%2C+B+R%3BCho%2C+S+J%3BIshaq%2C+K+S%3BChae%2C+K%3BKorach%2C+K+S&rft.aulast=Sadler&rft.aufirst=B&rft.date=1998-06-18&rft.volume=41&rft.issue=13&rft.spage=2261&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 - 1998-07-09 N1 - Date created - 1998-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trends in HIV incidence among young adults in the United States. AN - 79949115; 9634261 AB - Behaviors that result in potential exposure to human immunodeficiency virus (HIV) usually begin in adolescence or young adulthood, but trends in HIV incidence in young people remain unclear. To estimate trends in HIV incidence in teenagers and young adults. Back-calculation of past HIV incidence in persons born between 1960 and 1974 using US national acquired immunodeficiency syndrome (AIDS) incidence data and estimates of the distribution of times between HIV infection and AIDS. Incidence and prevalence of HIV in 1988 and 1993 in persons aged 20 and 25 years, respectively, in each of those years. As of January 1993, about 22000 men and 11000 women aged 18 to 22 years were living with HIV infection in the United States. Homosexual contact was the leading route of infection among young men. Heterosexual contact was the leading route of infection among young women. The HIV incidence attributed to homosexual contact or injection drug use decreased among persons aged 20 and 25 years between 1988 and 1993, but HIV incidence attributed to heterosexual contact was stable or increasing. Notably, in men aged 20 and 25 years, HIV prevalence declined by about 50% in white men but was relatively stable in black and Hispanic men. In contrast, HIV prevalence in women aged 20 and 25 years rose by 36% and 45%, respectively, because of increasing heterosexual transmission. Overall, HIV prevalence in persons aged 20 and 25 years declined by only 14% between 1988 and 1993. In young persons, HIV incidence in homosexual men and injection drug users was slowing by 1993; this favorable trend was offset by increasing heterosexual transmission, especially in minorities. JF - JAMA AU - Rosenberg, P S AU - Biggar, R J AD - Biostatistics Branch, National Cancer Institute, Bethesda, MD 20892, USA. philip_rosenberg@nih.gov Y1 - 1998/06/17/ PY - 1998 DA - 1998 Jun 17 SP - 1894 EP - 1899 VL - 279 IS - 23 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Homosexuality, Male KW - Humans KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - Hispanic Americans -- statistics & numerical data KW - Adult KW - Incidence KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Substance Abuse, Intravenous KW - HIV Infections -- transmission KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79949115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Trends+in+HIV+incidence+among+young+adults+in+the+United+States.&rft.au=Rosenberg%2C+P+S%3BBiggar%2C+R+J&rft.aulast=Rosenberg&rft.aufirst=P&rft.date=1998-06-17&rft.volume=279&rft.issue=23&rft.spage=1894&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-26 N1 - Date created - 1998-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Failure to down regulate NMDA receptors in the striatum and nucleus accumbens associated with neuroleptic-induced dyskinesia. AN - 80041912; 9689480 AB - The syndrome of vacuous chewing movements (VCMs) in rats is similar in many respects to tardive dyskinesia (TD) in humans. Both syndromes are characterized by delayed onset of persistent orofacial dyskinesias in a sub-group of subjects chronically treated with neuroleptics. Using the rat model, we examined the role of NMDA receptor-mediated corticostriatal neurotransmission in the expression of VCMs. Rats were treated for 36 weeks with haloperidol decanoate or vehicle and then withdrawn for an additional 28 weeks. Chronic persistent VCMs were induced in one subgroup of treated animals (+VCM), but not in another group (-VCM). Rats from +VCM, -VCM groups and vehicle-treated controls were selected for post mortem studies (n = 12 to 14 per group). NMDA receptor levels were assessed using [3H]-MK-801 binding in sections from the mid-striatum and nucleus accumbens. Chronic haloperidol treatment produced a marked reduction of NMDA receptor binding levels throughout the striatum and nucleus accumbens. Post hoc comparisons demonstrated that -VCM rats had lower NMDA receptor binding levels than +VCM and vehicle-treated controls. Ventromedial striatum and nucleus accumbens core were the most affected areas. These findings suggest that down-regulation of striatal NMDA receptor binding levels may protect against the expression of neuroleptic-induced dyskinesia. JF - Brain research AU - Hamid, E H AU - Hyde, T M AU - Baca, S M AU - Egan, M F AD - Clinical Research Services, National Institute of Mental Health, St. Elizabeth's Hospital, Washington, DC, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 291 EP - 295 VL - 796 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Antipsychotic Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - haloperidol decanoate KW - AC20PJ4101 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Excitatory Amino Acid Antagonists -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Dizocilpine Maleate -- metabolism KW - Mastication -- physiology KW - Synaptic Transmission -- physiology KW - Male KW - Dyskinesia, Drug-Induced -- metabolism KW - Down-Regulation -- physiology KW - Nucleus Accumbens -- drug effects KW - Corpus Striatum -- metabolism KW - Nucleus Accumbens -- metabolism KW - Corpus Striatum -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Dyskinesia, Drug-Induced -- physiopathology KW - Haloperidol -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80041912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Failure+to+down+regulate+NMDA+receptors+in+the+striatum+and+nucleus+accumbens+associated+with+neuroleptic-induced+dyskinesia.&rft.au=Hamid%2C+E+H%3BHyde%2C+T+M%3BBaca%2C+S+M%3BEgan%2C+M+F&rft.aulast=Hamid&rft.aufirst=E&rft.date=1998-06-15&rft.volume=796&rft.issue=1-2&rft.spage=291&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 - 1998-10-29 N1 - Date created - 1998-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of one-sided methods to identify significant individual outcomes in a multiple outcome setting: stepwise tests or global tests with closed testing. AN - 80013018; 9670413 AB - We compare two approaches to the identification of individual significant outcomes when a comparison of two groups involves multiple outcome variables. The approaches are all designed to control the familywise error rate (FWE) with any subset of the null hypothesis being true (in the strong sense). The first approach is initially to use a global test of the overall hypothesis that the groups are equivalent for all variables, followed by an application of the closed testing algorithm of Marcus, Peritz and Gabriel. The global tests considered here are ordinary least squares (OLS), generalized least squares (GLS), an approximation to a likelihood ratio test (ALR), and a new test based on an approximation to the most powerful similar test for simple alternatives. The second approach is that of stepwise testing, which tests the univariate hypotheses in a specific order with appropriate adjustment to the univariate p-values for multiplicity. The stepwise tests considered include both step-down and step-up tests of a general type, and likewise permutation tests that incorporate the dependence structure of the data. We illustrate the tests with two examples of birth outcomes: a comparison of cocaine-exposed new-borns to control new-borns on neurobehavioural and physical growth variables, and, in a separate study, a comparison of babies born to diabetic mothers and babies born to non-diabetic mothers on minor malformations. After describing the methods and analysing the birth outcome data, we use simulations on Gaussian data to provide guidelines for the use of these procedures in terms of power and computation. JF - Statistics in medicine AU - Troendle, J F AU - Legler, J M AD - Biometry and Mathematical Statistics Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 1245 EP - 1260 VL - 17 IS - 11 SN - 0277-6715, 0277-6715 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Probability KW - Analysis of Variance KW - Fetus -- drug effects KW - Infant, Newborn -- growth & development KW - Humans KW - Algorithms KW - Congenital Abnormalities -- etiology KW - Infant, Newborn -- physiology KW - Cocaine -- adverse effects KW - Likelihood Functions KW - Pregnancy KW - Computing Methodologies KW - Maternal Age KW - Adult KW - Pregnancy in Diabetics KW - Male KW - Female KW - Outcome Assessment (Health Care) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80013018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Localization+of+endogenous+ARF6+to+sites+of+cortical+actin+rearrangement+and+involvement+of+ARF6+in+cell+spreading.&rft.au=Song%2C+J%3BKhachikian%2C+Z%3BRadhakrishna%2C+H%3BDonaldson%2C+J+G&rft.aulast=Song&rft.aufirst=J&rft.date=1998-08-01&rft.volume=111+%28+Pt+15%29&rft.issue=&rft.spage=2257&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 - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Workgroup 3: transgenic and reconstitution models of prostate cancer. AN - 79976103; 9650918 JF - The Prostate AU - Green, J E AU - Greenberg, N M AU - Ashendel, C L AU - Barrett, J C AU - Boone, C AU - Getzenberg, R H AU - Henkin, J AU - Matusik, R AU - Janus, T J AU - Scher, H I Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 59 EP - 63 VL - 36 IS - 1 KW - Androgen-Binding Protein KW - 0 KW - probasin KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Genes, bcl-2 KW - Animals KW - Simian virus 40 -- genetics KW - Globins -- genetics KW - Artificial Gene Fusion KW - Androgen-Binding Protein -- genetics KW - Male KW - Models, Genetic KW - Prostatic Neoplasms -- genetics KW - Animals, Genetically Modified UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79976103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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+Prostate&rft.atitle=Workgroup+3%3A+transgenic+and+reconstitution+models+of+prostate+cancer.&rft.au=Green%2C+J+E%3BGreenberg%2C+N+M%3BAshendel%2C+C+L%3BBarrett%2C+J+C%3BBoone%2C+C%3BGetzenberg%2C+R+H%3BHenkin%2C+J%3BMatusik%2C+R%3BJanus%2C+T+J%3BScher%2C+H+I&rft.aulast=Green&rft.aufirst=J&rft.date=1998-06-15&rft.volume=36&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. AN - 79953258; 9635574 AB - The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors plus recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis. JF - Cancer research AU - Burke, L AU - Khan, M A AU - Freedman, A N AU - Gemma, A AU - Rusin, M AU - Guinee, D G AU - Bennett, W P AU - Caporaso, N E AU - Fleming, M V AU - Travis, W D AU - Colby, T V AU - Trastek, V AU - Pairolero, P C AU - Tazelaar, H D AU - Midthun, D E AU - Liotta, L A AU - Harris, C C AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 2533 EP - 2536 VL - 58 IS - 12 SN - 0008-5472, 0008-5472 KW - Genetic Markers KW - 0 KW - Neoplasm Proteins KW - Proteins KW - fragile histidine triad protein KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Index Medicus KW - Microsatellite Repeats -- genetics KW - Genetic Markers -- genetics KW - Alleles KW - Survival Rate KW - Humans KW - Adult KW - Prognosis KW - Chromosomes, Human, Pair 3 -- genetics KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gene Deletion KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Genes, Tumor Suppressor -- genetics KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Neoplasm Proteins -- genetics KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- mortality KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79953258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allelic+deletion+analysis+of+the+FHIT+gene+predicts+poor+survival+in+non-small+cell+lung+cancer.&rft.au=Burke%2C+L%3BKhan%2C+M+A%3BFreedman%2C+A+N%3BGemma%2C+A%3BRusin%2C+M%3BGuinee%2C+D+G%3BBennett%2C+W+P%3BCaporaso%2C+N+E%3BFleming%2C+M+V%3BTravis%2C+W+D%3BColby%2C+T+V%3BTrastek%2C+V%3BPairolero%2C+P+C%3BTazelaar%2C+H+D%3BMidthun%2C+D+E%3BLiotta%2C+L+A%3BHarris%2C+C+C&rft.aulast=Burke&rft.aufirst=L&rft.date=1998-06-15&rft.volume=58&rft.issue=12&rft.spage=2533&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res 1998 Aug 1;58(15):3488 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 1: rheumatologic and renal diseases. AN - 79911895; 9625665 AB - When cytotoxic agents were initially introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. Part 1 examines the manner in which these agents have been used to treat rheumatologic and renal diseases. JF - Annals of internal medicine AU - Langford, C A AU - Klippel, J H AU - Balow, J E AU - James, S P AU - Sneller, M C AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/15/ PY - 1998 DA - 1998 Jun 15 SP - 1021 EP - 1028 VL - 128 IS - 12 Pt 1 SN - 0003-4819, 0003-4819 KW - Immunosuppressive Agents KW - 0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Drug Therapy, Combination KW - Cell Survival -- drug effects KW - Humans KW - Cyclosporine -- adverse effects KW - Cyclosporine -- therapeutic use KW - Autoimmune Diseases -- drug therapy KW - Immunosuppressive Agents -- therapeutic use KW - Rheumatic Diseases -- drug therapy KW - Kidney Diseases -- drug therapy KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Annals+of+internal+medicine&rft.atitle=Use+of+cytotoxic+agents+and+cyclosporine+in+the+treatment+of+autoimmune+disease.+Part+1%3A+rheumatologic+and+renal+diseases.&rft.au=Langford%2C+C+A%3BKlippel%2C+J+H%3BBalow%2C+J+E%3BJames%2C+S+P%3BSneller%2C+M+C&rft.aulast=Langford&rft.aufirst=C&rft.date=1998-06-15&rft.volume=128&rft.issue=12+Pt+1&rft.spage=1021&rft.isbn=&rft.btitle=&rft.title=Annals+of+internal+medicine&rft.issn=00034819&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-10 N1 - Date created - 1998-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of Met-tRNA sub(i) super(M) super(e) super(t) binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast AN - 16521849; 4327217 AB - Delivery of the initiator methionine transfer RNA (Met-tRNA sub(i) super(M) super(e) super(t)) to the ribosome is a key step in the initiation of protein synthesis. Previous results have indicated that this step is catalyzed by the structurally dissimilar translation factors in prokaryotes and eukaryotes--initiation factor 2 (IF2) and eukaryotic initiation factor 2 (eIF2), respectively. A bacterial IF2 homolog has been identified in both eukaryotes and archaea. By using a combination of molecular genetic and biochemical studies, the Saccharomyces cerevisiae IF2 homolog is shown to function in general translation initiation by promoting Met-tRNA sub(i) super(M) super(e) super(t) binding to ribosomes. Thus, the mechanism of protein synthesis in eukaryotes and prokaryotes is more similar than was previously realized. JF - Science (Washington) AU - Choi, Sang Ki AU - Lee, Joon H AU - Zoll, W L AU - Merrick, W C AU - Dever, TE AD - Lab. Eukaryotic Gene Regul., Natl. Inst. Child Health and Hum. Dev., NIH, Bethesda, MD 20892-2716, USA, tdever@box-t.nih.gov Y1 - 1998/06/12/ PY - 1998 DA - 1998 Jun 12 SP - 1757 EP - 1760 PB - American Association for the Advancement of Science VL - 280 IS - 5370 SN - 0036-8075, 0036-8075 KW - budding yeast KW - initiation factor IF-2 KW - initiation factor eIF-2 KW - tRNA fMet KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Biochemistry Abstracts 2: Nucleic Acids KW - A 01002:Acids, amino acids, peptides & proteins KW - N 14420:Binding of tRNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16521849?accountid=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=Science+%28Washington%29&rft.atitle=Promotion+of+Met-tRNA+sub%28i%29+super%28M%29+super%28e%29+super%28t%29+binding+to+ribosomes+by+yIF2%2C+a+bacterial+IF2+homolog+in+yeast&rft.au=Choi%2C+Sang+Ki%3BLee%2C+Joon+H%3BZoll%2C+W+L%3BMerrick%2C+W+C%3BDever%2C+TE&rft.aulast=Choi&rft.aufirst=Sang&rft.date=1998-06-12&rft.volume=280&rft.issue=5370&rft.spage=1757&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 ER - TY - JOUR T1 - Lessons from the cat: Feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1 AN - 16516483; 4341750 AB - In July 1997 the Division of AIDS of the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled "Use of the FIV/Cat Model for Development of Anti-HIV Vaccines and Therapeutics." The purpose of this workshop was to provide a forum for presenting new data arising from FIV research, assess the utility of the FIV/cat model, identify areas applicable to HIV/AIDS research, and solicit input from investigators on scientific gaps that can benefit from additional support. The meeting brought to the fore numerous areas where the FIV/cat model can serve as a valuable tool for developing new therapeutic strategies and vaccine designs applicable to the treatment and prevention of HIV-1 infection. JF - AIDS Research and Human Retroviruses AU - Elder, J H AU - Dean, G A AU - Hoover, E A AU - Hoxie, JA AU - Malim, M H AU - Mathes, L AU - Neil, J C AU - North, T W AU - Sparger, E AU - Tompkins, M B AU - Tompkins, WAF AU - Yamamoto, J AU - Yuhki, N AU - Miller, R H AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/06/10/ PY - 1998 DA - 1998 Jun 10 SP - 797 EP - 801 VL - 14 IS - 9 SN - 0889-2229, 0889-2229 KW - Cats KW - HIV-1 KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - V 22006:AIDS: Other aspects KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16516483?accountid=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=AIDS+Research+and+Human+Retroviruses&rft.atitle=Lessons+from+the+cat%3A+Feline+immunodeficiency+virus+as+a+tool+to+develop+intervention+strategies+against+human+immunodeficiency+virus+type+1&rft.au=Elder%2C+J+H%3BDean%2C+G+A%3BHoover%2C+E+A%3BHoxie%2C+JA%3BMalim%2C+M+H%3BMathes%2C+L%3BNeil%2C+J+C%3BNorth%2C+T+W%3BSparger%2C+E%3BTompkins%2C+M+B%3BTompkins%2C+WAF%3BYamamoto%2C+J%3BYuhki%2C+N%3BMiller%2C+R+H&rft.aulast=Elder&rft.aufirst=J&rft.date=1998-06-10&rft.volume=14&rft.issue=9&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=AIDS+Research+and+Human+Retroviruses&rft.issn=08892229&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 - Human Immunodeficiency Virus Type 2 Lentivirus Vectors for Gene Transfer: Expression and Potential for Helper Virus-Free Packaging AN - 16431035; 4332861 AB - In addition to the long-term expression of the transgene provided by all retroviral vectors, lentiviruses present the opportunity to transduce nondividing cells and potentially achieve regulated expression. The development of lentiviral vectors requires the design of transfer vectors to ferry the transgene with efficient encapsidation of the transgene RNA and with full expression capability, and of a packaging vector to provide packaging machinery in trans but without helper virus production. For both vectors, a knowledge of packaging signal is required - the signal to be included in the transfer vector but excluded from the packaging vector. Among the human lentiviruses, human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2), we think HIV-2 is better suited for gene transfer than HIV-1. It is less pathogenic and thus safer during design and production; its desirable nuclear import and undesirable cell-cycle arrest functions are segregated on two separate genes. In HIV-1 infection, it is less likely to recombine with the resident HIV-1, and it may itself downregulate HIV-1 expression. Evidently, elements located both upstream and downstream of the splice donor site in the leader sequence participated in RNA encapsidation and these sequences appeared necessary and sufficient. Deletion of both sequence elements resulted in a dramatic curtailment of RNA encapsidation and helper virus production. This was accompanied by some but acceptable loss of gene expression capability. The helper virus-free phenotype and expression capability of the double mutant was maintained upon replacement of its 3' long terminal repeat with a minigene cassette containing a transcriptional termination signal and a drug resistance marker gene. Deletion of the splice donor site itself had a dramatic negative effect on gene expression, supporting the important role of this element in the life of RNA. JF - Human Gene Therapy AU - Arya, S K AU - Zamani, M AU - Kundra, P AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4255, Building 37, Room 6A11, Bethesda, MD 20892-4255, USA Y1 - 1998/06/10/ PY - 1998 DA - 1998 Jun 10 SP - 1371 EP - 1380 VL - 9 IS - 9 SN - 1043-0342, 1043-0342 KW - helper virus KW - human immunodeficiency virus 2 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16431035?accountid=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=Human+Immunodeficiency+Virus+Type+2+Lentivirus+Vectors+for+Gene+Transfer%3A+Expression+and+Potential+for+Helper+Virus-Free+Packaging&rft.au=Arya%2C+S+K%3BZamani%2C+M%3BKundra%2C+P&rft.aulast=Arya&rft.aufirst=S&rft.date=1998-06-10&rft.volume=9&rft.issue=9&rft.spage=1371&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 ER - TY - JOUR T1 - Involvement of carboxy-terminal amino acids in secretion of human lysosomal protease cathepsin L. AN - 79930303; 9622510 AB - Cathepsin L, a lysosomal cysteine protease, is overexpressed and secreted by malignantly transformed cells. However, the reason for secretion of this man 6-phosphate-containing lysosomal protease into the extracellular medium is not clear. We wished to determine whether there is a region within the primary sequence of the proenzyme form of cathepsin L which affects its subcellular and extracellular localization. High-level transient expression of human procathepsin L in mouse NIH 3T3 cells results in the secretion of most of this protein into the extracellular medium. At the same time, the endogenous mouse procathepsin L in these nontransformed cells is found in its usual location in lysosomes. Mutants of human procathepsin L with carboxy-terminus deletions involving the last 11 amino acids are not secreted into the medium. Deletion of as little as two amino acids, Thr and Val, from the carboxy terminus, blocked the secretion of the protein but did not affect its enzyme activity, posttranslational processing, or subcellular distribution. Replacement of Thr-Val by two bulky amino acids Tyr-Asn allowed secretion of the procathepsin L, but the replacement of these two amino acids by nonbulky alanines prevented its secretion. Single alanine substitutions of the last six amino acids (ASYPTV) indicated that substitution by alanine of Y or T does not affect the secretion of hproCAT L, but alanine substitutions of S, P, or V completely blocked its secretion into the culture medium. We therefore conclude that the carboxy terminus of procathepsin L contains a sequence essential for its secretion. JF - Biochemistry AU - Chauhan, S S AU - Ray, D AU - Kane, S E AU - Willingham, M C AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/06/09/ PY - 1998 DA - 1998 Jun 09 SP - 8584 EP - 8594 VL - 37 IS - 23 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Culture Media KW - Enzyme Precursors KW - Escherichia coli Proteins KW - Lac Repressors KW - Recombinant Proteins KW - Repressor Proteins KW - Cathepsins KW - EC 3.4.- KW - Endopeptidases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - CTSL1 protein, human KW - EC 3.4.22.15 KW - Cathepsin L KW - Ctsl protein, mouse KW - Index Medicus KW - Centrifugation, Density Gradient KW - 3T3 Cells KW - Animals KW - Bacterial Proteins -- genetics KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Mice KW - Glycosylation KW - Repressor Proteins -- genetics KW - Genetic Vectors -- metabolism KW - Culture Media -- metabolism KW - Enzyme Activation -- genetics KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Phosphorylation KW - Transfection KW - Molecular Sequence Data KW - Subcellular Fractions -- enzymology KW - Amino Acid Substitution KW - Sequence Deletion KW - Cathepsins -- secretion KW - Cathepsins -- genetics KW - Enzyme Precursors -- secretion KW - Amino Acid Sequence -- genetics KW - Lysosomes -- enzymology KW - Enzyme Precursors -- genetics KW - Cysteine Endopeptidases -- genetics KW - Cysteine Endopeptidases -- secretion KW - Amino Acid Sequence -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79930303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+carboxy-terminal+amino+acids+in+secretion+of+human+lysosomal+protease+cathepsin+L.&rft.au=Chauhan%2C+S+S%3BRay%2C+D%3BKane%2C+S+E%3BWillingham%2C+M+C%3BGottesman%2C+M+M&rft.aulast=Chauhan&rft.aufirst=S&rft.date=1998-06-09&rft.volume=37&rft.issue=23&rft.spage=8584&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of a Mycobacterium tuberculosis beta -ketoacyl ACP synthase by isoniazid AN - 16521288; 4327185 AB - Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta -ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug. JF - Science (Washington) AU - Mdluli, K AU - Slayden, R A AU - Zhu, YaQi AU - Ramaswamy, S AU - Pan, Xi AU - Mead, D AU - Crane, D D AU - Musser, J M AU - Barry, CE III AD - Tuberculosis Res. Unit, Lab. Intracell. Parasites, Rocky Mt. Lab., Natl. Inst. Allergy and Infect. Dis. (NIAID), NIH, Hamilton, MT 59840, USA, clifton_barry@nih.gov Y1 - 1998/06/05/ PY - 1998 DA - 1998 Jun 05 SP - 1607 EP - 1610 PB - American Association for the Advancement of Science VL - 280 IS - 5369 SN - 0036-8075, 0036-8075 KW - Inhibition KW - Isoniazid KW - KasA protein KW - Therapy KW - beta -Ketoacyl ACP synthase KW - beta -ketoacyl ACP synthase KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - A 01065:Antimycobacterial KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16521288?accountid=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=Inhibition+of+a+Mycobacterium+tuberculosis+beta+-ketoacyl+ACP+synthase+by+isoniazid&rft.au=Mdluli%2C+K%3BSlayden%2C+R+A%3BZhu%2C+YaQi%3BRamaswamy%2C+S%3BPan%2C+Xi%3BMead%2C+D%3BCrane%2C+D+D%3BMusser%2C+J+M%3BBarry%2C+CE+III&rft.aulast=Mdluli&rft.aufirst=K&rft.date=1998-06-05&rft.volume=280&rft.issue=5369&rft.spage=1607&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 ER - TY - JOUR T1 - Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results. AN - 80026245; 9676822 AB - Obsessive-compulsive disorder (OCD) has been linked to abnormal function of brain serotonin (5-HT) pathways. Since ondansetron is a highly selective 5-HT3 receptor antagonist, the present study was undertaken to investigate 5-HT3 function in OCD. We administered m-CPP (0.08 mg/kg i.v.) and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg i.v.), to 11 OCD patients. All of the subjects received four separate challenges (m-CPP + placebo, m-CPP + ondansetron, ondansetron + placebo and placebo + placebo). In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT3 receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in patients with OCD. JF - Psychiatry research AU - Broocks, A AU - Pigott, T A AU - Hill, J L AU - Canter, S AU - Grady, T A AU - L'Heureux, F AU - Murphy, D L AD - Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA. Y1 - 1998/06/02/ PY - 1998 DA - 1998 Jun 02 SP - 11 EP - 20 VL - 79 IS - 1 SN - 0165-1781, 0165-1781 KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin Antagonists KW - Serotonin Receptor Agonists KW - Ondansetron KW - 4AF302ESOS KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Drug Interactions KW - Analysis of Variance KW - Psychiatric Status Rating Scales KW - Behavioral Symptoms -- chemically induced KW - Injections, Intravenous KW - Double-Blind Method KW - Humans KW - Adult KW - Neurosecretory Systems -- drug effects KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Receptors, Serotonin -- physiology KW - Serotonin Receptor Agonists -- administration & dosage KW - Obsessive-Compulsive Disorder -- physiopathology KW - Ondansetron -- administration & dosage KW - Serotonin Antagonists -- administration & dosage KW - Obsessive-Compulsive Disorder -- metabolism KW - Receptors, Serotonin -- classification KW - Piperazines -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80026245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+intravenous+administration+of+ondansetron+and+m-CPP%2C+alone+and+in+combination%2C+in+patients+with+obsessive-compulsive+disorder+%28OCD%29%3A+behavioral+and+biological+results.&rft.au=Broocks%2C+A%3BPigott%2C+T+A%3BHill%2C+J+L%3BCanter%2C+S%3BGrady%2C+T+A%3BL%27Heureux%2C+F%3BMurphy%2C+D+L&rft.aulast=Broocks&rft.aufirst=A&rft.date=1998-06-02&rft.volume=79&rft.issue=1&rft.spage=11&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 - 1998-10-06 N1 - Date created - 1998-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of SH1-SH2-modified myosin subfragment-1 to actin. AN - 79910830; 9609698 AB - Myosin subfragment-1 (S1) was labeled with NPM in the presence of ATP or with pPDM in the presence of ADP at 0 degreesC, conditions which favor linking of maleimide groups to both Cys-707 (SH1) and Cys-697 (SH2). Unmodified S1 was removed by sedimentation with a small amount of F-actin, and the modified protein in the supernatant thoroughly dialyzed. The myosin high-salt EDTA and calcium ATPase activities of the isolated modified S1 were close to zero, suggesting nearly complete modification of SH1 and SH2. The binding of control and these modified myosins to actin was measured at 100 mM ionic strength using a co-sedimentation assay. In the presence of high MgATP concentration, control and NPM- and pPDM-reacted S1 all bind weakly to actin, with binding constants K3 of 4.9, 2.2, and 1.9 x 10(4) M-1, respectively. In the absence of MgATP, the binding constant K2 of pPDM-reacted S1 remains weak, 4.6 x 10(4) M-1,while that of NPM-reacted and control S1 becomes strong, 4.7 and 31 x 10(6) M-1, respectively. The binding constant for ATP to acto-NPM-reacted-S1 is approximately 2 x 10(4) M-1. Our data suggest that the binding of NPM-S1 to F-actin, in contrast to that of pPDM-S1, is ATP sensitive and can be quite strong at very low ATP concentration. They also suggest that while simple alkylation of SH1 and SH2 may be sufficient to inhibit myosin's ability to hydrolyze ATP, actual covalent linkage of SH1 and SH2 may be necessary to inhibit the weakly to strongly binding conformational change. JF - Biochemistry AU - Xie, L AU - Schoenberg, M AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA. Y1 - 1998/06/02/ PY - 1998 DA - 1998 Jun 02 SP - 8048 EP - 8053 VL - 37 IS - 22 SN - 0006-2960, 0006-2960 KW - Actins KW - 0 KW - Alkylating Agents KW - Maleimides KW - Myosin Subfragments KW - Sulfhydryl Compounds KW - Sulfhydryl Reagents KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - N-phenylmaleimide KW - 9U9KT462VW KW - N,N'-4-phenylenedimaleimide KW - BEC7P1E6J1 KW - Index Medicus KW - Animals KW - Kinetics KW - Rabbits KW - Protein Binding KW - Sulfhydryl Compounds -- metabolism KW - Sulfhydryl Compounds -- chemistry KW - Myosin Subfragments -- chemistry KW - Actins -- metabolism KW - Myosin Subfragments -- metabolism KW - Actins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Binding+of+SH1-SH2-modified+myosin+subfragment-1+to+actin.&rft.au=Xie%2C+L%3BSchoenberg%2C+M&rft.aulast=Xie&rft.aufirst=L&rft.date=1998-06-02&rft.volume=37&rft.issue=22&rft.spage=8048&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-22 N1 - Date created - 1998-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vocabulary Competence in Early Childhood: Measurement, Latent Construct, and Predictive Validity AN - 85685810; 9908543 AB - A systematic examination of relations among six measures of child language derived from three sources, including observations of the child's speech with mother, experimenter assessments, & maternal reports. A total of 184 20-month-olds & their mothers contributed complete information about child language comprehension & expression. Correlations of child language measures with socioeconomic status & maternal education were accounted for, as were correlations of child language measures with mothers' verbal intelligence, maternal report measures with mothers' tendency to respond in a socially desirable fashion, & experimenter assessments with child social competence. Structural equation modeling supported (1) strong relations among child language measures derived from observations of the child's speech with mother, experimenter assessments, & maternal reports; (2) the loading of multiple measures of child language from different sources on a single latent construct of vocabulary competence; & (3) the predictive validity of the vocabulary competence latent variable at 20 months, as well as receptive vocabulary specifically, for both verbal & performance IQ (verbal better than performance) at 48 months. Neither an index of child monologing (a nonvocabulary language measure) nor symbolic play (a nonlinguistic representational measure) covaried with vocabulary competence. Girls consistently outperformed boys on individual language measures, but no differences emerged in any model in the fit for boys & girls. 5 Tables, 3 Figures, 82 References. Adapted from the source document JF - Child Development AU - Bornstein, Marc H AU - Haynes, O Maurice AD - Child & Family Research, Laboratory of Comparative Ethology, National Instit of Child Health & Human Development, National Institutes of Health, Bldg 31-Rm B2B15, 9000 Rockville Pike, Bethesda MD 20892-2030 Marc_H_Bornstein@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 654 EP - 671 VL - 69 IS - 3 SN - 0009-3920, 0009-3920 KW - Child Language (11800) KW - Language Acquisition (41600) KW - Verbal Learning (93750) KW - Lexicon (47150) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85685810?accountid=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=Child+Development&rft.atitle=Vocabulary+Competence+in+Early+Childhood%3A+Measurement%2C+Latent+Construct%2C+and+Predictive+Validity&rft.au=Bornstein%2C+Marc+H%3BHaynes%2C+O+Maurice&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-06-01&rft.volume=69&rft.issue=3&rft.spage=654&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&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 - CHDEAW N1 - SubjectsTermNotLitGenreText - Language Acquisition (41600); Lexicon (47150); Verbal Learning (93750); Child Language (11800) ER - TY - JOUR T1 - A simplified method to measure the diffusion tensor from seven MR images. AN - 85267352; pmid-9621916 AB - Analytical expressions of the diffusion tensor of water, D, and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2, maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications. JF - Magnetic Resonance in Medicine AU - Basser, P J AU - Pierpaoli, C AD - Tissue Biophysics and Biomimetics Section, NICHD, National Institutes of Health, Bethesda, Maryland 20892-5766, USA. PY - 1998 SP - 928 EP - 934 VL - 39 IS - 6 SN - 0740-3194, 0740-3194 KW - Magnetic Resonance Imaging KW - Brain Mapping KW - Reference Values KW - Anisotropy KW - Human KW - Cats KW - Animal KW - Brain KW - Image Enhancement KW - Diffusion KW - Image Processing, Computer-Assisted UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85267352?accountid=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=Magnetic+Resonance+in+Medicine&rft.atitle=A+simplified+method+to+measure+the+diffusion+tensor+from+seven+MR+images.&rft.au=Basser%2C+P+J%3BPierpaoli%2C+C&rft.aulast=Basser&rft.aufirst=P&rft.date=1998-06-01&rft.volume=39&rft.issue=6&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers. AN - 85256708; pmid-9611670 AB - BACKGROUND: The N-methyl-D-aspartate receptor antagonist, ketamine, produces a clinical syndrome of thought disorder, perceptual distortion, and cognitive impairment. METHODS: We have administered ketamine to healthy volunteers to characterize the formal thought disorder and specific memory dysfunction associated with ketamine. Ten healthy volunteers underwent a double-blind, placebo-controlled, ketamine infusion (0.12 mg/kg bolus and 0.65 mg/kg/hour). Thought disorder was evaluated with the Scale for the Assessment of Thought, Language and Communication. Cognitive testing involved working and semantic memory tasks. RESULTS: Ketamine produced a formal thought disorder, as well as impairments in working and semantic memory. The degree of ketamine-induced thought disorder significantly correlated with ketamine-induced decreases in working memory and did not correlate with ketamine-induced impairments in semantic memory. CONCLUSIONS: This study characterizes the formal thought disorder associated with ketamine and may suggest that ketamine-induced deficits in working memory are associated with ketamine-induced thought disorder. JF - Biological Psychiatry AU - Adler, C M AU - Goldberg, T E AU - Malhotra, A K AU - Pickar, D AU - Breier, A AD - Experimental Therapeutics Branch, National Institute of Mental Health, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. PY - 1998 SP - 811 EP - 816 VL - 43 IS - 11 SN - 0006-3223, 0006-3223 KW - Verbal Behavior KW - Double-Blind Method KW - Thinking KW - Human KW - Brain KW - Mental Recall KW - Verbal Learning KW - Adult KW - Ketamine KW - Middle Age KW - Neuropsychological Tests KW - Retention (Psychology) KW - Receptors, N-Methyl-D-Aspartate KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256708?accountid=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=Biological+Psychiatry&rft.atitle=Effects+of+ketamine+on+thought+disorder%2C+working+memory%2C+and+semantic+memory+in+healthy+volunteers.&rft.au=Adler%2C+C+M%3BGoldberg%2C+T+E%3BMalhotra%2C+A+K%3BPickar%2C+D%3BBreier%2C+A&rft.aulast=Adler&rft.aufirst=C&rft.date=1998-06-01&rft.volume=43&rft.issue=11&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Biological+Psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Suppressive effect of antiflammin-2 on compound 48/80-induced conjunctivitis. Role of phospholipase A2s and inducible nitric oxide synthase. AN - 80046680; 9689636 AB - Phospholipase A2s (PLA2s) are a family of esterases that initiate the arachidonic acid cascade, which results in the production of numerous inflammatory mediators. We investigated the expression of Group I and II PLA2 proteins and Group II mRNA in normal conjunctivae and in the conjunctivae of mice with compound 48/80-induced conjunctivitis. Conjunctivitis was induced in C57BL/6 mice by topical instillation of compound 48/80 (C48/80). Mice were then treated with corticosteroid (Pred Forte), antiflammin-2 (AF2, a synthetic peptide that inhibits PLA2), or a placebo (Dacriose, an isotonic, buffered, sterile eye irrigating solution). Low levels of PLA2s were detected on the epithelium of normal conjunctivae. One hr after C48/80 instillation, the expression of PLA2s appeared and increased in the substantia propria, peaked at 6 hr, and returned to baseline 72 hr later. Compared to the placebo, the conjunctivitis was moderate in the AF2-treated group and mild in Pred Forte-treated group. The expression of PLA2s was suppressed in mice treated with Pred Forte and AF2. iNOS mRNA was also diminished in the AF2- and Pred Forte-treated groups. The mechanisms by which anti-allergic medications suppress conjunctivitis may involve the inhibition of PLA2s and iNOS. JF - Ocular immunology and inflammation AU - Li, Q AU - Luyo, D AU - Matteson, D M AU - Chan, C C AD - Section on Immunopathology, National Eye Institute, National Institute of Health, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 73 VL - 6 IS - 2 SN - 0927-3948, 0927-3948 KW - Anti-Inflammatory Agents KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - DNA Probes KW - Glucocorticoids KW - Oligopeptides KW - Ophthalmic Solutions KW - Peptide Fragments KW - RNA, Messenger KW - antiflammin P2 KW - 118850-72-9 KW - p-Methoxy-N-methylphenethylamine KW - 4091-50-3 KW - prednisolone acetate KW - 8B2807733D KW - Prednisolone KW - 9PHQ9Y1OLM KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - Animals KW - DNA Probes -- chemistry KW - Mice KW - Conjunctiva -- pathology KW - Conjunctiva -- enzymology KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Prednisolone -- analogs & derivatives KW - Prednisolone -- pharmacology KW - Mice, Inbred C57BL KW - Administration, Topical KW - Conjunctiva -- drug effects KW - Female KW - Immunoenzyme Techniques KW - Anti-Inflammatory Agents -- pharmacology KW - Phospholipases A -- genetics KW - Conjunctivitis, Allergic -- pathology KW - Conjunctivitis, Allergic -- chemically induced KW - Nitric Oxide Synthase -- genetics KW - Peptide Fragments -- pharmacology KW - Conjunctivitis, Allergic -- prevention & control KW - Oligopeptides -- pharmacology KW - Nitric Oxide Synthase -- metabolism KW - Phospholipases A -- metabolism KW - Conjunctivitis, Allergic -- enzymology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80046680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=Suppressive+effect+of+antiflammin-2+on+compound+48%2F80-induced+conjunctivitis.+Role+of+phospholipase+A2s+and+inducible+nitric+oxide+synthase.&rft.au=Li%2C+Q%3BLuyo%2C+D%3BMatteson%2C+D+M%3BChan%2C+C+C&rft.aulast=Li&rft.aufirst=Q&rft.date=1998-06-01&rft.volume=6&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of neem flowers, Thai and Chinese bitter gourd fruits and sweet basil leaves on hepatic monooxygenases and glutathione S-transferase activities, and in vitro metabolic activation of chemical carcinogens in rats. AN - 80030098; 9674955 AB - The objectives of this study were to determine the effects of feeding of four vegetables commonly consumed in Thailand, namely, flowers of the neem tree (Azadirachta indica var. siamensis), fruits of Thai and the Chinese bitter gourd (Momordica charantia Linn.) and leaves of sweet basil (Ocimum basilicum Linn) on the levels of phase I enzymes, which include cytochrome P450 (P450), aniline hydroxylase (ANH) and aminopyrine-N-demethylase (AMD) as well as the capacity to activate the mutagenicities of aflatoxin B1 (AFB1) and benzo[a]pyrene (BaP), and to induce the phase II enzymes [i.e. glutathione S-transferase (GST)] in rat liver. It was found that feeding of the diets containing 12.5% neem flowers and Thai bitter gourd fruits for 2 weeks strongly enhanced GST activity, 2.7- and 1.6- fold of the pair-fed control values, respectively, while resulting in a marked reduction of the levels of most phase I reactions. Fruits of the Chinese bitter gourd, which is in the same species as Thai bitter gourd, had no effect on GST activity but decreased AMD activity and the in vitro metabolic activation of AFB1 and BaP. On the other hand, however, dietary sweet basil leaves caused a significant increase in the levels of both GST and all phase I enzymes. Results in the present study clearly demonstrate that neem flowers and Thai bitter gourd fruits contain monofunctional phase II enzyme inducers and compounds capable of repressing some monooxygenases, especially those involved in the metabolic activation of chemical carcinogens, while sweet basil leaves contain compounds, probably bifunctional inducers, capable of inducing both phase I and phase II enzymes and Chinese bitter gourd fruits contain only compounds capable of repressing some monooxygenases. These results therefore suggest that neem flowers and Thai bitter gourd fruits may possess chemopreventive potential, while those of Chinese bitter gourd fruits and sweet basil leaves are uncertain. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Kusamran, W R AU - Ratanavila, A AU - Tepsuwan, A AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Bangkok, Thailand. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 475 EP - 484 VL - 36 IS - 6 SN - 0278-6915, 0278-6915 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Benzo(a)pyrene KW - 3417WMA06D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Aniline Hydroxylase KW - EC 1.14.14.- KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Vegetables KW - Thailand KW - Carcinogens -- pharmacokinetics KW - Benzo(a)pyrene -- pharmacokinetics KW - Rats KW - Animal Feed KW - Enzyme Induction -- drug effects KW - Aflatoxin B1 -- pharmacokinetics KW - Biotransformation KW - Microsomes, Liver -- enzymology KW - Toxicity Tests KW - Rats, Wistar KW - Microsomes, Liver -- drug effects KW - Fruit KW - Ocimum basilicum KW - China KW - Male KW - Liver -- enzymology KW - Aminopyrine N-Demethylase -- metabolism KW - Liver -- drug effects KW - Glutathione Transferase -- biosynthesis KW - Anticarcinogenic Agents -- pharmacology KW - Aniline Hydroxylase -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Anticarcinogenic Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80030098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Effects+of+neem+flowers%2C+Thai+and+Chinese+bitter+gourd+fruits+and+sweet+basil+leaves+on+hepatic+monooxygenases+and+glutathione+S-transferase+activities%2C+and+in+vitro+metabolic+activation+of+chemical+carcinogens+in+rats.&rft.au=Kusamran%2C+W+R%3BRatanavila%2C+A%3BTepsuwan%2C+A&rft.aulast=Kusamran&rft.aufirst=W&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection and analysis of rare second-site suppressors of Drosophila RNA polymerase II mutations. AN - 80016382; 9669327 AB - We used a mutagenesis and selection procedure in Drosophila melanogaster to recover rare allele-specific suppressor mutations. More than 11 million flies mutant for one of five recessive-lethal mutations in the two largest subunits of RNA polymerase II were selected for additional mutations that restored viability. Forty-one suppressor mutations were recovered. At least 16 are extragenic, identifying a minimum of three loci, two of which do not map near genes known to encode subunits of RNA polymerase II. At most, 25 are intragenic, 4 reverting the initial altered nucleotide back to wild type. Sequence analysis of interacting mutations in the two largest subunits identified a discrete domain in each subunit. These domains might be contact points for the subunits. Finally, our selections were large enough to allow recovery of multiple independent changes in the same nucleotides yet mutations in other equally likely targets were not recovered. The mutations recovered are not random and might provide insights into possible mechanisms for mutagenesis in eukaryotes. JF - Molecular & general genetics : MGG AU - Krasnoselskaya, I AU - Huang, J AU - Jones, T AU - Dezan, C AU - Mortin, M A AD - Laboratory of Biochemistry, NIH/NCI, Bethesda, MD 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 457 EP - 465 VL - 258 IS - 5 SN - 0026-8925, 0026-8925 KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Point Mutation -- genetics KW - Animals KW - Base Sequence KW - Alleles KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis KW - RNA Polymerase II -- genetics KW - Drosophila melanogaster -- genetics KW - Suppression, Genetic KW - Drosophila melanogaster -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80016382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+general+genetics+%3A+MGG&rft.atitle=Selection+and+analysis+of+rare+second-site+suppressors+of+Drosophila+RNA+polymerase+II+mutations.&rft.au=Krasnoselskaya%2C+I%3BHuang%2C+J%3BJones%2C+T%3BDezan%2C+C%3BMortin%2C+M+A&rft.aulast=Krasnoselskaya&rft.aufirst=I&rft.date=1998-06-01&rft.volume=258&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Molecular+%26+general+genetics+%3A+MGG&rft.issn=00268925&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular modeling studies on binding of bFGF to heparin and its receptor FGFR1. AN - 80011711; 9669548 AB - Sugar induced protein-protein interactions play an important role in several biological processes. The carbohydrate moieties of proteoglycans, the glycosaminoglycans, bind to growth factors with a high degree of specificity and induce interactions with growth factor receptors, thereby regulate the growth factor activity. We have used molecular modeling method to study the modes of binding of heparin or heparan sulfate proteoglycans (HSPGs) to bFGF that leads to the dimerization of FGF receptor 1 (FGFR1) and activation of receptor tyrosine kinase. Homology model of FGFR1 Ig D(II)-D(III) domains was built to investigate the interactions between heparin, bFGF and FGFR1. The structural requirements to bridge the two monomeric bFGF molecules by heparin or HSPGs and to simulate the dimerization and activation of FGFR1 have been examined. A structural model of the biologically functional dimeric bFGF-heparin complex is proposed based on: (a) the stability of dimeric complex, (b) the favorable binding energies between heparin and bFGF molecules, and (c) its accessibility to FGFR1. The modeled complex between heparin, bFGF and FGFR1 has a stoichiometry of 1 heparin: 2 bFGF: 2 FGFR1. The structural properties of the proposed model of bFGF/heparin/FGFR1 complex are consistent with the binding mechanism of FGF to its receptor, the receptor dimerization, and the reported site-specific mutagenesis and biochemical cross-linking data. In the proposed model heparin bridges the two bFGF monomers in a specific orientation and the resulting complex induces FGF receptor dimerization, suggesting that in the oligosaccharide induced recognition process sugars orient the molecules in a way that brings about specific protein-protein or protein-carbohydrate interactions. JF - Journal of biomolecular structure & dynamics AU - Lam, K AU - Rao, V S AU - Qasba, P K AD - Structural Glycobiology Section, Laboratory of Experimental and Computational Biology, National Cancer Institute, NCI-FCRDC, Frederick, Maryland 21702, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1009 EP - 1027 VL - 15 IS - 6 SN - 0739-1102, 0739-1102 KW - Receptors, Fibroblast Growth Factor KW - 0 KW - Trisaccharides KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Heparin KW - 9005-49-6 KW - FGFR1 protein, human KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 1 KW - Index Medicus KW - Trisaccharides -- metabolism KW - Humans KW - Dimerization KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Conformation KW - Carbohydrate Conformation KW - Fibroblast Growth Factor 2 -- metabolism KW - Fibroblast Growth Factor 2 -- chemistry KW - Computer Simulation KW - Models, Molecular KW - Heparin -- metabolism KW - Heparin -- chemistry KW - Receptors, Fibroblast Growth Factor -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biomolecular+structure+%26+dynamics&rft.atitle=Molecular+modeling+studies+on+binding+of+bFGF+to+heparin+and+its+receptor+FGFR1.&rft.au=Lam%2C+K%3BRao%2C+V+S%3BQasba%2C+P+K&rft.aulast=Lam&rft.aufirst=K&rft.date=1998-06-01&rft.volume=15&rft.issue=6&rft.spage=1009&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomolecular+structure+%26+dynamics&rft.issn=07391102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-28 N1 - Date created - 1998-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multigenic control of skin tumor susceptibility in SENCARA/Pt mice. AN - 80004377; 9667751 AB - Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty-one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice. JF - Carcinogenesis AU - Mock, B A AU - Lowry, D T AU - Rehman, I AU - Padlan, C AU - Yuspa, S H AU - Hennings, H AD - Laboratory of Genetics, DBS, NCI, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1109 EP - 1115 VL - 19 IS - 6 SN - 0143-3334, 0143-3334 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Phenotype KW - Genetic Linkage KW - Microsatellite Repeats KW - Animals KW - Alleles KW - Loss of Heterozygosity KW - Crosses, Genetic KW - Mice KW - Genetic Predisposition to Disease KW - Chromosome Mapping KW - Female KW - Skin Neoplasms -- genetics KW - Papilloma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multigenic+control+of+skin+tumor+susceptibility+in+SENCARA%2FPt+mice.&rft.au=Mock%2C+B+A%3BLowry%2C+D+T%3BRehman%2C+I%3BPadlan%2C+C%3BYuspa%2C+S+H%3BHennings%2C+H&rft.aulast=Mock&rft.aufirst=B&rft.date=1998-06-01&rft.volume=19&rft.issue=6&rft.spage=1109&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of CC10 modifies neoplastic potential in lung cancer cells. AN - 80002307; 9663466 AB - CC10 is infrequently expressed in non-small cell lung cancer cell lines, despite being abundantly produced by progenitor cells for normal and neoplastic airway epithelium. We overexpressed CC10 cDNA in the non-small cell lung cancer cell line A549 to determine its effect on the neoplastic phenotype. A549 cells transfected with CC10 demonstrated a marked reduction in invasiveness that was paralleled by diminished 92-kDa and absent 72-kDa metalloproteinase activity by zymography. Western analysis revealed the near absence of the corresponding matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the CC10-transfected cell lines, but not in the vector-transfected cell lines. The CC10-transfected cell lines also demonstrated decreased adhesiveness to fibronectin compared with the controls. CC10 expression was associated with decreased anchorage-independent growth but not with decreased anchorage-dependent growth. These data suggest that loss of CC10 may contribute to carcinogenesis, because CC10 antagonizes the neoplastic phenotype. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Szabo, E AU - Goheer, A AU - Witschi, H AU - Linnoila, R I AD - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA. szaboe@bprb.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 475 EP - 485 VL - 9 IS - 6 SN - 1044-9523, 1044-9523 KW - Enzyme Inhibitors KW - 0 KW - Extracellular Matrix Proteins KW - Proteins KW - RNA, Messenger KW - SCGB1A1 protein, human KW - Uteroglobin KW - 9060-09-7 KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Adenocarcinoma -- metabolism KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Cell Division -- physiology KW - Adenocarcinoma -- enzymology KW - Neoplastic Processes KW - Extracellular Matrix Proteins -- metabolism KW - Tumor Cells, Cultured KW - Transfection KW - Neoplasm Invasiveness -- pathology KW - Cell Communication -- physiology KW - Mesocricetus KW - Metalloendopeptidases -- metabolism KW - Cricetinae KW - Lung Neoplasms -- enzymology KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Enzyme Inhibitors -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Proteins -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80002307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overexpression+of+CC10+modifies+neoplastic+potential+in+lung+cancer+cells.&rft.au=Szabo%2C+E%3BGoheer%2C+A%3BWitschi%2C+H%3BLinnoila%2C+R+I&rft.aulast=Szabo&rft.aufirst=E&rft.date=1998-06-01&rft.volume=9&rft.issue=6&rft.spage=475&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. AN - 80001948; 9663185 AB - Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses, including pituitary secretion of beta-endorphin. This study evaluated whether administration of the pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and plasma beta-endorphin levels in the oral surgery model of acute pain. Subjects in a single-dose, double-blind, parallel-group study received either 200 mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels of immunoreactive beta-endorphin decreased over time coincident with the onset of analgesia in all groups but were significantly less than placebo after both doses of S(+)-ibuprofen from 30 to 120 minutes. These findings show that, compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen results in faster analgesic onset, greater peak analgesia, similar duration of action, and a low incidence of adverse effects, while suppressing nociceptive activation of the pituitary-adrenal axis. JF - Clinical pharmacology and therapeutics AU - Dionne, R A AU - McCullagh, L AD - National Institute of Dental Research, Nursing Department, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 694 EP - 701 VL - 63 IS - 6 SN - 0009-9236, 0009-9236 KW - Analgesics, Non-Narcotic KW - 0 KW - beta-Endorphin KW - 60617-12-1 KW - Ibuprofen KW - WK2XYI10QM KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Isomerism KW - Pain Measurement KW - Oral Surgical Procedures -- adverse effects KW - Time Factors KW - Male KW - Female KW - Analgesics, Non-Narcotic -- adverse effects KW - Pain, Postoperative -- etiology KW - Analgesics, Non-Narcotic -- therapeutic use KW - Pain, Postoperative -- blood KW - Ibuprofen -- therapeutic use KW - Ibuprofen -- adverse effects KW - Pain, Postoperative -- drug therapy KW - Ibuprofen -- administration & dosage KW - beta-Endorphin -- drug effects KW - beta-Endorphin -- blood KW - Analgesics, Non-Narcotic -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80001948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology+and+therapeutics&rft.atitle=Enhanced+analgesia+and+suppression+of+plasma+beta-endorphin+by+the+S%28%2B%29-isomer+of+ibuprofen.&rft.au=Dionne%2C+R+A%3BMcCullagh%2C+L&rft.aulast=Dionne&rft.aufirst=R&rft.date=1998-06-01&rft.volume=63&rft.issue=6&rft.spage=694&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-30 N1 - Date created - 1998-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen upregulation of BRCA1 expression with no effect on localization. AN - 79980607; 9655254 AB - Alterations in the expression of the breast and ovarian cancer susceptibility gene BRCA1 may contribute to the development of mammary and ovarian neoplasia. The sex-steroid estrogen modulates cell proliferation of normal and neoplastic breast and ovarian epithelial cells, but the role of estrogen regulation on the expression of BRCA1 remains to be defined. In this study, estrogen-regulated BRCA1 expression was examined in breast and ovarian cancer cells. Estrogen stimulated the proliferation of estrogen receptor (ER)-positive breast MCF-7, C7-MCF-7, and ovarian BG-1 cells as well as the expression of the estrogen-inducible pS2 gene. This was concomitant with upregulation of BRCA1 mRNA (2.5- to 5.0-fold) and a 3- to 10-fold induction of BRCA1 protein (230 kDa). Cell fractionation studies localized the BRCA1 protein to the nucleus in both unstimulated and estrogen-stimulated cells. The antiestrogen ICI-182780 inhibited estrogen-induced cell proliferation, BRCA1 mRNA induction, and BRCA1 protein expression in ER-positive cells. Conversely, estrogen did not influence expression of BRCA1 in HBL-100 cells that lacked the estrogen receptor, although the constitutive levels of BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in other breast and ovarian cancer cells. Secretion of the BRCA1 protein into the cell medium did not account for the discrepancy between the mRNA and protein levels in HBL-100 cells. Proliferation of HBL-100 cells was not affected by either estrogen or ICI-182780. Taken together, these data support a role for the steroid estrogen and the involvement of the estrogen receptor pathway in the modulation of expression of BRCA1. We therefore propose that stimulation of cell proliferation may be a prerequisite for upregulation of BRCA1 in breast and ovarian cancer cells. JF - Molecular carcinogenesis AU - Romagnolo, D AU - Annab, L A AU - Thompson, T E AU - Risinger, J I AU - Terry, L A AU - Barrett, J C AU - Afshari, C A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 102 EP - 109 VL - 22 IS - 2 SN - 0899-1987, 0899-1987 KW - Antineoplastic Agents KW - 0 KW - BRCA1 Protein KW - Estrogen Antagonists KW - Estrogens KW - RNA, Messenger KW - Receptors, Estrogen KW - fulvestrant KW - 22X328QOC4 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Breast Neoplasms -- genetics KW - Ovarian Neoplasms -- metabolism KW - Ovarian Neoplasms -- genetics KW - Humans KW - Estradiol -- pharmacology KW - Cell Division -- drug effects KW - Breast Neoplasms -- metabolism KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- physiology KW - Up-Regulation -- physiology KW - Stimulation, Chemical KW - Estradiol -- analogs & derivatives KW - Estrogen Antagonists -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Neoplasms, Hormone-Dependent -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Neoplasms, Hormone-Dependent -- genetics KW - Female KW - BRCA1 Protein -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- physiology KW - BRCA1 Protein -- metabolism KW - Estrogens -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79980607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Estrogen+upregulation+of+BRCA1+expression+with+no+effect+on+localization.&rft.au=Romagnolo%2C+D%3BAnnab%2C+L+A%3BThompson%2C+T+E%3BRisinger%2C+J+I%3BTerry%2C+L+A%3BBarrett%2C+J+C%3BAfshari%2C+C+A&rft.aulast=Romagnolo&rft.aufirst=D&rft.date=1998-06-01&rft.volume=22&rft.issue=2&rft.spage=102&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue of targeted regions of mammalian chromosomes by in vivo recombination in yeast. AN - 79979665; 9647640 AB - In contrast to other animal cell lines, the chicken pre-B cell lymphoma line, DT40, exhibits a high level of homologous recombination, which can be exploited to generate site-specific alterations in defined target genes or regions. In addition, the ability to generate human/chicken monochromosomal hybrids in the DT40 cell line opens a way for specific targeting of human genes. Here we describe a new strategy for direct isolation of a human chromosomal region that is based on targeting of the chromosome with a vector containing a yeast selectable marker, centromere, and an ARS element. This procedure allows rescue of the targeted region by transfection of total genomic DNA into yeast spheroplasts. Selection for the yeast marker results in isolation of chromosome sequences in the form of large circular yeast artificial chromosomes (YACs) up to 170 kb in size containing the targeted region. These YACs are generated by homologous recombination in yeast between common repeated sequences in the targeted chromosomal fragment. Alternatively, the targeted region can be rescued as a linear YACs when a YAC fragmentation vector is included in the yeast transformation mixture. Because the entire isolation procedure of the chromosomal region, once a target insertion is obtained, can be accomplished in approximately 1 week, the new method greatly expands the utility of the homologous recombinationproficient DT40 chicken cell system. JF - Genome research AU - Kouprina, N AU - Kawamoto, K AU - Barrett, J C AU - Larionov, V AU - Koi, M AD - Laboratory of Molecular Genetics, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 666 EP - 672 VL - 8 IS - 6 SN - 1088-9051, 1088-9051 KW - DNA, Circular KW - 0 KW - DNA, Fungal KW - Genetic Markers KW - Index Medicus KW - DNA, Circular -- genetics KW - Animals KW - Chickens KW - Humans KW - Hybrid Cells KW - Mice KW - DNA, Fungal -- genetics KW - Cell Line KW - Gene Targeting -- methods KW - Chromosomes, Artificial, Yeast -- genetics KW - Recombination, Genetic -- genetics KW - Chromosomes, Human, Pair 11 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79979665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Rescue+of+targeted+regions+of+mammalian+chromosomes+by+in+vivo+recombination+in+yeast.&rft.au=Kouprina%2C+N%3BKawamoto%2C+K%3BBarrett%2C+J+C%3BLarionov%2C+V%3BKoi%2C+M&rft.aulast=Kouprina&rft.aufirst=N&rft.date=1998-06-01&rft.volume=8&rft.issue=6&rft.spage=666&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-05 N1 - Date created - 1999-01-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1984 Feb;137(1):266-7 [6329026] Gene. 1982 Jun;18(3):277-88 [6290331] Nature. 1985 Sep 19-25;317(6034):230-4 [2995814] Mutat Res. 1986 Oct;163(1):3-13 [3018556] Science. 1987 May 15;236(4803):806-12 [3033825] Genetics. 1989 May;122(1):19-27 [2659436] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4645-9 [2162051] Gene. 1991 Sep 30;106(1):125-7 [1937033] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8794-7 [1528894] Science. 1993 Apr 16;260(5106):361-4 [8469989] Nat Genet. 1994 Jan;6(1):84-9 [8136839] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5513-7 [8202519] Genes Dev. 1994 May 1;8(9):1087-105 [7926789] Hum Mol Genet. 1994 Aug;3(8):1227-37 [7987296] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):491-6 [8552668] Nat Genet. 1996 Feb;12(2):174-82 [8563756] Gene. 1996 Feb 12;168(2):199-203 [8654944] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13925-30 [8943037] Cell. 1996 Nov 29;87(5):917-27 [8945518] Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):190-5 [8990184] Cell. 1997 Apr 18;89(2):185-93 [9108474] Nat Genet. 1997 May;16(1):37-43 [9140393] Cytogenet Cell Genet. 1997;76(1-2):72-6 [9154132] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7384-7 [9207100] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4469-74 [9539761] Am J Hum Genet. 1985 Jul;37(4):635-49 [9556655] Am J Hum Genet. 1984 Nov;36(6):1159-71 [6097109] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence. AN - 79978515; 9655250 AB - The cellular senescence program is controlled by multiple genetic pathways, one of which involves the regulation of telomerase and telomere shortening. The introduction of a normal human chromosome 3 into the human renal cell carcinoma cell line RCC23 caused repression of telomerase activity, progressive shortening of telomeres, and restoration of the cellular senescence program. We attributed the repression of telomerase activity to the marked downregulation of the gene encoding the catalytic subunit of telomerase (hEST2/hTRT) but not another protein component (TP1/TLP1) or the RNA component of telomerase. These results suggest that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT gene expression either directly or indirectly and support the notion that hEST2/hTRT is the major determinant of telomerase enzymatic activity in human cells. JF - Molecular carcinogenesis AU - Horikawa, I AU - Oshimura, M AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 72 VL - 22 IS - 2 SN - 0899-1987, 0899-1987 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - telomerase RNA KW - RNA KW - 63231-63-0 KW - TERT protein, human KW - EC 2.7.7.49 KW - Telomerase KW - Index Medicus KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- enzymology KW - Humans KW - Cell Aging -- physiology KW - Transcription, Genetic KW - Gene Expression Regulation, Neoplastic KW - Polymerase Chain Reaction KW - Carcinoma, Renal Cell -- enzymology KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Down-Regulation KW - Carcinoma, Renal Cell -- genetics KW - Telomerase -- antagonists & inhibitors KW - Chromosomes, Human, Pair 3 KW - Proteins -- antagonists & inhibitors KW - Telomerase -- genetics KW - Telomerase -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79978515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Repression+of+the+telomerase+catalytic+subunit+by+a+gene+on+human+chromosome+3+that+induces+cellular+senescence.&rft.au=Horikawa%2C+I%3BOshimura%2C+M%3BBarrett%2C+J+C&rft.aulast=Horikawa&rft.aufirst=I&rft.date=1998-06-01&rft.volume=22&rft.issue=2&rft.spage=65&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 - 1998-07-16 N1 - Date created - 1998-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the RNase A gene superfamily. AN - 79976106; 9647635 AB - We have localized the gene encoding human RNase k6 to within approximately 120 kb on the long (q) arm of chromosome 14 by HAPPY mapping. With this information, the relative positions of the six human RNase A ribonucleases that have been mapped to this locus can be inferred. To further our understanding of the individual lineages comprising the RNase A superfamily, we have isolated and characterized 10 novel genes orthologous to that encoding human RNase k6 from Great Ape, Old World, and New World monkey genomes. Each gene encodes a complete ORF with no less than 86% amino acid sequence identity to human RNase k6 with the eight cysteines and catalytic histidines (H15 and H123) and lysine (K38) typically observed among members of the RNase A superfamily. Interesting trends include an unusually low number of synonymous substitutions (Ks) observed among the New World monkey RNase k6 genes. When considering nonsilent mutations, RNase k6 is a relatively stable lineage, with a nonsynonymous substitution rate of 0.40 x 10(-9) nonsynonymous substitutions/nonsynonymous site/year (ns/ns/yr). These results stand in contrast to those determined for the primate orthologs of the two closely related ribonucleases, the eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), which have incorporated nonsilent mutations at very rapid rates (1.9 x 10(-9) and 2.0 x 10(-9) ns/ns/yr, respectively). The uneventful trends observed for RNase k6 serve to spotlight the unique nature of EDN and ECP and the unusual evolutionary constraints to which these two ribonuclease genes must be responding. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF037081-AF037090.] JF - Genome research AU - Deming, M S AU - Dyer, K D AU - Bankier, A T AU - Piper, M B AU - Dear, P H AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 599 EP - 607 VL - 8 IS - 6 SN - 1088-9051, 1088-9051 KW - Endoribonucleases KW - EC 3.1.- KW - ribonuclease k6 KW - EC 3.1.27.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Animals KW - Sequence Alignment KW - Humans KW - Cebidae KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cercopithecidae KW - Hominidae KW - Multigene Family -- genetics KW - Chromosome Mapping -- methods KW - Endoribonucleases -- genetics KW - Evolution, Molecular KW - Ribonuclease, Pancreatic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79976106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+research&rft.atitle=Ribonuclease+k6%3A+chromosomal+mapping+and+divergent+rates+of+evolution+within+the+RNase+A+gene+superfamily.&rft.au=Deming%2C+M+S%3BDyer%2C+K+D%3BBankier%2C+A+T%3BPiper%2C+M+B%3BDear%2C+P+H%3BRosenberg%2C+H+F&rft.aulast=Deming&rft.aufirst=M&rft.date=1998-06-01&rft.volume=8&rft.issue=6&rft.spage=599&rft.isbn=&rft.btitle=&rft.title=Genome+research&rft.issn=10889051&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-05 N1 - Date created - 1999-01-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF037090; GENBANK; AF037082; AF037081; AF037088; AF037086; AF037087; AF037085; AF037084; AF037089; AF037083 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. AN - 79973616; 9648597 AB - To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar. JF - Gynecologic oncology AU - Zelmanowicz, A AU - Hildesheim, A AU - Sherman, M E AU - Sturgeon, S R AU - Kurman, R J AU - Barrett, R J AU - Berman, M L AU - Mortel, R AU - Twiggs, L B AU - Wilbanks, G D AU - Brinton, L A AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7374, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 253 EP - 257 VL - 69 IS - 3 SN - 0090-8258, 0090-8258 KW - Contraceptives, Oral KW - 0 KW - Estrogens KW - Index Medicus KW - Demography KW - Contraceptives, Oral -- adverse effects KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Smoking -- adverse effects KW - Aged KW - Middle Aged KW - Estrogens -- adverse effects KW - Female KW - Obesity -- complications KW - Carcinoma -- etiology KW - Uterine Neoplasms -- etiology KW - Endometrial Neoplasms -- etiology KW - Mixed Tumor, Mullerian -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Evidence+for+a+common+etiology+for+endometrial+carcinomas+and+malignant+mixed+mullerian+tumors.&rft.au=Zelmanowicz%2C+A%3BHildesheim%2C+A%3BSherman%2C+M+E%3BSturgeon%2C+S+R%3BKurman%2C+R+J%3BBarrett%2C+R+J%3BBerman%2C+M+L%3BMortel%2C+R%3BTwiggs%2C+L+B%3BWilbanks%2C+G+D%3BBrinton%2C+L+A&rft.aulast=Zelmanowicz&rft.aufirst=A&rft.date=1998-06-01&rft.volume=69&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pesticides and childhood cancer. AN - 79973149; 9646054 AB - Children are exposed to potentially carcinogenic pesticides from use in homes, schools, other buildings, lawns and gardens, through food and contaminated drinking water, from agricultural application drift, overspray, or off-gassing, and from carry-home exposure of parents occupationally exposed to pesticides. Parental exposure during the child's gestation or even preconception may also be important. Malignancies linked to pesticides in case reports or case-control studies include leukemia, neuroblastoma, Wilms' tumor, soft-tissue sarcoma, Ewing's sarcoma, non-Hodgkin's lymphoma, and cancers of the brain, colorectum, and testes. Although these studies have been limited by nonspecific pesticide exposure information, small numbers of exposed subjects, and the potential for case-response bias, it is noteworthy that many of the reported increased risks are of greater magnitude than those observed in studies of pesticide-exposed adults, suggesting that children may be particularly sensitive to the carcinogenic effects of pesticides. Future research should include improved exposure assessment, evaluation of risk by age at exposure, and investigation of possible genetic-environment interactions. There is potential to prevent at least some childhood cancer by reducing or eliminating pesticide exposure. JF - Environmental health perspectives AU - Zahm, S H AU - Ward, M H AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892, USA. zahms@epndce.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 893 EP - 908 VL - 106 Suppl 3 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Pesticides KW - Index Medicus KW - Maternal Exposure -- adverse effects KW - Leukemia -- chemically induced KW - Disease Susceptibility KW - Paternal Exposure -- adverse effects KW - Environmental Exposure -- statistics & numerical data KW - Maternal Exposure -- statistics & numerical data KW - Humans KW - Child KW - Wilms Tumor -- chemically induced KW - Lymphoma, Non-Hodgkin -- chemically induced KW - Environmental Exposure -- classification KW - Sarcoma -- chemically induced KW - Brain Neoplasms -- chemically induced KW - Global Health KW - Cohort Studies KW - Case-Control Studies KW - Research Design -- standards KW - Neuroblastoma -- chemically induced KW - Paternal Exposure -- statistics & numerical data KW - Environmental Exposure -- adverse effects KW - United States -- epidemiology KW - Male KW - Female KW - Carcinogens -- classification KW - Pesticides -- classification KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79973149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pesticides+and+childhood+cancer.&rft.au=Zahm%2C+S+H%3BWard%2C+M+H&rft.aulast=Zahm&rft.aufirst=S&rft.date=1998-06-01&rft.volume=106+Suppl+3&rft.issue=&rft.spage=893&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 - 1998-09-17 N1 - Date created - 1998-09-17 N1 - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomonitoring of United States Army soldiers serving in Kuwait in 1991. AN - 79966493; 9641500 AB - Biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure and genetic biomarkers of potential cancer susceptibility were determined in a group of United States Army soldiers who were deployed to Kuwait and Saudi Arabia in 1991 in the aftermath of the Persian Gulf War. Because hundreds of oil well fires were still burning, there was concern that ground troops stationed in Kuwait might be exposed to high levels of PAHs and other toxicants. The United States Army Environmental Hygiene Agency monitored air and soil for ambient PAHs. In addition, a group of 61 soldiers was involved in the biomonitoring study reported here. These soldiers kept diaries of daily activities and provided blood and urine samples in Germany (June) before deployment to Kuwait, after 8 weeks in Kuwait (August), and 1 month after the return to Germany (October). Here we present data for PAH-DNA adducts measured by immunoassay in blood cell DNA samples obtained at all three sampling times from 22 soldiers and bulky aromatic adducts measured by 32P-postlabeling in blood cell DNA samples from 20 of the same soldiers. Urinary 1-hydroxypyrene-glucuronide levels were determined by synchronous fluorescence spectrometry in a matched set of samples from 33 soldiers. Contrary to expectations, environmental monitoring showed low ambient PAH levels in the areas where these soldiers were working in Kuwait. For both DNA adduct assays, levels were the lowest in Kuwait in August and increased significantly after the soldiers returned to Germany (October). Urinary 1-hydroxypyrene-glucuronide levels were also lowest in Kuwait and highest in Germany, but the differences were not statistically significant. The PAH-exposure biomarker levels were not significantly influenced by polymorphic variations of CYP1A1 (MspI) and glutathione S-transferases M1 and T1. Overall, the data suggest that this group of soldiers was not exposed to elevated levels of PAHs while deployed in Kuwait. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Poirier, M C AU - Weston, A AU - Schoket, B AU - Shamkhani, H AU - Pan, C F AU - McDiarmid, M A AU - Scott, B G AU - Deeter, D P AU - Heller, J M AU - Jacobson-Kram, D AU - Rothman, N AD - Carcinogen-DNA Interactions Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. poirierm@dc37a.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 545 EP - 551 VL - 7 IS - 6 SN - 1055-9965, 1055-9965 KW - DNA Primers KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - United States KW - Genotype KW - Polymerase Chain Reaction KW - Humans KW - Kuwait KW - Male KW - Population Surveillance KW - Polycyclic Aromatic Hydrocarbons -- blood KW - Military Personnel KW - Occupational Exposure -- adverse effects KW - Environmental Exposure -- adverse effects KW - Polycyclic Aromatic Hydrocarbons -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79966493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biomonitoring+of+United+States+Army+soldiers+serving+in+Kuwait+in+1991.&rft.au=Poirier%2C+M+C%3BWeston%2C+A%3BSchoket%2C+B%3BShamkhani%2C+H%3BPan%2C+C+F%3BMcDiarmid%2C+M+A%3BScott%2C+B+G%3BDeeter%2C+D+P%3BHeller%2C+J+M%3BJacobson-Kram%2C+D%3BRothman%2C+N&rft.aulast=Poirier&rft.aufirst=M&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=545&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and Caucasians. AN - 79962466; 9641486 AB - An understanding of why people smoke cigarettes can have an important impact on smoking prevention and cessation. People smoke cigarettes to maintain nicotine levels in the body, and nicotine has been implicated in the stimulation of brain reward mechanisms via central neuronal dopaminergic pathways. In this study, we evaluated the association of smoking and smoking cessation with a dopamine D4 receptor 48-bp variable nucleotide tandem repeat polymorphism in which the seven-repeat allele (D4.7) reduces dopamine affinity. Smokers (n = 283) and nonsmokers (n = 192) were recruited through local media for a case-control study of smoking. After giving informed consent and answering a behavioral questionnaire, smokers underwent a single minimal-contact session of smoking cessation counseling and then were followed for up to 1 year. The frequency of the dopamine D4 receptor genetic polymorphism using PCR was determined, and individuals were classified by the number of repeat alleles (two to five repeats as S and six to eight repeats as L). Persons with those genotypes including only S alleles (homozygote S/S) were compared with those with at least one L allele (heterozygote S/L and homozygote L/L). Chi2 tests of association, Fisher's exact test, and Student's t test were used. Ps were two-tailed. The data show that African-Americans (n = 72) who had at least one L allele had a higher risk of smoking (odds ratio, 7.7; 95% confidence interval, 1.5-39.9; P = 0.006), shorter time to the first cigarette in the morning (P = 0.03), and earlier age at smoking initiation (P = 0.09) compared with homozygote S/S genotypes. After smoking cessation counseling, none of the African-American smokers with an L allele were abstinent at 2 months, compared with 35% of the smokers who were homozygote S/S (P = 0.02). The analysis of Caucasians (n = 403) did not suggest a similar smoking risk for the D4 genotypes (odds ratio, 1.0; 95% confidence interval, 0.6-1.6; P = 0.90), or smoking cessation (P = 0.75). Although the number of African-Americans is small, this study is consistent with the hypothesis that the L alleles increase the risk of smoking because these individuals are prone to use nicotine to stimulate synaptic dopamine transmission. If replicated, the data indicate that a single minimal-contact session of cessation counseling, similar to what is typically provided in primary care physician offices, is ineffective in African-American smokers who have at least one L allele. The finding of an effect for these polymorphic loci in African-Americans, but not Caucasians, suggests that the variable nucleotide tandem repeat studied here is a marker for another polymorphic site in African-Americans, but not in Caucasians. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Shields, P G AU - Lerman, C AU - Audrain, J AU - Bowman, E D AU - Main, D AU - Boyd, N R AU - Caporaso, N E AD - Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Peter_G_Shields@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 453 EP - 458 VL - 7 IS - 6 SN - 1055-9965, 1055-9965 KW - DRD4 protein, human KW - 0 KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D4 KW - 137750-34-6 KW - Index Medicus KW - Genotype KW - Polymerase Chain Reaction KW - Odds Ratio KW - Alleles KW - Humans KW - Adult KW - Case-Control Studies KW - Male KW - Female KW - African Continental Ancestry Group -- genetics KW - Smoking Cessation KW - Smoking -- prevention & control KW - Receptors, Dopamine D2 -- genetics KW - Smoking -- genetics KW - European Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79962466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+D4+receptors+and+the+risk+of+cigarette+smoking+in+African-Americans+and+Caucasians.&rft.au=Shields%2C+P+G%3BLerman%2C+C%3BAudrain%2C+J%3BBowman%2C+E+D%3BMain%2C+D%3BBoyd%2C+N+R%3BCaporaso%2C+N+E&rft.aulast=Shields&rft.aufirst=P&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=453&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arrest among psychotic inpatients: assessing the relationship to diagnosis, gender, number of admissions, and social class. AN - 79960739; 9640096 AB - The present study of psychotic patients investigates the relationship of specific psychotic diagnoses (i.e., psychoactive-substance-induced psychosis, schizophrenia, bipolar disorder, other DSM-III Axis I psychotic disorders), social class, gender, and number of admissions to the rate of arrest in the community. All admissions with psychotic symptoms to hospitals providing inpatient psychiatric services in the Baltimore area were surveyed during a 6-year period. Study participants were assessed using a modified version of the Diagnostic Interview Schedule. During the course of the interview, patients were asked whether they had ever been arrested as a juvenile or as an adult. After adjusting for age, gender, number of admissions, and social class, we found that patients admitted for psychoactive-substance-induced psychosis were more likely to report having been arrested than patients with other psychotic diagnoses. Patients with schizophrenia were not more likely to have an history of arrest than patients with other psychotic disorders. Number of admissions and social class were independent predictors of history of arrest. The relationship between psychotic diagnosis and history of arrest was modified by gender. Psychotic patients with substance-induced diagnosis who were male were more likely to report a prior arrest in the community than their female counterparts. Our results suggest that type of psychotic diagnosis and social class, in addition to gender and number of admissions, are important predictors of differences in arrest-rate histories among psychotic patients. Gender appears to be an effect modifier of the relationship between psychotic diagnosis and history of arrest. JF - Social psychiatry and psychiatric epidemiology AU - Muntaner, C AU - Wolyniec, P AU - McGrath, J AU - Pulver, A E AD - Section Socio-environmental Studies, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 274 EP - 282 VL - 33 IS - 6 SN - 0933-7954, 0933-7954 KW - Index Medicus KW - Socioeconomic Factors KW - Odds Ratio KW - Logistic Models KW - Humans KW - Adult KW - Retrospective Studies KW - Patient Admission -- statistics & numerical data KW - Middle Aged KW - Baltimore -- epidemiology KW - Adolescent KW - Psychoses, Substance-Induced -- epidemiology KW - Male KW - Female KW - Inpatients -- statistics & numerical data KW - Crime -- statistics & numerical data KW - Psychotic Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79960739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Social+psychiatry+and+psychiatric+epidemiology&rft.atitle=Arrest+among+psychotic+inpatients%3A+assessing+the+relationship+to+diagnosis%2C+gender%2C+number+of+admissions%2C+and+social+class.&rft.au=Muntaner%2C+C%3BWolyniec%2C+P%3BMcGrath%2C+J%3BPulver%2C+A+E&rft.aulast=Muntaner&rft.aufirst=C&rft.date=1998-06-01&rft.volume=33&rft.issue=6&rft.spage=274&rft.isbn=&rft.btitle=&rft.title=Social+psychiatry+and+psychiatric+epidemiology&rft.issn=09337954&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. AN - 79958739; 9636868 AB - The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Walsh, T J AU - Hiemenz, J W AU - Seibel, N L AU - Perfect, J R AU - Horwith, G AU - Lee, L AU - Silber, J L AU - DiNubile, M J AU - Reboli, A AU - Bow, E AU - Lister, J AU - Anaissie, E J AD - Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1383 EP - 1396 VL - 26 IS - 6 SN - 1058-4838, 1058-4838 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 - Candidiasis -- drug therapy KW - Humans KW - Cryptococcosis -- drug therapy KW - Aspergillosis -- drug therapy KW - Adult KW - Creatinine -- blood KW - Male KW - Female KW - Phosphatidylcholines -- adverse effects KW - Antifungal Agents -- adverse effects KW - Phosphatidylcholines -- therapeutic use KW - Amphotericin B -- adverse effects KW - Phosphatidylglycerols -- therapeutic use KW - Mycoses -- drug therapy KW - Phosphatidylglycerols -- adverse effects KW - Amphotericin B -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79958739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amphotericin+B+lipid+complex+for+invasive+fungal+infections%3A+analysis+of+safety+and+efficacy+in+556+cases.&rft.au=Walsh%2C+T+J%3BHiemenz%2C+J+W%3BSeibel%2C+N+L%3BPerfect%2C+J+R%3BHorwith%2C+G%3BLee%2C+L%3BSilber%2C+J+L%3BDiNubile%2C+M+J%3BReboli%2C+A%3BBow%2C+E%3BLister%2C+J%3BAnaissie%2C+E+J&rft.aulast=Walsh&rft.aufirst=T&rft.date=1998-06-01&rft.volume=26&rft.issue=6&rft.spage=1383&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 - 1998-08-25 N1 - Date created - 1998-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Infect Dis. 2000 Jan;30(1):236-7 [10619780] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions. AN - 79951709; 9633903 AB - Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P=0.017), without a significant change in the donor frequencies against third party (P=0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs. JF - British journal of haematology AU - Mavroudis, D A AU - Dermime, S AU - Molldrem, J AU - Jiang, Y Z AU - Raptis, A AU - van Rhee, F AU - Hensel, N AU - Fellowes, V AU - Eliopoulos, G AU - Barrett, A J AD - Bone Marrow Transplantation Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 565 EP - 570 VL - 101 IS - 3 SN - 0007-1048, 0007-1048 KW - Index Medicus KW - Immunoassay -- methods KW - Humans KW - Transplantation, Homologous KW - Immune Tolerance KW - Flow Cytometry -- methods KW - Bone Marrow Transplantation -- methods KW - Graft vs Host Reaction -- immunology KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- immunology KW - Graft vs Host Disease -- immunology KW - Lymphocyte Depletion -- methods KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy KW - T-Lymphocytes, Helper-Inducer -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79951709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+depletion+of+alloreactive+T+cells+in+HLA-identical+siblings%3A+a+method+for+separating+graft-versus-host+and+graft-versus-leukaemia+reactions.&rft.au=Mavroudis%2C+D+A%3BDermime%2C+S%3BMolldrem%2C+J%3BJiang%2C+Y+Z%3BRaptis%2C+A%3Bvan+Rhee%2C+F%3BHensel%2C+N%3BFellowes%2C+V%3BEliopoulos%2C+G%3BBarrett%2C+A+J&rft.aulast=Mavroudis&rft.aufirst=D&rft.date=1998-06-01&rft.volume=101&rft.issue=3&rft.spage=565&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 - 1998-07-31 N1 - Date created - 1998-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-dependent number of implants and implications in developmental toxicity. AN - 79946230; 9629644 AB - This paper proposes a method for assessing risk in developmental toxicity studies with exposure prior to implantation. The method proposed in this paper was developed to account for a dose-dependent trend in the number of implantation sites per dam, which is a common problem in studies with exposure prior to implantation. Toxins may have the effect of interfering with the early reproductive process, which can prevent implantation in the uterine wall. An imputation procedure is presented for estimating the number of potential fetuses by sampling from the empirical distribution of the number of implants per litter in the control group. The marginal death outcomes and the joint malformation and survival outcomes for each potential fetus can be estimated using multiple imputation or the chained data augmentation algorithm. Logit models can then be fit and used to estimate the effect of dose on reducing the probability of a normal birth. These models accommodate multiple covariate effects and can be applied to low-dose extrapolation. A simulation study is done to evaluate the properties of model-based estimators of the mean response and the virtually safe dose level (VSD). It was found that both estimates were good approximations of the underlying dose effect. A dominant lethal assay data set (Luning et al., 1966, Mutation Research 3, 444-451) is analyzed, and the results are compared with those of Rai and Van Ryzin. JF - Biometrics AU - Dunson, D B AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. dunson@calvin.niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 558 EP - 569 VL - 54 IS - 2 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Rats KW - Probability KW - Animals KW - Litter Size KW - Biometry -- methods KW - Rodentia KW - Monte Carlo Method KW - Congenital Abnormalities KW - Female KW - Risk Assessment KW - Pregnancy KW - Fetal Death KW - Embryo Implantation KW - Teratology -- methods KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-dependent+number+of+implants+and+implications+in+developmental+toxicity.&rft.au=Dunson%2C+D+B&rft.aulast=Dunson&rft.aufirst=D&rft.date=1998-06-01&rft.volume=54&rft.issue=2&rft.spage=558&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vascular endothelial growth factor and basic fibroblast growth factor present in Kaposi's sarcoma (KS) are induced by inflammatory cytokines and synergize to promote vascular permeability and KS lesion development. AN - 79941119; 9626048 AB - All forms of Kaposi's sarcoma (KS) are characterized by spindle cell proliferation, angiogenesis, inflammatory cell infiltration, and edema. We have previously reported that spindle cells of primary KS lesions and KS-derived spindle cell cultures express high levels of basic fibroblast growth factor (bFGF), which is promoted by the inflammatory cytokines identified in these lesions. These cytokines, namely, tumor necrosis factor, interleukin-1, and interferon-gamma, induce production and release of bFGF, which stimulates angiogenesis and spindle cell growth in an autocrine fashion. Here we show that both AIDS-KS and classical KS lesions co-express vascular endothelial growth factor (VEGF) and bFGF. VEGF production by KS cells is promoted synergistically by inflammatory cytokines present in conditioned media from activated T cells and in KS lesions. KS cells show synthesis of VEGF isoforms that are mitogenic to endothelial cells but not to KS spindle cells, suggesting a prevailing paracrine effect of this cytokine. This may be due to the level of expression of the flt-1-VEGF receptor that is down-regulated in KS cells as compared with endothelial cells. KS-derived bFGF and VEGF synergize in inducing endothelial cell growth as shown by studies using both neutralizing antibodies and antisense oligodeoxynucleotides directed against these cytokines. In addition, VEGF and bFGF synergize to induce angiogenic KS-like lesions in nude mice and vascular permeability and edema in guinea pigs. These results indicate that inflammatory cytokines present in KS lesions stimulate the production of bFGF and VEGF, which, in turn, cooperate to induce angiogenesis, edema, and KS lesion formation. JF - The American journal of pathology AU - Samaniego, F AU - Markham, P D AU - Gendelman, R AU - Watanabe, Y AU - Kao, V AU - Kowalski, K AU - Sonnabend, J A AU - Pintus, A AU - Gallo, R C AU - Ensoli, B AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1433 EP - 1443 VL - 152 IS - 6 SN - 0002-9440, 0002-9440 KW - Cell Extracts KW - 0 KW - Culture Media, Conditioned KW - Cytokines KW - Endothelial Growth Factors KW - Lymphokines KW - Oligonucleotides, Antisense KW - Proto-Oncogene Proteins KW - Receptors, Growth Factor KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptors, Vascular Endothelial Growth Factor KW - Vascular Endothelial Growth Factor Receptor-1 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Extracellular Matrix -- metabolism KW - Guinea Pigs KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Mice, Nude KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Endothelium, Vascular -- physiology KW - Endothelium, Vascular -- drug effects KW - Tumor Cells, Cultured KW - Drug Synergism KW - Neovascularization, Pathologic -- physiopathology KW - Endothelium, Vascular -- metabolism KW - Cytokines -- pharmacology KW - Mice KW - Oligonucleotides, Antisense -- pharmacology KW - Culture Media, Conditioned -- metabolism KW - Receptors, Growth Factor -- metabolism KW - Edema -- physiopathology KW - Immunohistochemistry KW - Fibroblast Growth Factor 2 -- metabolism KW - Lymphokines -- metabolism KW - Sarcoma, Kaposi -- physiopathology KW - Sarcoma, Kaposi -- metabolism KW - Endothelial Growth Factors -- metabolism KW - Capillary Permeability -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79941119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vascular+endothelial+growth+factor+and+basic+fibroblast+growth+factor+present+in+Kaposi%27s+sarcoma+%28KS%29+are+induced+by+inflammatory+cytokines+and+synergize+to+promote+vascular+permeability+and+KS+lesion+development.&rft.au=Samaniego%2C+F%3BMarkham%2C+P+D%3BGendelman%2C+R%3BWatanabe%2C+Y%3BKao%2C+V%3BKowalski%2C+K%3BSonnabend%2C+J+A%3BPintus%2C+A%3BGallo%2C+R+C%3BEnsoli%2C+B&rft.aulast=Samaniego&rft.aufirst=F&rft.date=1998-06-01&rft.volume=152&rft.issue=6&rft.spage=1433&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 - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1995 May 4;332(18):1181-5 [7700310] J Immunol. 1995 Apr 1;154(7):3582-92 [7897237] J Neurosurg. 1995 May;82(5):864-73 [7714613] J Biol Chem. 1995 May 26;270(21):12607-13 [7759509] Oncogene. 1995 May 18;10(10):2007-16 [7761101] Proc Assoc Am Physicians. 1995 Apr;107(1):8-18 [8630748] Am J Pathol. 1996 Apr;148(4):1065-74 [8644848] Am J Pathol. 1996 Dec;149(6):1851-69 [8952523] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):979-84 [9023368] J Immunol. 1997 Feb 15;158(4):1887-94 [9029130] J Immunol. 1997 May 15;158(10):4992-5001 [9144519] Blood. 1998 Feb 1;91(3):956-67 [9446657] Blood. 1998 Feb 1;91(3):968-76 [9446658] J Cereb Blood Flow Metab. 1998 Sep;18(9):968-77 [9740100] Am J Pathol. 1983 Apr;111(1):62-77 [6301283] Ann Intern Med. 1983 Aug;99(2):145-51 [6603806] N Engl J Med. 1985 Jun 6;312(23):1518 [3990755] J Biol Response Mod. 1985 Aug;4(4):358-64 [3928825] Ann Intern Med. 1985 Nov;103(5):744-50 [3901851] J Clin Microbiol. 1987 Sep;25(9):1695-700 [3498739] Am J Dermatopathol. 1987 Oct;9(5):388-98 [2446517] Dermatologica. 1987;175(6):270-9 [3691903] Science. 1989 Jan 13;243(4888):223-6 [2643161] J Acquir Immune Defic Syndr. 1989;2(1):54-8 [2918461] J Biol Response Mod. 1989 Aug;8(4):359-65 [2666585] Clin Exp Immunol. 1989 Dec;78(3):329-33 [2612049] Nature. 1990 May 3;345(6270):84-6 [2184372] Am J Pathol. 1991 Jan;138(1):9-15 [1987771] Clin Exp Immunol. 1991 Apr;84(1):109-15 [1901776] Mol Endocrinol. 1991 Dec;5(12):1806-14 [1791831] Science. 1992 Mar 13;255(5050):1432-4 [1542793] Biochem Biophys Res Commun. 1992 Mar 31;183(3):1167-74 [1567395] Growth Factors. 1992;7(1):53-64 [1380254] J Exp Med. 1992 Nov 1;176(5):1375-9 [1402682] J Immunol. 1992 Dec 1;149(11):3727-34 [1431144] J Biol Chem. 1992 Dec 25;267(36):26031-7 [1464614] Biochem Biophys Res Commun. 1992 Dec 15;189(2):824-31 [1281999] Am J Pathol. 1993 Jul;143(1):240-9 [8100400] Clin Exp Immunol. 1993 Oct;94(1):43-50 [8403516] J Immunol. 1993 Nov 1;151(9):5031-40 [8409454] Curr Opin Oncol. 1993 Sep;5(5):835-44 [8218496] Lab Invest. 1993 Nov;69(5):508-17 [8246443] Am J Pathol. 1994 Jan;144(1):51-9 [7507301] Nature. 1994 Feb 10;367(6463):576-9 [8107827] J Acquir Immune Defic Syndr. 1994 Jul;7(7):695-9 [7911526] Am J Pathol. 1994 Jul;145(1):74-9 [8030759] J Exp Med. 1994 Sep 1;180(3):1141-6 [8064230] Clin Immunol Immunopathol. 1994 Nov;73(2):252-60 [7923932] Nature. 1994 Oct 20;371(6499):674-80 [7935812] J Clin Invest. 1994 Nov;94(5):1736-46 [7525646] J Clin Invest. 1995 Apr;95(4):1723-34 [7535796] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas. AN - 79940710; 9626206 AB - To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas (NHLs) for late effects and to attempt to assess the relative contributions of the primary treatment modalities to these late effects. Of 103 young survivors followed up for 1 to 20 years, 74 patients were interviewed and underwent various investigations, and an additional 12 patients were interviewed only. Of the 86 patients, 65 had previously suffered from small non-cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell lymphoma. Left ventricular dysfunction was identified in eight of 57 (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200 mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of whom had 30 children. Two of the 86 (2.3%) patients developed second cancers. Other major late effects included posttransfusion viral hepatitis, eight patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin B12 deficiency, two patients; esophageal stricture, one patient; urinary tract problems, two patients; and musculoskeletal defects, three patients. Major late effects occurred in 11 of 21 (52.4%) patients who had received radiation as well as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy alone. The predominant major late effects observed were late cardiac toxicity related to DOX therapy and hepatitis C virus infection that presumably resulted from blood product transfusions administered before the introduction of screening for the hepatitis C virus. Fertility was not greatly impaired, and second malignancies were uncommon. No patient had clinically significant impairment of growth. Radiation appeared to increase the likelihood of late effects. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Haddy, T B AU - Adde, M A AU - McCalla, J AU - Domanski, M J AU - Datiles, M AU - Meehan, S C AU - Pikus, A AU - Shad, A T AU - Valdez, I AU - Lopez Vivino, L AU - Magrath, I T AD - Pediatric Oncology Branch, National Cancer Institute, Division of Epidemiology and Clinical Applications, National Institutes of Health, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2070 EP - 2079 VL - 16 IS - 6 SN - 0732-183X, 0732-183X KW - Index Medicus KW - Hepatitis, Viral, Human -- complications KW - Humans KW - Neoplasms, Second Primary -- diagnosis KW - Child KW - Central Nervous System Diseases -- complications KW - Endocrine System Diseases -- epidemiology KW - Hepatitis, Viral, Human -- epidemiology KW - Musculoskeletal Diseases -- complications KW - Vitamin B 12 Deficiency -- epidemiology KW - Neoplasms, Second Primary -- epidemiology KW - Adult KW - Ventricular Dysfunction, Left -- epidemiology KW - Adolescent KW - Musculoskeletal Diseases -- epidemiology KW - Survivors KW - Esophageal Stenosis -- epidemiology KW - Male KW - Endocrine System Diseases -- complications KW - Infertility -- complications KW - Vitamin B 12 Deficiency -- complications KW - Infertility -- epidemiology KW - Ventricular Dysfunction, Left -- complications KW - Child, Preschool KW - Central Nervous System Diseases -- epidemiology KW - Urologic Diseases -- complications KW - Esophageal Stenosis -- complications KW - Urologic Diseases -- epidemiology KW - Female KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lymphoma, Non-Hodgkin -- therapy KW - Lymphoma, Non-Hodgkin -- complications KW - Lymphoma, Non-Hodgkin -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79940710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Late+effects+in+long-term+survivors+of+high-grade+non-Hodgkin%27s+lymphomas.&rft.au=Haddy%2C+T+B%3BAdde%2C+M+A%3BMcCalla%2C+J%3BDomanski%2C+M+J%3BDatiles%2C+M%3BMeehan%2C+S+C%3BPikus%2C+A%3BShad%2C+A+T%3BValdez%2C+I%3BLopez+Vivino%2C+L%3BMagrath%2C+I+T&rft.aulast=Haddy&rft.aufirst=T&rft.date=1998-06-01&rft.volume=16&rft.issue=6&rft.spage=2070&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. AN - 79926519; 9620846 AB - SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways. JF - Genes & development AU - de Caestecker, M P AU - Parks, W T AU - Frank, C J AU - Castagnino, P AU - Bottaro, D P AU - Roberts, A B AU - Lechleider, R J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055 USA. Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1587 EP - 1592 VL - 12 IS - 11 SN - 0890-9369, 0890-9369 KW - DNA-Binding Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Smad2 Protein KW - Trans-Activators KW - Epidermal Growth Factor KW - 62229-50-9 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Index Medicus KW - Animals KW - Transfection KW - Genes, Tumor Suppressor KW - Hepatocyte Growth Factor -- pharmacology KW - Epidermal Growth Factor -- pharmacology KW - Transcriptional Activation KW - Protein-Tyrosine Kinases -- physiology KW - Protein-Serine-Threonine Kinases -- physiology KW - Cell Line KW - Gene Expression Regulation -- physiology KW - Receptors, Transforming Growth Factor beta -- physiology KW - Gene Expression Regulation -- drug effects KW - DNA-Binding Proteins -- physiology KW - Signal Transduction KW - Receptors, Transforming Growth Factor beta -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79926519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad2+transduces+common+signals+from+receptor+serine-threonine+and+tyrosine+kinases.&rft.au=de+Caestecker%2C+M+P%3BParks%2C+W+T%3BFrank%2C+C+J%3BCastagnino%2C+P%3BBottaro%2C+D+P%3BRoberts%2C+A+B%3BLechleider%2C+R+J&rft.aulast=de+Caestecker&rft.aufirst=M&rft.date=1998-06-01&rft.volume=12&rft.issue=11&rft.spage=1587&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Fed Proc. 1983 Jun;42(9):2621-6 [6303865] Nature. 1997 Dec 4;390(6659):465-71 [9393997] J Biol Chem. 1990 Oct 25;265(30):18518-24 [2170414] Biochem J. 1992 Dec 1;288 ( Pt 2):351-5 [1334404] Nature. 1993 Jan 7;361(6407):68-71 [8421496] Development. 1994 Feb;120(2):415-24 [8149917] J Biol Chem. 1994 May 6;269(18):13231-7 [8175753] Anal Biochem. 1994 Feb 1;216(2):276-84 [8179182] Blood. 1994 Jul 1;84(1):151-7 [7517205] Nature. 1995 Feb 16;373(6515):573-80 [7531822] Science. 1995 Dec 22;270(5244):2008-11 [8533096] Nature. 1996 Jun 13;381(6583):620-3 [8637600] Cell. 1996 Jun 28;85(7):947-50 [8674122] J Biol Chem. 1996 May 31;271(22):13110-5 [8662798] J Biol Chem. 1996 Jul 26;271(30):17617-20 [8663601] J Biol Chem. 1996 Sep 13;271(37):22368-75 [8798398] J Biol Chem. 1996 Oct 4;271(40):24850-5 [8798760] Nature. 1996 Oct 31;383(6603):832-6 [8893010] Cell. 1996 Dec 27;87(7):1215-24 [8980228] J Biol Chem. 1997 Jan 31;272(5):2896-900 [9006934] J Cell Physiol. 1997 Jan;170(1):57-68 [9012785] J Biol Chem. 1997 Mar 7;272(10):6653-62 [9045696] Dev Biol. 1996 Aug 25;178(1):198-202 [8812122] Curr Biol. 1997 Apr 1;7(4):270-6 [9094310] Genes Dev. 1997 Apr 15;11(8):984-95 [9136927] Oncogene. 1997 Apr 24;14(16):1891-9 [9150356] J Biol Chem. 1997 May 23;272(21):13690-6 [9153220] Cell. 1997 Jun 27;89(7):1165-73 [9215638] Nature. 1997 Jul 17;388(6639):304-8 [9230443] Nature. 1997 Sep 4;389(6646):85-9 [9288972] Nature. 1997 Oct 9;389(6651):618-22 [9335504] Development. 1997 Sep;124(18):3511-23 [9342044] Adv Second Messenger Phosphoprotein Res. 1997;31:41-8 [9344240] J Biol Chem. 1997 Oct 31;272(44):27678-85 [9346908] J Biol Chem. 1997 Oct 31;272(44):28107-15 [9346966] Mol Cell Biol. 1997 Dec;17(12):7019-28 [9372933] Genes Dev. 1997 Dec 1;11(23):3157-67 [9389648] J Biol Chem. 1988 Mar 5;263(7):3111-5 [3125175] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients? AN - 79924663; 9623618 AB - The risk of contrast-associated nephrotoxicity (CAN) is increased in the presence of preexisting renal disease. Although routine determination of serum creatinine (Cr) prior to imaging studies is the traditional method of assessing renal function, it is a costly and time-consuming practice. The purpose of this study was to investigate whether a patient survey could identify patients with a high likelihood of having normal Cr values and who, therefore, did not require serum testing. A survey was administered to 673 consecutive adult patients who were scheduled for contrast-enhanced computed tomography. Survey questions were designed to elicit a history of renal disorders as well as additional risk factors for CAN. Each patient had a Cr level determined within 48 hours prior to the injection of iodinated contrast media. Cr levels were assessed in the patients who gave negative responses to all survey questions. The degree to which positive responses to each survey question predicted elevated Cr levels was determined using the odds ratio (OR). Among the 673 respondents, 577 (85%) had normal Cr values (1.7 mg/dL usually do not receive iodinated contrast media. Using this Cr cutoff value, 189 (99%) of 191 patients with negative responses had Cr values less than or equal to the cutoff value. The survey questions most strongly associated with elevated Cr values pertained to preexisting renal disease (OR 13.6), proteinuria (OR 8.7), prior kidney surgery (OR 8.1), hypertension (OR 5.4), gout (OR 4.6), and diabetes (OR 3.2). If the survey had been limited to these six questions, completely negative responses would have occurred in 450 (67%) of 673, 424 (94%) of these 450 would have normal Cr values, and 446 (99%) of 450 would have had Cr values at or below the 1.7 mg/dL cutoff for iodinated contrast. A completely negative response to a simple (six question) patient survey prior to iodinated contrast administration can identify a significant fraction of patients with normal Cr levels. Use of this survey could reduce by 67% the number of patients undergoing routine Cr determinations prior to imaging studies. This could reduce costs, decrease delays, and increase patient satisfaction associated with imaging studies. JF - Techniques in urology AU - Choyke, P L AU - Cady, J AU - DePollar, S L AU - Austin, H AD - Department of Diagnostic Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1182, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 65 EP - 69 VL - 4 IS - 2 SN - 1079-3259, 1079-3259 KW - Contrast Media KW - 0 KW - Iodine KW - 9679TC07X4 KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Risk Factors KW - Humans KW - Cost-Benefit Analysis KW - Mass Screening -- economics KW - Adult KW - Aged KW - Middle Aged KW - Unnecessary Procedures -- economics KW - Male KW - Female KW - Contrast Media -- adverse effects KW - Tomography, X-Ray Computed -- economics KW - Renal Insufficiency -- chemically induced KW - Kidney Diseases -- complications KW - Iodine -- adverse effects KW - Renal Insufficiency -- prevention & control KW - Creatinine -- blood KW - Renal Insufficiency -- diagnosis KW - Kidney Diseases -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Techniques+in+urology&rft.atitle=Determination+of+serum+creatinine+prior+to+iodinated+contrast+media%3A+is+it+necessary+in+all+patients%3F&rft.au=Choyke%2C+P+L%3BCady%2C+J%3BDePollar%2C+S+L%3BAustin%2C+H&rft.aulast=Choyke&rft.aufirst=P&rft.date=1998-06-01&rft.volume=4&rft.issue=2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Techniques+in+urology&rft.issn=10793259&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-27 N1 - Date created - 1998-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesic and cognitive effects of intravenous ketamine-alfentanil combinations versus either drug alone after intradermal capsaicin in normal subjects. AN - 79924450; 9620514 AB - Combinations of opioids and N-methyl-D-aspartate (NMDA) antagonists enhance acute antinociception and reduce opioid tolerance in some animal experiments but have received little rigorous study in humans. To quantitatively assess the nature of the interaction of these two classes of drugs in producing analgesia and cognitive impairment, we compared i.v. infusions of ketamine, alfentanil, and ketamine-alfentanil combinations in 12 normal volunteers after an intradermal injection of capsaicin. Drug doses for a 70-kg subject in this six-session, randomized, double-blind, cross-over study were: ketamine 20 mg, ketamine 5 mg, alfentanil 2 mg, alfentanil 0.5 mg, ketamine 10 mg + alfentanil 1 mg, and ketamine 2.5 mg + alfentanil 0.25 mg, given over 35 min. Outcome measures were background pain, area and magnitude of hyperalgesia to pinprick, and cognitive performance on the Digit Symbol Substitution Test and the Perception Speed Test. The results demonstrated simple additivity for the effects of ketamine and alfentanil on pain, pinprick hyperalgesia, and cognitive impairment. We conclude that, at least in this experimental pain model, there is no clear advantage or disadvantage of a ketamine-alfentanil combination over equianalgesic doses of either component. In a double-blind, controlled trial, we administered doses of an opioid analgesic (alfentanil), an N-methyl-D-aspartate receptor antagonist (ketamine), or their combination to normal volunteers and found no advantage of the combination over a larger dose of either drug alone in relieving pain caused by painful chemical stimulation. JF - Anesthesia and analgesia AU - Sethna, N F AU - Liu, M AU - Gracely, R AU - Bennett, G J AU - Max, M B AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-1258, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1250 EP - 1256 VL - 86 IS - 6 SN - 0003-2999, 0003-2999 KW - Analgesics KW - 0 KW - Analgesics, Opioid KW - Anesthetics, Dissociative KW - Drug Combinations KW - Excitatory Amino Acid Antagonists KW - Irritants KW - Alfentanil KW - 1N74HM2BS7 KW - Ketamine KW - 690G0D6V8H KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Hyperalgesia -- prevention & control KW - Double-Blind Method KW - Infusions, Intravenous KW - Humans KW - Injections, Intradermal KW - Psychomotor Performance -- drug effects KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Female KW - Hyperalgesia -- chemically induced KW - Male KW - Capsaicin -- adverse effects KW - Anesthetics, Dissociative -- administration & dosage KW - Excitatory Amino Acid Antagonists -- administration & dosage KW - Irritants -- adverse effects KW - Ketamine -- administration & dosage KW - Alfentanil -- administration & dosage KW - Pain -- prevention & control KW - Irritants -- administration & dosage KW - Anesthetics, Dissociative -- therapeutic use KW - Cognition -- drug effects KW - Pain -- chemically induced KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Alfentanil -- therapeutic use KW - Analgesics, Opioid -- therapeutic use KW - Ketamine -- therapeutic use KW - Analgesics, Opioid -- administration & dosage KW - Capsaicin -- administration & dosage KW - Analgesics -- administration & dosage KW - Analgesics -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analgesic+and+cognitive+effects+of+intravenous+ketamine-alfentanil+combinations+versus+either+drug+alone+after+intradermal+capsaicin+in+normal+subjects.&rft.au=Sethna%2C+N+F%3BLiu%2C+M%3BGracely%2C+R%3BBennett%2C+G+J%3BMax%2C+M+B&rft.aulast=Sethna&rft.aufirst=N&rft.date=1998-06-01&rft.volume=86&rft.issue=6&rft.spage=1250&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. AN - 79924362; 9616196 AB - Physiologically based pharmacokinetic modeling of the parent chemical primidone and its two metabolites phenobarbital and phenylethylmalonamide (PEMA) was applied to investigate the differences of primidone metabolism among humans, rats, and mice. The model simulated previously published pharmacokinetic data of the parent chemical and its metabolites in plasma and brain tissues from separate studies of the three species. Metabolism of primidone and its metabolites varied widely among a sample of three human subjects from two separate studies. Estimated primidone metabolism, as expressed by the maximal velocity Vmax, ranged from 0 to 0.24 mg. min-1.kg-1 for the production of phenobarbital and from 0.003 to 0. 02 mg.min-1.kg-1 for the production of PEMA among three human subjects. Further model simulations indicated that rats were more efficient at producing and clearing phenobarbital and PEMA than mice. However, the overall metabolism profile of primidone and its metabolites in mice indicated that mice were at higher risk of toxicity owing to higher residence of phenobarbital in their tissues and owing to the carcinogenic potential of phenobarbital as illustrated in long-term bioassays. This result was in agreement with a recently finished National Toxicology Program (NTP) carcinogenicity study of primidone in rats and mice. JF - Drug metabolism and disposition: the biological fate of chemicals AU - El-Masri, H A AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 585 EP - 594 VL - 26 IS - 6 SN - 0090-9556, 0090-9556 KW - Anticonvulsants KW - 0 KW - Primidone KW - 13AFD7670Q KW - Phenylethylmalonamide KW - 7206-76-0 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Mice KW - Species Specificity KW - Models, Biological KW - Phenylethylmalonamide -- pharmacokinetics KW - Anticonvulsants -- pharmacokinetics KW - Primidone -- pharmacokinetics KW - Phenobarbital -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79924362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Physiologically+based+pharmacokinetics+model+of+primidone+and+its+metabolites+phenobarbital+and+phenylethylmalonamide+in+humans%2C+rats%2C+and+mice.&rft.au=El-Masri%2C+H+A%3BPortier%2C+C+J&rft.aulast=El-Masri&rft.aufirst=H&rft.date=1998-06-01&rft.volume=26&rft.issue=6&rft.spage=585&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Drug Metab Dispos 1998 Dec;26(12):1222 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. AN - 79923658; 9620779 AB - CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin. JF - Nature genetics AU - Jones, P L AU - Veenstra, G J AU - Wade, P A AU - Vermaak, D AU - Kass, S U AU - Landsberger, N AU - Strouboulis, J AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-5431, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 187 EP - 191 VL - 19 IS - 2 SN - 1061-4036, 1061-4036 KW - Chromosomal Proteins, Non-Histone KW - 0 KW - DNA-Binding Proteins KW - MECP2 protein, Xenopus KW - Methyl-CpG-Binding Protein 2 KW - Repressor Proteins KW - SIN3 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Xenopus Proteins KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Transcription Factors -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Binding Sites KW - DNA Methylation KW - Repressor Proteins -- metabolism KW - Histone Deacetylases -- metabolism KW - Transcription, Genetic KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79923658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methylated+DNA+and+MeCP2+recruit+histone+deacetylase+to+repress+transcription.&rft.au=Jones%2C+P+L%3BVeenstra%2C+G+J%3BWade%2C+P+A%3BVermaak%2C+D%3BKass%2C+S+U%3BLandsberger%2C+N%3BStrouboulis%2C+J%3BWolffe%2C+A+P&rft.aulast=Jones&rft.aufirst=P&rft.date=1998-06-01&rft.volume=19&rft.issue=2&rft.spage=187&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF106951; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast. AN - 79921468; 9620780 AB - Heritable inactivation of specific regions of the genome is a widespread, possibly universal phenomenon for gene regulation in eukaryotes. Self-perpetuating, clonally inherited chromatin structure has been proposed as the explanation for such phenomena as position-effect variegation (PEV) and control of segment determination and differentiation in flies, X-chromosome inactivation and parental imprinting in mammals, gene silencing by paramutation in maize and silencing of the mating-type loci in yeasts. We have now found that the clr4 gene, which is essential for silencing of centromeres and the mating-type loci in Schizosaccharomyces pombe, encodes a protein with high homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila. Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure. Site-directed mutations in the conserved residues of the chromo domain confirm that it is required for proper silencing and directional switching of the mating type, like SET domain. Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci. These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p. JF - Nature genetics AU - Ivanova, A V AU - Bonaduce, M J AU - Ivanov, S V AU - Klar, A J AD - NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Gene Regulation and Chromosome Biology Laboratory, Frederick, Maryland 21702-1201, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 192 EP - 195 VL - 19 IS - 2 SN - 1061-4036, 1061-4036 KW - Cell Cycle Proteins KW - 0 KW - Codon, Terminator KW - Repressor Proteins KW - Schizosaccharomyces pombe Proteins KW - clr4 protein, S pombe KW - Methyltransferases KW - EC 2.1.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Centromere -- genetics KW - Animals KW - Sequence Alignment KW - Humans KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Spores KW - Structure-Activity Relationship KW - Cell Cycle Proteins -- physiology KW - Schizosaccharomyces -- genetics KW - Cell Cycle Proteins -- genetics KW - Repressor Proteins -- physiology KW - Schizosaccharomyces -- physiology KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79921468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+chromo+and+SET+domains+of+the+Clr4+protein+are+essential+for+silencing+in+fission+yeast.&rft.au=Ivanova%2C+A+V%3BBonaduce%2C+M+J%3BIvanov%2C+S+V%3BKlar%2C+A+J&rft.aulast=Ivanova&rft.aufirst=A&rft.date=1998-06-01&rft.volume=19&rft.issue=2&rft.spage=192&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - P23198; GENBANK; AF061854; P23197; P40381; L07515; P26017; P05205; X80070; L34658; A25081 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions. AN - 79906403; 9607923 AB - B cell malignancies arise with increased frequency in aging individuals and in patients with genetic or acquired immunodeficiency (e.g., AIDS) or autoimmune diseases. The mechanisms of lymphomagenesis in these individuals are poorly understood. In this report we investigated the possibility that mutations at the Fas (lpr) and Fasl (gld) loci, which prevent Fas-mediated apoptosis and cause an early onset benign lymphoid hyperplasia and autoimmunity, also predispose mice to malignant lymphomas later in life. Up to 6 mo of age, hyperplasia in lpr and gld mice results from the predominant accumulation of polyclonal T cell subsets and smaller numbers of polyclonal B cells and plasma cells. Here, we examined C3H-lpr, C3H-gld, and BALB-gld mice 6-15 mo of age for the emergence of clonal T and B cell populations and found that a significant proportion of aging mice exclusively developed B cell malignancies with many of the hallmarks of immunodeficiency-associated B lymphomas. By 1 yr of age, approximately 60% of BALB-gld and 30% of C3H-gld mice had monoclonal B cell populations that grew and metastasized in scid recipients but in most cases were rejected by immunocompetent mice. The tumors developed in a milieu greatly enriched for plasma cells, CD23- B cells and immunodeficient memory T cells and variably depleted of B220+ DN T cells. Growth factor-independent cell lines were established from five of the tumors. The majority of the tumors were CD23- and IgH isotype switched and a high proportion was CD5+ and dull Mac-1+. Considering their Ig secretion and morphology in vivo, most tumors were classified as malignant plasmacytoid lymphomas. The delayed development of the gld tumors indicated that genetic defects in addition to the Fas/Fasl mutations were necessary for malignant transformation. Interestingly, none of the tumors showed changes in the genomic organization of c-Myc but many had one or more somatically-acquired MuLV proviral integrations that were transmitted in scid passages and cell lines. Therefore, insertional mutagenesis may be a mechanism for transformation in gld B cells. Our panel of in vivo passaged and in vitro adapted gld lymphomas will be a valuable tool for the future identification of genetic abnormalities associated with B cell transformation in aging and autoimmune mice. JF - The Journal of experimental medicine AU - Davidson, W F AU - Giese, T AU - Fredrickson, T N AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. davidson@hlsun.recross.org Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1825 EP - 1838 VL - 187 IS - 11 SN - 0022-1007, 0022-1007 KW - Antigens, CD95 KW - 0 KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Membrane Glycoproteins KW - Index Medicus KW - T-Lymphocyte Subsets -- cytology KW - Animals KW - Leukemia Virus, Murine -- genetics KW - B-Lymphocyte Subsets -- cytology KW - Mice KW - Virus Integration KW - Mice, Inbred BALB C KW - Phenotype KW - Tumor Cells, Cultured KW - Mice, Inbred C3H KW - Proviruses -- genetics KW - Mice, Inbred MRL lpr KW - Mice, SCID KW - Aging -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- immunology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Membrane Glycoproteins -- immunology KW - Antigens, CD95 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79906403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spontaneous+development+of+plasmacytoid+tumors+in+mice+with+defective+Fas-Fas+ligand+interactions.&rft.au=Davidson%2C+W+F%3BGiese%2C+T%3BFredrickson%2C+T+N&rft.aulast=Davidson&rft.aufirst=W&rft.date=1998-06-01&rft.volume=187&rft.issue=11&rft.spage=1825&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Cancer. 1972 Sep 15;10(2):273-82 [4513130] Cancer Res. 1992 Oct 1;52(19 Suppl):5529s-5540s [1394168] Cell. 1980 Nov;22(1 Pt 1):187-96 [6775817] Proc Natl Acad Sci U S A. 1980 Oct;77(10):5774-8 [6255464] Nature. 1981 Apr 2;290(5805):372-8 [6783959] Nature. 1984 Mar 8-14;308(5955):153-8 [6546606] J Immunol. 1985 Jan;134(1):196-203 [3880569] J Exp Med. 1985 Mar 1;161(3):602-16 [2982991] Prog Allergy. 1986;37:259-300 [3515352] J Immunol. 1986 Jun 1;136(11):4075-84 [3009614] J Immunol. 1987 Nov 1;139(9):2970-6 [3117883] J Immunol. 1988 Feb 15;140(4):1022-7 [3125247] Immunol Rev. 1988 Feb;102:5-28 [2966762] J Immunol. 1992 Nov 1;149(9):3097-106 [1383337] Carcinogenesis. 1992 Oct;13(10):1681-97 [1423827] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756-60 [7680478] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4409-13 [8506280] J Immunol. 1993 Jul 15;151(2):597-609 [7687618] Eur J Immunol. 1993 Sep;23(9):2379-82 [8370416] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10734-8 [7504280] Cell. 1993 Dec 17;75(6):1169-78 [7505205] J Exp Med. 1994 Mar 1;179(3):873-9 [7509364] Cell. 1994 Mar 25;76(6):969-76 [7511063] N Engl J Med. 1994 May 5;330(18):1267-71 [8145781] J Immunol. 1994 Sep 15;153(6):2831-42 [8077685] AIDS. 1994 Aug;8(8):1025-49 [7986399] J Exp Med. 1995 Feb 1;181(2):641-8 [7530760] J Immunol. 1995 Mar 1;154(5):2063-74 [7868883] J Exp Med. 1995 Mar 1;181(3):1157-67 [7532679] J Immunol. 1995 May 15;154(10):4986-95 [7537297] Science. 1995 Jun 2;268(5215):1347-9 [7539157] In Vivo. 1994 Nov-Dec;8(6):953-9 [7772747] Cell. 1995 Jun 16;81(6):935-46 [7540117] Oncogene. 1995 Jun 15;10(12):2397-401 [7784089] J Exp Med. 1995 Jul 1;182(1):129-37 [7540646] Immunity. 1995 Oct;3(4):509-19 [7584141] Clin Immunol Immunopathol. 1996 Jan;78(1):21-9 [8599880] Biochim Biophys Acta. 1996 May 16;1287(1):29-57 [8639705] J Immunol. 1996 Jun 15;156(12):4932-9 [8648144] N Engl J Med. 1996 Nov 28;335(22):1643-9 [8929361] Blood. 1997 Feb 1;89(3):902-9 [9028321] J Exp Med. 1989 May 1;169(5):1747-56 [2469768] Science. 1989 Jul 21;245(4915):301-5 [2787530] Adv Immunol. 1989;46:221-61 [2528897] Br J Cancer. 1990 Feb;61(2):276-8 [2310679] Immunol Today. 1990 Jul;11(7):234-6 [2201308] Proc Natl Acad Sci U S A. 1990 Sep;87(18):6964-8 [2402486] J Exp Med. 1990 Dec 1;172(6):1625-31 [2124252] Nature. 1991 Jan 24;349(6307):331-4 [1898987] Int Rev Cytol. 1991;124:187-215 [2001916] Eur J Immunol. 1991 Apr;21(4):1081-4 [1902176] J Immunol. 1991 Jun 15;146(12):4138-48 [1674953] Cell. 1991 Jul 26;66(2):233-43 [1713127] Annu Rev Immunol. 1991;9:243-69 [1910678] J Exp Med. 1996 Sep 1;184(3):1149-54 [9064331] Blood. 1997 Dec 1;90(11):4266-70 [9373236] Lancet. 1991 Nov 9;338(8776):1175-6 [1682595] Cancer Res. 1992 Jan 15;52(2):437-43 [1370214] Nature. 1992 Mar 26;356(6367):314-7 [1372394] J Clin Invest. 1992 Aug;90(2):334-41 [1386609] AIDS. 1992 Jul;6(7):607-21 [1503680] J Natl Cancer Inst. 1974 Feb;52(2):377-85 [4361176] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Luteinizing hormone releasing hormone (LHRH) neurons maintained in nasal explants decrease LHRH messenger ribonucleic acid levels after activation of GABA(A) receptors. AN - 79905197; 9607779 AB - Inhibition of the LHRH system appears to play an important role in preventing precocious activation of the hypothalamic-pituitary-gonadal axis. Evidence points to gamma-aminobutyric acid (GABA) as the major negative regulator of postnatal LHRH neuronal activity. Changes in LHRH messenger RNA (mRNA) levels after alterations of GABAergic activity have been reported in vivo. However, the extent to which GABA acts directly on LHRH neurons to effect LHRH mRNA levels has been difficult to ascertain. The present work evaluates the effect of GABAergic activity, via GABA(A) receptors, on LHRH neuropeptide gene expression in LHRH neurons maintained in olfactory explants generated from E11.5 mouse embryos. These explants maintain large numbers of primary LHRH neurons that migrate from bilateral olfactory pits in a directed manner. Using in situ hybridization histochemistry and single cell analysis, we report dramatic alterations in LHRH mRNA levels. Inhibition of spontaneous synaptic activity by GABA(A) antagonists, bicuculline (10(-5) M) or picrotoxin (10(-4) M), or of electrical activity by tetrodotoxin (TTX, 10(-6) M) significantly increased LHRH mRNA levels. In contrast, LHRH mRNA levels decreased in explants cultured with the GABA(A) receptor agonist, muscimol (10(-4) M), or KCl (50 mM). The observed responses suggest that LHRH neurons possess functional pathways linking GABA(A) receptors to repression of neuropeptide gene expression and indicate that gene expression in embryonic LHRH neurons, outside the CNS, is highly responsive to alterations in neuronal activity. JF - Endocrinology AU - Fueshko, S M AU - Key, S AU - Wray, S AD - Laboratory of Neurochemistry, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4130, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2734 EP - 2740 VL - 139 IS - 6 SN - 0013-7227, 0013-7227 KW - GABA Antagonists KW - 0 KW - RNA, Messenger KW - Receptors, GABA-A KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mice -- embryology KW - Potassium Chloride -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Tetrodotoxin -- pharmacology KW - GABA Antagonists -- pharmacology KW - Gonadotropin-Releasing Hormone -- metabolism KW - Cytological Techniques KW - Receptors, GABA-A -- physiology KW - Neurons -- metabolism KW - RNA, Messenger -- metabolism KW - Neurons -- drug effects KW - Neurons -- physiology KW - Olfactory Mucosa -- physiology KW - Gonadotropin-Releasing Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79905197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Luteinizing+hormone+releasing+hormone+%28LHRH%29+neurons+maintained+in+nasal+explants+decrease+LHRH+messenger+ribonucleic+acid+levels+after+activation+of+GABA%28A%29+receptors.&rft.au=Fueshko%2C+S+M%3BKey%2C+S%3BWray%2C+S&rft.aulast=Fueshko&rft.aufirst=S&rft.date=1998-06-01&rft.volume=139&rft.issue=6&rft.spage=2734&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant human eosinophil-derived neurotoxin/RNase 2 functions as an effective antiviral agent against respiratory syncytial virus. AN - 79902147; 9607820 AB - A dose-dependent decrease in infectivity was observed on introduction of eosinophils into suspensions of respiratory syncytial virus group B (RSV-B). This antiviral effect was reversed by ribonuclease inhibitor, suggesting a role for the eosinophil secretory ribonucleases. Recombinant eosinophil-derived neurotoxin (rhEDN), the major eosinophil ribonuclease, promoted a dose-dependent decrease in RSV-B infectivity, with a 40-fold reduction observed in response to 50 nM rhEDN. Ribonucleolytically inactivated rhEDN (rhEDNdK38) had no antiviral activity. Semiquantitative reverse transcriptase-polymerase chain reaction demonstrated loss of viral genomic RNA in response to rhEDN, suggesting that this protein promotes the direct ribonucleolytic destruction of extracellular virions. Ribonuclease A had no antiviral activity even at approximately 1000-fold higher concentrations, suggesting that rhEDN has unique features other than ribonuclease activity that are crucial to its effectiveness. These results suggest that rhEDN may have potential as a therapeutic agent for prevention or treatment of disease caused by RSV. JF - The Journal of infectious diseases AU - Domachowske, J B AU - Dyer, K D AU - Bonville, C A AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1458 EP - 1464 VL - 177 IS - 6 SN - 0022-1899, 0022-1899 KW - Antiviral Agents KW - 0 KW - Placental Hormones KW - Proteins KW - Recombinant Fusion Proteins KW - placental ribonuclease inhibitor KW - 120178-77-0 KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cattle KW - Tumor Cells, Cultured KW - Placental Hormones -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- pharmacology KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Proteins -- pharmacology KW - Ribonuclease, Pancreatic -- physiology KW - Respiratory Syncytial Virus, Human -- genetics KW - Ribonuclease, Pancreatic -- pharmacology KW - Ribonuclease, Pancreatic -- antagonists & inhibitors KW - Eosinophils -- physiology KW - Eosinophils -- enzymology KW - Antiviral Agents -- pharmacology KW - Respiratory Syncytial Virus, Human -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79902147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+human+eosinophil-derived+neurotoxin%2FRNase+2+functions+as+an+effective+antiviral+agent+against+respiratory+syncytial+virus.&rft.au=Domachowske%2C+J+B%3BDyer%2C+K+D%3BBonville%2C+C+A%3BRosenberg%2C+H+F&rft.aulast=Domachowske&rft.aufirst=J&rft.date=1998-06-01&rft.volume=177&rft.issue=6&rft.spage=1458&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 - 1998-06-18 N1 - Date created - 1998-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Borrelia burgdorferi erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria. AN - 79889037; 9596729 AB - Borrelia burgdorferi, the causative agent of Lyme disease, can contain multiple genes encoding different members of the Erp lipoprotein family. Some arthropod-borne bacteria increase the synthesis of proteins required for transmission or mammalian infection when cultures are shifted from cool, ambient air temperature to a warmer, blood temperature. We found that all of the erp genes known to be encoded by infectious isolate B31 were differentially expressed in culture after a change in temperature, with greater amounts of message being produced by bacteria shifted from 23 to 35 degrees C than in those maintained at 23 degrees C. Mice infected with B31 by tick bite produced antibodies that recognized each of the Erp proteins within 4 weeks of infection, suggesting that the Erp proteins are produced by the bacteria during the early stages of mammalian infection and may play roles in transmission from ticks to mammals. Several of the B31 Erp proteins were also recognized by antibodies from patients with Lyme disease and may prove to be useful antigens for diagnostic testing or as components of a protective vaccine. JF - Infection and immunity AU - Stevenson, B AU - Bono, J L AU - Schwan, T G AU - Rosa, P 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. lkspic00@pop.uky.edu Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 2648 EP - 2654 VL - 66 IS - 6 SN - 0019-9567, 0019-9567 KW - Antibodies, Bacterial KW - 0 KW - Antigens, Bacterial KW - Lipoproteins KW - RNA, Bacterial KW - RNA, Messenger KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Animals KW - Genes, Bacterial KW - Peromyscus -- parasitology KW - Humans KW - Temperature KW - Antigens, Bacterial -- immunology KW - RNA, Bacterial -- genetics KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Lyme Disease -- blood KW - Antibodies, Bacterial -- blood KW - Molecular Sequence Data KW - Peromyscus -- microbiology KW - Ixodes KW - Borrelia burgdorferi Group -- immunology KW - Lipoproteins -- genetics KW - Lipoproteins -- immunology KW - Bites and Stings KW - Lipoproteins -- biosynthesis KW - Borrelia burgdorferi Group -- pathogenicity KW - Borrelia burgdorferi Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79889037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Borrelia+burgdorferi+erp+proteins+are+immunogenic+in+mammals+infected+by+tick+bite%2C+and+their+synthesis+is+inducible+in+cultured+bacteria.&rft.au=Stevenson%2C+B%3BBono%2C+J+L%3BSchwan%2C+T+G%3BRosa%2C+P&rft.aulast=Stevenson&rft.aufirst=B&rft.date=1998-06-01&rft.volume=66&rft.issue=6&rft.spage=2648&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U78764; GENBANK; AF020657 N1 - SuppNotes - Cited By: Cell. 1997 Jun 27;89(7):1111-9 [9215633] J Bacteriol. 1997 Jul;179(13):4285-91 [9209045] Nature. 1997 Dec 11;390(6660):580-6 [9403685] Microbiology. 1998 Apr;144 ( Pt 4):1033-44 [9579077] Microbiology. 1998 Jul;144 ( Pt 7):1869-79 [9695920] Res Microbiol. 1997 Feb;148(2):109-18 [9765792] Infect Immun. 1978 Aug;21(2):575-84 [211086] Science. 1982 Jun 18;216(4552):1317-9 [7043737] J Exp Med. 1982 Nov 1;156(5):1312-24 [7130901] Infect Immun. 1985 Apr;48(1):234-40 [3980086] J Infect Dis. 1987 Jun;155(6):1300-6 [3572040] J Med Entomol. 1987 Mar;24(2):201-5 [3585913] J Clin Microbiol. 1987 Nov;25(11):2054-8 [3693538] J Clin Microbiol. 1988 Mar;26(3):475-8 [3356787] Infect Immun. 1988 Aug;56(8):1831-6 [3397175] Science. 1989 Feb 17;243(4893):916-22 [2537530] Am J Trop Med Hyg. 1990 Apr;42(4):352-7 [2331043] Microb Pathog. 1990 Feb;8(2):109-18 [2348778] J Clin Microbiol. 1990 Jun;28(6):1329-37 [2380361] J Clin Microbiol. 1991 Feb;29(2):236-43 [2007630] Mol Microbiol. 1992 Feb;6(4):503-9 [1560779] Res Microbiol. 1993 Mar-Apr;144(3):211-9 [8210678] Infect Immun. 1994 Jan;62(1):290-8 [8262642] Infect Immun. 1994 May;62(5):2079-84 [8168973] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2909-13 [7708747] Proc Natl Acad Sci U S A. 1995 May 9;92(10):4269-73 [7753795] Infect Immun. 1995 Sep;63(9):3327-35 [7642261] J Clin Microbiol. 1995 Jul;33(7):1867-9 [7665661] Infect Immun. 1995 Nov;63(11):4535-9 [7591099] Am J Trop Med Hyg. 1995 Oct;53(4):397-404 [7485694] J Exp Med. 1996 Jan 1;183(1):271-5 [8551231] Infect Immun. 1996 Feb;64(2):392-8 [8550182] J Bacteriol. 1996 Apr;178(8):2287-98 [8636030] J Bacteriol. 1996 Jun;178(11):3293-307 [8655511] J Bacteriol. 1996 Jun;178(12):3508-16 [8655548] Science. 1996 Jul 19;273(5273):367-70 [8662526] Mol Microbiol. 1995 Nov;18(3):507-20 [8748034] Infect Immun. 1996 Sep;64(9):3870-6 [8751941] J Bacteriol. 1996 Oct;178(19):5615-26 [8824605] J Bacteriol. 1996 Oct;178(20):5946-53 [8830691] J Bacteriol. 1997 Jan;179(1):217-27 [8982001] J Clin Invest. 1997 Mar 1;99(5):987-95 [9062357] Mol Microbiol. 1997 Jul;25(2):361-73 [9282748] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A. AN - 79886849; 9584159 AB - Cells from complementation groups A through G of the heritable sun-sensitive disorder xeroderma pigmentosum (XP) show defects in nucleotide excision repair of damaged DNA. Proteins representing groups A, B, C, D, F, and G are subunits of the core recognition and incision machinery of repair. XP group E (XP-E) is the mildest form of the disorder, and cells generally show about 50% of the normal repair level. We investigated two protein factors previously implicated in the XP-E defect, UV-damaged DNA binding protein (UV-DDB) and replication protein A (RPA). Three newly identified XP-E cell lines (XP23PV, XP25PV, and a line formerly classified as an XP variant) were defective in UV-DDB binding activity but had levels of RPA in the normal range. The XP-E cell extracts did not display a significant nucleotide excision repair defect in vitro, with either UV-irradiated DNA or a uniquely placed cisplatin lesion used as a substrate. Purified UV-DDB protein did not stimulate repair of naked DNA by DDB- XP-E cell extracts, but microinjection of the protein into DDB- XP-E cells could partially correct the repair defect. RPA stimulated repair in normal, XP-E, or complemented extracts from other XP groups, and so the effect of RPA was not specific for XP-E cell extracts. These data strengthen the connection between XP-E and UV-DDB. Coupled with previous results, the findings suggest that UV-DDB has a role in the repair of DNA in chromatin. JF - Molecular and cellular biology AU - Rapić Otrin, V AU - Kuraoka, I AU - Nardo, T AU - McLenigan, M AU - Eker, A P AU - Stefanini, M AU - Levine, A S AU - Wood, R D AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-2725, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 3182 EP - 3190 VL - 18 IS - 6 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - DDB1 protein, human KW - DNA-Binding Proteins KW - RPA1 protein, human KW - Replication Protein A KW - Index Medicus KW - Ultraviolet Rays KW - Skin -- radiation effects KW - Cells, Cultured KW - Skin -- metabolism KW - Humans KW - Microinjections KW - DNA Repair KW - Chromatin -- metabolism KW - DNA Damage KW - DNA-Binding Proteins -- pharmacology KW - DNA-Binding Proteins -- genetics KW - Xeroderma Pigmentosum -- genetics KW - DNA-Binding Proteins -- administration & dosage KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79886849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Relationship+of+the+xeroderma+pigmentosum+group+E+DNA+repair+defect+to+the+chromatin+and+DNA+binding+proteins+UV-DDB+and+replication+protein+A.&rft.au=Rapi%C4%87+Otrin%2C+V%3BKuraoka%2C+I%3BNardo%2C+T%3BMcLenigan%2C+M%3BEker%2C+A+P%3BStefanini%2C+M%3BLevine%2C+A+S%3BWood%2C+R+D&rft.aulast=Rapi%C4%87+Otrin&rft.aufirst=V&rft.date=1998-06-01&rft.volume=18&rft.issue=6&rft.spage=3182&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 - 1998-06-17 N1 - Date created - 1998-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1974 Jan;22(1):87-91 [4842087] J Biol Chem. 1994 Apr 15;269(15):11121-32 [8157639] Science. 1988 Oct 28;242(4878):564-7 [3175673] EMBO J. 1989 Dec 1;8(12):3883-9 [2573521] Biochemistry. 1989 Oct 17;28(21):8287-92 [2605185] Mol Cell Biol. 1990 May;10(5):2041-8 [2325644] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4053-6 [8171034] Mutat Res. 1994 Oct 1;310(1):89-102 [7523888] J Biol Chem. 1995 Feb 10;270(6):2415-8 [7852297] Cell. 1995 Mar 24;80(6):859-68 [7697716] Nature. 1995 Apr 6;374(6522):566-9 [7700386] Biochemistry. 1995 Apr 18;34(15):5011-7 [7711023] J Biol Chem. 1995 Jun 2;270(22):12973-6 [7768886] Genomics. 1995 Sep 1;29(1):62-9 [8530102] Mutat Res. 1996 Jan 2;362(1):105-17 [8538642] Proc Natl Acad Sci U S A. 1996 May 14;93(10):5014-8 [8643521] J Biol Chem. 1996 Mar 22;271(12):7177-86 [8636155] J Biol Chem. 1996 Apr 5;271(14):8285-94 [8626523] J Biol Chem. 1996 Jul 19;271(29):17190-8 [8663296] J Biol Chem. 1996 Oct 4;271(40):24317-20 [8798680] EMBO J. 1997 Feb 3;16(3):625-38 [9034344] J Cell Sci. 1997 May;110 ( Pt 10):1159-68 [9191040] Annu Rev Biochem. 1997;66:61-92 [9242902] EMBO J. 1997 Nov 3;16(21):6559-73 [9351836] J Biol Chem. 1998 Jan 16;273(3):1453-61 [9430682] Nature. 1991 Feb 7;349(6309):538-41 [1992355] Biochem Biophys Res Commun. 1991 Mar 29;175(3):1139-43 [2025245] Cancer Res. 1991 Jul 1;51(13):3456-70 [2054785] J Biol Chem. 1991 Nov 25;266(33):22493-500 [1657999] Mutat Res. 1992 Mar;273(2):119-25 [1372095] Cell. 1992 Apr 17;69(2):367-74 [1348971] Mutat Res. 1992 Jan;273(1):49-56 [1376435] Nucleic Acids Res. 1992 Aug 11;20(15):3873-80 [1508673] Nucleic Acids Res. 1992 Nov 11;20(21):5805-10 [1454541] Biochemistry. 1993 Feb 16;32(6):1657-66 [8431446] Nature. 1993 May 13;363(6425):185-8 [8483505] Nucleic Acids Res. 1993 Jul 25;21(15):3399-404 [8346019] Nucleic Acids Res. 1993 Aug 25;21(17):4111-8 [8371985] Electrophoresis. 1993 Aug;14(8):682-92 [8404810] J Biol Chem. 1993 Oct 5;268(28):21293-300 [8407967] J Biol Chem. 1993 Oct 5;268(28):21301-8 [8407968] Am J Hum Genet. 1993 Oct;53(4):817-21 [8213812] Biochemistry. 1993 Nov 16;32(45):12096-104 [8218288] Biochemistry. 1976 Jun 1;15(11):2402-8 [1276148] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. AN - 79883017; 9593104 AB - Agents that antagonize the glutamatergic N-methyl-d-aspartate (NMDA) receptor, such as phenylcyclidine (PCP) and ketamine, produce a behavioral state in healthy volunteers that resembles some aspects of schizophrenia. A dysfunction in NMDA-dopaminergic interactions has been proposed as a mechanism for these behavioral effects. In this study, we examined the effects of ketamine on striatal dopamine release in healthy human subjects with a novel 11C-raclopride/PET displacement paradigm and compared these effects to administration of saline and the direct-acting dopamine agonist amphetamine. We found that the percent decreases (mean +/- SD) in specific 11C-raclopride binding from baseline for ketamine (11.2 +/- 8.9) was greater than for saline (1.9 +/- 3.7) (t = 2.4, df = 13, P = 0.003) indicating that ketamine caused increases in striatal synaptic dopamine concentrations. Ketamine-related binding changes were not significantly different than the decreases in percent change (mean +/- SD) in specific 11C-raclopride binding caused by amphetamine (15.5 +/- 6.2) (t = 1.3, df = 19, P = 0.21). Ketamine-induced changes in 11C-raclopride-specific binding were significantly correlated with induction of schizophrenia-like symptoms. The implications of this brain imaging method for studies of schizophrenia and the mechanism of action of antipsychotic drugs are discussed. JF - Synapse (New York, N.Y.) AU - Breier, A AU - Adler, C M AU - Weisenfeld, N AU - Su, T P AU - Elman, I AU - Picken, L AU - Malhotra, A K AU - Pickar, D AD - Experimental Therapeutics Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Breier_Alan@Lilly.com Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 142 EP - 147 VL - 29 IS - 2 SN - 0887-4476, 0887-4476 KW - Dopamine Antagonists KW - 0 KW - Dopamine Uptake Inhibitors KW - Salicylamides KW - Raclopride KW - 430K3SOZ7G KW - N-Methylaspartate KW - 6384-92-5 KW - Amphetamine KW - CK833KGX7E KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Psychoses, Substance-Induced -- diagnostic imaging KW - Humans KW - Behavior -- drug effects KW - Psychiatric Status Rating Scales KW - Adult KW - Tomography, Emission-Computed KW - Psychoses, Substance-Induced -- psychology KW - Amphetamine -- pharmacology KW - Image Processing, Computer-Assisted KW - Male KW - Dopamine Uptake Inhibitors -- pharmacology KW - Neostriatum -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors KW - Dopamine -- metabolism KW - Neostriatum -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79883017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+NMDA+antagonism+on+striatal+dopamine+release+in+healthy+subjects%3A+application+of+a+novel+PET+approach.&rft.au=Breier%2C+A%3BAdler%2C+C+M%3BWeisenfeld%2C+N%3BSu%2C+T+P%3BElman%2C+I%3BPicken%2C+L%3BMalhotra%2C+A+K%3BPickar%2C+D&rft.aulast=Breier&rft.aufirst=A&rft.date=1998-06-01&rft.volume=29&rft.issue=2&rft.spage=142&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic causes of female infertility: targeted mutagenesis in mice. AN - 79871852; 9585621 JF - American journal of human genetics AU - Greenhouse, S AU - Rankin, T AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892-2715, USA. sg162d@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 1282 EP - 1287 VL - 62 IS - 6 SN - 0002-9297, 0002-9297 KW - Index Medicus KW - Zona Pellucida -- physiology KW - Animals KW - Fertilization KW - Ovulation KW - Ovarian Follicle -- physiology KW - Oogenesis -- physiology KW - Mice KW - Female KW - Mutagenesis KW - Infertility, Female -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79871852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NBER+Working+Paper+Series&rft.atitle=Trade%2C+Growth+and+the+Environment&rft.au=Copeland%2C+Brian+R%3BTaylor%2C+M+Scott&rft.aulast=Copeland&rft.aufirst=Brian&rft.date=2003-07-01&rft.volume=&rft.issue=&rft.spage=9823&rft.isbn=&rft.btitle=&rft.title=NBER+Working+Paper+Series&rft.issn=&rft_id=info:doi/10.3386%2Fw9823 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The serotonin reuptake inhibitor sertraline reduces excessive alcohol consumption in nonhuman primates: effect of stress. AN - 79831539; 9571652 AB - Many monkeys that are reared without adult influence, with only peers, voluntarily consume alcohol in amounts producing intoxication on a relatively regular basis. Using a cross-over design, eight adolescent, peer-reared rhesus monkeys were allowed unfettered access to an 8.4% ethanol solution and treated with 20 mg/kg/24 h of sertraline during three phases: home-cage, social separation, and reunion with cage-mates. Although there was no immediate effect, sertraline reduced alcohol consumption beginning the second week of home-cage treatment, but only in subjects that consumed large amounts of alcohol. Initially, the social separation stress caused the sertaline-treated subjects' alcohol consumption rates to return to baseline levels, but when the stress was repeated, alcohol consumption fell below baseline and placebo levels. Sertraline treatment was ineffective in reducing consumption during the stressful period of home-cage reunion, a period characterized by high levels of aggressive behavior. Behaviorally, sertraline reduced aggression and anxiety-like self-directed behaviors. Our findings provide evidence that sertraline may be an effective pharmacological treatment for excessive alcohol consumption and aggression. On the other hand, stress during treatment may reduce sertraline's effectiveness as a treatment for excessive alcohol consumption. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Higley, J AU - Hasert, M AU - Suomi, S AU - Linnoila, M AD - Section on Neurochemistry and Neuro-endocrinology, NIAAA, Poolesville, Maryland 20837, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 431 EP - 443 VL - 18 IS - 6 SN - 0893-133X, 0893-133X KW - Hormones KW - 0 KW - Serotonin Uptake Inhibitors KW - 1-Naphthylamine KW - 9753I242R5 KW - Sertraline KW - QUC7NX6WMB KW - Index Medicus KW - Eating -- drug effects KW - Weight Gain -- drug effects KW - Animals KW - Hormones -- blood KW - Cross-Over Studies KW - Macaca mulatta KW - Time Factors KW - Male KW - Female KW - Alcohol Drinking -- drug therapy KW - 1-Naphthylamine -- analogs & derivatives KW - Serotonin Uptake Inhibitors -- cerebrospinal fluid KW - Serotonin Uptake Inhibitors -- blood KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Alcohol Drinking -- psychology KW - 1-Naphthylamine -- therapeutic use KW - Stress, Psychological -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79831539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=The+serotonin+reuptake+inhibitor+sertraline+reduces+excessive+alcohol+consumption+in+nonhuman+primates%3A+effect+of+stress.&rft.au=Higley%2C+J%3BHasert%2C+M%3BSuomi%2C+S%3BLinnoila%2C+M&rft.aulast=Higley&rft.aufirst=J&rft.date=1998-06-01&rft.volume=18&rft.issue=6&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-23 N1 - Date created - 1998-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific killing of HIV-infected lymphocytes by a recombinant immunotoxin directed against the HIV-1 envelope glycoprotein. AN - 79622923; 10780881 AB - 3B3 is a high-affinity anti-gp120 antibody that neutralizes a wide range of primary and laboratory isolates of HIV-1. The parental antibody was isolated from a combinatorial phage display library constructed from bone marrow RNA of an HIV-infected individual. We have generated a highly active immunotoxin using the 3B3 single-chain Fv (scFv) which can specifically kill lymphocytes infected by HIV-1. We used recombinant DNA technology to clone the Fv fragment of 3B3 and produce a single-chain Fv (scFv). 3B3 scFv was then fused to a truncated version of Pseudomonas exotoxin A (PE38), giving rise to a recombinant immunotoxin 3B3(Fv)-PE38 that was expressed in E. coli and purified to near homogeneity. 3B3(Fv)-PE38 binds with the same affinity as the parental Fab antibody to the MN strain of gp120. The immunotoxin specifically kills a gp120-expressing transfected cell line and a chronically HIV-infected lymphocytic cell line. The immunotoxin is very stable at 37 degrees C, retaining 80% of its original activity after 24 hr. Potent immunotoxins such as 3B3(Fv)-PE38 could be utilized in combination with multidrug cocktails that limit viral replication to help reduce viral reservoirs in patients with AIDS. JF - Molecular medicine (Cambridge, Mass.) AU - Bera, T K AU - Kennedy, P E AU - Berger, E A AU - Barbas, C F AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 384 EP - 391 VL - 4 IS - 6 SN - 1076-1551, 1076-1551 KW - Anti-HIV Agents KW - 0 KW - Antibodies, Viral KW - Antigens, CD4 KW - HIV Envelope Protein gp120 KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - immunoglobulin Fv KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Humans KW - Immunoglobulin Fragments -- genetics KW - Recombinant Proteins -- genetics KW - Antibodies, Viral -- immunology KW - Cross Reactions KW - Antigens, CD4 -- metabolism KW - Binding Sites KW - Cytotoxicity, Immunologic KW - Base Sequence KW - Antibodies, Viral -- genetics KW - Molecular Sequence Data KW - Immunoglobulin Fragments -- metabolism KW - Immunoglobulin Fragments -- immunology KW - Antibodies, Viral -- metabolism KW - HIV Envelope Protein gp120 -- immunology KW - Anti-HIV Agents -- pharmacology KW - HIV Infections -- drug therapy KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - HIV Envelope Protein gp120 -- metabolism KW - Immunotoxins -- pharmacology KW - Lymphocytes -- drug effects KW - Lymphocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79622923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%28Cambridge%2C+Mass.%29&rft.atitle=Specific+killing+of+HIV-infected+lymphocytes+by+a+recombinant+immunotoxin+directed+against+the+HIV-1+envelope+glycoprotein.&rft.au=Bera%2C+T+K%3BKennedy%2C+P+E%3BBerger%2C+E+A%3BBarbas%2C+C+F%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=1998-06-01&rft.volume=4&rft.issue=6&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+%28Cambridge%2C+Mass.%29&rft.issn=10761551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-25 N1 - Date created - 2000-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Immunol. 1996;14:49-71 [8717507] Nat Med. 1996 Mar;2(3):350-3 [8612238] Science. 1997 May 9;276(5314):960-4 [9139661] Nature. 1997 May 8;387(6629):188-91 [9144290] Nat Biotechnol. 1996 Oct;14(10):1239-45 [9631086] Science. 1983 May 20;220(4599):868-71 [6189183] Science. 1984 May 4;224(4648):497-500 [6200935] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Cell. 1987 Jan 16;48(1):129-36 [3098436] Nature. 1988 Sep 22;335(6188):369-72 [2843774] Science. 1988 Nov 25;242(4882):1166-8 [2847316] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1987-91 [2538826] Proc Natl Acad Sci U S A. 1990 Nov;87(22):8889-93 [1701055] J Immunol. 1991 Jun 15;146(12):4315-24 [1710247] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134-7 [1719545] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3809-13 [8170992] J Infect Dis. 1994 Oct;170(4):1009-13 [7930696] J Infect Dis. 1994 Nov;170(5):1180-8 [7963711] Science. 1994 Nov 11;266(5187):1024-7 [7973652] Ann N Y Acad Sci. 1995 Jun 30;758:345-54 [7625703] J Virol. 1995 Nov;69(11):6609-17 [7474069] AIDS Res Hum Retroviruses. 1997 May 1;13(7):575-82 [9135875] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV prevention with drug-using populations--current status and future prospects: introduction and overview. AN - 73919081; 9722806 JF - Public health reports (Washington, D.C. : 1974) AU - Needle, R H AU - Coyle, S L AU - Normand, J AU - Lambert, E AU - Cesari, H AD - National Institute on Drug Abuse, Division of Epidemiology and Prevention Research, Rockville, MD 20857, USA. rn28E@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 4 EP - 18 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Preventive Health Services KW - Primary Prevention -- methods KW - Disease Transmission, Infectious -- prevention & control KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications KW - Public Health -- trends KW - Community-Institutional Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73919081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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=HIV+prevention+with+drug-using+populations--current+status+and+future+prospects%3A+introduction+and+overview.&rft.au=Needle%2C+R+H%3BCoyle%2C+S+L%3BNormand%2C+J%3BLambert%2C+E%3BCesari%2C+H&rft.aulast=Needle&rft.aufirst=R&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=4&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Gen Psychiatry. 1972 Aug;27(2):149-55 [5042822] Rev Infect Dis. 1988 Mar-Apr;10(2):377-84 [3259712] Am J Med. 1984 Mar;76(3):487-92 [6608269] J Subst Abuse Treat. 1984;1(4):237-47 [6100315] Arch Intern Med. 1985 Aug;145(8):1413-7 [3875327] Soc Sci Med. 1985;21(11):1203-16 [3006260] Health Educ Q. 1986 Winter;13(4):383-93 [3781862] Public Health Rep. 1988 May-Jun;103(3):261-6 [3131815] J Health Soc Behav. 1988 Sep;29(3):214-26 [3241064] JAMA. 1989 May 12;261(18):2677-84 [2651732] Am J Community Psychol. 1990 Aug;18(4):587-96 [2075893] NIDA Res Monogr. 1991;106:1-19 [1922282] J Acquir Immune Defic Syndr. 1993 Sep;6(9):1049-56 [8340896] JAMA. 1994 Jun 15;271(23):1825-6; author reply 1826-7 [8196134] Int J Addict. 1994 Nov;29(13):1739-52 [7852000] J Am Med Womens Assoc. 1995 May-Aug;50(3-4):109-14 [7657943] Am J Epidemiol. 1995 Oct 15;142(8):864-74 [7572963] Am J Public Health. 1995 Nov;85(11):1531-7 [7485666] J Infect Dis. 1996 Apr;173(4):997-1000 [8603983] Sex Transm Dis. 1996 Jan-Feb;23(1):24-9 [8801639] J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul;12(3):282-9 [8673532] MMWR Morb Mortal Wkly Rep. 1997 Jun 20;46(24):565-8 [9221326] Arch Gen Psychiatry. 1981 Aug;38(8):875-80 [7259424] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Outreach-based HIV prevention for injecting drug users: a review of published outcome data. AN - 73896526; 9722807 AB - Over the past decade, a body of observational research has accrued about the effects of outreach-based human immunodeficiency virus (HIV) interventions for drug users. The authors reviewed the findings related to postintervention behavior changes and integrated findings across studies to provide the best estimate of program impact. The authors conducted a computerized literature search to locate published accounts of HIV intervention effects on drug users. Thirty-six publications covered outreach-based HIV risk reduction interventions for out-of-treatment injecting drug users (IDUs) and reported intervention effects on HIV-related behaviors or HIV seroincidence. Two-thirds of the publications reported that participation in street-based outreach interventions was followed with office-based HIV testing and counseling. The authors described the theoretical underpinnings of outreach intervention components, the content of the interventions, and the outcome measures that investigators used most frequently. The authors also described and critiqued the evaluation study designs that were in place. Because most of the evaluations were based on pretest and posttest measures of behavior rather than on controlled studies, results were examined with respect to accepted criteria for attributing intervention causality, that is, the plausibility of cause and effect, correct temporal sequence, consistency of findings across reports, strength of associations observed, specifically of associations, and dose-response relationships between interventions and observed outcomes. The majority of the published evaluations showed that IDUs in a variety of places and time periods changed their baseline drug-related and sex-related risk behaviors following their participation in a outreach-based HIV risk reduction intervention. More specifically, the publications indicated that IDUs regularly reported significant follow-up reductions in drug injection, multiperson reuse of syringes and needles, multiperson reuse of other injection equipment (cookers, cotton, rinse water), and crack use. The studies also showed significant intervention effects in promoting entry into drug treatment and increasing needle disinfection. Although drug users also significantly reduced sex-related risks and increased condom use, the majority still practiced unsafe sex. One quasi-experimental study found that reductions in injection risk led to significantly reduced HIV seroincidence among outreach participants. Few investigators looked at dosage effects, but two reports suggested that the longer the exposure to outreach-based interventions, the greater the reductions in drug injection frequency. Accumulated evidence from observational and quasi-experimental studies strongly indicate that outreach-based interventions have been effective in reaching out-of-treatment IDUs, providing the means for behavior changes and inducing behavior change in the desired direction. The findings provide sound evidence that participation in outreach-based prevention programs can lead to lower HIV incidence rates among program participants. JF - Public health reports (Washington, D.C. : 1974) AU - Coyle, S L AU - Needle, R H AU - Normand, J AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. sc91m@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 19 EP - 30 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Needles KW - Randomized Controlled Trials as Topic KW - Risk-Taking KW - Humans KW - Preventive Health Services KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications KW - Community-Institutional Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73896526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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=Outreach-based+HIV+prevention+for+injecting+drug+users%3A+a+review+of+published+outcome+data.&rft.au=Coyle%2C+S+L%3BNeedle%2C+R+H%3BNormand%2C+J&rft.aulast=Coyle&rft.aufirst=S&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul;12(3):282-9 [8673532] AIDS Educ Prev. 1995 Oct;7(5):379-90 [8672391] Drug Alcohol Depend. 1996 Sep;42(1):11-20 [8889399] AIDS Educ Prev. 1998 Feb;10(1):19-33 [9505096] Women Health. 1998;27(1-2):25-48 [9640633] Women Health. 1998;27(1-2):49-66 [9640634] Hosp Community Psychiatry. 1993 Nov;44(11):1066-72 [8288175] Drugs Soc (New York). 1996;9(1-2):173-84 [12348010] Health Educ Q. 1984 Spring;11(1):1-47 [6392204] Rev Infect Dis. 1988 Jan-Feb;10(1):151-8 [3281219] AIDS Educ Prev. 1990 Winter;2(4):253-71 [2099157] Am J Public Health. 1991 May;81(5):568-71 [2014855] Am J Drug Alcohol Abuse. 1991 Sep;17(3):337-53 [1928027] J Addict Dis. 1991;10(4):89-98 [1777502] Br J Addict. 1992 Mar;87(3):393-404 [1559038] Br J Addict. 1992 Apr;87(4):585-90 [1591512] P R Health Sci J. 1993 Apr;12(1):27-34 [8511243] Health Educ Q. 1993 Winter;20(4):523-38 [8307770] AIDS Educ Prev. 1995 Jun;7(3):195-209 [7646944] JAMA. 1995 Oct 18;274(15):1226-31 [7563513] AIDS Educ Prev. 1995 Aug;7(4):308-19 [7577307] AIDS. 1996 Mar;10(3):291-8 [8882669] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What we have learned from research about the prevention of HIV transmission among drug abusers. AN - 73876589; 9722825 AB - After more than 10 years of experience conducting behavioral changes interventions and with accumulated research results, several emergent principle have been identified for the effective prevention of HIV-transmission among drug abusers. In August 1997, a symposium was held in Flagstaff, Arizona, to achieve tow major purposes: (1) to synthesize the finding from HIV prevention research conducted to date for interventions targeting drug abusers and (2) to extract a preliminary set of prevention principles that could be linked to effectiveness across at least two or more studies. This chapter summarizes the key findings of that symposium. Major finding were abstracted from the conclusion sections of the presentations and from the chapters included in this special volume. Many consistencies regarding intervention approaches across studies were noted. These findings are discussed under the following headings: General Observations, Engagement, Multiple Interventions, Intervention Issues, Methodological Issues, and Translation from Research to Practice. Suggested areas for further research are also presented and discussed. Ten principles that have implications for HIV prevention interventions emerged from this preliminary review of the research. These principles engage drug users into the intervention; specify target behaviors and attitudes for intervention; suggest setting to optimize outreach: and recommend booster approaches to reinforce knowledge, skills, and attitudes learned through the intervention. The drug abuse community is threatened by the incursion of HIV and by the hepatitis viruses A, B, and C. The same behaviors are involved in transmitting all of these viruses. The first generation of research to assess the impact of a variety of interventions delivered among drug abusers to prevent HIV has shown consistently favorable findings, proving that drug abusers can be helped to change their risky drug-using behaviors and, to a lesser extent, their risky sexual behaviors. The need to translate these findings for community practitioners is heightened by the devastating impact of HIV and AIDS. JF - Public health reports (Washington, D.C. : 1974) AU - Sloboda, Z AD - National Institute on Drug Abuse, Division of Epidemiology and Prevention Research, Rockville Md 20857, USA. zs6n@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 194 EP - 204 VL - 113 Suppl 1 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Substance-Related Disorders -- therapy KW - Primary Prevention KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73876589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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=What+we+have+learned+from+research+about+the+prevention+of+HIV+transmission+among+drug+abusers.&rft.au=Sloboda%2C+Z&rft.aulast=Sloboda&rft.aufirst=Z&rft.date=1998-06-01&rft.volume=113+Suppl+1&rft.issue=&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Med Care. 1977 May;15(5 SUPPL):27-46 [853780] Int J Addict. 1994 Apr;29(6):681-705 [8034380] JAMA. 1995 Apr 12;273(14):1106-12 [7707598] Drug Alcohol Depend. 1997 Sep 25;47(3):227-35 [9306048] Public Health Rep. 1998 Jun;113 Suppl 1:151-9 [9722820] Public Health Rep. 1998 Jun;113 Suppl 1:42-57 [9722809] Public Health Rep. 1998 Jun;113 Suppl 1:97-106 [9722815] Public Health Rep. 1998 Jun;113 Suppl 1:116-28 [9722817] Public Health Rep. 1998 Jun;113 Suppl 1:19-30 [9722807] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caffeine--an atypical drug of dependence. AN - 73868929; 9716941 AB - Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. Caffeine has weak reinforcing properties, but with little or no evidence for upward dose adjustment, possibly because of the adverse effects of higher doses. Withdrawal symptoms, although relatively limited with respect to severity, do occur, and may contribute to maintenance of caffeine consumption. Health hazards are small if any and caffeine use is not associated with incapacitation. Thus, although caffeine can be argued to fulfill regulatory criteria as a dependence-producing drug, the extensive use of caffeine-containing beverages poses little apparent risk to the consumer or to society. The positive stimulatory effects of caffeine appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. However, blockade of striatal A1 receptors may also play a role. The mechanisms underlying negative effects of higher doses of caffeine are as yet not well defined. JF - Drug and alcohol dependence AU - Daly, J W AU - Fredholm, B B AD - Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 199 EP - 206 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Central Nervous System Stimulants KW - 0 KW - Phosphodiesterase Inhibitors KW - Receptors, Neurotransmitter KW - Receptors, Purinergic P1 KW - Caffeine KW - 3G6A5W338E KW - Index Medicus KW - Phosphodiesterase Inhibitors -- pharmacology KW - Animals KW - Drug Interactions KW - Substance Withdrawal Syndrome -- physiopathology KW - Receptors, Purinergic P1 -- drug effects KW - Down-Regulation KW - Corpus Striatum -- chemistry KW - Receptors, Neurotransmitter -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Receptors, Neurotransmitter -- drug effects KW - Corpus Striatum -- drug effects KW - Up-Regulation KW - Neural Pathways -- drug effects KW - Substance-Related Disorders -- physiopathology KW - Central Nervous System Stimulants -- pharmacology KW - Caffeine -- pharmacology KW - Caffeine -- adverse effects KW - Central Nervous System Stimulants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73868929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caffeine--an+atypical+drug+of+dependence.&rft.au=Daly%2C+J+W%3BFredholm%2C+B+B&rft.aulast=Daly&rft.aufirst=J&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=199&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-activation of brain reward pathways. AN - 73861688; 9716927 JF - Drug and alcohol dependence AU - Wise, R A AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. PY - 1998 SP - 13 EP - 22 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Central Nervous System Stimulants KW - 0 KW - Hallucinogens KW - Narcotics KW - Nicotinic Agonists KW - Receptors, Neurotransmitter KW - Street Drugs KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Central Nervous System Stimulants -- pharmacology KW - Nucleus Accumbens -- drug effects KW - Humans KW - Dopamine -- physiology KW - gamma-Aminobutyric Acid -- physiology KW - Narcotics -- pharmacology KW - Prefrontal Cortex -- drug effects KW - Neural Pathways -- drug effects KW - Rats KW - Hypothalamus, Middle -- drug effects KW - Hallucinogens -- pharmacology KW - Tegmentum Mesencephali -- drug effects KW - Nicotinic Agonists -- pharmacology KW - gamma-Aminobutyric Acid -- drug effects KW - Self Stimulation -- physiology KW - Substance-Related Disorders -- physiopathology KW - Street Drugs -- pharmacology KW - Reward KW - Brain -- drug effects KW - Receptors, Neurotransmitter -- drug effects KW - Models, Neurological KW - Behavior, Addictive -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug-activation+of+brain+reward+pathways.&rft.au=Wise%2C+R+A&rft.aulast=Wise&rft.aufirst=R&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=13&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug addiction research: moving toward the 21st century. AN - 73861630; 9716925 JF - Drug and alcohol dependence AU - Leshner, A I AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. PY - 1998 SP - 5 EP - 7 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - United States KW - Brain -- physiopathology KW - Humans KW - National Institutes of Health (U.S.) KW - Behavior, Addictive -- physiopathology KW - Neurobiology -- trends KW - Substance-Related Disorders -- physiopathology KW - Research -- trends KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73861630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug+addiction+research%3A+moving+toward+the+21st+century.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=5&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of individual versus group caging on the incidence of pituitary and Leydig cell tumors in F344 rats: proposed mechanism. AN - 73854451; 9710329 AB - Recently, an increase in pituitary tumor (pars distalis adenoma) incidence, and decrease in testicular interstitial cell tumor incidence, has been noted in F344 rats, in 2 year National Toxicology Program dermal and inhalation studies. One of the factors that may have contributed to this correlation is the difference in housing protocols. Rats in inhalation and dermal toxicity studies are singly caged, in contrast to other types of studies in which rats are group-caged, such as dosed-feed, dosed-water, or gavage studies. We propose that stress, related to individual caging, particularly among males, directly impairs testosterone synthesis and produces Leydig cell atrophy which leads to a feedback increase in the synthesis of luteinizing hormone by the anterior pituitary. This is followed by anterior pituitary cell functional hypertrophy, hyperplasia, and eventually neoplasia. It is known that individual caging of male rats produces a stress response associated with increased serum corticosteroids. The testicular interstitial cells (Leydig cells) have specific receptors for the glucocorticoid hormones. The Leydig cell enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) inactivates gluococorticoids; however, prolonged stress depletes this enzyme, enabling the gluococorticoids to impair steroidogenesis and eventually to lead to compensatory pituitary proliferations, including neoplasms. JF - Medical hypotheses AU - Nyska, A AU - Leininger, J R AU - Maronpot, R R AU - Haseman, J K AU - Hailey, J R AD - National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 525 EP - 529 VL - 50 IS - 6 SN - 0306-9877, 0306-9877 KW - Adrenal Cortex Hormones KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Rats KW - Hypothalamo-Hypophyseal System -- physiology KW - Animals KW - Rats, Inbred F344 KW - Risk Factors KW - Incidence KW - Testosterone -- physiology KW - Reproduction KW - Male KW - Adrenal Cortex Hormones -- physiology KW - Pituitary Neoplasms -- epidemiology KW - Stress, Physiological -- complications KW - Housing, Animal KW - Models, Biological KW - Testicular Neoplasms -- epidemiology KW - Leydig Cell Tumor -- epidemiology KW - Social Environment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73854451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hypotheses&rft.atitle=Effect+of+individual+versus+group+caging+on+the+incidence+of+pituitary+and+Leydig+cell+tumors+in+F344+rats%3A+proposed+mechanism.&rft.au=Nyska%2C+A%3BLeininger%2C+J+R%3BMaronpot%2C+R+R%3BHaseman%2C+J+K%3BHailey%2C+J+R&rft.aulast=Nyska&rft.aufirst=A&rft.date=1998-06-01&rft.volume=50&rft.issue=6&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Medical+hypotheses&rft.issn=03069877&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. AN - 73852929; 9714301 AB - Thalidomide has been shown to be an inhibitor of angiogenesis in a rabbit cornea micropocket model; however, it has failed to demonstrate this activity in other models. These results suggest that the anti-angiogenic effects of thalidomide may only be observed following metabolic activation of the compound. This activation process may be species specific, similar to the teratogenic properties associated with thalidomide. Using a rat aorta model and human aortic endothelial cells, we co-incubated thalidomide in the presence of either human, rabbit, or rat liver microsomes. These experiments demonstrated that thalidomide inhibited microvessel formation from rat aortas and slowed human aortic endothelial cell proliferation in the presence of human or rabbit microsomes, but not in the presence of rat microsomes. In the absence of microsomes, thalidomide had no effect on either microvessel formation or cell proliferation, thus demonstrating that a metabolite of thalidomide is responsible for its anti-angiogenic effects and that this metabolite can be formed in both humans and rabbits, but not in rodents. JF - Biochemical pharmacology AU - Bauer, K S AU - Dixon, S C AU - Figg, W D AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 1827 EP - 1834 VL - 55 IS - 11 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents KW - 0 KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Coculture Techniques KW - Animals KW - Aorta, Thoracic -- drug effects KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Aorta, Thoracic -- cytology KW - Humans KW - Aorta, Thoracic -- metabolism KW - Cell Division -- drug effects KW - Rabbits KW - Species Specificity KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Microsomes, Liver -- metabolism KW - Antineoplastic Agents -- metabolism KW - Thalidomide -- metabolism KW - Neovascularization, Physiologic -- drug effects KW - Thalidomide -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Neovascularization, Pathologic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73852929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+angiogenesis+by+thalidomide+requires+metabolic+activation%2C+which+is+species-dependent.&rft.au=Bauer%2C+K+S%3BDixon%2C+S+C%3BFigg%2C+W+D&rft.aulast=Bauer&rft.aufirst=K&rft.date=1998-06-01&rft.volume=55&rft.issue=11&rft.spage=1827&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 - 1998-08-31 N1 - Date created - 1998-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The neurobiology of alcohol abuse and alcoholism: building knowledge, creating hope. AN - 73852384; 9716926 JF - Drug and alcohol dependence AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 9 EP - 11 VL - 51 IS - 1-2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - United States KW - Brain -- physiopathology KW - Animals KW - Humans KW - National Institutes of Health (U.S.) KW - Behavior, Addictive -- physiopathology KW - Alcohol-Related Disorders -- physiopathology KW - Alcohol-Related Disorders -- prevention & control KW - Research -- trends KW - Neurobiology -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73852384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+neurobiology+of+alcohol+abuse+and+alcoholism%3A+building+knowledge%2C+creating+hope.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1998-06-01&rft.volume=51&rft.issue=1-2&rft.spage=9&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 - 1998-11-12 N1 - Date created - 1998-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Dealing with alcoholism--networking of social resources in Kochi prefecture]. AN - 73847813; 9701999 JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Takeshima, T AU - Tani, N AD - National Institute of Mental Health, NCNP, Ichikawa, Japan. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 219 EP - 224 VL - 33 IS - 3 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Humans KW - Health Education KW - Japan KW - Alcoholism -- therapy KW - Community Networks KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73847813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BDealing+with+alcoholism--networking+of+social+resources+in+Kochi+prefecture%5D.&rft.au=Takeshima%2C+T%3BTani%2C+N&rft.aulast=Takeshima&rft.aufirst=T&rft.date=1998-06-01&rft.volume=33&rft.issue=3&rft.spage=219&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 - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Coordination or competence: an emerging problem in the development of network treatment for alcoholics]. AN - 73841853; 9702000 AB - The author recognizes the significance and relevance of the network treatment for alcoholics is such a way as an effort to respond not only to the medical needs but also to social service needs, in order to support the recovery of alcoholics. Consequently we are faced to an indispensable task to look back historically the developmental process of the treatment service for alcoholics in Japan. A recent policy development in the alcohol treatment is stimulating the shift from the overweight medical approach to a more comprehensive approach including social services. This innovation is bringing about not only a wider treatment options but also a newly emerging problem of "coordination or competence" as well. It was implied in this paper that a concept of "shared function" is promising to consider this new problem. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Shimizu, S AD - National Institute of Mental Health, NCNP, Chiba, Japan. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 225 EP - 233 VL - 33 IS - 3 SN - 1341-8963, 1341-8963 KW - Index Medicus KW - Humans KW - Social Work KW - Health Education KW - Self-Help Groups KW - Japan KW - Alcoholism -- therapy KW - Community Networks KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73841853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BCoordination+or+competence%3A+an+emerging+problem+in+the+development+of+network+treatment+for+alcoholics%5D.&rft.au=Shimizu%2C+S&rft.aulast=Shimizu&rft.aufirst=S&rft.date=1998-06-01&rft.volume=33&rft.issue=3&rft.spage=225&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 - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity. AN - 73835122; 9704898 AB - We investigated the effects of nitric oxide on an in vitro and in vivo generation of hydroxyl radicals, and in vivo neurotoxicity caused by intranigral infusion of ferrous citrate in rats. The formation of hydroxyl radicals in vitro, without exogenous hydrogen peroxide, was dose-dependent. Some nitric oxide donors (e.g. sodium nitroprusside) stimulated, while others (nitroglycerin, diethylamine/nitric oxide, nitric oxide in Ringer's solution) suppressed hydroxyl radical generation in vitro. A significant increase in extra-cellular hydroxyl radicals was detected in a brain microdialysis study. Intranigral infusion of ferrous citrate caused long-lasting lipid peroxidation and dopamine depletion in the ipsilateral nigral region and striatum, respectively. Sub-acute dopamine depletion in the striatum was positively correlated with acute lipid peroxidation in substantia nigra. Intranigral administration of nitric oxide did not affect striatal dopamine. Interestingly, nitric oxide in Ringer's protected nigral neurones against the oxidative injury. The results demonstrate that a regional increase in the levels of iron can result in hydroxyl radical generation and lipid peroxidation leading to neurotoxicity. It also demonstrates that exogenous nitric oxide can act as hydroxyl radical scavenger and protect neurones from oxidative injury. JF - Journal of chemical neuroanatomy AU - Mohanakumar, K P AU - Hanbauer, I AU - Chiueh, C C AD - Unit on Neurotoxicity and Neuroprotection, Laboratory of Clinical Sciences, NIMH, NIH, Bethesda, MD 20892, USA. iichbio@giasc101.vsn1.net.in Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 195 EP - 205 VL - 14 IS - 3-4 SN - 0891-0618, 0891-0618 KW - Ferrous Compounds KW - 0 KW - Lipid Peroxides KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - monoferrous acid citrate KW - 33KM3X4QQW KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Ferrous Compounds -- metabolism KW - Drug Interactions KW - Corpus Striatum -- metabolism KW - In Vitro Techniques KW - Dopamine -- metabolism KW - Corpus Striatum -- drug effects KW - Lipid Peroxides -- metabolism KW - Male KW - Substantia Nigra -- drug effects KW - Nitric Oxide -- pharmacology KW - Hydroxyl Radical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73835122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemical+neuroanatomy&rft.atitle=Neuroprotection+by+nitric+oxide+against+hydroxyl+radical-induced+nigral+neurotoxicity.&rft.au=Mohanakumar%2C+K+P%3BHanbauer%2C+I%3BChiueh%2C+C+C&rft.aulast=Mohanakumar&rft.aufirst=K&rft.date=1998-06-01&rft.volume=14&rft.issue=3-4&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemical+neuroanatomy&rft.issn=08910618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histopathology and molecular biology of ovarian epithelial tumors. AN - 70130600; 9845739 AB - Carcinogenesis in the ovary presents special features related to that organ. First, the preinvasive or even invasive lesions are difficult to detect, which explains why most cases are diagnosed at an advanced stage. Second, the group of tumors of low malignant potential (borderline tumors) are still a controversial category of ovarian lesions. Finally, familial ovarian tumors represent an interesting hereditary model of carcinogenesis at the molecular level. Flow cytometry and immunohistochemistry for proliferative markers or oncogenes provide important prognostic information in patients with ovarian tumors. Molecular data, such as loss of heterozygosity at specific genetic loci, also have been correlated with prognosis. Clonality studies in patients with multiple ovarian/pelvian lesions analyzing chromosome X inactivation patterns and genetic deletions or mutations have contributed to the understanding of the origin of these lesions. New technologies to study gene expression patterns, such as cDNA library construction and DNA microarray technologies, are being applied to study histologic phases of tumor progression, such as normal, preinvasive, and tumor tissues. It is hoped that these studies will contribute important information not only for a better understanding of the process of carcinogenesis, but also for assessing the biology and behavior of individual tumors, determining patient prognosis, and eventually influencing therapy. JF - Annals of diagnostic pathology AU - Chuaqui, R F AU - Cole, K A AU - Emmert-Buck, M R AU - Merino, M J AD - Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 195 EP - 207 VL - 2 IS - 3 SN - 1092-9134, 1092-9134 KW - Index Medicus KW - Genes, Tumor Suppressor KW - Humans KW - Molecular Biology -- trends KW - Female KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70130600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+diagnostic+pathology&rft.atitle=Histopathology+and+molecular+biology+of+ovarian+epithelial+tumors.&rft.au=Chuaqui%2C+R+F%3BCole%2C+K+A%3BEmmert-Buck%2C+M+R%3BMerino%2C+M+J&rft.aulast=Chuaqui&rft.aufirst=R&rft.date=1998-06-01&rft.volume=2&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Annals+of+diagnostic+pathology&rft.issn=10929134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-06 N1 - Date created - 1999-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. AN - 70121051; 9776829 AB - Air sampling of the rooms and corridors of the oncology wards of the hospital was carried out over a 54-week period to assess the concentration of viable Aspergillus conidia. A. fumigatus and A. flavus were recovered at a mean of 1.83 cfu m-3 air sampled. Individual samplings yielded concentrations of up to 11.6 cfu m-3. Other Aspergillus spp. were recovered at a mean of 2.38 cfu m-3 (maximum 32.6 cfu m-3). Concentration was not correlated with season or hospital ward. Review of autopsy results showed an average of 6.6 cases of aspergillosis annually over a 22-year period. No seasonal variation in case incidence was found. Six cases of invasive aspergillosis were diagnosed on the three cancer wards during the air-sampling period, but no association was seen linking these cases with changes in recovery of airborne Aspergillus. A seasonal pattern was not observed in the overall incidence of aspergillosis cases nor concentrations of airborne conidia. JF - Medical mycology AU - Hospenthal, D R AU - Kwon-Chung, K J AU - Bennett, J E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. dhospenthal@atlas.niaid.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 165 EP - 168 VL - 36 IS - 3 SN - 1369-3786, 1369-3786 KW - Index Medicus KW - United States KW - Autopsy KW - Air Pollution, Indoor KW - Patients' Rooms KW - Humans KW - National Institutes of Health (U.S.) KW - Retrospective Studies KW - Incidence KW - Aspergillus fumigatus -- isolation & purification KW - Aspergillus flavus -- isolation & purification KW - Air Microbiology KW - Aspergillosis -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70121051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mycology&rft.atitle=Concentrations+of+airborne+Aspergillus+compared+to+the+incidence+of+invasive+aspergillosis%3A+lack+of+correlation.&rft.au=Hospenthal%2C+D+R%3BKwon-Chung%2C+K+J%3BBennett%2C+J+E&rft.aulast=Hospenthal&rft.aufirst=D&rft.date=1998-06-01&rft.volume=36&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Medical+mycology&rft.issn=13693786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-28 N1 - Date created - 1999-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Med Mycol. 1999 Oct;37(5):373-4 [10520163] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of inhibition of ornithine decarboxylase activity in a model of acute hepatocellular necrosis. AN - 70118315; 9855067 AB - The effect of blockade of the enzyme ornithine decarboxylase by difluoromethylornithine (DFMO) on hepatocellular necrosis and survival in rats treated with thioacetamide (TAA) was investigated. In one experiment, the effect of DFMO on survival of rats with TAA-induced acute hepatocellular necrosis was determined. In another experiment, blood and liver specimens were obtained from DFMO or saline-treated rats 24 h after the administration of TAA for determinations of serum alanine aminotransferase (ALT) and liver content of polyamines and microsomal cytochrome P-450 and for assessment of hepatic histology. Liver polyamines were determined by reversed-phase HPLC and microsomal cytochrome P-450 content by dithionite-difference spectroscopy of CO-treated homogenates. The severity of hepatocellular necrosis was scored blindly. TAA-treated rats that received DFMO survived longer than saline-treated controls (P < 0.01). Serum ALT and liver putrescine concentrations were lower and the histological severity of acute hepatocellular necrosis was less in DFMO-treated rats with TAA-induced hepatocellular necrosis than in saline-treated controls (P < 0.05, P < 0.01 and P < 0.05, respectively). Total cytochrome P-450 levels were similar in DFMO and saline-treated rats with TAA-induced hepatocellular necrosis. DFMO increases survival in TAA-induced fulminant hepatic failure by decreasing the severity of acute hepatocellular necrosis. The beneficial effects of DFMO do not appear to be mediated by its effects on polyamine metabolism, but may be attributable to an effect of DFMO on thioacetamide metabolism or on an alternative pathway of ornithine metabolism. JF - European journal of gastroenterology & hepatology AU - Yurdaydin, C AU - Swain, M G AU - Mininberg, E D AU - Vergalla, J AU - Kleiner, D AU - Paul, S M AU - Jones, E A AD - Liver Diseases Section, NIDDK, National Institutes of Health, Bethesda, MD, USA. yurdaydi@dialp.ankara.edu.tr Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 503 EP - 507 VL - 10 IS - 6 SN - 0954-691X, 0954-691X KW - Enzyme Inhibitors KW - 0 KW - Ornithine Decarboxylase Inhibitors KW - Thioacetamide KW - 075T165X8M KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Eflornithine KW - ZQN1G5V6SR KW - Index Medicus KW - Rats KW - Ornithine Decarboxylase -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- pharmacology KW - Disease Models, Animal KW - Eflornithine -- pharmacology KW - Male KW - Hepatic Encephalopathy -- physiopathology KW - Hepatic Encephalopathy -- enzymology KW - Hepatic Encephalopathy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70118315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gastroenterology+%26+hepatology&rft.atitle=Effect+of+inhibition+of+ornithine+decarboxylase+activity+in+a+model+of+acute+hepatocellular+necrosis.&rft.au=Yurdaydin%2C+C%3BSwain%2C+M+G%3BMininberg%2C+E+D%3BVergalla%2C+J%3BKleiner%2C+D%3BPaul%2C+S+M%3BJones%2C+E+A&rft.aulast=Yurdaydin&rft.aufirst=C&rft.date=1998-06-01&rft.volume=10&rft.issue=6&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=European+journal+of+gastroenterology+%26+hepatology&rft.issn=0954691X&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 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-function analysis of muscarinic acetylcholine receptors. AN - 69993070; 9789820 AB - The structural basis underlying the G protein coupling selectivity of different muscarinic receptor subtypes was analyzed by using a combined molecular genetic/biochemical approach. These studies led to the identification of key residues on the receptors as well as the associated G proteins that are critically involved in determining proper receptor/G protein recognition. Mutational analysis of the m3 muscarinic receptor showed that most native cysteine residues are not required for productive receptor/G protein coupling. The putative extracellular disulfide bond was found to be essential for efficient trafficking of the receptor protein to the cell surface but not for receptor-mediated G protein activation. JF - Journal of physiology, Paris AU - Kostenis, E AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 265 EP - 268 VL - 92 IS - 3-4 SN - 0928-4257, 0928-4257 KW - Receptors, Muscarinic KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Cysteine -- chemistry KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- physiology KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69993070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+physiology%2C+Paris&rft.atitle=Structure-function+analysis+of+muscarinic+acetylcholine+receptors.&rft.au=Kostenis%2C+E%3BZeng%2C+F+Y%3BWess%2C+J&rft.aulast=Kostenis&rft.aufirst=E&rft.date=1998-06-01&rft.volume=92&rft.issue=3-4&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Journal+of+physiology%2C+Paris&rft.issn=09284257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-13 N1 - Date created - 1999-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis: a novel therapeutic tool? AN - 69260543; 15992005 AB - Apoptosis is a genetically programmed cell death mechanism that appears to occur in all multicellular organisms. It is a normal process that serves to maintain cellular homeostasis. However, in many diseases there is a disruption in the equilibrium between cell proliferation and cell death that contributes directly to the disease. In these cases, a possible therapeutic intervention would be to restore the skewed equilibrium by pushing it in the desired direction through the use of pharmacological agents or genetic approaches. These observations have instigated substantial research in the field of apoptosis, resulting in an increasingly detailed analysis of the molecular mechanisms and the sequence of events that occur in this cell death pathway. In addition, by trying to understand this pathway, several potential therapeutic agents have arisen from those used in chemo-, radio-, and cytokine therapy. While these agents have been relatively successful, it is rare that their effect is complete. Thus, the search continues for a strategy to conquer those cells that are resistant to these regimens. Genetic approaches are novel and have been shown to be quite successful in several in vitro and animal models. They also tend to have low toxicity. It is believed that using a more traditional front-line approach of therapy, supplemented by appropriate genetic intervention, will allow substantial increases in the efficacy of treatment, while at the same time introducing little or no additional toxicity. JF - Expert opinion on investigational drugs AU - Dixon, S C AU - Arah, I N AD - Medicine Branch, Clinical Pharmacokinetics Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. nemra@box-n.nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 889 EP - 904 VL - 7 IS - 6 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69260543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+opinion+on+investigational+drugs&rft.atitle=Apoptosis%3A+a+novel+therapeutic+tool%3F&rft.au=Dixon%2C+S+C%3BArah%2C+I+N&rft.aulast=Dixon&rft.aufirst=S&rft.date=1998-06-01&rft.volume=7&rft.issue=6&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-14 N1 - Date created - 2005-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The first-order giant neurons of the giant fiber system in the squid: electrophysiological and ultrastructural observations. AN - 69189361; 10192523 AB - The giant fiber system controlling mantle contraction used for jet propulsion in squid consists of two sets of three giant neurons organized in tandem. The somata of the 1st- and 2nd-order giant cells are located in the brain, while the perikarya of the 3rd-order giant cells are encountered in the stellate ganglia of the mantle. The somata and dendrites of one fused pair of 1st-order giant cells are thought to receive synaptic input from the eye, statocyst, skin proprioceptors, and supraesophageal lobes. To define the cellular properties for integration of such an extensive synaptic load, especially given its diversity, intracellular recordings and electron microscopic observations were performed on 1st-order giant cells in an isolated head preparation. Spontaneous bursts of action potentials and spikes evoked by extracellular stimulation of the brachial lobe were sensitive to the Na+ channel blocker TTX. Action potentials were also abolished by recording with microelectrodes containing the membrane impermeant, use dependent Na+ channel blocker QX-314. The small action potential amplitude and the abundant synaptic input imply that the spike initiation zone is remotely located from the recording site. The high spontaneous activity in the isolated head preparation, as well as the presence of synaptic junctions resembling inhibitory synapses, suggest; that afferent synapses on 1st-order giant neurons might represent the inhibitory control of the giant fiber system. The characterization of the electroresponsive properties of the 1st-order giant neurons will provide a description of the single cell integrative properties that trigger the rapid jet propulsion necessary for escape behavior in squid. JF - Journal of neurocytology AU - Pozzo-Miller, L D AU - Moreira, J E AU - Llinás, R R AD - Laboratory of Neurobiology, NINDS, NIH, Bethesda, MD 20892, USA. Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 419 EP - 429 VL - 27 IS - 6 SN - 0300-4864, 0300-4864 KW - Anesthetics, Local KW - 0 KW - QX-314 KW - 21306-56-9 KW - Tetrodotoxin KW - 4368-28-9 KW - Lidocaine KW - 98PI200987 KW - Index Medicus KW - Action Potentials -- physiology KW - Animals KW - Anesthetics, Local -- pharmacology KW - Evoked Potentials -- physiology KW - Axons -- ultrastructure KW - Action Potentials -- drug effects KW - Decapodiformes KW - Electric Stimulation KW - Axons -- physiology KW - Synapses -- physiology KW - Synapses -- ultrastructure KW - Cells, Cultured KW - In Vitro Techniques KW - Escape Reaction -- physiology KW - Lidocaine -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Lidocaine -- analogs & derivatives KW - Nerve Fibers -- physiology KW - Neurons -- drug effects KW - Nerve Fibers -- ultrastructure KW - Neurons -- physiology KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69189361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurocytology&rft.atitle=The+first-order+giant+neurons+of+the+giant+fiber+system+in+the+squid%3A+electrophysiological+and+ultrastructural+observations.&rft.au=Pozzo-Miller%2C+L+D%3BMoreira%2C+J+E%3BLlin%C3%A1s%2C+R+R&rft.aulast=Pozzo-Miller&rft.aufirst=L&rft.date=1998-06-01&rft.volume=27&rft.issue=6&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurocytology&rft.issn=03004864&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 - Sources of Child Vocabulary Competence: A Multivariate Model AN - 58376126; 9902062 AB - Sources of individual variation in child vocabulary competence are examined in the context of a multivariate developmental ecological model. Maternal sociodemographic characteristics, personological characteristcs, & vocabulary, as well as child gender, social competence, & vocabulary competence were evaluated simultaneously in 126 children age 1:8 & their mothers. Measures of child vocabulary competence included two measures each of spontaneous speech, experimenter assessments, & maternal reports. Maternal measures, from proximal to distal, included vocabulary, verbal intelligence, personality, attitudes toward parenting, knowledge of parenting, & SES. Structural equation modelling supported several direct unique predictive relations: child gender (girls higher) & social competence as well as maternal attitudes toward parenting predicted child vocabulary competence, & mothers' vocabulary predicted child vocabulary comprehension & two measures of mother-reported child vocabulary expression. In addition, children's vocabulary competence was influenced indirectly by mothers' vocabulary, social personality, & knowledge of child development. Maternal vocabulary itself was positively influenced by SES, maternal verbal intelligence, & mothers' knowledge about parenting. Individual variation in child vocabulary competence might best be understood as arising within a nexus of contextual factors both proximal & distal to the child. 5 Tables, 2 Figures, 55 References. Adapted from the source document JF - Journal of Child Language AU - Bornstein, Marc H AU - Haynes, Maurice O AU - Painter, Kathleen M AD - Laboratory Comparative Ethnology National Instit Child Health & Human Development National Instits Health, Bethesda MD 20892-2030 Marc_H_Bornstein@nih.gov Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 367 EP - 393 VL - 25 IS - 2 SN - 0305-0009, 0305-0009 KW - Attitudes (05450) KW - Infants (35660) KW - Language Acquisition (41600) KW - Sex Differences (77850) KW - Lexicon (47150) KW - Social Factors (79910) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/58376126?accountid=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=Journal+of+Child+Language&rft.atitle=Sources+of+Child+Vocabulary+Competence%3A+A+Multivariate+Model&rft.au=Bornstein%2C+Marc+H%3BHaynes%2C+Maurice+O%3BPainter%2C+Kathleen+M&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=1998-06-01&rft.volume=25&rft.issue=2&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Language&rft.issn=03050009&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 - JCLGBJ N1 - SubjectsTermNotLitGenreText - Infants (35660); Language Acquisition (41600); Lexicon (47150); Social Factors (79910); Attitudes (05450); Sex Differences (77850) ER - TY - JOUR T1 - Coupling of mantle-upwelling and shearing; Mesozoic dyke-swarms in Da-Hinggan Mountains, Northeast China AN - 52483630; 1999-038532 AB - The morphological and petrologico-geochemical features, and the time-space evolution history of Mesozoic dyke-swarms in Da Hinggan Mts. are studied to explore the polytopism and polytrope of the driving forces for deformation of the continental lithosphere. It is found that two dynamic mechanisms were coupled in the deformation of the upper lithosphere when upwelling and intrusion of the mantle-derived magma occurred. JF - Episodes AU - Shao, Ji'an AU - Gai, Fengying AU - Zhang, Luqiao Y1 - 1998/06// PY - 1998 DA - June 1998 SP - 99 EP - 103 PB - International Union of Geological Sciences (IUGS), Ottawa, ON VL - 21 IS - 2 SN - 0705-3797, 0705-3797 KW - upwelling KW - Far East KW - igneous rocks KW - mantle KW - dike swarms KW - plutonic rocks KW - mineral composition KW - Linxi China KW - tectonics KW - rare earths KW - crystal fractionation KW - chemical composition KW - Asia KW - geochemistry KW - China KW - Inner Mongolia China KW - concentration KW - petrology KW - lithosphere KW - deformation KW - Mesozoic KW - orogeny KW - intrusions KW - dikes KW - Da Hinggan Ling KW - metals KW - magmas KW - shear KW - diabase KW - magma chambers KW - 02C:Geochemistry of rocks, soils, and sediments KW - 05A:Igneous and metamorphic petrology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52483630?accountid=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=Episodes&rft.atitle=Coupling+of+mantle-upwelling+and+shearing%3B+Mesozoic+dyke-swarms+in+Da-Hinggan+Mountains%2C+Northeast+China&rft.au=Shao%2C+Ji%27an%3BGai%2C+Fengying%3BZhang%2C+Luqiao&rft.aulast=Shao&rft.aufirst=Ji%27an&rft.date=1998-06-01&rft.volume=21&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Episodes&rft.issn=07053797&rft_id=info:doi/ L2 - http://www.episodes.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1999-01-01 N1 - Number of references - 10 N1 - PubXState - ON N1 - Document feature - illus. incl. 4 tables, geol. sketch map N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - Asia; chemical composition; China; concentration; crystal fractionation; Da Hinggan Ling; deformation; diabase; dike swarms; dikes; Far East; geochemistry; igneous rocks; Inner Mongolia China; intrusions; Linxi China; lithosphere; magma chambers; magmas; mantle; Mesozoic; metals; mineral composition; orogeny; petrology; plutonic rocks; rare earths; shear; tectonics; upwelling ER - TY - JOUR T1 - Epitope Mapping of a Series of Human Thymidylate Synthase Monoclonal Antibodies AN - 17209380; 4495061 AB - We have reported previously the development and application of several monoclonal antibodies to thymidylate synthase (TS). In this study, we used a series of overlapping 17-mer peptides that spanned the entire TS protein to map the epitope recognized by three TS monoclonal antibodies (TS 106, TS 109, and TS 110). Using an ELISA, we identified two peptides (R super(126)-F super(142) and L super(131)-R super(147)) that bound all three antibodies, which suggests that each antibody recognized a similar epitope on TS. A second set of peptides, representing sequential single-residue truncations from either the amino terminus or the carboxyl terminus starting with a G super(129)-E super(145) 17-mer, was synthesized. A 10-amino acid sequence P super(133)-F super(142) (PVYG-FQWRHF) was identified as the binding epitope for all three antibodies. Further investigation via substitution mutational analysis of each residue within this epitope revealed that residues F super(137), W super(139), R super(140), H super(141), and F super(142) were critical for maximal binding of TS 106 and TS 110. TS 109 showed a similar pattern except in regard to R super(140), with which there was no apparent loss of binding. In addition to the utility of the three antibodies in detecting and measuring TS levels, identification of the binding locus permits the potential application of these antibodies in the investigation of TS enzymatic and regulatory function. JF - Cancer Research AU - Behan, KA AU - Johnston, P G AU - Allegra, C J AD - National Cancer Institute, Medicine Branch at the National Naval Medical Center, 8901 Wisconsin Avenue, Building 8, Room 5101, Bethesda, MD 20889-5105, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2606 EP - 2611 VL - 58 IS - 12 SN - 0008-5472, 0008-5472 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Monoclonal antibodies KW - Thymidylate synthase KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17209380?accountid=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=Epitope+Mapping+of+a+Series+of+Human+Thymidylate+Synthase+Monoclonal+Antibodies&rft.au=Behan%2C+KA%3BJohnston%2C+P+G%3BAllegra%2C+C+J&rft.aulast=Behan&rft.aufirst=KA&rft.date=1998-06-01&rft.volume=58&rft.issue=12&rft.spage=2606&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 - Thymidylate synthase; Monoclonal antibodies ER - TY - JOUR T1 - Peptides Derived from Self-Proteins as Partial Agonists and Antagonists of Human CD8 super(+) T-Cell Clones Reactive to Melanoma/Melanocyte Epitope MART1 sub(27-35) AN - 17205370; 4494462 AB - The self-peptide MART1 sub(27-35) derives from the melanocyte/melanoma protein Melan A/MART1 and is a target epitope of CD8 super(+) T cells, commonly recovered from tumor-infiltrating lymphocytes of HLA-A2.1 super(+) melanoma patients. Despite their prevalence in such patients, these CTLs generally appear to be ineffective in mediating tumor regression in vivo. We have noted previously that numerous peptides from both endogenous and foreign proteins are similar to MART1 sub(27-35) and, potentially, are capable of productively engaging the T-cell receptors of patient-derived CTLs. This observation raised the question of whether CTLs in vivo might encounter self-peptide analogues of MART1 sub(27-35) that lack full agonist activity, perhaps to the detriment of the antitumor CTL response. This possibility was evaluated using cloned, patient-derived CTLs with a panel of self-derived natural analogues of MART1 sub(27-35) in assays for cytolysis, cytokine release, and phosphorylation of T-cell receptor signaling constituents. Several peptides were identified as partial agonists, capable of eliciting cytolysis and/or release of cytokines tumor necrosis factor- alpha and IFN- gamma but not interleukin 2. Several other peptides showed antagonist behavior, effectively inhibiting cytolysis of MART1 sub(27-35)-pulsed targets, but did not inhibit killing of cells prepulsed with a synthetic, heteroclitic variant of MART1 sub(27-35). Some of these antagonists also had lasting effects on interleukin 2 secretion by CTLs under experimental conditions involving sequential exposure to ligands. Together, these observations suggest that encounters with self-peptide analogues of MART1 sub(27-35) may contribute to the peripheral maintenance of these CTLs, while ultimately impairing the efficacy of this antitumor T-cell response. JF - Cancer Research AU - Loftus, D J AU - Squarcina, P AU - Nielsen, M-B AU - Geisler, C AU - Castelli, C AU - Oedum, N AU - Appella, E AU - Parmiani, G AU - Rivoltini, L AD - Laboratory of Cell Biology, National Cancer Institute, NIH, Building 37, Room 1B03, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2433 EP - 2439 VL - 58 IS - 11 SN - 0008-5472, 0008-5472 KW - CD8 antigen KW - MART-1 antigen KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Lymphocytes T KW - Vaccines KW - Melanocytes KW - Melanoma KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17205370?accountid=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=Peptides+Derived+from+Self-Proteins+as+Partial+Agonists+and+Antagonists+of+Human+CD8+super%28%2B%29+T-Cell+Clones+Reactive+to+Melanoma%2FMelanocyte+Epitope+MART1+sub%2827-35%29&rft.au=Loftus%2C+D+J%3BSquarcina%2C+P%3BNielsen%2C+M-B%3BGeisler%2C+C%3BCastelli%2C+C%3BOedum%2C+N%3BAppella%2C+E%3BParmiani%2C+G%3BRivoltini%2C+L&rft.aulast=Loftus&rft.aufirst=D&rft.date=1998-06-01&rft.volume=58&rft.issue=11&rft.spage=2433&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 - Melanoma; Melanocytes; Vaccines; Lymphocytes T ER - TY - JOUR T1 - Plasmid DNA Encoding Transforming Growth Factor- beta 1 Suppresses Chronic Disease in a Streptococcal Cell Wall-induced Arthritis Model AN - 17191068; 4484320 AB - Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF- beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF- beta , we administered a plasmid DNA encoding human TGF- beta 1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 mu g plasmid DNA encoding TGF- beta 1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17 plus or minus 0.17 vs. 1.25 plus or minus 0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF- beta 1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF- beta 1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF- beta 1 protein were detected in the circulation of TGF- beta 1 DNA-treated animals, consistent with the observed therapeutic effects being TGF- beta 1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF- beta 1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. JF - Journal of Clinical Investigation AU - Song, Xiao-yu AU - Gu, MiLi AU - Jin, Wen-wen AU - Klinman, D M AU - Wahl, S M AD - Bldg. 30, Room 332, 30 Convent Drive, MSC 4352, Bethesda, MD 20892-4352, USA, smwahl@yoda.nidr.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 2615 EP - 2621 VL - 101 IS - 12 SN - 0021-9738, 0021-9738 KW - rats KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene transfer KW - Arthritis KW - Animal models KW - Plasmids KW - Inflammation 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/17191068?accountid=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+Clinical+Investigation&rft.atitle=Plasmid+DNA+Encoding+Transforming+Growth+Factor-+beta+1+Suppresses+Chronic+Disease+in+a+Streptococcal+Cell+Wall-induced+Arthritis+Model&rft.au=Song%2C+Xiao-yu%3BGu%2C+MiLi%3BJin%2C+Wen-wen%3BKlinman%2C+D+M%3BWahl%2C+S+M&rft.aulast=Song&rft.aufirst=Xiao-yu&rft.date=1998-06-01&rft.volume=101&rft.issue=12&rft.spage=2615&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Investigation&rft.issn=00219738&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 - Plasmids; Gene transfer; Animal models; Inflammation; Arthritis ER - TY - JOUR T1 - Clarification of the relationship between free radical spin trapping and carbon tetrachloride metabolism in microsomal systems AN - 17182161; 4480770 AB - It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl radical adduct PBN/ super( times )CCl sub(3) is metabolized to either the C-phenyl-N-tert-butylnitrone/carbon dioxide anion radical adduct (PBN/ super( times )CO sub(2) super(-)) or the glutathione (GSH) and CCl sub(4)-dependent PBN radical adduct (PBN/[GSH- super( times )CCl sub(3)]). Inclusion of PBN/ super( times )CCl sub(3) in microsomal incubations containing GSH, nicotinamide adenine dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH- super( times )CCl sub(3)] or PBN/ super( times )CO sub(2) super(-) radical adducts. Microsomes alone or with GSH had no effect on the PBN/ super( times )CCl sub(3) radical adduct. Addition of NADPH to a microsomal system containing PBN/ super( times )CCl sub(3) presumably reduced the radical adduct to its ESR-silent hydroxylamine because no ESR signal was observed. The Folch extract of this system produced an ESR spectrum that was a composite of two radicals, one of which had hyperfine coupling constants identical to those of PBN/ super( times )CCl sub(3). We conclude that PBN/ super( times )CCl sub(3) is not metabolized into either PBN/[GSH- super( times )CCl sub(3)] or PBN/ super( times )CO sub(2) super(-) in microsomal systems. JF - Free Radical Biology & Medicine AU - Connor, H D AU - Thurman, R G AU - Chen, G AU - Poyer, J L AU - Janzen, E G AU - Mason, R P AD - National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 1364 EP - 1368 VL - 24 IS - 9 SN - 0891-5849, 0891-5849 KW - metabolism KW - spin trapping KW - Toxicology Abstracts KW - Microsomes KW - Carbon tetrachloride KW - Free radicals KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17182161?accountid=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=Free+Radical+Biology+%26+Medicine&rft.atitle=Clarification+of+the+relationship+between+free+radical+spin+trapping+and+carbon+tetrachloride+metabolism+in+microsomal+systems&rft.au=Connor%2C+H+D%3BThurman%2C+R+G%3BChen%2C+G%3BPoyer%2C+J+L%3BJanzen%2C+E+G%3BMason%2C+R+P&rft.aulast=Connor&rft.aufirst=H&rft.date=1998-06-01&rft.volume=24&rft.issue=9&rft.spage=1364&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carbon tetrachloride; Microsomes; Free radicals ER - TY - JOUR T1 - Effect of ionic state of 2'-deoxyguanosine and solvent on its aralkylation by benzyl bromide AN - 17117961; 4423129 AB - To extend studies of the aralkylation of nucleic acid components under a variety of solvent conditions, we determined product distributions from the reactions of benzyl bromide with 2'-deoxyguanosine and the anion of 2'-deoxyguanosine in 2,2,2-trifluoroethanol (TFE) and compared these distributions with those from the reaction of the anion with benzyl bromide in N,N-dimethylacetamide (DMA). 7-Benzylguanine was the only benzylated product detected in the reaction with the neutral nucleoside in TFE. In striking contrast, the reaction of the anion of 2'-deoxyguanosine with benzyl bromide in TFE produced N super(2)-benzyl-2'-deoxyguanosine in significant yield and with high selectivity. The reaction of the anion of 2'-deoxyguanosine with benzyl bromide in DMA produced products derived only from reaction at the 1- and/or 7-position of the nucleoside. The weakly nucleophilic but protic polar solvent TFE and the iminolate tautomeric form of the 2'-deoxyguanosine anion appear to be essential for benzylation at the exocyclic N super(2)-position. JF - Chemical Research in Toxicology AU - Moon, Ki-Young AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD 21702, USA Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 696 EP - 702 VL - 11 IS - 6 SN - 0893-228X, 0893-228X KW - Dimethylacetamide KW - aralkylation KW - benzyl bromide KW - benzylation KW - deoxyguanosine KW - Toxicology Abstracts KW - Solvents KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17117961?accountid=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=Effect+of+ionic+state+of+2%27-deoxyguanosine+and+solvent+on+its+aralkylation+by+benzyl+bromide&rft.au=Moon%2C+Ki-Young%3BMoschel%2C+R+C&rft.aulast=Moon&rft.aufirst=Ki-Young&rft.date=1998-06-01&rft.volume=11&rft.issue=6&rft.spage=696&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 - Solvents ER - TY - JOUR T1 - Design of delta -opioid peptide antagonists for emerging drug applications AN - 16559769; 4400181 AB - The need for delta -receptor-selective opioid antagonists has led to their development based on structure-activity relationships of delta - and mu -opioid agonists. The unusual amino acid 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), found in a series of H-Tyr-Tic-Phe-(Phe)-OH peptides, is an essential feature of derivatives discussed in this article. Elimination of Phe yields the H-Tyr-Tic-OH dipeptide antagonists, while substitution of Tyr by 2',6'-dimethyl-L-tyrosine (Dmt) gives H-Dmt-Tic-OH and numerous potent, high-affinity and ultraselective delta -opioid antagonists. This article reviews the emergence of derivatives based on the Tyr-Tic and Dmt-Tic pharmacophores as lead structures, and discusses potential clinical and therapeutic applications. JF - Drug Discovery Today AU - Lazarus, L H AU - Bryant, S D AU - Cooper, P S AU - Guerrini, R AU - Balboni, G AU - Salvadori, S AD - Peptide Neurochemistry, LCBRA, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, lazarus@niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 284 EP - 294 VL - 3 IS - 6 SN - 1359-6446, 1359-6446 KW - opioid antagonists KW - opioids (type delta ) KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Therapeutic applications KW - Drug development KW - Antagonists KW - Reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16559769?accountid=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=Drug+Discovery+Today&rft.atitle=Design+of+delta+-opioid+peptide+antagonists+for+emerging+drug+applications&rft.au=Lazarus%2C+L+H%3BBryant%2C+S+D%3BCooper%2C+P+S%3BGuerrini%2C+R%3BBalboni%2C+G%3BSalvadori%2C+S&rft.aulast=Lazarus&rft.aufirst=L&rft.date=1998-06-01&rft.volume=3&rft.issue=6&rft.spage=284&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&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 - Antagonists; Reviews; Drug development; Therapeutic applications ER - TY - JOUR T1 - Parental occupational exposures and risk of childhood cancer AN - 16555607; 4392663 AB - Occupational exposures of parents might be related to cancer in their offspring. Forty-eight published studies on this topic have reported relative risks for over 1000 specific occupation/cancer combinations. Virtually all of the studies employed the case-control design. Occupations and exposures of fathers were investigated much more frequently than those of the mother. Information about parental occupations was derived through interviews or from birth certificates and other administrative records. Specific exposures were typically estimated by industrial hygienists or were self-reported. The studies have several limitations related to the quality of the exposure assessment, small numbers of exposed cases, multiple comparisons, and possible bias toward the reporting of positive results. Despite these limitations, they provide evidence that certain parental exposures may be harmful to children and deserve further study. The strongest evidence is for childhood leukemia and paternal exposure to solvents, paints, and employment in motor vehicle-related occupations; and childhood nervous system cancers and paternal exposure to paints. To more clearly evaluate the importance of these and other exposures in future investigations, we need improvements in four areas: a) more careful attention must be paid to maternal exposures; b) studies should employ more sophisticated exposure assessment techniques; c) careful attention must be paid to the postulated mechanism, timing, and route of exposure; and d) if postnatal exposures are evaluated, studies should provide evidence that the exposure is actually transferred from the workplace to the child's environment. JF - Environmental Health Perspectives AU - Colt, J S AU - Blair, A AD - National Cancer Institute, 6130 Executive Boulevard, Room 418, Rockville, MD 20892, USA, coltj@epndce.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 909 EP - 925 VL - 106 SN - 0091-6765, 0091-6765 KW - man KW - parent-offspring interactions KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Solvents KW - Children KW - Cancer KW - Leukemia KW - Parent-offspring interactions KW - Occupational exposure KW - Paints KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16555607?accountid=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=Parental+occupational+exposures+and+risk+of+childhood+cancer&rft.au=Colt%2C+J+S%3BBlair%2C+A&rft.aulast=Colt&rft.aufirst=J&rft.date=1998-06-01&rft.volume=106&rft.issue=&rft.spage=909&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 - Children; Leukemia; Occupational exposure; Solvents; Cancer; Paints; Parent-offspring interactions ER - TY - JOUR T1 - Genes and the environment: Their impact on children's health AN - 16555310; 4392651 AB - Because the human population is biologically diverse and genetically heterogeneous, it is not surprising that differences in susceptibility to disease among individuals with or without exposure to environmental agents exist. Individuals vary greatly in their susceptibility to disease. This is true of adults and children. The etiologies of many diseases of childhood are due to a combination of factors, including genetic susceptibility and environmental exposures during vulnerable periods of development. Genes regulate cellular growth and development, DNA replication and repair, the metabolism of endogenous agents in the body, and the metabolism and excretion of exogenous agents that the body comes in contact with in the environment. This regulation varies over the life span, contributing to the cellular consequences of the environmental exposures. This paper summarizes the contributions of genetics in understanding the etiology of environmentally induced diseases in children. The use of biomarkers of genetic susceptibility in the study of these diseases will be discussed. Future research needs for expanding our knowledge of the interactions between genetic and environmental components of childhood diseases will be presented. JF - Environmental Health Perspectives AU - Suk, WA AU - Collman, G W AD - Office of Program Development, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, MD EC-27, P.O. Box 12233, Research Triangle Park, NC 27709, USA, suk@niehs.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 817 EP - 820 VL - 106 SN - 0091-6765, 0091-6765 KW - man KW - Toxicology Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Genetic factors KW - Environmental health KW - Genetics KW - Environmental effects KW - Children KW - X 24240:Miscellaneous 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/16555310?accountid=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=Genes+and+the+environment%3A+Their+impact+on+children%27s+health&rft.au=Suk%2C+WA%3BCollman%2C+G+W&rft.aulast=Suk&rft.aufirst=WA&rft.date=1998-06-01&rft.volume=106&rft.issue=&rft.spage=817&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 - Environmental effects; Environmental health; Children; Genetic factors; Genetics ER - TY - JOUR T1 - Transient transfection of primary T helper cells by particle-mediated gene transfer AN - 16535265; 4388437 AB - The study of the molecular basis of normal CD4+ T cell function, such as the control of commitment to the TH sub(1) or TH sub(2) phenotypes has been difficult due to the resistance of these cells to transfection by conventional methods. We used antibodies specific to T cell surface molecules to immobilize these cells and optimized conditions for transiently transfecting them by means of particle-mediated gene transfer. Using this technique, a construct encompassing -577 to +1 of the IL-4 promoter allowed transcription of a luciferase reporter gene in recently-differentiated TH2 cells stimulated by anti-CD3, consistent with regulation of endogenous IL-4 gene expression. JF - Journal of Immunological Methods AU - Huang, H AU - Pannetier, C AU - Hu-Li, J AU - Paul, W E AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive-MSC 1892, Bethesda, MD 20892-1892, USA Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 173 EP - 177 PB - Elsevier Science B.V. VL - 215 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16535265?accountid=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=Transient+transfection+of+primary+T+helper+cells+by+particle-mediated+gene+transfer&rft.au=Huang%2C+H%3BPannetier%2C+C%3BHu-Li%2C+J%3BPaul%2C+W+E&rft.aulast=Huang&rft.aufirst=H&rft.date=1998-06-01&rft.volume=215&rft.issue=1-2&rft.spage=173&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 ER - TY - JOUR T1 - Variables affecting results of sodium chloride tolerance test for identification of rapidly growing mycobacteria AN - 16525737; 4401585 AB - The sodium chloride tolerance test is often used in the identification of rapidly growing mycobacteria, particularly for distinguishing between Mycobacterium abscessus and Mycobacterium chelonae. This test, however, is frequently unreliable for the identification of some species. In this study we examined the following variables: medium manufacturer, inoculum concentration, and atmosphere and temperature of incubation. Results show that reliability is improved if the test and control slants are inoculated with an organism suspension spectrophotometrically equal to a 1 McFarland standard. Slants should be incubated at 35 degree C in ambient air and checked weekly for 4 weeks. Growth on control slants should be critically evaluated to determine the adequacy of the inoculum; colonies should number greater than 50. Salt-containing media should be examined carefully to detect pinpoint or tiny colonies, and colonies should number greater than 50 for a positive reaction. Concurrent use of a citrate slant may be helpful for distinguishing between M. abscessus and M. chelonae. Molecular methodologies are probably the most reliable means for the identification of rapidly growing mycobacteria and should be used, if possible, when unequivocal species identification is of particular importance. JF - Journal of Clinical Microbiology AU - Conville, P S AU - Witebsky, F G AD - Microbiology Service, Clinical Pathology Department, National Institutes of Health, 10 Center Dr. MSC 1508, Bethesda, MD 20892- 1508, USA, pconville@nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 1555 EP - 1559 VL - 36 IS - 6 SN - 0095-1137, 0095-1137 KW - Salt tolerance test KW - Sodium chloride KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - A 01116:Bacteria KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16525737?accountid=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=Variables+affecting+results+of+sodium+chloride+tolerance+test+for+identification+of+rapidly+growing+mycobacteria&rft.au=Conville%2C+P+S%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=1555&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 ER - TY - JOUR T1 - Rapid extraction of genomic DNA from medically important yeasts and filamentous fungi by high-speed cell disruption AN - 16497261; 4401591 AB - Current methods of DNA extraction from different fungal pathogens are often time-consuming and require the use of toxic chemicals. DNA isolation from some fungal organisms is difficult due to cell walls or capsules that are not readily susceptible to lysis. We therefore investigated a new and rapid DNA isolation method using high-speed cell disruption (HSCD) incorporating chaotropic reagents and lysing matrices in comparison to standard phenol-chloroform (PC) extraction protocols for isolation of DNA from three medically important yeasts (Candida albicans, Cryptococcus neoformans, and Trichosporon beigelii) and two filamentous fungi (Aspergillus fumigatus and Fusarium solani). Additional extractions by HSCD were performed on Saccharomyces cerevisiae, Pseudallescheria boydii, and Rhizopus arrhizus. Two different inocula (10 super(8) and 10 super(7) CFU) were compared for optimization of obtained yields. The entire extraction procedure was performed on as many as 12 samples within 1 h compared to 6 h for PC extraction. In comparison to the PC procedure, HSCD DNA extraction demonstrated significantly greater yields for 10 super(8) CFU of C. albicans, T. beigelii, A. fumigatus, and F. solani (P less than or equal to 0.005), 10 super(7) CFU of C. neoformans (P less than or equal to 0.05), and 10 super(7) CFU of A. fumigatus (P less than or equal to 0.01). Yields were within the same range for 10 super(8) CFU of C. neoformans and 10 super(7) CFU of C. albicans for both HSCD extraction and PC extraction. For 10 super(7) CFU of T. beigelii, PC extraction resulted in a greater yield than did HSCD (P less than or equal to 0.05). Yields obtained from 10 super(8) and 10 super(7) CFU were significantly greater for filamentous fungi than for yeasts by the HSCD extraction procedure (P < 0.0001). By the PC extraction procedure, differences were not significant. For all eight organisms, the rapid extraction procedure resulted in good yield, integrity, and quality of DNA as demonstrated by restriction fragment length polymorphism, PCR, and random amplified polymorphic DNA. We conclude that mechanical disruption of fungal cells by HSCD is a safe, rapid, and efficient procedure for extracting genomic DNA from medically important yeasts and especially from filamentous fungi. JF - Journal of Clinical Microbiology AU - Muller, F-MC AU - Werner, KE AU - Kasai, M AU - Francesconi, A AU - Chanock, S J AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Building 10, Room 13N240, Bethesda, MD 20892, USA, walsht@pbmac.nci.nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 1625 EP - 1629 VL - 36 IS - 6 SN - 0095-1137, 0095-1137 KW - DNA extraction KW - High-speed cell disruption KW - filamentous fungi KW - high-speed cell disruption KW - yeasts KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - K 03015:Fungi KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16497261?accountid=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+Clinical+Microbiology&rft.atitle=Rapid+extraction+of+genomic+DNA+from+medically+important+yeasts+and+filamentous+fungi+by+high-speed+cell+disruption&rft.au=Muller%2C+F-MC%3BWerner%2C+KE%3BKasai%2C+M%3BFrancesconi%2C+A%3BChanock%2C+S+J%3BWalsh%2C+T+J&rft.aulast=Muller&rft.aufirst=F-MC&rft.date=1998-06-01&rft.volume=36&rft.issue=6&rft.spage=1625&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 ER - TY - JOUR T1 - Enhanced levels of Staphylococcus aureus stress protein GroEL and DnaK homologs early in infection of human epithelial cells AN - 16480747; 4322935 AB - Antibodies to Staphylococcus aureus heat shock proteins (Hsps) are present in the sera of patients with S. aureus endocarditis. Although these proteins are immunogenic, their role in infection has not been established. We developed a cell culture system as a model to examine the potential involvement of staphylococcal Hsps in the initial events of infection. This study supports a model in which a clinical endocarditis isolate responds to host cell signals by selectively regulating the synthesis of numerous proteins, including the stress proteins Hsp60 (GroEL homolog) and Hsp70 (DnaK homolog) and a unique 58-kDa protein. JF - Infection and Immunity AU - Qoronfleh, M W AU - Bortner, CA AU - Schwartzberg, P AU - Wilkinson, B J AD - SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Structural Biochemistry Program (SBP), Bldg. 320, P.O. Box B, Frederick, MD 21702-1201, USA, ooronfle@ncifcrf.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 3024 EP - 3027 VL - 66 IS - 6 SN - 0019-9567, 0019-9567 KW - DnaK protein KW - GroEL protein KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16480747?accountid=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=Enhanced+levels+of+Staphylococcus+aureus+stress+protein+GroEL+and+DnaK+homologs+early+in+infection+of+human+epithelial+cells&rft.au=Qoronfleh%2C+M+W%3BBortner%2C+CA%3BSchwartzberg%2C+P%3BWilkinson%2C+B+J&rft.aulast=Qoronfleh&rft.aufirst=M&rft.date=1998-06-01&rft.volume=66&rft.issue=6&rft.spage=3024&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 ER - TY - JOUR T1 - Acid stress, anaerobiosis and gadCB: lessons from Lactococcus lactis and Escherichia coli AN - 16474193; 4342450 AB - Bacteria employ multiple strategies for maintaining neutral cytoplasmic pH (pH sub(i)) despite an acidic external environment. Although the mechanisms for maintaining pH homeostasis are not fully understood, the genetic basis of these systems has been the subject of intense investigation in the past few years. JF - Trends in Microbiology AU - Small, PLC AU - Waterman AD - NIH, National Institutes of Allergy and Infectious Disease, Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, MT 59840, USA, pam_small@nih.gov Y1 - 1998/06// PY - 1998 DA - Jun 1998 SP - 214 EP - 216 VL - 6 IS - 6 SN - 0966-842X, 0966-842X KW - gadCB gene KW - Microbiology Abstracts B: Bacteriology KW - J 02732:Other cell constituents and metabolites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16474193?accountid=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=Trends+in+Microbiology&rft.atitle=Acid+stress%2C+anaerobiosis+and+gadCB%3A+lessons+from+Lactococcus+lactis+and+Escherichia+coli&rft.au=Small%2C+PLC%3BWaterman&rft.aulast=Small&rft.aufirst=PLC&rft.date=1998-06-01&rft.volume=6&rft.issue=6&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&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 - Syntaxin and 25-kDa synaptosomal-associated protein: Differential effects of botulinum neurotoxins C1 and A on neuronal survival AN - 16429620; 4328810 AB - The Clostridium botulinum neurotoxins (BoNTs) A and C1 cleave specific proteins required for neuroexocytosis. We demonstrated that, in intact neurons, BoNT A cleaves 25-kDa synaptosomal-associated protein (SNAP-25), and BoNT C1 cleaves both syntaxin and SNAP-25. Here, we compare the actions of BoNT A and BoNT C1 on mature and developing mouse spinal cord neurons in cell culture and demonstrate that BoNT C1 is severely neurotoxic. In mature cultures, synaptic terminals become enlarged shortly after BoNT C1 exposure, and, subsequently, axons, dendrites, and cell bodies degenerate. Electron microscopy confirms that early degenerative changes occur in synaptic terminals when the somatic cytoplasm appears normal. In newly plated cultures, few neurons survive exposure to BoNT C1. Whereas both BoNT A and BoNT C1 cleave SNAP-25, BoNT A has no adverse effect on neurite outgrowth, synaptogenesis, or neuron survival. This cytotoxicity is unique to BoNT C1, is specific to neurons, and is initiated at the synaptic terminal, suggesting either a novel role for syntaxin or additional actions of BoNT C1. The neurodegeneration induced by BoNT C1 may be significant in terms of its efficacy for the clinical treatment of dystonia and spasticity. JF - Journal of Neuroscience Research AU - Williamson, L C AU - Neale, E A AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Building 49, Room 5A38, Bethesda, MD 20892-4480, USA, eneale@codon.nih.gov Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 569 EP - 583 VL - 52 IS - 5 SN - 0360-4012, 0360-4012 KW - Clostridium botulinum KW - SNAP-25 protein KW - cell culture KW - mice KW - syntaxin KW - CSA Neurosciences Abstracts; Microbiology Abstracts B: Bacteriology; Toxicology Abstracts 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/16429620?accountid=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+Neuroscience+Research&rft.atitle=Syntaxin+and+25-kDa+synaptosomal-associated+protein%3A+Differential+effects+of+botulinum+neurotoxins+C1+and+A+on+neuronal+survival&rft.au=Williamson%2C+L+C%3BNeale%2C+E+A&rft.aulast=Williamson&rft.aufirst=L&rft.date=1998-06-01&rft.volume=52&rft.issue=5&rft.spage=569&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - IL-12 Promotes Drug-Induced Clearance of Mycobacterium avium Infection in Mice AN - 16427894; 4321873 AB - The intracellular pathogen Mycobacterium avium is a major cause of opportunistic infection in AIDS patients and is difficult to manage using conventional chemotherapeutic approaches. In the current study, we describe a strategy for the treatment of M. avium in T cell-deficient hosts based on the simultaneous administration of antibiotics and the immunomodulatory cytokine IL-12. In contrast to SCID mice, which were partially resistant, animals lacking a functional IL-12 p40 gene were found to be highly susceptible to M. avium infection, suggesting that the cytokine can control bacterial growth even in immunodeficient mice. Indeed, rIL-12 that was injected into infected SCID mice in high doses caused small but significant reductions in splenic pathogen loads. Moreover, a lower dose of IL-12, when combined with the antimycobacterial drugs clarithromycin or rifabutin, induced a decrease in bacterial numbers that was significantly greater than that resulting from the administration of the cytokine or drug alone. A similar synergistic effect of IL-12 and antibiotics was seen when immunocompetent mice were treated with the same regimen. The activity of IL-12 in these experiments was shown to be dependent upon the induction of endogenous IFN- gamma . Nevertheless, IFN- gamma itself, even when given at a higher dose than IL-12, failed to significantly enhance antibiotic clearance of bacteria. Together these findings suggest that IL-12 may be a particularly potent adjunct for chemotherapy of M. avium infection in immunocompromised individuals and may result in more effective control of the pathogen without the need for increased drug dosage. JF - Journal of Immunology AU - Doherty, T M AU - Sher, A AD - Laboratory of Parasitic Diseases, Building 4, Room B1-06, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/06/01/ PY - 1998 DA - 1998 Jun 01 SP - 5428 EP - 5435 VL - 160 IS - 11 SN - 0022-1767, 0022-1767 KW - Mycobacterium avium KW - mice KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - F 06840:Immunotherapy of immune diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16427894?accountid=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=IL-12+Promotes+Drug-Induced+Clearance+of+Mycobacterium+avium+Infection+in+Mice&rft.au=Doherty%2C+T+M%3BSher%2C+A&rft.aulast=Doherty&rft.aufirst=T&rft.date=1998-06-01&rft.volume=160&rft.issue=11&rft.spage=5428&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 ER - TY - JOUR T1 - In vivo correlates of central serotonin function after high-dose fenfluramine administration. AN - 80015192; 9668672 AB - High doses of fenfluramine (FEN) are known to deplete central serotonin (5-HT) in animals, but functional impairments associated with such 5-HT depletion have been difficult to identify. In the present work, we examined neuroendocrine responsiveness in rats exposed to repeated high-dose FEN treatment. Male rats fitted with indwelling catheters received FEN (20 mg/kg, subcutaneously, twice a day) or saline for 4 days. At 1 and 2 weeks after treatment, rats were challenged with intravenous FEN (1.5 & 3 mg/kg) or saline. Repeated blood samples were drawn, and plasma was assayed for prolactin and corticosterone by radioimmunoassay. Acute FEN challenge caused dose-dependent elevations of plasma prolactin and corticosterone in all rats. However, the FEN-induced hormone responses were significantly blunted (p 50%) postmortem 5-HT levels in the mediobasal hypothalamus, basolateral amygdala, and hippocampus, while the lateral hypothalamus was unaffected. These data suggest that high-dose FEN causes alterations in central 5-HT systems involved with pituitary hormone secretion. The relevance of the present data to the clinical use of FEN is unclear. Because the neuroendocrine challenge paradigm is able to identify functional 5-HT deficits in rats, we propose that similar experiments should be performed in humans. Neuroendocrine challenge tests represent a reliable method to test the existence of FEN-induced neurotoxicity in human patients undergoing long-term FEN treatment. JF - Annals of the New York Academy of Sciences AU - Baumann, M H AU - Ayestas, M A AU - Rothman, R B AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. mbaumann@irp.nida.nih.gov Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 138 EP - 152 VL - 844 SN - 0077-8923, 0077-8923 KW - Serotonin Agents KW - 0 KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Prolactin KW - 9002-62-4 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Prolactin -- blood KW - Dose-Response Relationship, Drug KW - Corticosterone -- blood KW - Hydroxyindoleacetic Acid -- metabolism KW - Time Factors KW - Male KW - Fenfluramine -- administration & dosage KW - Serotonin Agents -- pharmacology KW - Brain -- drug effects KW - Brain -- metabolism KW - Fenfluramine -- pharmacology KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80015192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+correlates+of+central+serotonin+function+after+high-dose+fenfluramine+administration.&rft.au=Baumann%2C+M+H%3BAyestas%2C+M+A%3BRothman%2C+R+B&rft.aulast=Baumann&rft.aufirst=M&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=138&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phentermine and fenfluramine. Preclinical studies in animal models of cocaine addiction. AN - 80011880; 9668665 AB - Combined dopamine (DA) and 5-hydroxytryptamine (5-HT) releases such as phentermine (PHEN) and fenfluramine (FEN) are reported, in open label studies, to reduce craving for alcohol and cocaine and to prevent relapse. The objective of the studies reported here was to assess the actions of these agents alone and in combination in various animal models of drug addiction. Study 1. In vivo microdialysis experiments demonstrate that these agents preferentially release mesolimbic DA (PHEN) and 5-HT (FEN). Patients who relapse and use cocaine while taking these medications report diminished cocaine-like subjective effects. Microdialysis experiments were performed in awake rats, and dialysate samples were analyzed for DA and 5-HT. PHEN (1 mg/kg, intravenously (i.v.)) elevated DA (2-3-fold) for over 1.5 hr. Administration of cocaine (3 mg/kg, i.v.) increased DA 6-fold in saline-treated rats, but only 3-fold in PHEN-treated rats. PHEN did not reduce cocaine-induced increases in 5-HT. Study 2. These agents were assessed in a mouse model of cocaine-conditioned motoric activity (CCMA). Pretreatment with non-activating doses of PHEN (4.6 mg/kg, intraperitoneally (i.p.)) enhanced CCMA, whereas non-depressing doses of FEN (0.1 mg/kg, i.p.) did not alter CCMA or the PHEN-induced increase in CCMA. In contrast, sub-effective doses of FEN reduced CCMA stereotypy-like locomotion, whereas sub-effective doses of PHEN were without effect. PHEN reversed the FEN-induced increase in CCMA stereotypy-like locomotion. Study 3. PHEN and FEN were assessed in the conditional place preference model. FEN produced marked aversions for an environment previously associated with its administration and the minimum dose producing this effect was 3.0 mg/kg. In contrast, administration of PHEN, amphetamine (1.0-3.0 mg/kg) or morphine (3.0-5.0 mg/kg) produced dose-related preferences for the drug-paired place. However, the magnitude of the response to PHEN was less than that produced by the other prototypic drugs of abuse. In rats that received FEN (0.3 or 3.0 mg/kg) in combination with PHEN (3.0 mg/kg), the conditioned rewarding effects of PHEN were abolished. These data demonstrate that the rewarding effects of PHEN can be conditioned to stimuli previously associated with its administration. However, the conditioned response to this agent is less than that produced by prototypic drugs of abuse. The finding that PHEN-induced place preferences were attenuated by doses of FEN demonstrates that the combination of FEN/PHEN is devoid of motivational effects. The preclinical data obtained with PHEN/FEN in various models of drug provide a strong rationale for pursuing controlled clinical trials in humans with agents that act via a similar mechanism of action. JF - Annals of the New York Academy of Sciences AU - Rothman, R B AU - Elmer, G I AU - Shippenberg, T S AU - Rea, W AU - Baumann, M H AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. RRothman@iep.nida.nih.gov Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 59 EP - 74 VL - 844 SN - 0077-8923, 0077-8923 KW - Dopamine Agents KW - 0 KW - Drug Combinations KW - Serotonin Agents KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Phentermine KW - C045TQL4WP KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Limbic System -- metabolism KW - Dopamine -- metabolism KW - Mice KW - Motor Activity -- physiology KW - Cocaine -- administration & dosage KW - Rats KW - Microdialysis KW - Rats, Sprague-Dawley KW - Self Administration KW - Conditioning (Psychology) -- physiology KW - Serotonin -- metabolism KW - Cocaine -- pharmacology KW - Drug Evaluation, Preclinical KW - Male KW - Dopamine Agents -- therapeutic use KW - Fenfluramine -- therapeutic use KW - Cocaine-Related Disorders -- drug therapy KW - Serotonin Agents -- therapeutic use KW - Phentermine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phentermine+and+fenfluramine.+Preclinical+studies+in+animal+models+of+cocaine+addiction.&rft.au=Rothman%2C+R+B%3BElmer%2C+G+I%3BShippenberg%2C+T+S%3BRea%2C+W%3BBaumann%2C+M+H&rft.aulast=Rothman&rft.aufirst=R&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=59&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice. AN - 80011459; 9668667 AB - The present study was conducted to investigate the effects of methamphetamine (METH)-induced toxicity on brain cortical and striatal antioxidant defense systems. Because METH-induced toxicity is attenuated in copper/zinc-superoxide dismutase transgenic (Cu/Zn-SOD-Tg) mice, we sought to determine if METH had differential effect on antioxidant enzymes on these mice in comparison to non-Tg mice. METH (4 x 1) mg/kg) induced a significant decrease in Cu/Zn-SOD activity in the cortical region without altering striatal enzymatic activity in non-Tg mice; whereas homozygous SOD-Tg mice showed a significant increase in the striatum. In addition, METH caused decrease in catalase (CAT) activity in the striatum of non-Tg mice and significant increase in the cortex of homozygous SOD-Tg mice. METH also induced decreases in glutathione peroxidase (GSH-Px) in both cortical and striatal regions of non-Tg mice and in the striatum of heterozygous SOD-Tg mice. Lipid peroxidation was increased in both cortices and striata of non-Tg and heterozygous SOD-Tg, mice, whereas the homozygous SOD-Tg mice were not affected. These results are discussed in terms of their substantiation of a role for oxygen-based radicals in METH-induced toxicity in rodents. JF - Annals of the New York Academy of Sciences AU - Jayanthi, S AU - Ladenheim, B AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute of Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA. Y1 - 1998/05/30/ PY - 1998 DA - 1998 May 30 SP - 92 EP - 102 VL - 844 SN - 0077-8923, 0077-8923 KW - Dopamine Agents KW - 0 KW - Lipid Peroxides KW - Methamphetamine KW - 44RAL3456C KW - Malondialdehyde KW - 4Y8F71G49Q KW - Oxidoreductases KW - EC 1.- KW - Catalase KW - EC 1.11.1.6 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Malondialdehyde -- metabolism KW - Catalase -- metabolism KW - Animals KW - Homozygote KW - Glutathione Peroxidase -- metabolism KW - Frontal Lobe -- drug effects KW - Heterozygote KW - Glutathione -- metabolism KW - Corpus Striatum -- metabolism KW - Frontal Lobe -- metabolism KW - Corpus Striatum -- drug effects KW - Mice KW - Male KW - Dopamine Agents -- poisoning KW - Oxidoreductases -- metabolism KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- genetics KW - Lipid Peroxides -- metabolism KW - Methamphetamine -- poisoning KW - Mice, Transgenic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80011459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methamphetamine-induced+changes+in+antioxidant+enzymes+and+lipid+peroxidation+in+copper%2Fzinc-superoxide+dismutase+transgenic+mice.&rft.au=Jayanthi%2C+S%3BLadenheim%2C+B%3BCadet%2C+J+L&rft.aulast=Jayanthi&rft.aufirst=S&rft.date=1998-05-30&rft.volume=844&rft.issue=&rft.spage=92&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 - 1998-08-13 N1 - Date created - 1998-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. AN - 79981176; 9652737 AB - AP-1 transactivation appears to be required for mouse JB6 cell neoplastic transformation induced by the tumor promoter TPA or epidermal growth factor (EGF). Exposure to AP-1 transrepressing retinoids and glucocorticoids and expression of a dominant negative c-jun (TAM67) blocked tumor promoter-induced AP-1 transactivation and neoplastic transformation. The aim of the present study was to extend the inquiry of the role of AP-1 and other transcription factors to human neoplastic progression. Expression of human papillomavirus (HPV) 16 or 18 E6 and E7 immortalizes human keratinocytes and inhibits serum/calcium-stimulated differentiation. Further transformation by v-fos co-expression renders these keratinocytes tumorigenic in nude mice. We have analysed two series of E6/E7 immortalized human keratinocyte cell lines that show progressing phenotypes ranging from differentiation sensitive to anchorage-independent to tumorigenic in nude mice. We analysed the activities of AP-1 and NF-kappaB which may 'cross-talk'. Both DNA binding and transactivation of AP-1 and NF-kappaB transcription factors showed elevation in the anchorage-independent (16RH) and tumorigenic (18 v-fos) keratinocyte lines compared to the less progressed but immortalized cell lines. HPV E7 was expressed at a constant level shown by quantitative RT-PCR in both the more and the less progressed lines, indicating that E7 is not the factor limiting this progression. Blocked shift/supershift analysis indicates that Fos family member proteins especially Fra-1 and Fra-2 are related to progression and no changes found in the Jun family member proteins although they are present in the AP-1/DNA binding complex. When a dominant negative mutant c-jun driven by a human keratin 14 promoter was co-transfected with AP-1 or NF-kappaB reporters, both AP-1 and NF-kappaB activities were suppressed in the more progressed cell lines 16RH and 18 v-fos but not in the less progressed 16RL or 18 cell lines. Overexpression of the same dominant negative c-jun did not inhibit p53 dependent reporter transactivation, indicating the specificity of inhibition of AP-1 and NF-kappaB transactivation in the HPV-immortalized cells. Stable transfectants of this mutant c-jun in the two more progressed cell lines 16RH and 18 v-fos showed reduced AP-1 and NF-kappaB activation and reduced anchorage-independent growth. Together, these results indicate that activation of AP-1, NF-kappaB or both may contribute to neoplastic progression in HPV immortalized human keratinocytes and that specific targeting of the elevated levels seen in benign or malignant tumors might be effective for prevention or treatment of human cancer. JF - Oncogene AU - Li, J J AU - Rhim, J S AU - Schlegel, R AU - Vousden, K H AU - Colburn, N H AD - Laboratory of Biochemical Physiology, National Cancer Institute, FCRDC, Frederick, Maryland 21702-1201, USA. Y1 - 1998/05/28/ PY - 1998 DA - 1998 May 28 SP - 2711 EP - 2721 VL - 16 IS - 21 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - E6 protein, Human papillomavirus type 16 KW - E6 protein, Human papillomavirus type 18 KW - E7 protein, Human papillomavirus type 18 KW - FOSL2 protein, human KW - Fos-Related Antigen-2 KW - KRT14 protein, human KW - Keratin-14 KW - Krt1-14 protein, mouse KW - NF-kappa B KW - Oncogene Proteins v-fos KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - fos-related antigen 1 KW - oncogene protein E7, Human papillomavirus type 16 KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Keratins -- genetics KW - Oncogene Proteins v-fos -- metabolism KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Transcription Factors -- metabolism KW - Humans KW - Mutagenesis KW - Phenotype KW - Promoter Regions, Genetic KW - Transfection KW - Oncogene Proteins, Viral -- genetics KW - Cell Line KW - Cell Transformation, Viral KW - Cell Division KW - DNA-Binding Proteins -- metabolism KW - Proto-Oncogene Proteins c-jun -- genetics KW - Keratinocytes -- cytology KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Papillomaviridae -- genetics KW - Keratinocytes -- metabolism KW - Transcription Factor AP-1 -- genetics KW - Transcriptional Activation KW - NF-kappa B -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79981176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+dominant+negative+Jun+inhibits+elevated+AP-1+and+NF-kappaB+transactivation+and+suppresses+anchorage+independent+growth+of+HPV+immortalized+human+keratinocytes.&rft.au=Li%2C+J+J%3BRhim%2C+J+S%3BSchlegel%2C+R%3BVousden%2C+K+H%3BColburn%2C+N+H&rft.aulast=Li&rft.aufirst=J&rft.date=1998-05-28&rft.volume=16&rft.issue=21&rft.spage=2711&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-28 N1 - Date created - 1998-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin-like growth factor in HIV-infected patients. AN - 79946227; 9631143 AB - To study the immunologic effects of recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the combination, in patients with moderately advanced HIV infection. Randomized but not blinded trial. Government medical research center. Twenty-four HIV-infected patients with CD4 cell counts of 100-400 x 10(6)/l who were receiving nucleoside antiretroviral therapy. Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12 weeks. Immunologic parameters, including T-cell subsets and assays of in vitro interleukin (IL)-2 production in response to antigens and mitogens, and safety profile. Plasma IGF-1 levels were low or low-normal prior to treatment and increased with all three therapies. There were no significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer cell function, immunoglobulin levels, or in vitro IL-2 production in response to mitogen or alloantigens. However, there was an upward trend (and for p18IIIB a statistically significant increase) in the in vitro IL-2 production in response to each of five HIV envelope peptides. Potential toxic effects included fatigue, arthralgia, edema, myalgia, and headache. Patients also were noted to have weight gain averaging 4 kg early in the course of treatment. These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection. JF - AIDS (London, England) AU - Nguyen, B Y AU - Clerici, M AU - Venzon, D J AU - Bauza, S AU - Murphy, W J AU - Longo, D L AU - Baseler, M AU - Gesundheit, N AU - Broder, S AU - Shearer, G AU - Yarchoan, R AD - HIV and AIDS Malignancy Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda 20892-1906, USA. Y1 - 1998/05/28/ PY - 1998 DA - 1998 May 28 SP - 895 EP - 904 VL - 12 IS - 8 SN - 0269-9370, 0269-9370 KW - HIV Core Protein p24 KW - 0 KW - Immunoglobulins KW - Interleukin-2 KW - Recombinant Proteins KW - Human Growth Hormone KW - 12629-01-5 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - AIDS/HIV KW - HIV Core Protein p24 -- blood KW - Humans KW - Interleukin-2 -- biosynthesis KW - Pilot Projects KW - Leukocytes, Mononuclear -- immunology KW - CD4 Lymphocyte Count KW - Body Weight KW - T-Lymphocyte Subsets -- immunology KW - Adult KW - Immunoglobulins -- blood KW - Middle Aged KW - T-Lymphocytes, Helper-Inducer -- physiology KW - Recombinant Proteins -- therapeutic use KW - Female KW - Killer Cells, Natural -- immunology KW - Male KW - Human Growth Hormone -- therapeutic use KW - Insulin-Like Growth Factor I -- therapeutic use KW - Insulin-Like Growth Factor I -- adverse effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Insulin-Like Growth Factor I -- analysis KW - Human Growth Hormone -- adverse effects KW - Human Growth Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pilot+study+of+the+immunologic+effects+of+recombinant+human+growth+hormone+and+recombinant+insulin-like+growth+factor+in+HIV-infected+patients.&rft.au=Nguyen%2C+B+Y%3BClerici%2C+M%3BVenzon%2C+D+J%3BBauza%2C+S%3BMurphy%2C+W+J%3BLongo%2C+D+L%3BBaseler%2C+M%3BGesundheit%2C+N%3BBroder%2C+S%3BShearer%2C+G%3BYarchoan%2C+R&rft.aulast=Nguyen&rft.aufirst=B&rft.date=1998-05-28&rft.volume=12&rft.issue=8&rft.spage=895&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability. AN - 80042861; 9685581 AB - The genomes of all organisms contain an abundance of DNA repeats which are at-risk for causing genetic change. We have used the yeast Saccharomyces cerevisiae to investigate various repeat categories in order to understand their potential for causing genomic instability and the role of DNA metabolism factors. Several types of repeats can increase enormously the likelihood of genetic changes such as mutation or recombination when present either in wild type or mutants defective in replication or repair. Specifically, we have investigated inverted repeats, homonucleotide runs, and short distant repeats and the consequences of various DNA metabolism mutants. Because the at-risk motifs (ARMs) that we characterized are sensitive indicators, we have found that they are useful tools to reveal new genetic factors affecting genome stability as well as to distinguish subtle differences between alleles. Copyright 1998 Elsevier Science B.V. All rights reserved. JF - Mutation research AU - Gordenin, D A AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 101 Alexander Dr., P.O. Box 12233, Research Triangle Park, NC 27709, USA. gordenin@niehs.nih.gov Y1 - 1998/05/25/ PY - 1998 DA - 1998 May 25 SP - 45 EP - 58 VL - 400 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Mutagenesis -- drug effects KW - Animals KW - Humans KW - Genetic Diseases, Inborn -- genetics KW - Mutagenesis -- physiology KW - Mutagenesis -- genetics KW - Hazardous Substances -- toxicity KW - Saccharomyces cerevisiae -- genetics KW - Trinucleotide Repeat Expansion -- genetics KW - Trinucleotide Repeat Expansion -- drug effects KW - Genome, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80042861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Yeast+ARMs+%28DNA+at-risk+motifs%29+can+reveal+sources+of+genome+instability.&rft.au=Gordenin%2C+D+A%3BResnick%2C+M+A&rft.aulast=Gordenin&rft.aufirst=D&rft.date=1998-05-25&rft.volume=400&rft.issue=1-2&rft.spage=45&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 - 1998-09-23 N1 - Date created - 1998-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium suppresses apoptosis induced by chromium. AN - 79981104; 9652551 AB - Cadmium and chromium are both well-known human carcinogens, and common exposures to these metals are not infrequent. Recent studies have shown that hexavalent chromium induces apoptosis in Chinese hamster ovary (CHO) cells, suggesting an association of apoptosis with carcinogenesis. In contrast, induction of apoptosis by cadmium has been inconsistently observed. The present study was designed to determine if cadmium could induce apoptosis in CHO cells and if common exposure to cadmium and chromium would modify any apoptotic response. Apoptosis was evaluated by both agarose gel and in situ end-labeling methods. Apoptosis was observed at 48 h after treatment with 300 microM chromium (Na2CrO4) for 2 h. Cadmium alone at concentrations of 1, 5, or 10 microM (as CdCl2) did not induce apoptosis in these cells even at times up to 72 h after treatment. However, when CHO cells were concurrently exposed to cadmium and chromium, chromium-induced apoptosis was markedly suppressed in a cadmium concentration-related fashion. Cadmium did not consistently modify the cytotoxic effects of chromium, and significant increases in metallothionein were not induced by these metal treatments. These findings indicate that cadmium can block chromium-induced apoptosis. The suppression of apoptosis by cadmium may be a significant aspect of its carcinogenic mechanism. JF - Journal of toxicology and environmental health. Part A AU - Shimada, H AU - Shiao, Y H AU - Shibata, M AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis and Office of Laboratory Animal Science, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 159 EP - 168 VL - 54 IS - 2 SN - 1528-7394, 1528-7394 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Chromium KW - 0R0008Q3JB KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Animals KW - Drug Interactions KW - Cricetulus KW - In Vitro Techniques KW - Carcinogens -- toxicity KW - CHO Cells KW - Metallothionein -- metabolism KW - Cell Transformation, Neoplastic KW - Cricetinae KW - Cadmium -- pharmacology KW - Apoptosis -- drug effects KW - Chromium -- pharmacology KW - Cadmium -- toxicity KW - Chromium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79981104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cadmium+suppresses+apoptosis+induced+by+chromium.&rft.au=Shimada%2C+H%3BShiao%2C+Y+H%3BShibata%2C+M%3BWaalkes%2C+M+P&rft.aulast=Shimada&rft.aufirst=H&rft.date=1998-05-22&rft.volume=54&rft.issue=2&rft.spage=159&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 - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disposition of 2-methylimidazole in rats. AN - 79979736; 9652548 AB - 2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present in cigarette smoke and may form in food and forage as a result of ammoniation of simple sugars. 2-MI has been shown to be neurotoxic in several animal species and to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the rat, apparently leading to hyperplasia of thyroid follicular cells. In order to better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has been investigated following p.o. administration of either 5, 50, or 150 mg/kg to male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid and proportional to dose in the range studied. Approximately 90% of the total dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted in feces and as expired 14CO2. Excretion data were similar following i.v. administration of 5 mg/kg. Little or no enterohepatic circulation of compound occurred, since biliary excretion of 2-MI-derived 14C was negligible. Approximately 70% of the 14C excreted in urine, following all dosing, consisted of parent compound. High-performance liquid chromatography (HPLC) chromatograms for all treatment groups were similar, indicating that metabolism of 2-MI in rats was not affected by dose or route of administration. JF - Journal of toxicology and environmental health. Part A AU - Sanders, J M AU - Griffin, R J AU - Burka, L T AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 121 EP - 132 VL - 54 IS - 2 SN - 1528-7394, 1528-7394 KW - Imidazoles KW - 0 KW - 2-methylimidazole KW - T0049Z45LZ KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Metabolic Clearance Rate KW - Tissue Distribution KW - Male KW - Chromatography, High Pressure Liquid KW - Imidazoles -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79979736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disposition+of+2-methylimidazole+in+rats.&rft.au=Sanders%2C+J+M%3BGriffin%2C+R+J%3BBurka%2C+L+T%3BMatthews%2C+H+B&rft.aulast=Sanders&rft.aufirst=J&rft.date=1998-05-22&rft.volume=54&rft.issue=2&rft.spage=121&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 - 1998-07-15 N1 - Date created - 1998-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm. AN - 79885992; 9582337 AB - We have studied the intracellular localization of poly(A)-binding protein 1 (PABP1) by indirect immunofluorescence as well as by tagging with the green fluorescent protein (GFP) in living cells. We show that PABP1 is able to enter the nucleus. Accumulation of PABP1 in the nuclei was observed upon transcription inhibition, suggesting that active transcription is required for PABP1 export. The nuclear import of PABP1 is an energy-dependent process since PABP1 fails to enter the nucleus upon ATP depletion and at low temperature. Transfection of PABP1 or PABP1-GFP resulted in heterogeneity of intracellular distribution of the protein. In the low expressing cells, PABP1 was localized in the cytoplasm, whereas in the high expressors, we observed accumulation of the protein in the nucleus. Nuclear PABP1 observed either after overexpression or after transcription inhibition was found in speckles and colocalized with splicing factor SC35. The ability of PABP1 to shuttle between nucleus and cytoplasm was also shown by heterokaryon formation upon cell fusion. Deletion mutagenesis showed that the minimal part of PABP1 retaining the ability to shuttle consists of the first two RNA-binding domains. This mutant interacted with poly(A) RNA with high affinity and accumulated in the nucleus. Deletion mutants exhibiting reduced RNA binding affinity did not accumulate in the nucleus. PABP1 has been proposed to participate at various steps of mRNA utilization. Our results suggest involvement of PABP1 in nuclear events associated with the formation and transport of mRNP to the cytoplasm and identify a new trafficking pattern for RNA-binding proteins. JF - The Journal of biological chemistry AU - Afonina, E AU - Stauber, R AU - Pavlakis, G N AD - Human Retrovirus Section, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 13015 EP - 13021 VL - 273 IS - 21 SN - 0021-9258, 0021-9258 KW - Poly(A)-Binding Proteins KW - 0 KW - RNA-Binding Proteins KW - Index Medicus KW - Transfection KW - HeLa Cells KW - Humans KW - Biological Transport KW - Transcription, Genetic KW - RNA-Binding Proteins -- metabolism KW - Cytoplasm -- metabolism KW - Cell Nucleus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79885992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+poly%28A%29-binding+protein+1+shuttles+between+the+nucleus+and+the+cytoplasm.&rft.au=Afonina%2C+E%3BStauber%2C+R%3BPavlakis%2C+G+N&rft.aulast=Afonina&rft.aufirst=E&rft.date=1998-05-22&rft.volume=273&rft.issue=21&rft.spage=13015&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Highly mutagenic bypass synthesis by T7 RNA polymerase of site-specific benzo[a]pyrene diol epoxide-adducted template DNA. AN - 79883997; 9582358 AB - We have previously developed an in vitro system that allows quantitative evaluation of the fidelity of transcription during synthesis on a natural template in the presence of all four nucleotides. Here, we have employed this system using a TAA ochre codon reversion assay to examine the fidelity of transcription by T7 RNA polymerase past an adenine residue adducted at the N6-position with (-)-anti-trans- or (+)-anti-trans-benzo[a]pyrene diol epoxide (BPDE). T7 RNAP was capable of transcribing past either BPDE isomer to generate full-length run-off transcripts. The extent of bypass was found to be 32% for the (-)-anti-trans-isomer and 18% for the (+)-anti-trans-isomer. Transcription past both adducts was highly mutagenic. The reversion frequency of bypass synthesis of the (-)-anti-trans-isomer was elevated 11,000-fold and that of the (+)-anti-trans-isomer 6000-fold, relative to the reversion frequency of transcription on unadducted template. Adenine was misinserted preferentially, followed by guanine, opposite the adenine adducted with either BPDE isomer. Although base substitution errors were by far the most frequent mutation on the adducted template, three- and six-base deletions were also observed. These results suggest that transcriptional errors, particularly with regard to damage bypass, may contribute to the mutational burden of the cell. JF - The Journal of biological chemistry AU - Remington, K M AU - Bennett, S E AU - Harris, C M AU - Harris, T M AU - Bebenek, K AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/22/ PY - 1998 DA - 1998 May 22 SP - 13170 EP - 13176 VL - 273 IS - 21 SN - 0021-9258, 0021-9258 KW - DNA Adducts KW - 0 KW - Mutagens KW - Viral Proteins KW - benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - bacteriophage T7 RNA polymerase KW - EC 2.7.7.- KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Base Sequence KW - Isomerism KW - Transcription, Genetic KW - Templates, Genetic KW - DNA Adducts -- chemistry KW - Mutagens -- metabolism KW - DNA-Directed RNA Polymerases -- metabolism KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemical synthesis KW - DNA Adducts -- chemical synthesis KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Bacteriophage T7 -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79883997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Highly+mutagenic+bypass+synthesis+by+T7+RNA+polymerase+of+site-specific+benzo%5Ba%5Dpyrene+diol+epoxide-adducted+template+DNA.&rft.au=Remington%2C+K+M%3BBennett%2C+S+E%3BHarris%2C+C+M%3BHarris%2C+T+M%3BBebenek%2C+K&rft.aulast=Remington&rft.aufirst=K&rft.date=1998-05-22&rft.volume=273&rft.issue=21&rft.spage=13170&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism. AN - 73928317; 9754450 AB - This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism. JF - Psychiatry research AU - Streeter, C C AU - Ciraulo, D A AU - Harris, G J AU - Kaufman, M J AU - Lewis, R F AU - Knapp, C M AU - Ciraulo, A M AU - Maas, L C AU - Ungeheuer, M AU - Szulewski, S AU - Renshaw, P F AD - Department of Psychiatry/116A, Outpatient Clinic, Boston National Institute on Drug Abuse/Veterans Administration Medication Development Research Unit, MA 02114, USA. streeter.chris@boston.va.gov Y1 - 1998/05/20/ PY - 1998 DA - 1998 May 20 SP - 69 EP - 82 VL - 82 IS - 2 SN - 0165-1781, 0165-1781 KW - Anti-Anxiety Agents KW - 0 KW - Alprazolam KW - YU55MQ3IZY KW - Index Medicus KW - Affect -- drug effects KW - Double-Blind Method KW - Humans KW - Adult KW - Cross-Over Studies KW - Male KW - Functional Laterality KW - Female KW - Echo-Planar Imaging KW - Anti-Anxiety Agents -- pharmacology KW - Brain -- blood supply KW - Alprazolam -- pharmacology KW - Alcoholism -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73928317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+magnetic+resonance+imaging+of+alprazolam-induced+changes+in+humans+with+familial+alcoholism.&rft.au=Streeter%2C+C+C%3BCiraulo%2C+D+A%3BHarris%2C+G+J%3BKaufman%2C+M+J%3BLewis%2C+R+F%3BKnapp%2C+C+M%3BCiraulo%2C+A+M%3BMaas%2C+L+C%3BUngeheuer%2C+M%3BSzulewski%2C+S%3BRenshaw%2C+P+F&rft.aulast=Streeter&rft.aufirst=C&rft.date=1998-05-20&rft.volume=82&rft.issue=2&rft.spage=69&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 - 1998-11-25 N1 - Date created - 1998-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine bone marrow expressing the neomycin resistance gene has no competitive disadvantage assessed in vivo AN - 16412848; 4323879 AB - The neomycin phosphotransferase (neo) gene is one of the most common marker genes used in gene transfer experimentation, but potential effects of neo gene expression in vivo have not been systematically investigated. Several early clinical retroviral gene transfer studies have suggested that neo gene expression could have deleterious effects on hematopoiesis, owing to a discrepancy between the level of neo-marked transduced marrow progenitor cells compared with mature circulating progeny cells posttransplantation. We examined the long-term in vivo repopulating ability of bone marrow from transgenic mice expressing neo from a strong constitutive promoter using a competitive repopulation assay. Different ratios of neo transgenic and wild-type congenic marrow cells were cotransplanted into W/W super(v) recipient mice. The percentages of blood cells containing the neo transgene in each group of recipient mice monitored for 4 months posttransplantation closely matched the input ratios of neo transgenic to congenic control marrow cells. Similar concordances of engraftment with input ratios of neo transgenic cells were also found in spleen, thymus, and whole marrow of recipient mice at 4 months posttransplantation. Analysis of the beta -hemoglobin phenotype ( beta super(single) for the neo transgenic and C57 control cells and beta super(diffuse) for the congenic competitor HW80 cells) in recipients confirmed erythroid repopulation from neo transgenic marrow cells at levels matching the input ratios. We conclude that hematopoietic cells expressing neo had no engraftment or maturation defects detectable in vivo. These results suggest that the low-level contribution of vector-marked cells to circulating populations in clinical trials is not due to direct deleterious effects of neo gene expression on hematopoiesis. JF - Human Gene Therapy AU - Wu, Tong AU - Bloom, M L AU - Yu, Jian-Mei AU - Tisdale, J F AU - Dunbar, CE AD - Hematology Branch, NHLBI, NIH, Building 10, Room 7C103, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1998/05/20/ PY - 1998 DA - 1998 May 20 SP - 1157 EP - 1164 VL - 9 IS - 8 SN - 1043-0342, 1043-0342 KW - animal models KW - mice KW - neomycin KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/16412848?accountid=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=Murine+bone+marrow+expressing+the+neomycin+resistance+gene+has+no+competitive+disadvantage+assessed+in+vivo&rft.au=Wu%2C+Tong%3BBloom%2C+M+L%3BYu%2C+Jian-Mei%3BTisdale%2C+J+F%3BDunbar%2C+CE&rft.aulast=Wu&rft.aufirst=Tong&rft.date=1998-05-20&rft.volume=9&rft.issue=8&rft.spage=1157&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 ER - TY - JOUR T1 - Characterization of D10S and K71E mutants of human cytosolic hsp70. AN - 79889186; 9585537 AB - To determine the effect of mutations at the nucleotide-binding site of recombinant Hsp70 on its interaction with protein and peptide substrates, point mutations were made at D10 and K71, two residues at the active site. The D10S mutation weakened both ATP and ADP binding, while the K71E mutation weakened only ATP binding. In binding experiments using Hsp70 with no bound nucleotide, the mutated Hsp70s interacted with clathrin and peptide just like the wild-type Hsp70. However, the D10 mutation completely abolished the effects of both ATP and ADP on peptide and clathrin binding. The K71 mutation also abolished the effect of ATP on substrate binding, but ADP, which still bound tightly, had its normal effect on substrate binding. In addition, the D10S and K71E mutants had greatly reduced ability to uncoat clathrin-coated vesicles at pH 7.0, bind to clathrin baskets at pH 6.0, and undergo polymerization induced by YDJ1 in the presence of ATP. We conclude, first, that nucleotides must bind strongly to Hsp70 to affect substrate binding and, second, that interaction of Hsp70 with DnaJ homologues may also require a strongly bound ATP. JF - Biochemistry AU - Rajapandi, T AU - Wu, C AU - Eisenberg, E AU - Greene, L AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/05/19/ PY - 1998 DA - 1998 May 19 SP - 7244 EP - 7250 VL - 37 IS - 20 SN - 0006-2960, 0006-2960 KW - Clathrin KW - 0 KW - Cytochrome c Group KW - HSP40 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - Heat-Shock Proteins KW - Nucleotides KW - Peptides KW - Recombinant Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Heat-Shock Proteins -- metabolism KW - Nucleotides -- metabolism KW - Clathrin -- metabolism KW - Aspartic Acid -- genetics KW - Humans KW - Peptides -- metabolism KW - Lysine -- genetics KW - Serine -- genetics KW - Glutamic Acid -- genetics KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Recombinant Proteins -- chemistry KW - Cytochrome c Group -- metabolism KW - Adenosine Diphosphate -- metabolism KW - HSP70 Heat-Shock Proteins -- metabolism KW - HSP70 Heat-Shock Proteins -- genetics KW - Cytosol -- metabolism KW - HSP70 Heat-Shock Proteins -- chemistry KW - Mutagenesis, Insertional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79889186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+D10S+and+K71E+mutants+of+human+cytosolic+hsp70.&rft.au=Rajapandi%2C+T%3BWu%2C+C%3BEisenberg%2C+E%3BGreene%2C+L&rft.aulast=Rajapandi&rft.aufirst=T&rft.date=1998-05-19&rft.volume=37&rft.issue=20&rft.spage=7244&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-22 N1 - Date created - 1998-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats. AN - 79950540; 9630617 AB - In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Jöhren, O AU - Häuser, W AU - Saavedra, J M AD - Section on Pharmacology, National Institute of Mental Health, 10 Center Drive MSC 1514, Building 10, Room 2D-57, Bethesda, MD 20892, USA. johreno@irp.nimh.nih.gov Y1 - 1998/05/18/ PY - 1998 DA - 1998 May 18 SP - 176 EP - 186 VL - 793 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Iodine Radioisotopes KW - 0 KW - Pyridines KW - RNA, Messenger KW - Receptor, Angiotensin, Type 2 KW - Receptors, Angiotensin KW - 3-acetylpyridine KW - 00QT8FX306 KW - 1-Sarcosine-8-Isoleucine Angiotensin II KW - 9088-01-1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - RNA, Messenger -- analysis KW - Iodine Radioisotopes -- metabolism KW - Pyridines -- pharmacology KW - Immunohistochemistry KW - Male KW - Olivary Nucleus -- drug effects KW - Receptors, Angiotensin -- metabolism KW - Cerebellar Cortex -- chemistry KW - Olivary Nucleus -- physiology KW - Olivary Nucleus -- metabolism KW - Cerebellar Cortex -- drug effects KW - 1-Sarcosine-8-Isoleucine Angiotensin II -- metabolism KW - Cerebellar Cortex -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79950540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+lesion+of+the+inferior+olive+reduces+%5B125I%5Dsarcosine1-angiotensin+II+binding+to+AT2+receptors+in+the+cerebellar+cortex+of+young+rats.&rft.au=J%C3%B6hren%2C+O%3BH%C3%A4user%2C+W%3BSaavedra%2C+J+M&rft.aulast=J%C3%B6hren&rft.aufirst=O&rft.date=1998-05-18&rft.volume=793&rft.issue=1-2&rft.spage=176&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 - 1999-03-29 N1 - Date created - 1999-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. AN - 79890138; 9585410 AB - The mechanism by which cholera toxin (CT) is internalized from the plasma membrane before its intracellular reduction and subsequent activation of adenylyl cyclase is not well understood. Ganglioside GM1, the receptor for CT, is predominantly clustered in detergent-insoluble glycolipid rafts and in caveolae, noncoated, cholesterol-rich invaginations on the plasma membrane. In this study, we used filipin, a sterol-binding agent that disrupts caveolae and caveolae-like structures, to explore their role in the internalization and activation of CT in CaCo-2 human intestinal epithelial cells. When toxin internalization was quantified, only 33% of surface-bound toxin was internalized by filipin-treated cells within 1 h compared with 79% in untreated cells. However, CT activation as determined by its reduction to form the A1 peptide and CT activity as measured by cyclic AMP accumulation were inhibited in filipin-treated cells. Another sterol-binding agent, 2-hydroxy-beta-cyclodextrin, gave comparable results. The cationic amphiphilic drug chlorpromazine, an inhibitor of clathrin-dependent, receptor-mediated endocytosis, however, affected neither CT internalization, activation, nor activity in contrast to its inhibitory effects on diphtheria toxin cytotoxicity. As filipin did not inhibit the latter, the two drugs appeared to distinguish between caveolae- and coated pit-mediated processes. In addition to its effects in CaCo-2 cells that express low levels of caveolin, filipin also inhibited CT activity in human epidermoid carcinoma A431 and Jurkat T lymphoma cells that are, respectively, rich in or lack caveolin. Thus, filipin inhibition correlated more closely with alterations in the biochemical characteristics of CT-bound membranes due to the interactions of filipin with cholesterol rather than with the expressed levels of caveolin and caveolar structure. Our results indicated that the internalization and activation of CT was dependent on and mediated through cholesterol- and glycolipid-rich microdomains at the plasma membrane rather than through a specific morphological structure and that these glycolipid microdomains have the necessary components required to mediate endocytosis. JF - The Journal of cell biology AU - Orlandi, P A AU - Fishman, P H AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892-4440, USA. Y1 - 1998/05/18/ PY - 1998 DA - 1998 May 18 SP - 905 EP - 915 VL - 141 IS - 4 SN - 0021-9525, 0021-9525 KW - Cyclodextrins KW - 0 KW - Diphtheria Toxin KW - Glycolipids KW - Membrane Lipids KW - Filipin KW - 87Z59R7D14 KW - Cholera Toxin KW - 9012-63-9 KW - Cholesterol KW - 97C5T2UQ7J KW - Cyclic AMP KW - E0399OZS9N KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Imipramine KW - OGG85SX4E4 KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Diphtheria Toxin -- toxicity KW - Membrane Lipids -- metabolism KW - Jurkat Cells KW - Adenylyl Cyclases -- metabolism KW - Cell Membrane -- ultrastructure KW - Cell Membrane -- physiology KW - Chlorpromazine -- pharmacology KW - Biological Transport -- drug effects KW - Cyclodextrins -- pharmacology KW - Tumor Cells, Cultured KW - Cholesterol -- metabolism KW - Kinetics KW - Imipramine -- pharmacology KW - Endocytosis -- drug effects KW - Cyclic AMP -- metabolism KW - Carcinoma, Squamous Cell KW - Glycolipids -- metabolism KW - Endocytosis -- physiology KW - Coated Pits, Cell-Membrane -- physiology KW - Colonic Neoplasms KW - Intestinal Mucosa -- physiology KW - Cholera Toxin -- pharmacology KW - Intestinal Mucosa -- drug effects KW - Cholera Toxin -- antagonists & inhibitors KW - Cholera Toxin -- pharmacokinetics KW - Filipin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79890138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Filipin-dependent+inhibition+of+cholera+toxin%3A+evidence+for+toxin+internalization+and+activation+through+caveolae-like+domains.&rft.au=Orlandi%2C+P+A%3BFishman%2C+P+H&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1998-05-18&rft.volume=141&rft.issue=4&rft.spage=905&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 - 1998-06-17 N1 - Date created - 1998-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1982 Apr 15;296(5858):651-3 [7070509] Nature. 1997 Jun 5;387(6633):569-72 [9177342] J Biol Chem. 1982 Oct 25;257(20):12148-52 [6288709] J Cell Biol. 1982 Jun;93(3):860-5 [6288736] J Cell Biol. 1983 Nov;97(5 Pt 1):1592-600 [6415070] Mol Pharmacol. 1984 Sep;26(2):206-13 [6207420] J Cell Biol. 1985 Aug;101(2):548-59 [2862151] Proc Natl Acad Sci U S A. 1987 Nov;84(22):7957-61 [2446314] Biochemistry. 1988 Aug 23;27(17):6197-202 [3064805] J Cell Biol. 1990 Dec;111(6 Pt 2):2931-8 [2148564] Biochemistry. 1991 Mar 12;30(10):2563-70 [1848091] Science. 1992 Jan 24;255(5043):410-1 [1310359] Cell. 1992 Feb 7;68(3):533-44 [1531449] Cell. 1992 Feb 21;68(4):673-82 [1739974] Biochemistry. 1992 May 26;31(20):4773-8 [1317209] J Biol Chem. 1992 Jun 5;267(16):11525-31 [1597480] J Cell Biol. 1992 Jul;118(1):63-9 [1618907] FEBS Lett. 1992 Dec 7;314(1):45-8 [1360410] EMBO J. 1993 Apr;12(4):1597-605 [8385608] J Biol Chem. 1993 Jun 5;268(16):12010-6 [8389369] Biochemistry. 1993 Jun 29;32(25):6365-73 [8518282] J Biol Chem. 1993 Aug 15;268(23):17038-44 [8349592] J Cell Biol. 1993 Aug;122(4):789-807 [8349730] Adv Lipid Res. 1993;25:165-87 [8396312] J Cell Biol. 1993 Dec;123(5):1107-17 [8245121] J Histochem Cytochem. 1994 Feb;42(2):155-66 [8288861] Science. 1994 Jun 24;264(5167):1948-51 [7516582] J Cell Biol. 1994 Dec;127(5):1185-97 [7962084] J Cell Biol. 1994 Dec;127(5):1217-32 [7525606] J Biol Chem. 1994 Dec 9;269(49):30745-8 [7982998] J Cell Biol. 1995 May;129(3):619-27 [7537273] J Biol Chem. 1995 May 19;270(20):12117-22 [7744860] J Biol Chem. 1995 Jun 16;270(24):14399-404 [7782301] Science. 1995 Sep 8;269(5229):1398-9 [7660120] Science. 1995 Sep 8;269(5229):1435-9 [7660128] J Cell Biol. 1995 Nov;131(4):951-62 [7490296] J Membr Biol. 1980;54(1):51-60 [6259358] FEBS Lett. 1995 Nov 13;375(1-2):11-4 [7498456] J Cell Biol. 1996 May;133(4):777-89 [8666663] J Cell Biol. 1996 May;133(4):791-9 [8666664] FEBS Lett. 1996 Jun 24;389(1):52-4 [8682205] J Biol Chem. 1996 Aug 30;271(35):21604-13 [8702948] Curr Opin Cell Biol. 1996 Aug;8(4):542-8 [8791446] Am J Physiol. 1996 Sep;271(3 Pt 1):C887-94 [8843719] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12339-43 [8901582] J Biol Chem. 1997 Feb 14;272(7):4591-9 [9020187] Biochim Biophys Acta. 1982 Apr 29;720(2):181-7 [7082684] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory monoclonal antibody to human cytochrome P450 2B6. AN - 79952007; 9633999 AB - The human cytochrome P450 2B6 metabolizes, among numerous other substrates, diazepam, 7-ethoxycoumarin, testosterone, and phenanthrene. A recombinant baculovirus containing the human 2B6 cDNA was constructed and used to express 2B6 in Sf9 insect cells. The 2B6 was present at 1.8 +/- 0.4% of the total cellular protein and was purified to a specific content of 13.3 nmol/mg protein. Mice were immunized with the purified 2B6, and a total of 811 hybridomas were obtained from the fusion of NS-1 myeloma cells and spleen cells of the immunized mice. Monoclonal antibodies (MAbs) from 24 of the hybrids exhibited immunobinding to 2B6 as determined by ELISA. One of the MAbs, 49-10-20, showed a strong immunoblotting activity and was highly inhibitory to 2B6 enzyme activity. MAb 49-10-20 inhibited cDNA-expressed 2B6-catalyzed metabolism of diazepam, phenanthrene, 7-ethoxycoumarin, and testosterone by 90-91%. MAb 49-10-20 showed extremely high specificity for 2B6 and did not bind to 17 other human and rodent P450s or inhibit the metabolism of phenanthrene catalyzed by human 1A2, 2A6, 2C8, 2C9, 2D6, 2E1, 3A4, and 3A5. MAb 49-10-20 was used to determine the contribution of 2B6 to the metabolism of phenanthrene and diazepam in human liver. In ten liver samples, MAb 49-10-20 inhibited phenanthrene metabolism variably by a wide range of 8-42% and diazepam demethylation by 1-23%. The degree of inhibition by the 2B6 specific MAb 49-10-20 defines the contribution of 2B6 to phenanthrene and diazepam metabolism in each human liver. This technique using inhibitory MAb 49-10-20 determines the contribution of 2B6 to the metabolism of its substrates in a human tissue containing multiple P450s. This study is a prototype for the use of specific and highly inhibitory MAbs to determine individual P450 function. JF - Biochemical pharmacology AU - Yang, T J AU - Krausz, K W AU - Shou, M AU - Yang, S K AU - Buters, J T AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1633 EP - 1640 VL - 55 IS - 10 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Phenanthrenes KW - Recombinant Proteins KW - phenanthrene KW - 448J8E5BST KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2B6 protein, human KW - Cytochrome P-450 CYP2B6 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Phenanthrenes -- metabolism KW - Animals KW - Liver -- enzymology KW - Spodoptera KW - Diazepam -- metabolism KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Substrate Specificity KW - Mice, Inbred BALB C KW - Recombinant Proteins -- antagonists & inhibitors KW - Cell Line KW - Oxidoreductases, N-Demethylating -- antagonists & inhibitors KW - Antibodies, Monoclonal -- pharmacology KW - Oxidoreductases, N-Demethylating -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79952007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibitory+monoclonal+antibody+to+human+cytochrome+P450+2B6.&rft.au=Yang%2C+T+J%3BKrausz%2C+K+W%3BShou%2C+M%3BYang%2C+S+K%3BButers%2C+J+T%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Yang&rft.aufirst=T&rft.date=1998-05-15&rft.volume=55&rft.issue=10&rft.spage=1633&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective depletion of DNA precursors: an evolving strategy for potentiation of dideoxynucleoside activity against human immunodeficiency virus. AN - 79946978; 9633990 AB - Human immunodeficiency virus type 1 (HIV-1) is wholly dependent on its host cell for a variety of essential metabolites. Among the latter are the deoxynucleoside-5'-triphosphates (dNTPs) required for reverse transcription of the single-stranded RNA viral genome into double-stranded viral DNA. Since viral DNA synthesis has an absolute requirement for all four dNTPs, restriction of a single one of these is sufficient to inhibit HIV-1 replication. To date, this therapeutic strategy has been most successful when depletion of the individual dNTP is coupled with exposure to its corresponding chain-terminating dideoxynucleoside (ddN). While several examples of such combined therapy have been defined and studied in vitro, that which has been investigated most extensively at both the laboratory and the clinical level is ddATP exposure combined with dATP depletion [with dATP restriction being induced by the ribonucleotide reductase inhibitor hydroxyurea (HU) and ddATP generated from its prodrug 2',3'-dideoxyinosine (ddI)]. Several long-term clinical trials of the hydroxyurea/2',3'-dideoxyinosine combination have been completed, with plasma viral RNA being reduced to undetectable levels in a substantial fraction (one-third to one-half) of the patients treated. The major advantages of this and analogous combinations discussed in this review are their low cost relative to other current multiple drug protocols and their potential for retention of activity against drug-resistant HIV mutants. JF - Biochemical pharmacology AU - Johns, D G AU - Gao, W Y AD - Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. johnsd@dc37a.nci.nih.gov Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1551 EP - 1556 VL - 55 IS - 10 SN - 0006-2952, 0006-2952 KW - Anti-HIV Agents KW - 0 KW - Dideoxynucleosides KW - Enzyme Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Ribonucleotide Reductases KW - EC 1.17.4.- KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Humans KW - Zidovudine -- pharmacology KW - Ribonucleotide Reductases -- antagonists & inhibitors KW - Clinical Trials as Topic KW - Enzyme Inhibitors -- pharmacology KW - Zidovudine -- administration & dosage KW - Drug Synergism KW - Dideoxynucleosides -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Anti-HIV Agents -- administration & dosage KW - Hydroxyurea -- pharmacology KW - HIV-1 -- drug effects KW - Hydroxyurea -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79946978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+depletion+of+DNA+precursors%3A+an+evolving+strategy+for+potentiation+of+dideoxynucleoside+activity+against+human+immunodeficiency+virus.&rft.au=Johns%2C+D+G%3BGao%2C+W+Y&rft.aulast=Johns&rft.aufirst=D&rft.date=1998-05-15&rft.volume=55&rft.issue=10&rft.spage=1551&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 - 1998-07-02 N1 - Date created - 1998-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. AN - 79896772; 9605766 AB - The isolation of genes involved in cancer development is critical for uncovering the molecular basis of cancer. We report here the isolation of the full-length cDNA and chromosomal localization of a new gene frequently deleted in liver cancer (DLC-1) that was identified by representational difference analysis. Loss of heterozygosity was detected for DLC-1 in 7 of 16 primary hepatocellular carcinomas (HCCs) and in 10 of 11 HCC cell lines. Although mRNA for DLC-1 was expressed in all normal human tissues, it was not expressed in 4 of 14 HCC cell lines. Full-length cDNA for DLC-1 of 3800 bp encodes a protein of 1091 amino acids, has 86% homology with rat p122 RhoGAP gene, and was localized by fluorescence in situ hybridization on chromosome 8 at bands p21.3-22. Deletions on the short arm of chromosome 8 are recurrent in liver, breast, lung, and prostate cancers, suggesting the presence of tumor suppressor genes. DLC-1 may be a tumor suppressor gene in liver cancer as well as in other cancers. JF - Cancer research AU - Yuan, B Z AU - Miller, M J AU - Keck, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 2196 EP - 2199 VL - 58 IS - 10 SN - 0008-5472, 0008-5472 KW - DLC1 protein, human KW - 0 KW - GTPase-Activating Proteins KW - Proteins KW - Tumor Suppressor Proteins KW - Index Medicus KW - Rats KW - Animals KW - Loss of Heterozygosity KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Chromosome Mapping KW - Gene Deletion KW - Genes, Tumor Suppressor -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Chromosomes, Human, Pair 8 -- genetics KW - Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79896772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+characterization%2C+and+chromosomal+localization+of+a+gene+frequently+deleted+in+human+liver+cancer+%28DLC-1%29+homologous+to+rat+RhoGAP.&rft.au=Yuan%2C+B+Z%3BMiller%2C+M+J%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Yuan&rft.aufirst=B&rft.date=1998-05-15&rft.volume=58&rft.issue=10&rft.spage=2196&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 - 1998-06-10 N1 - Date created - 1998-06-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF035119; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. AN - 79866613; 9587128 AB - In uncontrolled clinical trials, the administration of oral zinc sulfate has been reported both to prevent and correct taste abnormalities in cancer patients receiving external radiotherapy (ERT) to the head and neck region. Eighteen patients were randomized to receive either zinc sulfate tablets (a dose of 45 mg) or placebo tablets three times a day at the onset of subjective perception of taste alterations during the course of ERT and up to 1 month after ERT termination. Taste acuity was determined by measuring detection and recognition thresholds for four taste qualities. Intolerance of zinc sulfate or placebo administration was investigated, and the oral cavity was examined. All the evaluations were studied prior to, at weekly intervals during, and 1 month after ERT administration. Taste acuity for one or more taste qualities was already impaired before ERT. During ERT treatment, taste alterations were experienced at least once for a minimum of 3 of the 8 measured thresholds by 100% of the patients, and 33.3% of the patients became aware of some alteration within the first week of treatment. The patients treated with placebo experienced a greater worsening of taste acuity during ERT treatment compared with those treated with zinc sulfate. One month after ERT was terminated, the patients receiving zinc sulfate had a quicker recovery of taste acuity than those receiving placebo. Statistically significant differences between the two groups emerged for urea detection and sodium chloride recognition thresholds during ERT treatment and for sodium chloride, saccharose, and hydrogen chloride recognition thresholds after the termination of ERT treatment. This pharmacologic therapy is effective and well tolerated; it could become a routine in clinical practice to improve the supportive care of patients with taste alterations resulting from head and neck cancer. JF - Cancer AU - Ripamonti, C AU - Zecca, E AU - Brunelli, C AU - Fulfaro, F AU - Villa, S AU - Balzarini, A AU - Bombardieri, E AU - De Conno, F AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1998/05/15/ PY - 1998 DA - 1998 May 15 SP - 1938 EP - 1945 VL - 82 IS - 10 SN - 0008-543X, 0008-543X KW - Zinc Sulfate KW - 7733-02-0 KW - Abridged Index Medicus KW - Index Medicus KW - Evaluation Studies as Topic KW - Administration, Oral KW - Double-Blind Method KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Statistics, Nonparametric KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Zinc Sulfate -- therapeutic use KW - Head and Neck Neoplasms -- complications KW - Taste Disorders -- etiology KW - Head and Neck Neoplasms -- radiotherapy KW - Taste Disorders -- prevention & control KW - Head and Neck Neoplasms -- surgery KW - Taste Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79866613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=A+randomized%2C+controlled+clinical+trial+to+evaluate+the+effects+of+zinc+sulfate+on+cancer+patients+with+taste+alterations+caused+by+head+and+neck+irradiation.&rft.au=Ripamonti%2C+C%3BZecca%2C+E%3BBrunelli%2C+C%3BFulfaro%2C+F%3BVilla%2C+S%3BBalzarini%2C+A%3BBombardieri%2C+E%3BDe+Conno%2C+F&rft.aulast=Ripamonti&rft.aufirst=C&rft.date=1998-05-15&rft.volume=82&rft.issue=10&rft.spage=1938&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. AN - 79936147; 9627117 AB - Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rho-guanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound specifically to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogen-responsive reporter revealed that Brx augmented gene activation by the ER in an element-specific and ligand-dependent manner. Moreover, activation of ER by Brx could be specifically inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors. JF - Oncogene AU - Rubino, D AU - Driggers, P AU - Arbit, D AU - Kemp, L AU - Miller, B AU - Coso, O AU - Pagliai, K AU - Gray, K AU - Gutkind, S AU - Segars, J AD - Office of the Scientific Director, National Institute of Child Health and Human Development, and DEB, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05/14/ PY - 1998 DA - 1998 May 14 SP - 2513 EP - 2526 VL - 16 IS - 19 SN - 0950-9232, 0950-9232 KW - A Kinase Anchor Proteins KW - 0 KW - AKAP13 protein, human KW - Adaptor Proteins, Signal Transducing KW - Cell Cycle Proteins KW - DNA, Complementary KW - Guanine Nucleotide Exchange Factors KW - MCF2 protein, human KW - Minor Histocompatibility Antigens KW - Oncogene Proteins KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - Retroviridae Proteins, Oncogenic KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - cdc42 GTP-Binding Protein KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Humans KW - Tissue Distribution KW - Mutagenesis KW - Tumor Cells, Cultured KW - Cell Cycle Proteins -- genetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Breast -- metabolism KW - Male KW - Testis -- immunology KW - Testis -- pathology KW - Amino Acid Sequence KW - Rabbits KW - GTP-Binding Proteins -- genetics KW - Cloning, Molecular KW - Cell Cycle Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Breast -- pathology KW - Female KW - Oncogene Proteins -- classification KW - Oncogene Proteins -- genetics KW - Receptors, Estrogen -- metabolism KW - Receptors, Estrogen -- physiology KW - Oncogene Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79936147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+Brx%2C+a+novel+Dbl+family+member+that+modulates+estrogen+receptor+action.&rft.au=Rubino%2C+D%3BDriggers%2C+P%3BArbit%2C+D%3BKemp%2C+L%3BMiller%2C+B%3BCoso%2C+O%3BPagliai%2C+K%3BGray%2C+K%3BGutkind%2C+S%3BSegars%2C+J&rft.aulast=Rubino&rft.aufirst=D&rft.date=1998-05-14&rft.volume=16&rft.issue=19&rft.spage=2513&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF126008; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alzheimer's-specific effects of soluble beta-amyloid on protein kinase C-alpha and -gamma degradation in human fibroblasts. AN - 79861686; 9576922 AB - Alzheimer's disease (AD) is a multifactorial disease in which beta-amyloid peptide (betaAP) plays a critical role. We report here that the soluble fraction 1-40 of betaAP differentially degrades protein kinase C-alpha and -gamma (PKCalpha and PKCgamma) isoenzymes in normal (age-matched controls, AC) and AD fibroblasts most likely through proteolytic cascades. Treatment with nanomolar concentrations of betaAP(1-40) induced a 75% decrease in PKCalpha, but not PKCgamma, immunoreactivity in AC fibroblasts. In the AD fibroblasts, a 70% reduction of the PKCgamma, but not PKCalpha, immunoreactivity was observed after betaAP treatment. Preincubation of AC or AD fibroblasts with 50 microM lactacystine, a selective proteasome inhibitor, prevented beta-AP(1-40)-mediated degradation of PKCalpha in the AC cells, and PKCgamma in the AD fibroblasts. The effects of betaAP(1-40) on PKCalpha in AC fibroblasts were prevented by inhibition of protein synthesis and reversed by PKC activation. A 3-hr treatment with 100 nM phorbol 12-myristate 13-acetate restored the PKCalpha signal in treated AC cells but it did not reverse the effects of betaAP(1-40) on PKCgamma in the AD fibroblasts. Pretreatment with the protein synthesis inhibitor, cycloheximide (CHX, 100 microM), inhibited the effects of betaAP(1-40) on PKCalpha and blocked the rescue effect of phorbol 12-myristate 13-acetate in AC fibroblasts but did not modify PKCgamma immunoreactivity in AD cells. These results suggest that betaAP(1-40) differentially affects PKC regulation in AC and AD cells via proteolytic degradation and that PKC activation exerts a protective role via de novo protein synthesis in normal but not AD cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Favit, A AU - Grimaldi, M AU - Nelson, T J AU - Alkon, D L AD - Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5562 EP - 5567 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - Amyloid beta-Peptides KW - 0 KW - Isoenzymes KW - Peptide Fragments KW - Protein Synthesis Inhibitors KW - amyloid beta-protein (1-40) KW - lactacystin KW - 133343-34-7 KW - Cycloheximide KW - 98600C0908 KW - protein kinase C gamma KW - EC 2.7.1.- KW - PRKCA protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Animals KW - Fibroblasts -- enzymology KW - Acetylcysteine -- analogs & derivatives KW - Brain -- drug effects KW - Humans KW - Acetylcysteine -- pharmacology KW - Rats KW - Brain -- enzymology KW - Blotting, Western KW - Protein Synthesis Inhibitors -- pharmacology KW - Cells, Cultured KW - Cycloheximide -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- metabolism KW - Peptide Fragments -- metabolism KW - Amyloid beta-Peptides -- metabolism KW - Alzheimer Disease -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79861686?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alzheimer%27s-specific+effects+of+soluble+beta-amyloid+on+protein+kinase+C-alpha+and+-gamma+degradation+in+human+fibroblasts.&rft.au=Favit%2C+A%3BGrimaldi%2C+M%3BNelson%2C+T+J%3BAlkon%2C+D+L&rft.aulast=Favit&rft.aufirst=A&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5562&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8209-13 [8367484] N Engl J Med. 1991 Dec 26;325(26):1849-57 [1961223] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9195-8 [8415676] J Biol Chem. 1993 Nov 5;268(31):22959-62 [8226807] J Neurochem. 1993 Dec;61(6):2326-9 [8245986] Trends Neurosci. 1993 Oct;16(10):409-14 [7504356] Neurology. 1993 Dec;43(12):2581-6 [8255461] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):534-8 [8290560] Neurochem Res. 1994 Jan;19(1):89-95 [8139769] Science. 1994 Apr 8;264(5156):276-9 [8146663] FEBS Lett. 1994 Nov 14;354(3):274-8 [7957938] Biochim Biophys Acta. 1994 Nov 29;1227(3):183-7 [7986826] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11993-7 [7991571] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3060-4 [7708775] Brain Res. 1995 Sep 11;691(1-2):169-79 [8590049] Dev Biol. 1995 Dec;172(2):675-82 [8612981] J Neurochem. 1996 Apr;66(4):1752-61 [8627334] Neurosci Lett. 1995 Dec 1;201(1):1-5 [8830300] Acta Neurol Scand Suppl. 1996;165:25-32 [8740986] Life Sci. 1996;59(5-6):477-89 [8761336] Science. 1996 Oct 4;274(5284):99-102 [8810256] Mol Pharmacol. 1997 Mar;51(3):439-47 [9058599] Mol Med. 1997 Mar;3(3):204-11 [9100226] N Engl J Med. 1986 Apr 10;314(15):964-73 [2870433] Science. 1992 Feb 7;255(5045):726-8 [1738846] Science. 1992 Feb 7;255(5045):728-30 [1738847] J Neurosci. 1992 Feb;12(2):376-89 [1346802] Neurosci Lett. 1991 Nov 25;133(1):89-92 [1792001] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3055-9 [1557413] J Cereb Blood Flow Metab. 1992 Jul;12(4):638-45 [1352303] Biochem Biophys Res Commun. 1992 Sep 30;187(3):1285-90 [1417805] Science. 1992 Oct 2;258(5079):126-9 [1439760] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71 [8380642] Science. 1993 Jan 22;259(5094):514-6 [8424174] Exp Gerontol. 1993 Jan-Feb;28(1):51-8 [8436204] Pharmacol Ther. 1992;56(1):97-117 [1297146] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2628-32 [8464868] Nat Genet. 1992 Dec;2(4):340-2 [1303291] J Biol Chem. 1993 Jul 15;268(20):14616-21 [8100816] Neurology. 1993 Jul;43(7):1407-13 [8327146] Biochem Biophys Res Commun. 1993 Aug 31;195(1):97-103 [8395841] J Immunol Methods. 1986 Sep 27;92(2):261-70 [3760586] Arch Neurol. 1989 Nov;46(11):1195-9 [2684108] Science. 1990 Apr 27;248(4954):492-5 [1691865] J Neurosci. 1990 Jul;10(7):2113-24 [2376771] Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003-6 [2116015] Neurobiol Aging. 1990 Jul-Aug;11(4):425-31 [2381502] Science. 1990 Oct 12;250(4978):279-82 [2218531] Brain Res. 1990 Nov 19;533(2):315-20 [2289145] J Biol Chem. 1991 Jun 25;266(18):11915-22 [1646818] Brain Res. 1991 Mar 8;543(1):139-47 [1647256] J Neurosci. 1991 Sep;11(9):2759-67 [1880547] J Biol Chem. 1993 Oct 5;268(28):21097-101 [8407946] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The chromatin unfolding domain of chromosomal protein HMG-14 targets the N-terminal tail of histone H3 in nucleosomes. AN - 79861574; 9576905 AB - Nonhistone chromosomal protein HMG-14 is a nucleosomal binding protein that unfolds the higher-order chromatin structure and enhances the transcriptional potential of chromatin, but not that of DNA. Both the transcriptional enhancement and the chromatin unfolding activities of HMG-14 are mediated through the C-terminal region of the protein. Here we study the molecular interactions of both this region and the N-terminal region of HMG-14 with nucleosome cores. By protein photocrosslinking we demonstrate that the N-terminal domain of HMG-14 targets a restricted region in histone H2B, whereas the C-terminal chromatin unfolding domain of HMG-14 targets a restricted region in the N terminus of histone H3. The N-terminal regions of the core histones are involved in the folding of oligonucleosomes and are the target of various activities associated with chromatin unfolding and transcriptional activation. We suggest that specific interactions between the C-terminal domain of HMG-14 and the N-terminal tail of histone H3 reduce the compaction of chromatin. These findings provide insights into the molecular mechanism whereby HMG-14/-17 proteins reduce the repressive effect of chromatin, and they also broaden the scope of the molecular interactions involving the N termini of the core histones in nucleosomes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Trieschmann, L AU - Martin, B AU - Bustin, M AD - Protein Section, Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5468 EP - 5473 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - Chromatin KW - 0 KW - Cross-Linking Reagents KW - High Mobility Group Proteins KW - Histones KW - Nucleosomes KW - Index Medicus KW - Photochemistry KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Models, Molecular KW - HeLa Cells KW - Humans KW - Cross-Linking Reagents -- metabolism KW - Binding Sites -- genetics KW - High Mobility Group Proteins -- chemistry KW - Chromatin -- metabolism KW - High Mobility Group Proteins -- genetics KW - Histones -- metabolism KW - Nucleosomes -- metabolism KW - Histones -- chemistry KW - Protein Folding KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79861574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chromatin+unfolding+domain+of+chromosomal+protein+HMG-14+targets+the+N-terminal+tail+of+histone+H3+in+nucleosomes.&rft.au=Trieschmann%2C+L%3BMartin%2C+B%3BBustin%2C+M&rft.aulast=Trieschmann&rft.aufirst=L&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5468&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1987 Nov 1;166(2):368-79 [2449095] Biochemistry. 1986 Mar 25;25(6):1421-8 [3964683] Methods Enzymol. 1989;170:532-49 [2770549] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Biochemistry. 1992 Jan 21;31(2):364-70 [1731893] Trends Biochem Sci. 1992 May;17(5):187-91 [1595128] J Biol Chem. 1992 Sep 25;267(27):19587-95 [1527076] Cell. 1993 Feb 12;72(3):305-8 [8431942] EMBO J. 1993 Oct;12(10):3855-64 [8404854] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10489-93 [8248135] J Biol Chem. 1989 Jan 25;264(3):1799-803 [2912984] J Biol Chem. 1986 Dec 5;261(34):16185-90 [3782113] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Science. 1994 Jul 1;265(5168):90-2 [8016656] Science. 1994 Aug 5;265(5173):796-9 [8047885] Annu Rev Biochem. 1994;63:265-97 [7979240] EMBO J. 1994 Dec 15;13(24):6031-40 [7813441] EMBO J. 1995 Apr 3;14(7):1478-89 [7729423] Genes Dev. 1995 Aug 15;9(16):1978-91 [7649479] Curr Opin Cell Biol. 1995 Jun;7(3):371-5 [7662367] 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] Semin Cell Biol. 1995 Aug;6(4):247-55 [8562917] Biochem J. 1996 Jun 1;316 ( Pt 2):395-400 [8687379] Curr Opin Genet Dev. 1996 Apr;6(2):176-84 [8722174] Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 [8768072] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10548-55 [8855215] Biochemistry. 1997 Sep 23;36(38):11381-8 [9298957] EMBO J. 1997 Aug 1;16(15):4717-26 [9303316] Nature. 1997 Sep 18;389(6648):251-60 [9305837] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Mol Cell Biol. 1997 Oct;17(10):5843-55 [9315642] J Mol Biol. 1997 Oct 31;273(3):503-8 [9356240] J Mol Biol. 1997 Dec 12;274(4):454-65 [9417927] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cell. 1977 Sep;12(1):101-7 [561660] Science. 1980 Sep 26;209(4464):1534-6 [7433974] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Biosci Rep. 1984 May;4(5):365-86 [6375755] J Mol Biol. 1985 Sep 20;185(2):329-39 [4057250] Biochem Biophys Res Commun. 1985 Nov 15;132(3):1031-7 [4074344] Erratum In: Proc Natl Acad Sci U S A 1998 Jul 21;95(15):9059 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic induction of immune tolerance to human clotting factor VIII in a mouse model for hemophilia A AN - 16381328; 4290298 AB - Patients with severe coagulation factor VIII deficiency require frequent infusions of human factor VIII (hFVIII) concentrates to treat life-threatening hemorrhages. Because these patients are immunologically hFVIII-naive, a significant treatment complication is the development of inhibitors or circulating alloantibodies against hFVIII, which bind the replaced glycoprotein, increase its plasma clearance, and inhibit its activity, preventing subsequent treatments from having a therapeutic effect. A genetic approach toward the induction of immunologic unresponsiveness to hFVIII has the conceptual advantage of a long-term, stable elimination of undesired immune responses against hFVIII. Here, we report that in a factor VIII (FVIII)-deficient mouse model for severe hemophilia A, genetic modification of donor bone marrow cells with a retroviral vector encoding hFVIII, and transplant to hemophiliac mouse recipients, results in the induction of immune tolerance to FVIII in 50% of treated animals after immunization with hFVIII, despite the fact that hFVIII protein or activity is undetectable. In tolerized animals, the titers of anti-hFVIII binding antibodies and of hFVIII inhibitor antibodies were significantly reduced, and there was evidence for hFVIII unresponsiveness in CD4 super(+) T cells. Importantly, the plasma clearance of hFVIII was significantly decreased in tolerized animals and was not significantly different from that seen in a FVIII-naive hemophiliac mouse. This model system will prove useful for the evaluation of genetic therapies for hFVIII immunomodulation and bring genetic therapies for hFVIII tolerance closer to clinical application for patients with hemophilia A. JF - Proceedings of the National Academy of Sciences, USA AU - Evans, G L AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, MSC 1851, Building 10, Room 10C103, Bethesda, MD 20892-1851, rmorgan@nhgri.nih.gov Y1 - 1998/05/12/ PY - 1998 DA - 1998 May 12 SP - 5734 EP - 5739 VL - 95 IS - 10 SN - 0027-8424, 0027-8424 KW - clotting factor VIII KW - coagulation factor VIII KW - man KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Immunology Abstracts KW - G 07480:Hematological disorders KW - F 06878:Blood (non-immunological parts: RBC, platelets) 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/16381328?accountid=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=Genetic+induction+of+immune+tolerance+to+human+clotting+factor+VIII+in+a+mouse+model+for+hemophilia+A&rft.au=Evans%2C+G+L%3BMorgan%2C+R+A&rft.aulast=Evans&rft.aufirst=G&rft.date=1998-05-12&rft.volume=95&rft.issue=10&rft.spage=5734&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 ER - TY - JOUR T1 - Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. AN - 79888082; 9603607 AB - To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis. JF - American journal of medical genetics AU - Long, J C AU - Knowler, W C AU - Hanson, R L AU - Robin, R W AU - Urbanek, M AU - Moore, E AU - Bennett, P H AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8110, USA. jeff long@nih.gov Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 216 EP - 221 VL - 81 IS - 3 SN - 0148-7299, 0148-7299 KW - Index Medicus KW - Genotype KW - Humans KW - Adult KW - Genetic Predisposition to Disease KW - Male KW - Female KW - Matched-Pair Analysis KW - Genetic Linkage KW - Chromosomes, Human, Pair 4 -- genetics KW - Chromosomes, Human, Pair 11 -- genetics KW - Alcoholism -- ethnology KW - Alcoholism -- genetics KW - Indians, North American -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+genetics&rft.atitle=Evidence+for+genetic+linkage+to+alcohol+dependence+on+chromosomes+4+and+11+from+an+autosome-wide+scan+in+an+American+Indian+population.&rft.au=Long%2C+J+C%3BKnowler%2C+W+C%3BHanson%2C+R+L%3BRobin%2C+R+W%3BUrbanek%2C+M%3BMoore%2C+E%3BBennett%2C+P+H%3BGoldman%2C+D&rft.aulast=Long&rft.aufirst=J&rft.date=1998-05-08&rft.volume=81&rft.issue=3&rft.spage=216&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 - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal properties of prion protein with insertional mutations in different cell types. AN - 79836085; 9565627 AB - Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) have been associated with mutations in the normal soluble, protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein contains five copies of a repeating eight-amino acid region, and PrP molecules with six or more copies of this region are associated with disease in familial CJD. It has been hypothesized that these mutations might facilitate spontaneous formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res, associated with clinical CJD and other transmissible spongiform encephalopathies (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7, 9, or 11 copies of this repeat region were generated and expressed in mouse fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat sequence showed altered cell surface expression, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of aggregation and increased protease resistance. By contrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had abnormal properties of aggregation and increased protease resistance. Overall, regardless of cell type, hamster PrP molecules with greater than 7 octapeptide repeats were more aggregated and more protease-resistant than molecules with 7 repeats or less. However, these abnormal molecules were at least 1000-fold less protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue, and they showed no increased ability to form PrP-res in a cell-free system. JF - The Journal of biological chemistry AU - Priola, S A AU - Chesebro, B AD - Laboratory of Persistent Viral Diseases, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA. spriola@nih.gov Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11980 EP - 11985 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Prions KW - 0 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Endopeptidases KW - EC 3.4.- KW - Endopeptidase K KW - EC 3.4.21.64 KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Index Medicus KW - Animals KW - Mice KW - Protein Binding KW - Endopeptidase K -- metabolism KW - Neuroblastoma KW - Type C Phospholipases -- metabolism KW - Structure-Activity Relationship KW - Fibroblasts KW - Mutagenesis KW - Cells, Cultured KW - Cell Compartmentation KW - Endopeptidases -- metabolism KW - Creutzfeldt-Jakob Syndrome -- metabolism KW - Cell Membrane -- metabolism KW - Repetitive Sequences, Nucleic Acid KW - Cricetinae KW - Prions -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79836085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Abnormal+properties+of+prion+protein+with+insertional+mutations+in+different+cell+types.&rft.au=Priola%2C+S+A%3BChesebro%2C+B&rft.aulast=Priola&rft.aufirst=S&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11980&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse. AN - 79836035; 9565625 AB - Some of the actions of estradiol occur through stimulation of growth factor pathways in target organs. Tyrosine-phosphorylated (Tyr(P)) insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor substrate (IRS)-1 are found in the uterus of mice treated with estradiol. Immunoprecipitates of uterine Tyr(P) IRS-1 contained both p85, the regulatory subunit of phosphatidylinositol (PI) 3-kinase, and PI 3-kinase catalytic activity. Estradiol also stimulated binding of IRS-1 and PI 3-kinase to the IGF-1R. Depletion of IRS-1 from uterine extracts reduced PI 3-kinase associated with the receptor, which suggests that binding of the enzyme to IGF-1R occurs primarily in a complex that also contains IRS-1. Following treatment with estradiol, formation of Tyr(P) IGF-1R, Tyr(P) IRS-1, and the p85.IRS-1 complex was very weak in the uterus of IGF-1(m/m) mice, which are severely deficient in IGF-1. This indicated that most, if not all, of the estradiol-stimulated Tyr phosphorylation of uterine IRS-1 originates from ligand activation of IGF-1R kinase. IRS-2 was also Tyr-phosphorylated in the normal uterus and bound more IGF-1R and p85 in response to estradiol; however, a marked decrease in levels of uterine IRS-2 occurred 12-24 h after treatment with estradiol. Since IRS-2 was present in IGF-1R precipitates and a recombinant form of IGF-1 (long R3 IGF-1) stimulated formation of Tyr(P) IRS-2, hormonal activation of this docking protein probably occurs through the IGF-1R. In summary, our findings show that estrogen activation of uterine IGF-1R kinase results in enhanced binding of p85 (PI 3-kinase) to IRS-1 and IRS-2. The formation of one or both of these complexes may be important for the potent mitogenic action of this steroid. That estradiol stimulated a decrease of IRS-2, but not of IRS-1, suggests that these docking proteins have different roles in hormone-induced signaling in the uterus. JF - The Journal of biological chemistry AU - Richards, R G AU - Walker, M P AU - Sebastian, J AU - DiAugustine, R P AD - Hormones and Cancer Group, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11962 EP - 11969 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Insulin Receptor Substrate Proteins KW - Intracellular Signaling Peptides and Proteins KW - Irs1 protein, mouse KW - Irs2 protein, mouse KW - Phosphoproteins KW - Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Estradiol KW - 4TI98Z838E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, IGF Type 1 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1 KW - EC 3.1.3.48 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 - Index Medicus KW - Animals KW - Insulin-Like Growth Factor I -- deficiency KW - Protein Tyrosine Phosphatases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Phosphotyrosine -- metabolism KW - Mice KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - src Homology Domains KW - Signal Transduction KW - Female KW - Cell Division KW - Uterus -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Estradiol -- pharmacology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79836035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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-like+growth+factor-1+%28IGF-1%29+receptor-insulin+receptor+substrate+complexes+in+the+uterus.+Altered+signaling+response+to+estradiol+in+the+IGF-1%28m%2Fm%29+mouse.&rft.au=Richards%2C+R+G%3BWalker%2C+M+P%3BSebastian%2C+J%3BDiAugustine%2C+R+P&rft.aulast=Richards&rft.aufirst=R&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11962&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of an active site residue of tryptophan synthase (beta-serine 377) alters cofactor chemistry. AN - 79832356; 9565551 AB - To better understand how an enzyme controls cofactor chemistry, we have changed a tryptophan synthase residue that interacts with the pyridine nitrogen of the pyridoxal phosphate cofactor from a neutral Ser (beta-Ser377) to a negatively charged Asp or Glu. The spectroscopic properties of the mutant enzymes are altered and become similar to those of tryptophanase and aspartate aminotransferase, enzymes in which an Asp residue interacts with the pyridine nitrogen of pyridoxal phosphate. The absorption spectrum of each mutant enzyme undergoes a pH-dependent change (pKa approximately 7.7) from a form with a protonated internal aldimine nitrogen (lambdamax = 416 nm) to a deprotonated form (lambdamax = 336 nm), whereas the absorption spectra of the wild type tryptophan synthase beta2 subunit and alpha2 beta2 complex are pH-independent. The reaction of the S377D alpha2 beta2 complex with L-serine, L-tryptophan, and other substrates results in the accumulation of pronounced absorption bands (lambdamax = 498-510 nm) ascribed to quinonoid intermediates. We propose that the engineered Asp or Glu residue changes the cofactor chemistry by stabilizing the protonated pyridine nitrogen of pyridoxal phosphate, reducing the pKa of the internal aldimine nitrogen and promoting formation of quinonoid intermediates. JF - The Journal of biological chemistry AU - Jhee, K H AU - Yang, L H AU - Ahmed, S A AU - McPhie, P AU - Rowlett, R AU - Miles, E W AD - National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05/08/ PY - 1998 DA - 1998 May 08 SP - 11417 EP - 11422 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - Bacterial Proteins KW - 0 KW - Glutamates KW - Macromolecular Substances KW - Schiff Bases KW - Aspartic Acid KW - 30KYC7MIAI KW - Serine KW - 452VLY9402 KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Tryptophan KW - 8DUH1N11BX KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Hydrogen-Ion Concentration KW - Tryptophan -- chemistry KW - Aspartic Acid -- chemistry KW - Binding Sites KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Bacterial Proteins -- chemistry KW - Spectrum Analysis KW - Glutamates -- chemistry KW - Pyridoxal Phosphate -- metabolism KW - Tryptophan Synthase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79832356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+of+an+active+site+residue+of+tryptophan+synthase+%28beta-serine+377%29+alters+cofactor+chemistry.&rft.au=Jhee%2C+K+H%3BYang%2C+L+H%3BAhmed%2C+S+A%3BMcPhie%2C+P%3BRowlett%2C+R%3BMiles%2C+E+W&rft.aulast=Jhee&rft.aufirst=K&rft.date=1998-05-08&rft.volume=273&rft.issue=19&rft.spage=11417&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 - 1998-06-05 N1 - Date created - 1998-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychomotor slowing, negative symptoms and dopamine receptor availability--an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients. AN - 79943790; 9633833 AB - Anhedonia and psychomotor slowing in schizophrenia have been attributed to a dysfunction of dopaminergic neurotransmission. To differentiate between disease and drug-induced negative symptoms, we examined eight drug-free and eight neuroleptic-treated schizophrenic patients. Positive and negative symptoms and extrapyramidal side effects were assessed using standardized rating scales (PSAS, AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer-aided system and striatal dopamine D2/D3 receptor availability was assessed using [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening and avolition were increased in treated patients relative to the untreated cohort and were negatively correlated with dopamine D2/D3 receptor availability. Significant positive correlations were found between parkinsonism and affective flattening and between psychomotor slowing and avolition. Positive symptoms were not significantly associated with striatal IBZM binding. These findings support the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum can mimic certain negative symptoms, such as affective flattening and avolition, and indicates that psychomotor testing may be helpful in differentiating between disease and drug-induced negative symptoms. JF - Schizophrenia research AU - Heinz, A AU - Knable, M B AU - Coppola, R AU - Gorey, J G AU - Jones, D W AU - Lee, K S AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH, NIMH Neuroscience Center, Center at St. Elizabeths, Washington, DC 20032, USA. Y1 - 1998/05/04/ PY - 1998 DA - 1998 May 04 SP - 19 EP - 26 VL - 31 IS - 1 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Benzamides KW - Dopamine Antagonists KW - Pyrrolidines KW - Receptors, Dopamine KW - 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide KW - 84226-06-2 KW - Haloperidol KW - J6292F8L3D KW - Risperidone KW - L6UH7ZF8HC KW - Index Medicus KW - Acute Disease KW - Humans KW - Adult KW - Middle Aged KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Reaction Time KW - Receptors, Dopamine -- drug effects KW - Haloperidol -- adverse effects KW - Psychomotor Disorders -- diagnosis KW - Tomography, Emission-Computed, Single-Photon KW - Schizophrenia -- drug therapy KW - Risperidone -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Schizophrenia -- complications KW - Psychomotor Disorders -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79943790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Psychomotor+slowing%2C+negative+symptoms+and+dopamine+receptor+availability--an+IBZM+SPECT+study+in+neuroleptic-treated+and+drug-free+schizophrenic+patients.&rft.au=Heinz%2C+A%3BKnable%2C+M+B%3BCoppola%2C+R%3BGorey%2C+J+G%3BJones%2C+D+W%3BLee%2C+K+S%3BWeinberger%2C+D+R&rft.aulast=Heinz&rft.aufirst=A&rft.date=1998-05-04&rft.volume=31&rft.issue=1&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-14 N1 - Date created - 1998-09-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Schizophr Res 1998 Nov 9;34(1-2):121 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A trial of dextromethorphan in parkinsonian patients with motor response complications. AN - 85406657; pmid-9613730 AB - The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications. JF - Movement disorders : official journal of the Movement Disorder Society AU - Verhagen Metman, L AU - Blanchet, P J AU - van den Munckhof, P AU - Del Dotto, P AU - Natté, R AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 414 EP - 417 VL - 13 IS - 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Double-Blind Method KW - Dyskinesia, Drug-Induced -- drug therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Dyskinesia, Drug-Induced -- diagnosis KW - Aged KW - Dextromethorphan -- therapeutic use KW - Parkinson Disease -- drug therapy KW - Parkinson Disease -- diagnosis KW - Drug Therapy, Combination KW - Dextromethorphan -- adverse effects KW - Neurologic Examination -- drug effects KW - Activities of Daily Living -- classification KW - Cross-Over Studies KW - Middle Aged KW - Male KW - Female KW - Antiparkinson Agents -- adverse effects KW - Motor Skills -- drug effects KW - N-Methylaspartate -- antagonists & inhibitors KW - Carbidopa -- adverse effects KW - Antiparkinson Agents -- therapeutic use KW - Carbidopa -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85406657?accountid=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=A+trial+of+dextromethorphan+in+parkinsonian+patients+with+motor+response+complications.&rft.au=Verhagen+Metman%2C+L%3BBlanchet%2C+P+J%3Bvan+den+Munckhof%2C+P%3BDel+Dotto%2C+P%3BNatt%C3%A9%2C+R%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-05-01&rft.volume=13&rft.issue=3&rft.spage=414&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 - 2008-01-14 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The role of dendrites in auditory coincidence detection. AN - 85231130; pmid-9607764 AB - Coincidence-detector neurons in the auditory brainstem of mammals and birds use interaural time differences to localize sounds. Each neuron receives many narrow-band inputs from both ears and compares the time of arrival of the inputs with an accuracy of 10-100 micros. Neurons that receive low-frequency auditory inputs (up to about 2 kHz) have bipolar dendrites, and each dendrite receives inputs from only one ear. Using a simple model that mimics the essence of the known electrophysiology and geometry of these cells, we show here that dendrites improve the coincidence-detection properties of the cells. The biophysical mechanism for this improvement is based on the nonlinear summation of excitatory inputs in each of the dendrites and the use of each dendrite as a current sink for inputs to the other dendrite. This is a rare case in which the contribution of dendrites to the known computation of a neuron may be understood. Our results show that, in these neurons, the cell morphology and the spatial distribution of the inputs enrich the computational power of these neurons beyond that expected from 'point neurons' (model neurons lacking dendrites). JF - Nature AU - Agmon-Snir, H AU - Carr, C E AU - Rinzel, J AD - Mathematical Research Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 268 EP - 272 VL - 393 IS - 6682 SN - 0028-0836, 0028-0836 KW - Chickens KW - Support, U.S. Gov't, P.H.S. KW - Auditory Pathways KW - Animal KW - Brain Stem KW - Action Potentials KW - Support, Non-U.S. Gov't KW - Dendrites KW - Models, Neurological KW - Hearing KW - Auditory Perception UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231130?accountid=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=Nature&rft.atitle=The+role+of+dendrites+in+auditory+coincidence+detection.&rft.au=Agmon-Snir%2C+H%3BCarr%2C+C+E%3BRinzel%2C+J&rft.aulast=Agmon-Snir&rft.aufirst=H&rft.date=1998-05-01&rft.volume=393&rft.issue=6682&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. AN - 85225910; pmid-9603736 AB - DFNB3, a locus for nonsyndromic sensorineural recessive deafness, maps to a 3-centimorgan interval on human chromosome 17p11.2, a region that shows conserved synteny with mouse shaker-2. A human unconventional myosin gene, MYO15, was identified by combining functional and positional cloning approaches in searching for shaker-2 and DFNB3. MYO15 has at least 50 exons spanning 36 kilobases. Sequence analyses of these exons in affected individuals from three unrelated DFNB3 families revealed two missense mutations and one nonsense mutation that cosegregated with congenital recessive deafness. JF - Science AU - Wang, A AU - Liang, Y AU - Fridell, R A AU - Probst, F J AU - Wilcox, E R AU - Touchman, J W AU - Morton, C C AU - Morell, R J AU - Noben-Trauth, K AU - Camper, S A AU - Friedman, Thomas B AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 1447 EP - 1451 VL - 280 IS - 5368 SN - 0036-8075, 0036-8075 KW - Pedigree KW - Cochlea KW - Animals KW - Chromosomes, Human, Pair 17 KW - Exons KW - Humans KW - Myosins KW - Brain KW - Gene Expression KW - Mice KW - Amino Acid Sequence KW - Cosmids KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Research Support, U.S. Gov't, P.H.S. KW - Deafness KW - Sequence Alignment KW - Research Support, U.S. Gov't, Non-P.H.S. KW - Molecular Sequence Data KW - Point Mutation KW - Mutation KW - Genes, Recessive KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85225910?accountid=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=Science&rft.atitle=Association+of+unconventional+myosin+MYO15+mutations+with+human+nonsyndromic+deafness+DFNB3.&rft.au=Wang%2C+A%3BLiang%2C+Y%3BFridell%2C+R+A%3BProbst%2C+F+J%3BWilcox%2C+E+R%3BTouchman%2C+J+W%3BMorton%2C+C+C%3BMorell%2C+R+J%3BNoben-Trauth%2C+K%3BCamper%2C+S+A%3BFriedman%2C+Thomas+B&rft.aulast=Wang&rft.aufirst=A&rft.date=1998-05-01&rft.volume=280&rft.issue=5368&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. AN - 85225450; pmid-9603735 AB - The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea. JF - Science AU - Probst, F J AU - Fridell, R A AU - Raphael, Y AU - Saunders, T L AU - Wang, A AU - Liang, Y AU - Morell, R J AU - Touchman, J W AU - Lyons, R H AU - Noben-Trauth, K AU - Friedman, Thomas B AU - Camper, S A AD - Department of Human Genetics, 4701 MSRB III, University of Michigan, 1500 West Medical Center Drive, Ann Arbor, MI 48109, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 1444 EP - 1447 VL - 280 IS - 5368 SN - 0036-8075, 0036-8075 KW - Labyrinth KW - Support, U.S. Gov't, P.H.S. KW - Hair Cells KW - Human KW - Transgenes KW - Myosins KW - Animal KW - Brain KW - Mice KW - Amino Acid Sequence KW - Mice, Transgenic KW - Binding Sites KW - Phenotype KW - Deafness KW - Mice, Mutant Strains KW - Chromosomes, Bacterial KW - Liver KW - Genetic Complementation Test KW - Mice, Inbred C57BL KW - Point Mutation KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85225450?accountid=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=Science&rft.atitle=Correction+of+deafness+in+shaker-2+mice+by+an+unconventional+myosin+in+a+BAC+transgene.&rft.au=Probst%2C+F+J%3BFridell%2C+R+A%3BRaphael%2C+Y%3BSaunders%2C+T+L%3BWang%2C+A%3BLiang%2C+Y%3BMorell%2C+R+J%3BTouchman%2C+J+W%3BLyons%2C+R+H%3BNoben-Trauth%2C+K%3BFriedman%2C+Thomas+B%3BCamper%2C+S+A&rft.aulast=Probst&rft.aufirst=F&rft.date=1998-05-01&rft.volume=280&rft.issue=5368&rft.spage=1444&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Development of the mouse inner ear and origin of its sensory organs. AN - 85219243; pmid-9547240 AB - The molecular mechanisms dictating the morphogenesis and differentiation of the mammalian inner ear are largely unknown. To better elucidate the normal development of this organ, two approaches were taken. First, the membranous labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were filled with paint to reveal their gross development. Particular attention was focused on the developing utricle, saccule, and cochlea. Second, we used bone morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to identify the origin of the sensory structures. Our data showed that BMP4 was an early marker for the superior, lateral, and posterior cristae, whereas Fng served as an early marker for the macula utriculi, macula sacculi, and the sensory portion of the cochlea. The posterior crista was the first organ to appear at 11.5 dpc and was followed by the superior crista, the lateral crista, and the macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12 dpc but became distinguishable from each other by 13 dpc. Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst. JF - The Journal of Neuroscience AU - Morsli, H AU - Choo, D AU - Ryan, A AU - Johnson, R AU - Wu, Doris Kar-Wah AD - National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1998 SP - 3327 EP - 3335 VL - 18 IS - 9 SN - 0270-6474, 0270-6474 KW - Labyrinth KW - Support, U.S. Gov't, P.H.S. KW - Sense Organs KW - DNA-Binding Proteins KW - Morphogenesis KW - Animal KW - Cell Differentiation KW - Mice KW - Nerve Growth Factors KW - Fetal Proteins KW - Transcription Factors KW - Embryo and Fetal Development KW - Bone Morphogenetic Proteins KW - Neurotrophin 3 KW - Gene Expression Regulation, Developmental KW - Biological Markers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219243?accountid=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=Development+of+the+mouse+inner+ear+and+origin+of+its+sensory+organs.&rft.au=Morsli%2C+H%3BChoo%2C+D%3BRyan%2C+A%3BJohnson%2C+R%3BWu%2C+Doris+Kar-Wah&rft.aulast=Morsli&rft.aufirst=H&rft.date=1998-05-01&rft.volume=18&rft.issue=9&rft.spage=3327&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 - Role of wild-type p53 in the enhancement of camptothecin cytotoxicity against human prostate tumor cells. AN - 80027208; 9673414 AB - The role of wild-type human p53 protein in enhancing camptothecin cytotoxicity was examined by infecting human prostate PC3 cells with adenovirus expressing human wild-type p53 gene (Adwtp53). The prostate PC3 cells are null for p53 gene. Infection induced the synthesis of both wtp53, and WAF1 (p21) proteins, resulting in growth arrest of PC3 cells. In the presence of camptothecin, an inhibitor of topoisomerase 1, significant increases in both p53 and p21 proteins were detected in Adwtp53-infected PC3 cells. While Adwtp53 and camptothecin, as single agents, caused apoptosis and cell death, combinations of camptothecin and Adwtp53 were better in inducing apoptosis and cell death in PC3 cells. In contrast, cisplatin neither stabilized p53 and p21 proteins nor enhanced DNA fragmentation when combined with Adwtp53 in PC3 cells, indicating specificity for camptothecin. These observations suggest that introduction of wild-type p53 gene with topoisomerase I inhibitors may offer a clinical advantage for the treatment of prostate tumors containing mut53 or null for p53 gene. JF - Anticancer research AU - Arah, I N AU - Song, K AU - Seth, P AU - Cowan, K H AU - Sinha, B K AD - Department of Developmental Therapeutics, National Cancer Institute, NIH, Bethesda, Maryland 20982, USA. PY - 1998 SP - 1845 EP - 1849 VL - 18 IS - 3A SN - 0250-7005, 0250-7005 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Enzyme Inhibitors KW - Recombinant Proteins KW - Tumor Suppressor Protein p53 KW - Cisplatin KW - Q20Q21Q62J KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Adenoviridae KW - Cyclins -- biosynthesis KW - Recombinant Proteins -- biosynthesis KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Death -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Tumor Cells, Cultured KW - Transfection KW - Cisplatin -- toxicity KW - Genetic Vectors KW - Kinetics KW - Apoptosis -- drug effects KW - Enzyme Inhibitors -- metabolism KW - Male KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Prostatic Neoplasms -- pathology KW - Genes, p53 KW - Camptothecin -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80027208?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+wild-type+p53+in+the+enhancement+of+camptothecin+cytotoxicity+against+human+prostate+tumor+cells.&rft.au=Arah%2C+I+N%3BSong%2C+K%3BSeth%2C+P%3BCowan%2C+K+H%3BSinha%2C+B+K&rft.aulast=Arah&rft.aufirst=I&rft.date=1998-05-01&rft.volume=18&rft.issue=3A&rft.spage=1845&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 - 1998-08-10 N1 - Date created - 1998-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between glucocorticoids and corticotropin releasing hormone (CRH) in the regulation of the pituitary CRH receptor in vivo in the rat. AN - 80004174; 9663650 AB - Acute stress causes biphasic changes in corticotropin releasing hormone (CRH) receptor mRNA expression with an early decrease followed by an increase. However, in the absence of glucocorticoids in adrenalectomized rats, stress results in prolonged CRH receptor (CRH-R) mRNA loss, suggesting that interactions between glucocorticoids and hypothalamic factors are critical for regulation of CRH receptor mRNA. To address this question, CRH binding, type-1 CRH-R mRNA, POMC mRNA and POMC hnRNA expression were measured by binding autoradiography and in situ hybridization in pituitaries from intact and adrenalectomized rats. CRH-R mRNA decreased by 59% 5 h after injection of corticosterone (10 mg s.c.) and returned to basal levels by 18 h, a time when plasma corticosterone concentrations were still elevated, and CRH binding and POMC hnRNA were significantly reduced. Elevations in plasma corticosterone in the range of acute stress by injection of 2 mg s.c. caused CRH-R mRNA expression to return to near basal values by 6 h, after a 52% and 39% decrease at 2 h and 4 h. More transient changes were seen after a single injection of CRH (1 microg), with a 44% decrease in CRH-R mRNA and a 175% increase in POMC hnRNA by 2 h, returning to basal values by 4 h. The transient effect of CRH was not due to clearance of CRH from the circulation or receptor desensitization since CRH receptor mRNA expression also recovered after injection of a higher dose (10 microg) or repeated injections of CRH which caused sustained increases in plasma CRH and pituitary POMC hnRNA levels. CRH injection in adrenalectomized rats decreased CRH-R mRNA for up to 6 h, suggesting that glucocorticoids are permissive for the recovery of CRH-R mRNA. Supporting this hypothesis, simultaneous injection of corticosterone and CRH restored CRH-R mRNA expression by 4 h, and increased CRH binding 4 h and 6 h after injection. The data show that interaction between CRH and glucocorticoids counteracts individual inhibitory effects of these regulators alone, and that such effects are likely to contribute to the regulatory pattern of pituitary CRH receptors during acute stress. JF - Journal of neuroendocrinology AU - Ochedalski, T AU - Rabadan-Diehl, C AU - Aguilera, G AD - Section on Endocrine Physiology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 363 EP - 369 VL - 10 IS - 5 SN - 0953-8194, 0953-8194 KW - Glucocorticoids KW - 0 KW - RNA, Messenger KW - Receptors, Corticotropin-Releasing Hormone KW - RNA KW - 63231-63-0 KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - RNA, Messenger -- metabolism KW - RNA -- metabolism KW - Cell Nucleus -- metabolism KW - Pro-Opiomelanocortin -- genetics KW - Corticosterone -- pharmacology KW - Male KW - Pro-Opiomelanocortin -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- metabolism KW - Receptors, Corticotropin-Releasing Hormone -- drug effects KW - Receptors, Corticotropin-Releasing Hormone -- genetics KW - Pituitary Gland -- metabolism KW - Corticotropin-Releasing Hormone -- pharmacology KW - Glucocorticoids -- pharmacology KW - Pituitary Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80004174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+between+glucocorticoids+and+corticotropin+releasing+hormone+%28CRH%29+in+the+regulation+of+the+pituitary+CRH+receptor+in+vivo+in+the+rat.&rft.au=Ochedalski%2C+T%3BRabadan-Diehl%2C+C%3BAguilera%2C+G&rft.aulast=Ochedalski&rft.aufirst=T&rft.date=1998-05-01&rft.volume=10&rft.issue=5&rft.spage=363&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 - 1998-09-18 N1 - Date created - 1998-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis. AN - 79983248; 9651822 AB - This study used the induction of squamous cell carcinomas on mouse skin as an experimental model to evaluate molecular and biochemical changes that contribute to the neoplastic phenotype. The study was facilitated by the development of keratinocyte cell culture assays that reproduce each stage of the carcinogenesis process, by discoveries of stage-specific genetic and epigenetic changes and by application of pharmacological and molecular tools that modify each step. An early event in the transformation of keratinocytes involves mutation and activation of the rasHa gene, producing a benign tumor. The phenotypic consequences of ras mutations are mediated by activation of the epidermal growth factor receptor (EGFR), upregulation of protein kinase C (PKC) alpha and AP-1 mediated transcriptional activity and inactivation of PKC delta through tyrosine phosphorylation. These changes in benign tumors are manifested by hyperproliferation (EGFR), aberrant expression of keratinocyte genes (PKC alpha and AP-1) and delayed terminal differentiation (PKC delta). Accumulated chromosomal abnormalities, multifocal phenotypic changes and alterations in gene expression are associated with premalignant progression. Upregulation of the fos gene and AP-1 transcriptional activity causes malignant conversion of benign keratinocytes. In the absence of c-fos, benign tumor cells fail to upregulate secreted angiogenic and proteolytic factors and this may prevent malignant conversion. These pathways provide targets for preventive strategies to interrupt the process of carcinogenesis prior to the evolution of the fully malignant tumor. JF - Journal of dermatological science AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4335, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1 EP - 7 VL - 17 IS - 1 SN - 0923-1811, 0923-1811 KW - Index Medicus KW - Animals KW - Precancerous Conditions -- physiopathology KW - Papilloma -- etiology KW - Humans KW - Disease Progression KW - Papilloma -- metabolism KW - Carcinoma, Squamous Cell -- etiology KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatological+science&rft.atitle=The+pathogenesis+of+squamous+cell+cancer%3A+lessons+learned+from+studies+of+skin+carcinogenesis.&rft.au=Yuspa%2C+S+H&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1998-05-01&rft.volume=17&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+dermatological+science&rft.issn=09231811&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-18 N1 - Date created - 1998-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident. AN - 79978456; 9520360 AB - In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes. JF - Environmental health perspectives AU - Landi, M T AU - Consonni, D AU - Patterson, D G AU - Needham, L L AU - Lucier, G AU - Brambilla, P AU - Cazzaniga, M A AU - Mocarelli, P AU - Pesatori, A C AU - Bertazzi, P A AU - Caporaso, N E AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 273 EP - 277 VL - 106 IS - 5 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Polychlorinated Dibenzodioxins KW - 1,2,3,4-tetrachlorodibenzodioxin KW - HF5S8P28CC KW - Index Medicus KW - Meat KW - Demography KW - Sex Characteristics KW - Humans KW - Middle Aged KW - Diet KW - Aging -- blood KW - Male KW - Italy KW - Female KW - Multivariate Analysis KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- blood KW - Environmental Pollutants -- blood KW - Accidents, Occupational UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79978456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin+plasma+levels+in+Seveso+20+years+after+the+accident.&rft.au=Landi%2C+M+T%3BConsonni%2C+D%3BPatterson%2C+D+G%3BNeedham%2C+L+L%3BLucier%2C+G%3BBrambilla%2C+P%3BCazzaniga%2C+M+A%3BMocarelli%2C+P%3BPesatori%2C+A+C%3BBertazzi%2C+P+A%3BCaporaso%2C+N+E&rft.aulast=Landi&rft.aufirst=M&rft.date=1998-05-01&rft.volume=106&rft.issue=5&rft.spage=273&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 - 1998-09-02 N1 - Date created - 1998-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int Arch Occup Environ Health. 1979 Mar 7;43(1):1-15 [107126] Teratog Carcinog Mutagen. 1997-1998;17(4-5):225-40 [9508732] J Natl Cancer Inst. 1986 Feb;76(2):229-34 [3456061] JAMA. 1986 Nov 21;256(19):2683-6 [3490589] J Occup Med. 1987 May;29(5):422-9 [2439670] J Natl Cancer Inst. 1987 Oct;79(4):693-9 [3116310] Carcinogenesis. 1988 Sep;9(9):1677-9 [3409472] J Occup Med. 1989 Feb;31(2):121-3 [2709162] Hum Toxicol. 1989 May;8(3):173-203 [2663703] Helv Chir Acta. 1989 Apr;55(6):861-8 [2753726] Int Arch Occup Environ Health. 1990;62(2):139-57 [2139014] N Engl J Med. 1991 Jan 24;324(4):212-8 [1985242] Cancer Res. 1991 Mar 1;51(5):1391-7 [1671757] J Toxicol Environ Health. 1991 Apr;32(4):357-66 [1826746] Lancet. 1991 Oct 19;338(8773):959-64 [1681339] Lancet. 1991 Oct 26;338(8774):1027-32 [1681353] Drug Metab Dispos. 1993 Jan-Feb;21(1):43-9 [8095225] Epidemiology. 1993 Sep;4(5):398-406 [8399687] Am J Epidemiol. 1994 Feb 1;139(3):272-81 [8116602] Eur J Pharmacol. 1995 May 26;293(1):1-40 [7545581] Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):529-33 [7549810] J Toxicol Environ Health. 1996 Mar;47(4):363-78 [8600289] J Toxicol Environ Health. 1996 Feb 23;47(3):209-20 [8604146] J Biol Chem. 1996 May 3;271(18):10533-7 [8631852] Cancer Causes Control. 1996 May;7(3):312-21 [8734824] Lancet. 1996 Aug 10;348(9024):409 [8709758] Occup Environ Med. 1996 Sep;53(9):606-12 [8882118] Am J Ind Med. 1996 Dec;30(6):647-54 [8914711] Epidemiology. 1997 Nov;8(6):646-52 [9345664] Nature. 1982 Nov 18;300(5889):271-3 [7144882] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictors of mortality in bacteremic cancer patients: retrospective analysis of 64 deaths occurring among 262 bacteremic episodes. AN - 79941087; 9629885 AB - A total of 262 bacteremic episodes were observed in cancer patients in a single cancer institution during the last 7 years, and the recorded outcome was death in 65. The 65 patients who died (24.8% overall mortality) were divided retrospectively into two subgroups: (a) those who died of underlying disease with bacteremia (45 cases, 16.9% crude mortality) and (b) those who died of bacteremia (20 patients, 7.7% attributable mortality). Comparison of several risk factors in subgroups of patients who achieved a cure (197 cases) and of those who died and whose deaths were attributable (20 cases) revealed six risk factors that were associated with attributable mortality: (1) chemotherapy-induced neutropenia (P < 0.03), (2) Acinetobacter/Stenotrophomonas spp. bacteremias (P < 0.001), (3) liver failure (P < 0.001), (4) inappropriate therapy (P < 0.0001), (5) organ complications (P < 0.003) and (6) multiresistant organisms (P < 0.001). Enterococci and Pseudomonas aeruginosa, surprisingly, were found more frequently in those who died of an underlying disease with bacteremia than among patients who were cured (17.6% vs 7.6%, P < 0.05 and 29.1% vs 13.8%, P < 0.02). Those who died of infection had higher numbers of positive blood cultures, with 2.05 per episode, than did those who died of underlying disease with bacteremia (1.82) or those who were cured (1.51). Other risk factors, such as underlying disease, type of chemotherapy, origin of bacteremia, age, and catheters did not predict either overall or attributable mortality within the study group. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Spanik, S AU - Sufliarsky, J AU - Mardiak, J AU - Sorkovska, D AU - Trupl, J AU - Kunova, A AU - Kukuckova, E AU - Rusnakova, V AU - Demitrovicova, A AU - Pichna, P AU - Krupova, I AU - Kralovicova, K AU - Mateićka, F AU - West, D AU - Krcmery, V AD - Department of Medicine and Microbiology, National Cancer Institute, Bratislava, Slovakia. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 291 EP - 294 VL - 6 IS - 3 SN - 0941-4355, 0941-4355 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Neutropenia -- mortality KW - Humans KW - Retrospective Studies KW - Aged KW - Bacteria -- isolation & purification KW - Neutropenia -- chemically induced KW - Antineoplastic Agents -- adverse effects KW - Risk Factors KW - Adult KW - Antibiotic Prophylaxis KW - Middle Aged KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Bacteremia -- mortality KW - Neoplasms -- mortality KW - Opportunistic Infections -- mortality KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79941087?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Predictors+of+mortality+in+bacteremic+cancer+patients%3A+retrospective+analysis+of+64+deaths+occurring+among+262+bacteremic+episodes.&rft.au=Spanik%2C+S%3BSufliarsky%2C+J%3BMardiak%2C+J%3BSorkovska%2C+D%3BTrupl%2C+J%3BKunova%2C+A%3BKukuckova%2C+E%3BRusnakova%2C+V%3BDemitrovicova%2C+A%3BPichna%2C+P%3BKrupova%2C+I%3BKralovicova%2C+K%3BMatei%C4%87ka%2C+F%3BWest%2C+D%3BKrcmery%2C+V&rft.aulast=Spanik&rft.aufirst=S&rft.date=1998-05-01&rft.volume=6&rft.issue=3&rft.spage=291&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 - 1998-08-24 N1 - Date created - 1998-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures. AN - 79939388; 9626992 AB - Activation of brain glial cells with the bacterial endotoxin lipopolysaccharide (LPS), the HIV-1 coat protein gp120, or beta-amyloid-derived peptides, stimulates the expression of several cytokines, including tumor necrosis factor-alpha (TNFalpha), interleukin-1 (IL-1) and IL-6. and nitric oxide (NO) which have been proposed as causes of neurodegeneration in the brain. In the present study, the neurotoxic effects of several cytokines, alone or in various combinations, and the correlations of the release of lactate dehydrogenase, the loss of neurons, and the secretion of NO in brain neuronal cell injury were investigated in murine primary mixed neuronal/glial cell cultures. A specific combination of cytokines, i.e., IL-1 (1 ng/ml)+ TNFalpha (10 ng/ml)/interferon-gamma (IFNgamma) (200 u/ml), induced a dramatic neuronal cell injury in the neuron/glia cultures, and its cytotoxic profile was very similar to that seen with the LPS/IFNgamma-induced neuron injury. This indicates that among the many toxic immune mediators secreted in response to LPS, IL-1 and TNFalpha can mimic LPS as the triggering signals and primary mediators for glia-mediated neuron injury in the presence of IFNgamma. This study provides new insights about the cytotoxic mechanism(s) for cytokine-mediated neuron injury. JF - Journal of neuroimmunology AU - Jeohn, G H AU - Kong, L Y AU - Wilson, B AU - Hudson, P AU - Hong, J S AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 1 EP - 10 VL - 85 IS - 1 SN - 0165-5728, 0165-5728 KW - Cytokines KW - 0 KW - Drug Combinations KW - Enzyme Inhibitors KW - Interleukin-1 KW - Lipopolysaccharides KW - Neurotoxins KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Interferon-gamma KW - 82115-62-6 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Coculture Techniques KW - Interleukin-1 -- pharmacology KW - NG-Nitroarginine Methyl Ester -- pharmacology KW - Lipopolysaccharides -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Nitric Oxide -- metabolism KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Inbred Strains KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - L-Lactate Dehydrogenase -- metabolism KW - Neuroglia -- metabolism KW - Neurons -- metabolism KW - Cytokines -- pharmacology KW - Neurons -- drug effects KW - Neurotoxins -- pharmacology KW - Neuroglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79939388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+neurotoxic+effects+of+combined+treatments+with+cytokines+in+murine+primary+mixed+neuron%2Fglia+cultures.&rft.au=Jeohn%2C+G+H%3BKong%2C+L+Y%3BWilson%2C+B%3BHudson%2C+P%3BHong%2C+J+S&rft.aulast=Jeohn&rft.aufirst=G&rft.date=1998-05-01&rft.volume=85&rft.issue=1&rft.spage=1&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 - 1998-07-07 N1 - Date created - 1998-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. AN - 79938123; 9626024 AB - Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency. JF - The American journal of medicine AU - Termanini, B AU - Gibril, F AU - Sutliff, V E AU - Yu, F AU - Venzon, D J AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 422 EP - 430 VL - 104 IS - 5 SN - 0002-9343, 0002-9343 KW - Anti-Ulcer Agents KW - 0 KW - Folic Acid KW - 935E97BOY8 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Omeprazole KW - KG60484QX9 KW - Vitamin B 12 KW - P6YC3EG204 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Folic Acid -- blood KW - Drug Monitoring KW - Adult KW - Aged KW - Vitamin B 12 -- blood KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Vitamin B 12 Deficiency -- blood KW - Anti-Ulcer Agents -- adverse effects KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- adverse effects KW - Adenosine Triphosphatases -- antagonists & inhibitors KW - Vitamin B 12 Deficiency -- chemically induced KW - Achlorhydria -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79938123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicine&rft.atitle=Effect+of+long-term+gastric+acid+suppressive+therapy+on+serum+vitamin+B12+levels+in+patients+with+Zollinger-Ellison+syndrome.&rft.au=Termanini%2C+B%3BGibril%2C+F%3BSutliff%2C+V+E%3BYu%2C+F%3BVenzon%2C+D+J%3BJensen%2C+R+T&rft.aulast=Termanini&rft.aufirst=B&rft.date=1998-05-01&rft.volume=104&rft.issue=5&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside. AN - 79935138; 9626559 AB - Sodium nitroprusside (disodium nitroferricyanide) has been suggested to cause cytotoxicity through either the release of cyanide and/or nitric oxide. The present study investigated a possible mechanism that after a brief release of nitric oxide, iron moiety of breakdown products of sodium nitroprusside could cause a long lasting oxidative stress, such as hydroxyl radical generation, lipid peroxidation and cytotoxicity. Intranigral administration of sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the caudate nucleus. Photodegraded (nitric oxide-exhausted) sodium nitroprusside, however, still produced lipid peroxidation and neurotoxicity in the midbrain. Moreover, non-iron containing nitric oxide-donor compounds, such as S-nitroso-N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro studies demonstrated that both freshly prepared (nitric oxide donor) and photodegraded (nitric oxide-exhausted) sodium nitroprusside generated hydroxyl radicals in the presence of ascorbate and also increased lipid peroxidation in brain homogenates. These pro-oxidative effects of sodium nitroprusside were blocked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin, and deferoxamine (iron chelator). The present results suggest that iron moiety, rather than nitric oxide, may mediate the pro-oxidative properties of sodium nitroprusside. With this new information in mind, the misuse of sodium nitroprusside as a selective nitric oxide donor in both basic and clinical uses should be urgently addressed. JF - Free radical biology & medicine AU - Rauhala, P AU - Khaldi, A AU - Mohanakumar, K P AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1065 EP - 1073 VL - 24 IS - 7-8 SN - 0891-5849, 0891-5849 KW - Oxyhemoglobins KW - 0 KW - S-nitro-N-acetylpenicillamine KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Iron KW - E1UOL152H7 KW - Penicillamine KW - GNN1DV99GX KW - Deferoxamine KW - J06Y7MXW4D KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Oxyhemoglobins -- pharmacology KW - Animals KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Lipid Peroxidation -- drug effects KW - Nerve Degeneration -- chemically induced KW - Nitric Oxide -- metabolism KW - Ascorbic Acid -- pharmacology KW - Iron -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Deferoxamine -- pharmacology KW - In Vitro Techniques KW - Oxidative Stress -- drug effects KW - Nitric Oxide -- pharmacology KW - Male KW - Hydroxyl Radical -- metabolism KW - Nitroprusside -- toxicity KW - Brain Injuries -- chemically induced KW - Brain Injuries -- pathology KW - Brain Injuries -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79935138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apparent+role+of+hydroxyl+radicals+in+oxidative+brain+injury+induced+by+sodium+nitroprusside.&rft.au=Rauhala%2C+P%3BKhaldi%2C+A%3BMohanakumar%2C+K+P%3BChiueh%2C+C+C&rft.aulast=Rauhala&rft.aufirst=P&rft.date=1998-05-01&rft.volume=24&rft.issue=7-8&rft.spage=1065&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 - 1998-09-16 N1 - Date created - 1998-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transfection of interleukin-12 cDNAs into tumor cells induces cytotoxic immune responses against native tumor: implications for tumor vaccination. AN - 79927210; 9622098 AB - Interleukin-12 (IL-12) is a heterodimeric cytokine that is central to the development of T helper 1-dependent cellular immunity. Although this cytokine has potential therapeutic application as an antineoplastic agent, the systemic infusion of IL-12 has led to toxic fatalities; hence, restriction of expression of IL-12 to the microenvironment of target tumor cells has obvious appeal. In this study, we examined whether tumor cells that were liposome-transfected with IL-12 could enhance the induction of cytolytic lymphocyte immunity to the native tumor. The plasmid expression vector that we used has several useful features including replication to high copy number as an episome and a polycistronic message enabling the production of both the p35 and p40 subunits of IL-12 without alternative splicing; up to 3 ng/mL/10(6)/48 hours of IL-12 was produced following transfection. Tumor cells transfected with IL-12 were superior to untransfected cells in the induction of lymphocyte-mediated cytolysis. IL-12 transfectants induced a heterogeneous population of natural killer, lymphokine activated killer, and cytolytic T lymphocytes, the latter of which exhibited tumor-specific activity. Our studies suggest that liposome-mediated transfection of tumor cells with an episomal, high copy number plasmid vector expressing both IL-12 subunits is a promising approach to cancer vaccination, a strategy that could be implemented ex vivo in treating malignancies such as metastatic ovarian cancer. JF - Cancer gene therapy AU - Hoshino, T AU - Jiang, Y Z AU - Dunn, D AU - Paul, D AU - Qazilbash, M AU - Cowan, K AU - Wang, J AU - Barrett, J AU - Liu, J AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 150 EP - 157 VL - 5 IS - 3 SN - 0929-1903, 0929-1903 KW - Cancer Vaccines KW - 0 KW - DNA, Complementary KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Lymphocytes -- immunology KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - Genetic Vectors KW - Dependovirus -- genetics KW - Enzyme-Linked Immunosorbent Assay KW - Cytotoxicity, Immunologic KW - Cancer Vaccines -- administration & dosage KW - Cancer Vaccines -- immunology KW - Interleukin-12 -- biosynthesis KW - Interleukin-12 -- genetics KW - Interleukin-12 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79927210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gene+therapy&rft.atitle=Transfection+of+interleukin-12+cDNAs+into+tumor+cells+induces+cytotoxic+immune+responses+against+native+tumor%3A+implications+for+tumor+vaccination.&rft.au=Hoshino%2C+T%3BJiang%2C+Y+Z%3BDunn%2C+D%3BPaul%2C+D%3BQazilbash%2C+M%3BCowan%2C+K%3BWang%2C+J%3BBarrett%2C+J%3BLiu%2C+J&rft.aulast=Hoshino&rft.aufirst=T&rft.date=1998-05-01&rft.volume=5&rft.issue=3&rft.spage=150&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 completed - 1998-08-05 N1 - Date created - 1998-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. AN - 79923309; 9619195 AB - The PET H2 15O-bolus method was used to image regional brain activity in normal human subjects during intense pain induced by intradermal injection of capsaicin and during post-capsaicin mechanical allodynia (the perception of pain from a normally non-painful stimulus). Images of regional cerebral blood flow were acquired during six conditions: (i) rest; (ii) light brushing of the forearm; (iii) forearm intradermal injection of capsaicin, (iv) and (v) the waning phases of capsaicin pain; and (vi) allodynia. Allodynia was produced by light brushing adjacent to the capsaicin injection site after ongoing pain from the capsaicin injection had completely subsided. Capsaicin treatment produced activation in many discrete brain regions which we classified as subserving four main functions: sensation-perception (primary somatosensory cortex, thalamus and insula); attention (anterior cingulate cortex); descending pain control (periaqueductal grey); and an extensive network related to sensory-motor integration (supplementary motor cortex, bilateral putamen and insula, anterior lobe and vermis of the cerebellum and superior colliculus). Comparison of the noxious and non-noxious stimuli yielded several new insights into neural organization of pain and tactile sensations. Capsaicin pain, which had no concomitant tactile component, produced little or no activation in secondary somatosensory cortex (SII), whereas light brushing produced a prominent activation of SII, suggesting a differential sensitivity of SII to tactile versus painful stimuli. The cerebellar vermis was strongly activated by capsaicin, whereas light brush and experimental allodynia produced little or no activation, suggesting a selective association with C-fibre stimulation and nociceptive second-order spinal neurons. The experimental allodynia activated a network that partially overlapped those activated by both pain and light brush alone. Unlike capsaicin-induced pain, allodynia was characterized by bilateral activation of inferior prefrontal cortex, suggesting that prefrontal responses to pain are context dependent. JF - Brain : a journal of neurology AU - Iadarola, M J AU - Berman, K F AU - Zeffiro, T A AU - Byas-Smith, M G AU - Gracely, R H AU - Max, M B AU - Bennett, G J AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4410, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 931 EP - 947 VL - 121 ( Pt 5) SN - 0006-8950, 0006-8950 KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Dose-Response Relationship, Drug KW - Cerebrovascular Circulation -- drug effects KW - Humans KW - Perception -- physiology KW - Evaluation Studies as Topic KW - Stress, Mechanical KW - Adult KW - Injections, Subcutaneous KW - Middle Aged KW - Image Processing, Computer-Assisted KW - Female KW - Male KW - Capsaicin -- toxicity KW - Tomography, Emission-Computed KW - Neuralgia -- chemically induced KW - Neuralgia -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79923309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%3A+a+journal+of+neurology&rft.atitle=Neural+activation+during+acute+capsaicin-evoked+pain+and+allodynia+assessed+with+PET.&rft.au=Iadarola%2C+M+J%3BBerman%2C+K+F%3BZeffiro%2C+T+A%3BByas-Smith%2C+M+G%3BGracely%2C+R+H%3BMax%2C+M+B%3BBennett%2C+G+J&rft.aulast=Iadarola&rft.aufirst=M&rft.date=1998-05-01&rft.volume=121+%28+Pt+5%29&rft.issue=&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Brain+%3A+a+journal+of+neurology&rft.issn=00068950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-23 N1 - Date created - 1998-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of static magnetic fields on the photohemolysis of human erythrocytes by ketoprofen. AN - 79911557; 9613243 AB - Ultraviolet irradiation (lambda > 300 nm) of the nonsteroidal anti-inflammatory agent ketoprofen (KP, 3-benzoyl-alpha-methylbenzoacetic acid) in aqueous solution, pH 7.4, results in heterolytic decarboxylation of the drug to give 3-ethylbenzophenone (EtBP). Ketoprofen caused the photohemolysis of human erythrocytes probably as a result of lipid peroxidation. Application of a static magnetic field (250-1500 G) during UV (> 300 nm) irradiation of KP and erythrocytes significantly decreased the time required for photohemolysis. This observation suggests that KP-induced photohemolysis involves the initial generation of a triplet radical pair derived from the reaction of triplet state KP (or 3-EtBP) with erythrocyte component(s) probably lipids. The magnetic field increases the concentration and/or lifetime of free radicals that escape from the radical pair so that the critical radical concentration needed to initiate membrane damage and cause cell lysis is reached sooner. Spin-trapping studies with 2,6-dibromo-1-nitrosobenzene-4-sulfonate confirmed that the application of an external static magnetic field increased the concentration of radicals released during the photolysis of either KP or 3-EtBP dissolved in organized media such as sodium dodecylsulfate micelles. JF - Photochemistry and photobiology AU - Chignell, C F AU - Sik, R H AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chignell@niehs.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 591 EP - 595 VL - 67 IS - 5 SN - 0031-8655, 0031-8655 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Ketoprofen KW - 90Y4QC304K KW - Index Medicus KW - Photochemistry KW - Hemolysis -- drug effects KW - Ultraviolet Rays KW - Humans KW - Hemolysis -- radiation effects KW - Erythrocytes -- drug effects KW - Electromagnetic Fields KW - Erythrocytes -- radiation effects KW - Anti-Inflammatory Agents, Non-Steroidal -- adverse effects KW - Ketoprofen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79911557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+static+magnetic+fields+on+the+photohemolysis+of+human+erythrocytes+by+ketoprofen.&rft.au=Chignell%2C+C+F%3BSik%2C+R+H&rft.aulast=Chignell&rft.aufirst=C&rft.date=1998-05-01&rft.volume=67&rft.issue=5&rft.spage=591&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 - 1998-06-24 N1 - Date created - 1998-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a National Toxicology Program update. AN - 79910076; 9608650 AB - Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (50.5%), adrenal gland pheochromocytoma (31.9%), and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituitary gland neoplasms (54.2%), mammary gland fibroadenoma (41.2%), and mononuclear cell leukemia (28.1%). The most frequently occurring neoplasms in untreated male B6C3F1 mice were liver adenoma/carcinoma (42.2%), lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F1 mice, the most frequently occurring neoplasms were liver adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland adenoma/carcinoma (14.8%). The tumor rates observed in feeding study (untreated) and inhalation study (chamber) control rats were generally similar. The major exceptions were pituitary gland tumors and testicular adenoma in male F344 rats. The overall incidence of testicular adenoma was much lower in chamber controls (69.4%) than in feeding study controls (89.1%), whereas pituitary gland neoplasm showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this difference is related to the individual housing of chamber controls and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure consistency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review procedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with increased incidences of certain site-specific neoplasms, especially pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The presence of Helicobacter hepaticus has been associated with an increased incidence of liver neoplasms in male B6C3F1 mice. Other factors that may produce differences in control tumor rates from study to study include diet, environmental factors, genetic drift, study duration, and survival differences. The NTP database provides historical control data that may be useful in the evaluation of possible chemically related changes in tumor incidence. However, it is essential that the study being evaluated be comparable to those in the NTP database with respect to those factors that are known to influence tumor occurrence. JF - Toxicologic pathology AU - Haseman, J K AU - Hailey, J R AU - Morris, R W AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1998 SP - 428 EP - 441 VL - 26 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Survival Rate KW - Mice KW - Male KW - Female KW - Neoplasms -- veterinary KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Neoplasms -- pathology KW - Rodent Diseases -- epidemiology KW - Neoplasms -- epidemiology KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79910076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spontaneous+neoplasm+incidences+in+Fischer+344+rats+and+B6C3F1+mice+in+two-year+carcinogenicity+studies%3A+a+National+Toxicology+Program+update.&rft.au=Haseman%2C+J+K%3BHailey%2C+J+R%3BMorris%2C+R+W&rft.aulast=Haseman&rft.aufirst=J&rft.date=1998-05-01&rft.volume=26&rft.issue=3&rft.spage=428&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in cyclophosphamide-associated bladder cancer. AN - 79908839; 9610789 AB - Cyclophosphamide is a known bladder carcinogen, with cumulative dose directly related to increased risk. There is no consensus, however, on which major cyclophosphamide metabolite (i.e., acrolein or phosphoramide mustard) drives bladder carcinogenesis. We examined 19 cyclophosphamide-related bladder tumors to test the hypothesis that they might contain somatic mutations in the p53 tumor suppressor gene that could link a specific metabolite to the etiology of these cancers. Forty-three % (9 of 19) of the cases had a mutation in p53, with a predominance at G:C bp (7 of 9, 77%), a preference for non-CpG sites (6 of 7, 86%), and frequent G:C-->A:T transitions (5 of 7, 71%). The p53 mutation spectrum of these cyclophosphamide-associated bladder cancers differed significantly from patterns reported for sporadic (P = 0.020), smoking-related (0.043), and schistosomiasis-linked (P = 0.002) tumors but not arylamine-associated neoplasms (P = 0.860). Differences between the cyclophosphamide and arylamine-associated spectra included an unusual degree of clustering of exon 6 mutations (43% versus 17%, respectively) and an absence of multiple mutations in the former. Notably lacking in our series were G:C-->T:A transversions, the principal mutation associated with acrolein. Instead, the mutation spectrum matches the phosphoramide mustard adduction sequences determined by a repetitive primer-extension assay (P = 0.024), indicating that this metabolite might be a key mutagen in cyclophosphamide-related bladder cancer. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Khan, M A AU - Travis, L B AU - Lynch, C F AU - Soini, Y AU - Hruszkewycz, A M AU - Delgado, R M AU - Holowaty, E J AU - van Leeuwen, F E AU - Glimelius, B AU - Stovall, M AU - Boice, J D AU - Tarone, R E AU - Bennett, W P AD - Laboratory of Human Carcinogenesis, Radiation Epidemiology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 397 EP - 403 VL - 7 IS - 5 SN - 1055-9965, 1055-9965 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Humans KW - DNA Mutational Analysis KW - Lymphoma, Non-Hodgkin -- complications KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Genes, p53 -- drug effects KW - Urinary Bladder Neoplasms -- secondary KW - Urinary Bladder Neoplasms -- genetics KW - Mutation -- genetics KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Urinary Bladder Neoplasms -- chemically induced KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79908839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+cyclophosphamide-associated+bladder+cancer.&rft.au=Khan%2C+M+A%3BTravis%2C+L+B%3BLynch%2C+C+F%3BSoini%2C+Y%3BHruszkewycz%2C+A+M%3BDelgado%2C+R+M%3BHolowaty%2C+E+J%3Bvan+Leeuwen%2C+F+E%3BGlimelius%2C+B%3BStovall%2C+M%3BBoice%2C+J+D%3BTarone%2C+R+E%3BBennett%2C+W+P&rft.aulast=Khan&rft.aufirst=M&rft.date=1998-05-01&rft.volume=7&rft.issue=5&rft.spage=397&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 - 1999-01-12 N1 - Date created - 1999-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glycine modulates the toxicity of benzyl acetate in F344 rats. AN - 79908384; 9608646 AB - The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity. JF - Toxicologic pathology AU - Abdo, K M AU - Wenk, M L AU - Harry, G J AU - Mahler, J AU - Goehl, T J AU - Irwin, R D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. abdok@niehs.nih.gov PY - 1998 SP - 395 EP - 402 VL - 26 IS - 3 SN - 0192-6233, 0192-6233 KW - Air Pollutants, Occupational KW - 0 KW - Benzyl Compounds KW - benzyl acetate KW - 0ECG3V79ZJ KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Ataxia -- chemically induced KW - Dose-Response Relationship, Drug KW - Brain -- drug effects KW - Air Pollutants, Occupational -- adverse effects KW - Hypertrophy -- prevention & control KW - Seizures -- prevention & control KW - Rats KW - Rats, Inbred F344 KW - Necrosis KW - Survival Rate KW - Brain -- pathology KW - Weight Loss -- drug effects KW - Dietary Supplements KW - Hypertrophy -- chemically induced KW - Ataxia -- prevention & control KW - Male KW - Organ Size -- drug effects KW - Neurodegenerative Diseases -- chemically induced KW - Benzyl Compounds -- adverse effects KW - Glycine -- pharmacology KW - Neurodegenerative Diseases -- pathology KW - Neurodegenerative Diseases -- mortality KW - Neurodegenerative Diseases -- prevention & control KW - Glycine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79908384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glycine+modulates+the+toxicity+of+benzyl+acetate+in+F344+rats.&rft.au=Abdo%2C+K+M%3BWenk%2C+M+L%3BHarry%2C+G+J%3BMahler%2C+J%3BGoehl%2C+T+J%3BIrwin%2C+R+D&rft.aulast=Abdo&rft.aufirst=K&rft.date=1998-05-01&rft.volume=26&rft.issue=3&rft.spage=395&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 - 1998-08-12 N1 - Date created - 1998-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive oxygen-mediated protein oxidation in aging and disease. AN - 79904399; 9606602 AB - Highly reactive oxygen species that are formed during normal metabolism and under conditions of oxidative stress are able to oxidize proteins or convert lipid and carbohydrate derivatives to compounds that react with functional groups on proteins. Among other changes, these ROS-mediated reactions lead to the formation of protein carbonyl derivatives, which serves as a marker of ROS-mediated protein damage. On the basis of this marker, it is established that oxidatively damaged protein is associated with aging and some diseases. The accumulation of oxidatively damaged protein reflects the balance among a myriad of factors that govern the rates of ROS generation and the rate at which damaged protein is degraded. Peroxynitrite, which is formed under normal physiological conditions, is able to oxidize methionine residues in proteins and to nitrate tyrosine residues; however, its ability to do so is dependent on the availability of CO2, which stimulates the nitration of tyrosine residues but inhibits the oxidation of methionine residues. Nitration of tyrosine residues may contribute to peroxynitrite toxicity, as nitration precludes the phosphorylation or nucleotidylation of tyrosine residues and thereby seriously compromises one of the most important mechanisms of cellular regulation and signal transduction. JF - Drug metabolism reviews AU - Stadtman, E R AU - Berlett, B S AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0342, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 225 EP - 243 VL - 30 IS - 2 SN - 0360-2532, 0360-2532 KW - Oxidants KW - 0 KW - Proteins KW - Reactive Oxygen Species KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Oxidants -- adverse effects KW - Humans KW - Aging -- metabolism KW - Disease -- etiology KW - Reactive Oxygen Species -- physiology KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79904399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+metabolism+reviews&rft.atitle=Reactive+oxygen-mediated+protein+oxidation+in+aging+and+disease.&rft.au=Stadtman%2C+E+R%3BBerlett%2C+B+S&rft.aulast=Stadtman&rft.aufirst=E&rft.date=1998-05-01&rft.volume=30&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-23 N1 - Date created - 1998-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. AN - 79903327; 9608532 AB - To ascertain the function of an orphan nuclear receptor Nurr1, a transcription factor belonging to a large gene family that includes receptors for steroids, retinoids, and thyroid hormone, we generated Nurr1-null mice by homologous recombination. Mice, heterozygous for a single mutated Nurr1 allele, appear normal, whereas mice homozygous for the null allele die within 24 h after birth. Dopamine (DA) was absent in the substantia nigra (SN) and ventral tegmental area (VTA) of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase, and other DA neuron markers. TH immunoreactivity and mRNA expression in hypothalamic, olfactory, and lower brain stem regions were unaffected. L-Dihydroxyphenylalanine treatments, whether given to the pregnant dams or to the newborns, failed to rescue the Nurr1-null mice. We were unable to discern differences between null and wild-type mice in the cellularity, presence of neurons, or axonal projections to the SN and VTA. These findings provide evidence for a new mechanism of DA depletion in vivo and suggest a unique role for Nurr1 in fetal development and/or postnatal survival. JF - Molecular and cellular neurosciences AU - Castillo, S O AU - Baffi, J S AU - Palkovits, M AU - Goldstein, D S AU - Kopin, I J AU - Witta, J AU - Magnuson, M A AU - Nikodem, V M AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1766, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 36 EP - 46 VL - 11 IS - 1-2 SN - 1044-7431, 1044-7431 KW - Biomarkers KW - 0 KW - DNA-Binding Proteins KW - Nr4a2 protein, mouse KW - Nuclear Receptor Subfamily 4, Group A, Member 2 KW - RNA, Messenger KW - Transcription Factors KW - Levodopa KW - 46627O600J KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Exons KW - RNA, Messenger -- analysis KW - Mice KW - Pregnancy KW - Phenotype KW - Levodopa -- pharmacology KW - Brain Chemistry -- genetics KW - Heterozygote KW - Mice, Inbred C57BL KW - Mice, Neurologic Mutants KW - Female KW - Mutagenesis, Insertional KW - Substantia Nigra -- metabolism KW - Neurons -- metabolism KW - Dopamine -- deficiency KW - Ventral Tegmental Area -- pathology KW - Substantia Nigra -- pathology KW - Hypothalamus -- metabolism KW - Dopamine -- physiology KW - Dopamine -- biosynthesis KW - Ventral Tegmental Area -- metabolism KW - Transcription Factors -- deficiency KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79903327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosciences&rft.atitle=Dopamine+biosynthesis+is+selectively+abolished+in+substantia+nigra%2Fventral+tegmental+area+but+not+in+hypothalamic+neurons+in+mice+with+targeted+disruption+of+the+Nurr1+gene.&rft.au=Castillo%2C+S+O%3BBaffi%2C+J+S%3BPalkovits%2C+M%3BGoldstein%2C+D+S%3BKopin%2C+I+J%3BWitta%2C+J%3BMagnuson%2C+M+A%3BNikodem%2C+V+M&rft.aulast=Castillo&rft.aufirst=S&rft.date=1998-05-01&rft.volume=11&rft.issue=1-2&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+neurosciences&rft.issn=10447431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-07 N1 - Date created - 1998-08-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis. AN - 79900353; 9609100 AB - Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. To examine the roles of TGF-beta1, -beta2, and -beta3 and TGF-beta RI and RII in chemically induced mouse lung tumorigenesis, we used immunohistochemical and in situ hybridization analyses to measure the expression of their proteins and mRNAs in A/J mice treated with the carcinogen urethane to induce lung adenomas. Immunostaining for the TGF-beta ligands and receptors was detected in the epithelia of the bronchioles of untreated and treated A/J mice at similar levels. Immunostaining for the TGF-beta ligands and receptors was also detected in adenomas by 2 mo. While immunostaining for TGF-beta1, -beta2, and -beta3 and TGF-beta RI in adenomas was detected at levels comparable to those in bronchioles, immunostaining for TGF-beta RII was less intense in adenomas than in bronchioles. Decreased immunostaining for TGF-beta RII in adenomas persisted for at least 8 mo after exposure to urethane, whereas immunostaining for TGF-beta1, -beta2, and -beta3 and TGF-beta RI persisted at levels comparable to those in normal bronchioles. In situ hybridization studies conducted with TGF-beta receptor riboprobes showed a corresponding reduction in expression of TGF-beta RII mRNA but not of TGF-beta RI mRNA in adenomas compared with expression in bronchioles. Expression of TGF-beta RII mRNA was also examined in non-tumorigenic and tumorigenic mouse lung cells; expression of TGF-beta RII mRNA was lower in the tumorigenic cells derived from urethane-induced lung tumors. These data suggest that a decrease in expression of TGF-beta RII may contribute to autonomous cell growth and may play an important role in mouse lung carcinogenesis induced by urethane. JF - Molecular carcinogenesis AU - Jakowlew, S B AU - Moody, T W AU - You, L AU - Mariano, J M AD - Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, Rockville, Maryland 20850, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 46 EP - 56 VL - 22 IS - 1 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Urethane KW - 3IN71E75Z5 KW - TGF-beta type I receptor KW - EC 2.7.1.11 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Activin Receptors, Type I KW - EC 2.7.11.30 KW - transforming growth factor-beta type II receptor KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Carcinogens -- toxicity KW - Mice KW - RNA, Messenger -- biosynthesis KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Mice, Inbred A KW - Polymerase Chain Reaction KW - Down-Regulation KW - Epithelial Cells KW - Urethane -- toxicity KW - Cell Line KW - Female KW - Cell Division KW - Transforming Growth Factor beta -- biosynthesis KW - Lung -- immunology KW - Lung Neoplasms -- immunology KW - Lung -- drug effects KW - Transcription, Genetic KW - Receptors, Transforming Growth Factor beta -- biosynthesis KW - Lung -- metabolism KW - Cell Transformation, Neoplastic KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduction+in+transforming+growth+factor-beta+type+II+receptor+in+mouse+lung+carcinogenesis.&rft.au=Jakowlew%2C+S+B%3BMoody%2C+T+W%3BYou%2C+L%3BMariano%2C+J+M&rft.aulast=Jakowlew&rft.aufirst=S&rft.date=1998-05-01&rft.volume=22&rft.issue=1&rft.spage=46&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 - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific vanilloid responses in C6 rat glioma cells. AN - 79900088; 9602075 AB - Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. Here, we describe specific vanilloid responses in rat C6 glioma cells. Capsaicin and RTX stimulated 45Ca uptake in a similar fashion to that found for cultured rat dorsal root ganglion neurons (DRGs); this response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of C6 cells with capsaicin or RTX produced desensitization to subsequent stimulation of 45Ca uptake. The potency for desensitization by RTX in the C6 cells corresponded to that for 45Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high affinity [3H]RTX binding site. Consistent with this difference, in C6 cells we were unable to detect [3H]RTX binding. These characteristics suggest the presence of C-type but not R-type vanilloid receptors on C6 cells. After 2 day treatment, capsaicin but not RTX inhibited the proliferation and altered the differentiation of the cells and produced apoptosis. In the long term experiments, capsazepine, instead of antagonizing the effect of capsaicin, acted as an agonist. Moreover, capsazepine displayed these effects with higher potency than that of capsaicin. The different potencies and structure activity relations suggest a distinct mechanism for these long-term vanilloid effects. Our finding that C6 cells can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of response to vanilloids, and highlights the importance of the neuron-glial network. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Bíró, T AU - Brodie, C AU - Modarres, S AU - Lewin, N E AU - Acs, P AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 89 EP - 98 VL - 56 IS - 1-2 SN - 0169-328X, 0169-328X KW - Calcium Radioisotopes KW - 0 KW - Diterpenes KW - Neurotoxins KW - Receptors, Drug KW - resiniferatoxin KW - A5O6P1UL4I KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Diterpenes -- pharmacology KW - Calcium Radioisotopes -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Cell Division -- drug effects KW - Neurotoxins -- pharmacology KW - Diterpenes -- antagonists & inhibitors KW - Cell Differentiation -- drug effects KW - Capsaicin -- analogs & derivatives KW - Capsaicin -- antagonists & inhibitors KW - Capsaicin -- pharmacology KW - Receptors, Drug -- metabolism KW - Glioma -- metabolism KW - Receptors, Drug -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79900088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specific+vanilloid+responses+in+C6+rat+glioma+cells.&rft.au=B%C3%ADr%C3%B3%2C+T%3BBrodie%2C+C%3BModarres%2C+S%3BLewin%2C+N+E%3BAcs%2C+P%3BBlumberg%2C+P+M&rft.aulast=B%C3%ADr%C3%B3&rft.aufirst=T&rft.date=1998-05-01&rft.volume=56&rft.issue=1-2&rft.spage=89&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 - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation. AN - 79897039; 9602092 AB - We have recently shown that the secreted form of amyloid precursor protein (APPs) potentiates the neurotrophic actions of nerve growth factor (NGF). The combined presence of NGF and APPs in low concentrations resulted in a synergistic potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of APPs on NGF receptor-binding has been examined. In the presence of APPs, the apparent affinity of NGF's low affinity binding site increased by a factor of 2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed, although APPs did not compete with NGF for the same binding sites. These effects of APPs were not caused by direct interaction with NGF itself. In addition, APPs synergistically potentiated the tyrosine phosphorylation of trkA due to NGF. These results suggest that an increased affinity of p75 for NGF may underlie the potentiation of neurotrophic actions of NGF by APPs, and that increase may be caused by an indirect interaction between APPs and p75. Copyright 1998 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Akar, C A AU - Wallace, W C AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, Gerontology Research Center, 4940 Eastern Ave., Baltimore, MD 21224, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 125 EP - 132 VL - 56 IS - 1-2 SN - 0169-328X, 0169-328X KW - Amyloid beta-Protein Precursor KW - 0 KW - Nerve Growth Factors KW - Proto-Oncogene Proteins KW - Receptor, Nerve Growth Factor KW - Receptors, Nerve Growth Factor KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, trkA KW - Index Medicus KW - Rats KW - Animals KW - Protein Binding -- drug effects KW - Humans KW - Kidney -- cytology KW - Enzyme Activation -- drug effects KW - Drug Synergism KW - Cell Line KW - Phosphorylation -- drug effects KW - Binding Sites KW - Receptors, Nerve Growth Factor -- physiology KW - Nerve Growth Factors -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Amyloid beta-Protein Precursor -- secretion KW - Amyloid beta-Protein Precursor -- physiology KW - Amyloid beta-Protein Precursor -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Receptors, Nerve Growth Factor -- metabolism KW - Nerve Growth Factors -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79897039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amyloid+precursor+protein+modulates+the+interaction+of+nerve+growth+factor+with+p75+receptor+and+potentiates+its+activation+of+trkA+phosphorylation.&rft.au=Akar%2C+C+A%3BWallace%2C+W+C&rft.aulast=Akar&rft.aufirst=C&rft.date=1998-05-01&rft.volume=56&rft.issue=1-2&rft.spage=125&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 - 1999-01-14 N1 - Date created - 1999-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in dogs. AN - 79893613; 9603114 AB - We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min, and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45 microg x kg(-1) given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and L-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because L-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also significantly increased PCWP and CVP, and abolished the beneficial preload effect of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac-depressant effects of TNF and L-NMMA given together became equal to the sum of those produced by TNF and L-NMMA given separately. Although L-NMMA significantly decreased serum nitrite/nitrate levels, TNF did not increase these end products of nitric oxide (NO) production relative to controls. Therefore, after preload abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect on TNF-induced cardiac depression, and TNF did not increase end products of NO production. These findings are not consistent with NO being the mechanism of TNF-induced acute cardiac depression. JF - American journal of respiratory and critical care medicine AU - Quezado, Z M AU - Karzai, W AU - Danner, R L AU - Freeman, B D AU - Yan, L AU - Eichacker, P Q AU - Banks, S M AU - Cobb, J P AU - Cunnion, R E AU - Quezado, M J AU - Sevransky, J E AU - Natanson, C AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1397 EP - 1405 VL - 157 IS - 5 Pt 1 SN - 1073-449X, 1073-449X KW - Enzyme Inhibitors KW - 0 KW - Isotonic Solutions KW - Tumor Necrosis Factor-alpha KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Ringer's solution KW - 8026-10-6 KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Animals KW - Venous Pressure -- drug effects KW - Infusions, Intravenous KW - Pulmonary Wedge Pressure -- drug effects KW - Isotonic Solutions -- administration & dosage KW - Dogs KW - Hypotension -- chemically induced KW - Tumor Necrosis Factor-alpha -- toxicity KW - Enzyme Inhibitors -- pharmacology KW - omega-N-Methylarginine -- pharmacology KW - Ventricular Dysfunction, Left -- physiopathology KW - Water-Electrolyte Balance KW - Hypotension -- physiopathology KW - Ventricular Dysfunction, Left -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79893613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+critical+care+medicine&rft.atitle=Effects+of+L-NMMA+and+fluid+loading+on+TNF-induced+cardiovascular+dysfunction+in+dogs.&rft.au=Quezado%2C+Z+M%3BKarzai%2C+W%3BDanner%2C+R+L%3BFreeman%2C+B+D%3BYan%2C+L%3BEichacker%2C+P+Q%3BBanks%2C+S+M%3BCobb%2C+J+P%3BCunnion%2C+R+E%3BQuezado%2C+M+J%3BSevransky%2C+J+E%3BNatanson%2C+C&rft.aulast=Quezado&rft.aufirst=Z&rft.date=1998-05-01&rft.volume=157&rft.issue=5+Pt+1&rft.spage=1397&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+and+critical+care+medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin. AN - 79890083; 9603495 AB - We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium. JF - Experimental parasitology AU - Shahabuddin, M AU - Fields, I AU - Bulet, P AU - Hoffmann, J A AU - Miller, L H AD - Medical Entomology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shahabuddin@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 103 EP - 112 VL - 89 IS - 1 SN - 0014-4894, 0014-4894 KW - Anti-Infective Agents KW - 0 KW - Blood Proteins KW - Defensins KW - Index Medicus KW - Animals KW - Chickens KW - Insects -- chemistry KW - Zygote -- drug effects KW - Diptera -- chemistry KW - Insect Vectors -- parasitology KW - Plasmodium gallinaceum -- growth & development KW - Aedes -- parasitology KW - Anti-Infective Agents -- pharmacology KW - Plasmodium gallinaceum -- drug effects KW - Blood Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79890083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+parasitology&rft.atitle=Plasmodium+gallinaceum%3A+differential+killing+of+some+mosquito+stages+of+the+parasite+by+insect+defensin.&rft.au=Shahabuddin%2C+M%3BFields%2C+I%3BBulet%2C+P%3BHoffmann%2C+J+A%3BMiller%2C+L+H&rft.aulast=Shahabuddin&rft.aufirst=M&rft.date=1998-05-01&rft.volume=89&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Experimental+parasitology&rft.issn=00144894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virusType 2: definition of subtypes based on DNA sequence analysis of ten complete genomes. AN - 79888950; 9603329 AB - Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5.1 kb genome of nine urinary strains of JCV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian JCV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in Japan was also sequenced. Here, we report the analysis of these ten DNA sequences and their deduced protein translations. Two phylogenetically distinct subtypes of Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the coding region sequence. A 215 bp product amplified with primers in the VP1 gene contains enough sequence information to distinguish the major types and subtypes of JCV and is suitable for application in viral epidemiological studies. The investigation of these genomic variations is of special interest because JCV Type 2 strains are found at a significantly higher frequency in brain tissue of patients with PML than would be predicted from their excretion in a control population. JF - The Journal of general virology AU - Agostini, H T AU - Shishido-Hara, Y AU - Baumhefner, R W AU - Singer, E J AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1143 EP - 1151 VL - 79 ( Pt 5) SN - 0022-1317, 0022-1317 KW - Capsid Proteins KW - 0 KW - DNA, Viral KW - VP1 protein, polyomavirus KW - Index Medicus KW - Regulatory Sequences, Nucleic Acid KW - Genetic Variation KW - Base Sequence KW - Humans KW - Adult KW - Point Mutation KW - Molecular Sequence Data KW - Aged KW - Middle Aged KW - Male KW - Female KW - Tumor Virus Infections -- virology KW - JC Virus -- genetics KW - JC Virus -- classification KW - Capsid -- genetics KW - Papillomavirus Infections -- virology KW - Genome, Viral KW - Sequence Analysis, DNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79888950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+general+virology&rft.atitle=JC+virusType+2%3A+definition+of+subtypes+based+on+DNA+sequence+analysis+of+ten+complete+genomes.&rft.au=Agostini%2C+H+T%3BShishido-Hara%2C+Y%3BBaumhefner%2C+R+W%3BSinger%2C+E+J%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=79+%28+Pt+5%29&rft.issue=&rft.spage=1143&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-15 N1 - Date created - 1998-06-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015529; GENBANK; AF015536; AF015535; AF015534; AF015533; AF015532; AF015531; AF030085; AF015530; AF015684 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activity-dependent neurotrophic factor: structure-activity relationships of femtomolar-acting peptides. AN - 79886286; 9580606 AB - Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is neuroprotective at femtomolar concentrations. A 14-amino acid peptide of ADNF (ADNF-14) has been reported that protects cultured neurons from multiple neurotoxins. Structure-activity relationships of peptides related to ADNF-14 now have been determined. A 9-amino acid core peptide (ADNF-9) has been identified that has greater potency and a broader effective concentration range (10(-16) to 10(-13) M) than ADNF or ADNF-14 in preventing cell death associated with tetrodotoxin treatment of cerebral cortical cultures. Deletions or conservative amino acid substitutions to ADNF-9 resulted in reduced potency, narrower effective concentration range and/or decreased efficacy. Removal of the N-terminal serine or the COOH-terminal isoleucine-proline-alanine from ADNF-9 produced a significant reduction in survival-promoting activity. Comparative studies of ADNF-9 action in mixed (glia plus neurons) vs. glia-depleted neuronal cultures indicated that ADNF-9 can act directly on neurons, although the potency of the peptide was 10,000-fold greater in mixed cultures. Kinetic studies showed that exposure to ADNF-9 for only 2 hr was sufficient to produce a 4-day protection against the cell-killing action of tetrodotoxin. Treatment with bafilomycin A1 (an inhibitor of receptor-mediated endocytosis) for 2 hr prevented the ADNF- and ADNF-9-mediated neuroprotection. ADNF-9, like ADNF-14, was neuroprotective against N-methyl-D-aspartate and the beta-amyloid peptide (amino acids 25-35), and had a much broader range of effective concentrations than ADNF-14. These studies identify ADNF-9 as an attractive lead compound for the development of therapeutic agents against neurodegenerative diseases. JF - The Journal of pharmacology and experimental therapeutics AU - Brenneman, D E AU - Hauser, J AU - Neale, E AU - Rubinraut, S AU - Fridkin, M AU - Davidson, A AU - Gozes, I AD - Section on Developmental and Molecular Pharmacology, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 619 EP - 627 VL - 285 IS - 2 SN - 0022-3565, 0022-3565 KW - Nerve Tissue Proteins KW - 0 KW - Neuroprotective Agents KW - Index Medicus KW - Rats KW - Animals KW - Cerebral Cortex -- drug effects KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Structure-Activity Relationship KW - Nerve Tissue Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79886286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activity-dependent+neurotrophic+factor%3A+structure-activity+relationships+of+femtomolar-acting+peptides.&rft.au=Brenneman%2C+D+E%3BHauser%2C+J%3BNeale%2C+E%3BRubinraut%2C+S%3BFridkin%2C+M%3BDavidson%2C+A%3BGozes%2C+I&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1998-05-01&rft.volume=285&rft.issue=2&rft.spage=619&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 - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Levodopa therapy: consequences of the nonphysiologic replacement of dopamine. AN - 79884378; 9591518 AB - Normal motor function is dependent on the highly regulated synthesis and release of the transmitter dopamine by neurons projecting from the substantia nigra to the corpus striatum. Parkinson's disease involves the progressive degeneration of these neurons. Its core symptoms are a direct consequence of a striatal insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the treatment of PD, acts after its conversion to dopamine by restoring striatal dopaminergic transmission. However, there are significant differences between the normally functioning dopamine system and the restoration of function provided by standard levodopa treatment. Increasing clinical and preclinical evidence suggests that the intermittent stimulation of dopamine receptors resulting from current therapeutic regimens contributes to the response complications that ultimately affect most parkinsonian patients. It now appears that chronic nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic neurons activates characteristic signaling pathways, leading to a potentiation of the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype. As a result, function of these GABAergic efferent neurons changes in ways that favor the appearance of motor complications. Conceivably, use of dopaminomimetic replacement strategies that provide more continuous dopamine receptor stimulation will act to prevent or alleviate these disabling complications. A number of promising approaches to achieving this goal are now under development. JF - Neurology AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - S17 EP - S25 VL - 50 IS - 5 Suppl 5 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Catechol O-Methyltransferase Inhibitors KW - Delayed-Action Preparations KW - Dopamine Agents KW - Enzyme Inhibitors KW - Levodopa KW - 46627O600J KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Delayed-Action Preparations -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Humans KW - Disease Models, Animal KW - Dyskinesia, Drug-Induced -- etiology KW - Antiparkinson Agents -- adverse effects KW - Dopamine Agents -- therapeutic use KW - Parkinson Disease -- metabolism KW - Levodopa -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Dopamine Agents -- adverse effects KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79884378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Levodopa+therapy%3A+consequences+of+the+nonphysiologic+replacement+of+dopamine.&rft.au=Chase%2C+T+N&rft.aulast=Chase&rft.aufirst=T&rft.date=1998-05-01&rft.volume=50&rft.issue=5+Suppl+5&rft.spage=S17&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-09 N1 - Date created - 1998-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. AN - 79880205; 9595981 AB - To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications. JF - Neurology AU - Verhagen Metman, L AU - Del Dotto, P AU - van den Munckhof, P AU - Fang, J 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 - 1998/05// PY - 1998 DA - May 1998 SP - 1323 EP - 1326 VL - 50 IS - 5 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - Levodopa KW - 46627O600J KW - Amantadine KW - BF4C9Z1J53 KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Logistic Models KW - Humans KW - Adult KW - Treatment Outcome KW - Cross-Over Studies KW - Aged KW - Motor Activity -- drug effects KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Female KW - Dyskinesia, Drug-Induced -- drug therapy KW - Amantadine -- therapeutic use KW - Excitatory Amino Acid Antagonists -- therapeutic use KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Antiparkinson Agents -- therapeutic use KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79880205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Amantadine+as+treatment+for+dyskinesias+and+motor+fluctuations+in+Parkinson%27s+disease.&rft.au=Verhagen+Metman%2C+L%3BDel+Dotto%2C+P%3Bvan+den+Munckhof%2C+P%3BFang%2C+J%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Verhagen+Metman&rft.aufirst=L&rft.date=1998-05-01&rft.volume=50&rft.issue=5&rft.spage=1323&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-08 N1 - Date created - 1998-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 1998 May;50(5):1211-2 [9595964] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simultaneous binding of heparin and platelet factor-4 to platelets: further insights into the mechanism of heparin-induced thrombocytopenia. AN - 79878550; 9590145 AB - Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor-4 (PF4) and heparin. Although it has been assumed that these complexes bind to platelets and provide a target for the antibody, this has never been demonstrated. Furthermore, there is evidence suggesting that heparin-PF4 complexes do not bind to platelets. We have analyzed the effect of each ligand on the platelet binding of the other. We particularly focused on the result when heparin and PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT-IgG increased on the platelet surface. We found that when the molar concentration of PF4 approximates or exceeds that of heparin, the ligands bind simultaneously to the cells and HIT-IgG binds also. However, when heparin is in molar excess, both PF4 binding and HIT-IgG binding are diminished. Our data are consistent with the hypothesis that heparin-PF4 complexes bind via their heparin component to heparin binding sites on the platelet membrane rather than by their PF4 component to PF4 sites. The conditions promoting the binding of the complexes also lead to binding of HIT-IgG. JF - American journal of hematology AU - Horne, M K AU - Hutchison, K J AD - Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 24 EP - 30 VL - 58 IS - 1 SN - 0361-8609, 0361-8609 KW - Immunoglobulin G KW - 0 KW - Ligands KW - Platelet Factor 4 KW - 37270-94-3 KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Swine KW - Osmolar Concentration KW - Animals KW - Immunoglobulin G -- metabolism KW - Time Factors KW - Platelet Factor 4 -- metabolism KW - Thrombocytopenia -- chemically induced KW - Heparin -- metabolism KW - Thrombocytopenia -- blood KW - Blood Platelets -- metabolism KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79878550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Simultaneous+binding+of+heparin+and+platelet+factor-4+to+platelets%3A+further+insights+into+the+mechanism+of+heparin-induced+thrombocytopenia.&rft.au=Horne%2C+M+K%3BHutchison%2C+K+J&rft.aulast=Horne&rft.aufirst=M&rft.date=1998-05-01&rft.volume=58&rft.issue=1&rft.spage=24&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. AN - 79872834; 9585239 AB - Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children. The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors associated with the syndrome. igf2, implicated in the formation of RMSs, was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by ionizing radiation. We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome. JF - Nature medicine AU - Hahn, H AU - Wojnowski, L AU - Zimmer, A M AU - Hall, J AU - Miller, G AU - Zimmer, A AD - Section on Genetics, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 619 EP - 622 VL - 4 IS - 5 SN - 1078-8956, 1078-8956 KW - Cesium Radioisotopes KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Membrane Proteins KW - Oncogene Proteins KW - Patched Receptors KW - Patched-1 Receptor KW - Ptch1 protein, mouse KW - Receptors, Cell Surface KW - Trans-Activators KW - Transcription Factors KW - Zinc Finger Protein GLI1 KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Embryo, Mammalian -- radiation effects KW - Oncogene Proteins -- genetics KW - Mice KW - Dose-Response Relationship, Radiation KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Oncogene Proteins -- biosynthesis KW - Heterozygote KW - Molecular Sequence Data KW - Crosses, Genetic KW - Rhabdomyosarcoma -- genetics KW - Basal Cell Nevus Syndrome -- complications KW - Rhabdomyosarcoma -- complications KW - Membrane Proteins -- genetics KW - Basal Cell Nevus Syndrome -- genetics KW - Mutation KW - Radiation Tolerance -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79872834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rhabdomyosarcomas+and+radiation+hypersensitivity+in+a+mouse+model+of+Gorlin+syndrome.&rft.au=Hahn%2C+H%3BWojnowski%2C+L%3BZimmer%2C+A+M%3BHall%2C+J%3BMiller%2C+G%3BZimmer%2C+A&rft.aulast=Hahn&rft.aufirst=H&rft.date=1998-05-01&rft.volume=4&rft.issue=5&rft.spage=619&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 - 1998-05-29 N1 - Date created - 1998-05-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - W65013; GENBANK N1 - SuppNotes - Comment In: Nat Med. 1998 May;4(5):559-60 [9585226] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laboratory and diagnostic testing in child and adolescent psychiatry: a review of the past 10 years. AN - 79871377; 9585646 AB - To review in a critical fashion the literature of the past decade covering diagnostic and laboratory testing in the field of child and adolescent psychiatry. A computerized search of articles published during the past decade was made, and selected articles are presented. Because of the paucity of articles specifically relating to minors, selected articles from adult psychiatry are cited. With a few notable exceptions, few controlled studies on the specificity and sensitivity of any laboratory test for any specific disorder of behavior presenting in children have been conducted in children and adolescents. A high index of suspicion will remain the clinician's best ally in utilizing laboratory measures in the assessment of psychopathology. Nonetheless, studies have appeared that will guide the clinician as to what tests are not clinically useful. Indications and the lack of indications for specific laboratory studies are an integral part of the knowledge base that child psychiatrists must have. Much more empirical data will need to be collected prospectively to inform the field and to move the judicious use of the laboratory from an art to a science. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Zametkin, A J AU - Ernst, M AU - Silver, R AD - National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. zametkin@box-z.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 464 EP - 472 VL - 37 IS - 5 SN - 0890-8567, 0890-8567 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Mental Disorders -- diagnosis KW - Mental Disorders -- drug therapy KW - Humans KW - Adult KW - Psychotropic Drugs -- pharmacokinetics KW - Mental Disorders -- etiology KW - Child KW - Psychotropic Drugs -- adverse effects KW - Psychotropic Drugs -- administration & dosage KW - Adolescent KW - Diagnostic Tests, Routine KW - Adolescent Psychiatry -- education KW - Child Psychiatry -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79871377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Laboratory+and+diagnostic+testing+in+child+and+adolescent+psychiatry%3A+a+review+of+the+past+10+years.&rft.au=Zametkin%2C+A+J%3BErnst%2C+M%3BSilver%2C+R&rft.aulast=Zametkin&rft.aufirst=A&rft.date=1998-05-01&rft.volume=37&rft.issue=5&rft.spage=464&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 - 1998-06-11 N1 - Date created - 1998-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus. AN - 79869859; 9581699 AB - The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein. JF - Hepatology (Baltimore, Md.) AU - Yu, M AU - Emerson, S U AU - Cote, P AU - Shapiro, M AU - Purcell, R H AD - Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1408 EP - 1414 VL - 27 IS - 5 SN - 0270-9139, 0270-9139 KW - DNA, Viral KW - 0 KW - Protein Precursors KW - RNA, Viral KW - Viral Envelope Proteins KW - Index Medicus KW - Virus Replication KW - Humans KW - Protein Precursors -- physiology KW - Morphogenesis KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Genetic Complementation Test KW - Molecular Sequence Data KW - RNA, Viral -- metabolism KW - Cell Line KW - DNA, Viral -- metabolism KW - Hepatitis B Virus, Woodchuck -- genetics KW - Viral Envelope Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79869859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+GDPAL+region+of+the+pre-S1+envelope+protein+is+important+for+morphogenesis+of+woodchuck+hepatitis+virus.&rft.au=Yu%2C+M%3BEmerson%2C+S+U%3BCote%2C+P%3BShapiro%2C+M%3BPurcell%2C+R+H&rft.aulast=Yu&rft.aufirst=M&rft.date=1998-05-01&rft.volume=27&rft.issue=5&rft.spage=1408&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 - 1998-05-19 N1 - Date created - 1998-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in expression of 15-lipoxygenase and prostaglandin-H synthase during differentiation of human tracheobronchial epithelial cells. AN - 79845185; 9569236 AB - The purpose of our studies was to examine differentiation-dependent expression of 15-lipoxygenase (15-LO) and prostaglandin H synthase (PGHS) isoforms in cultured normal human tracheobronchial epithelial cells. In the presence of retinoic acid (RA) the cultures differentiated into a mucociliary epithelium. When cultured in RA-depleted media, the cultures differentiated into a squamous epithelium. In the absence of RA the cultures did not express 15-LO or either of the PGHS isoforms. The PGHS-1 isoform was not expressed in RA-sufficient cultures, but both PGHS-2 messenger RNA (mRNA) and protein were strongly expressed, and prostaglandin E2 (PGE2) was produced during the predifferentiation phase. No PGHS-2 expression or PGE2 could be detected in fully differentiated mucociliary cultures. 15-LO showed the opposite expression pattern: neither mRNA nor protein were detected during the predifferentiation stage, but both were strongly expressed once mucous differentiation had occurred. Cytosolic phospholipase A2 protein was expressed throughout all stages of growth and differentiation. The cultures generated no 15-LO metabolites when incubated with 10 microM to 50 microM arachidonic acid (AA) and stimulated with ionophore. However, lysates prepared from such cultures generated 15-hydroxyeicosatetraenoic acid (15-HETE) and 12-HETE from AA, indicating that the cells contained active enzyme. When cultures expressing 15-LO protein were incubated with 10 microM linoleic acid (LA) instead of AA, and were stimulated with ionophore, they generated 13-hydroxy-9,11-octadecadienoic acid. LA rather than AA appeared to be the preferred substrate for the 15-LO enzyme. Our studies indicated that the expression of 15-LO and PGHS-2 is differentiation dependent in airway epithelial cells. JF - American journal of respiratory cell and molecular biology AU - Hill, E M AU - Eling, T AU - Nettesheim, P AD - Laboratories of Molecular Carcinogenesis and Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 662 EP - 669 VL - 18 IS - 5 SN - 1044-1549, 1044-1549 KW - Antithrombins KW - 0 KW - Hydroxyeicosatetraenoic Acids KW - Isoenzymes KW - Linoleic Acids KW - Retinoids KW - Arachidonic Acid KW - 27YG812J1I KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid KW - 59985-28-3 KW - 15-hydroxy-5,8,11,13-eicosatetraenoic acid KW - 73945-47-8 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Phospholipases A KW - EC 3.1.1.32 KW - Phospholipases A2 KW - EC 3.1.1.4 KW - Index Medicus KW - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid -- genetics KW - Linoleic Acids -- genetics KW - Arachidonic Acid -- pharmacology KW - Cytosol -- enzymology KW - Humans KW - Cell Differentiation -- genetics KW - Retinoids -- pharmacology KW - Chromatography, High Pressure Liquid KW - Antithrombins -- genetics KW - Hydroxyeicosatetraenoic Acids -- genetics KW - Phospholipases A -- genetics KW - Cells, Cultured KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Cilia -- enzymology KW - Gene Expression Regulation, Enzymologic -- physiology KW - Mucous Membrane -- cytology KW - Linoleic Acid -- pharmacology KW - Isoenzymes -- analysis KW - Epithelial Cells -- cytology KW - Epithelial Cells -- enzymology KW - Bronchi -- cytology KW - Arachidonate 15-Lipoxygenase -- genetics KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- analysis KW - Trachea -- cytology KW - Arachidonate 15-Lipoxygenase -- analysis KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79845185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Changes+in+expression+of+15-lipoxygenase+and+prostaglandin-H+synthase+during+differentiation+of+human+tracheobronchial+epithelial+cells.&rft.au=Hill%2C+E+M%3BEling%2C+T%3BNettesheim%2C+P&rft.aulast=Hill&rft.aufirst=E&rft.date=1998-05-01&rft.volume=18&rft.issue=5&rft.spage=662&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 - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociation kinetics of RecA protein-three-stranded DNA complexes reveals a low fidelity of RecA-assisted recognition of homology. AN - 79840204; 9571054 AB - We determined that the incorporation of one mismatch into RecA mediated synaptic complexes between oligonucleotide single-stranded DNAs and target duplex DNAs destabilizes the complex by 0.8 to 1.9 kcal/mol. This finding supports our previous result, that RecA binding per se can significantly decrease the loss in free energy associated with mismatch incorporation even in the absence of ATP hydrolysis. We show that the specificity is mostly driven by the dissociation process. We found that the relative destabilization induced by different mismatches depends on their position. Thus, while there is a good correlation between the ranking order of mismatches at the 5' end of synaptic complexes and mismatches in heteroduplexes (D-loops), there is no correlation between the ranking order for mismatches at the 3' end and mismatches in various DNA structures. This difference between the 5' and 3' ends of synaptic complexes agrees well with the established 5' to 3' polarity of the strand exchange promoted by RecA protein. The lack of a correlation between mismatches at the 3' end of synaptic complexes and mismatches in D-loops suggests the intermediate is probably not a canonical protein-free D-loop. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Malkov, V A AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, National Institutes of Health (NIDDK), Building 10 Room 9D15, Bethesda, MD, 20892, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 317 EP - 330 VL - 278 IS - 2 SN - 0022-2836, 0022-2836 KW - Nucleic Acid Heteroduplexes KW - 0 KW - Oligonucleotides KW - DNA KW - 9007-49-2 KW - Rec A Recombinases KW - EC 2.7.7.- KW - Index Medicus KW - Plasmids -- metabolism KW - Kinetics KW - Oligonucleotides -- metabolism KW - Nucleic Acid Conformation KW - Mutagenesis KW - Rec A Recombinases -- genetics KW - DNA -- metabolism KW - Rec A Recombinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dissociation+kinetics+of+RecA+protein-three-stranded+DNA+complexes+reveals+a+low+fidelity+of+RecA-assisted+recognition+of+homology.&rft.au=Malkov%2C+V+A%3BCamerini-Otero%2C+R+D&rft.aulast=Malkov&rft.aufirst=V&rft.date=1998-05-01&rft.volume=278&rft.issue=2&rft.spage=317&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 - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic changes associated with primary Merkel cell carcinoma. AN - 79834798; 9576574 AB - Merkel cell carcinoma (MCC) is a malignant tumor of the skin with a well-established neuroendocrine phenotype but an unknown histogenetic origin. Cytogenetic and molecular studies have shown evidence for genetic changes on the distal portion of chromosome 1p in different tumors with well-established neuroendocrine origins, specifically neuroblastomas, malignant melanomas, and pheochromocytomas. Involvement of chromosome 1 in MCC recently has been demonstrated by cytogenetic analysis and analysis of loss of heterozygosity (LOH) in metastatic tumor tissue. We performed analysis of LOH of the distal portion of chromosome 1p in paraffin material of 10 primary MCCs after tissue microdissection, using the polymorphic markers D1S160, D1S243, D1S468, D1S1646, and D1S1598. Seven of 10 analyzed MCCs shared a distal deletion involving 1p35-36. None of the cases showed 1p involvement proximal to 1p35. The findings are similar to those described for malignant melanoma, pheochromocytoma, and neuroblastoma, tumors known to originate from neural crest cells. In conjunction with previous cytogenetic data, we conclude that Merkel cell carcinogenesis shares pathogenetic mechanisms with other neoplasms of neural crest derivation. JF - American journal of clinical pathology AU - Vortmeyer, A O AU - Merino, M J AU - Böni, R AU - Liotta, L A AU - Cavazzana, A AU - Zhuang, Z AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 565 EP - 570 VL - 109 IS - 5 SN - 0002-9173, 0002-9173 KW - Abridged Index Medicus KW - Index Medicus KW - Chromosomes, Human, Pair 1 KW - Loss of Heterozygosity KW - Polymorphism, Genetic KW - Aged, 80 and over KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Gene Deletion KW - Skin Neoplasms -- genetics KW - Carcinoma, Merkel Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79834798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+pathology&rft.atitle=Genetic+changes+associated+with+primary+Merkel+cell+carcinoma.&rft.au=Vortmeyer%2C+A+O%3BMerino%2C+M+J%3BB%C3%B6ni%2C+R%3BLiotta%2C+L+A%3BCavazzana%2C+A%3BZhuang%2C+Z&rft.aulast=Vortmeyer&rft.aufirst=A&rft.date=1998-05-01&rft.volume=109&rft.issue=5&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=American+journal+of+clinical+pathology&rft.issn=00029173&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome. AN - 79834760; 9573539 AB - Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct water channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary expression of the descending limb water channel, aquaporin-1, was not significantly altered, pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity. JF - Kidney international AU - Fernández-Llama, P AU - Andrews, P AU - Nielsen, S AU - Ecelbarger, C A AU - Knepper, M A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1244 EP - 1253 VL - 53 IS - 5 SN - 0085-2538, 0085-2538 KW - Aqp1 protein, rat KW - 0 KW - Aqp2 protein, rat KW - Aqp3 protein, rat KW - Aqp4 protein, rat KW - Aquaporin 2 KW - Aquaporin 4 KW - Aquaporin 6 KW - Aquaporins KW - Carrier Proteins KW - HSP70 Heat-Shock Proteins KW - Ion Channels KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - urea transporter KW - Aquaporin 1 KW - 146410-94-8 KW - Aquaporin 3 KW - 158801-98-0 KW - Doxorubicin KW - 80168379AG KW - Urea KW - 8W8T17847W KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Urea -- metabolism KW - Kidney Tubules, Collecting -- metabolism KW - Animals KW - HSP70 Heat-Shock Proteins -- metabolism KW - Kidney Medulla -- ultrastructure KW - Adenylyl Cyclases -- metabolism KW - Doxorubicin -- toxicity KW - Kidney Tubules, Collecting -- ultrastructure KW - Rats KW - Rats, Sprague-Dawley KW - Kidney Medulla -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Microscopy, Electron KW - Immunohistochemistry KW - Male KW - Carrier Proteins -- metabolism KW - Nephrotic Syndrome -- metabolism KW - Nephrotic Syndrome -- chemically induced KW - Membrane Glycoproteins -- metabolism KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79834760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Impaired+aquaporin+and+urea+transporter+expression+in+rats+with+adriamycin-induced+nephrotic+syndrome.&rft.au=Fern%C3%A1ndez-Llama%2C+P%3BAndrews%2C+P%3BNielsen%2C+S%3BEcelbarger%2C+C+A%3BKnepper%2C+M+A&rft.aulast=Fern%C3%A1ndez-Llama&rft.aufirst=P&rft.date=1998-05-01&rft.volume=53&rft.issue=5&rft.spage=1244&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-30 N1 - Date created - 1998-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Kidney Int. 1998 May;53(5):1417-8 [9573561] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. AN - 79827136; 9563949 AB - Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors. JF - Science (New York, N.Y.) AU - Duesbery, N S AU - Webb, C P AU - Leppla, S H AU - Gordon, V M AU - Klimpel, K R AU - Copeland, T D AU - Ahn, N G AU - Oskarsson, M K AU - Fukasawa, K AU - Paull, K D AU - Vande Woude, G F AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 734 EP - 737 VL - 280 IS - 5364 SN - 0036-8075, 0036-8075 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Enzyme Inhibitors KW - Myelin Basic Protein KW - Recombinant Fusion Proteins KW - anthrax toxin KW - MAP2K2 protein, human KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - MAP Kinase Kinase 1 KW - EC 2.7.12.2 KW - MAP Kinase Kinase 2 KW - MAP2K1 protein, human KW - Map2k1 protein, mouse KW - Mitogen-Activated Protein Kinase Kinases KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Enzyme Inhibitors -- toxicity KW - Oocytes -- physiology KW - Mice KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Metalloendopeptidases -- toxicity KW - Xenopus laevis KW - Phosphorylation KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors KW - Myelin Basic Protein -- metabolism KW - Cell Line, Transformed KW - Metalloendopeptidases -- metabolism KW - Signal Transduction KW - Sequence Deletion KW - Protein-Serine-Threonine Kinases -- chemistry KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein-Tyrosine Kinases -- genetics KW - Bacterial Toxins -- metabolism KW - Bacterial Toxins -- toxicity KW - Bacillus anthracis -- enzymology KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79827136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Proteolytic+inactivation+of+MAP-kinase-kinase+by+anthrax+lethal+factor.&rft.au=Duesbery%2C+N+S%3BWebb%2C+C+P%3BLeppla%2C+S+H%3BGordon%2C+V+M%3BKlimpel%2C+K+R%3BCopeland%2C+T+D%3BAhn%2C+N+G%3BOskarsson%2C+M+K%3BFukasawa%2C+K%3BPaull%2C+K+D%3BVande+Woude%2C+G+F&rft.aulast=Duesbery&rft.aufirst=N&rft.date=1998-05-01&rft.volume=280&rft.issue=5364&rft.spage=734&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 - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Science. 1998 Jun 12;280(5370):1671, 1673-4 [9660700] Science. 1998 May 1;280(5364):676 [9599144] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase beta as revealed by site-directed mutagenesis. DNA binding and 5'-deoxyribose phosphate lyase activities. AN - 79822765; 9556598 AB - The amino-terminal 8-kDa domain of DNA polymerase beta functions in binding single-stranded DNA (ssDNA), recognition of a 5'-phosphate in gapped DNA structures, and as a 5'-deoxyribose phosphate (dRP) lyase. NMR and x-ray crystal structures of this domain have suggested several residues that may interact with ssDNA or play a role in the dRP lyase reaction. Nine of these residues were altered by site-directed mutagenesis. Each mutant was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. CD spectra of these mutant proteins indicated that the alteration did not adversely affect the global protein structure. Single-stranded DNA binding was probed by photochemical cross-linking to oligo(dT)16. Several mutants (F25W, K35A, K60A, and K68A) were impaired in ssDNA binding activity, whereas other mutants (H34G, E71Q, K72A, E75A, and K84A) retained near wild-type binding activity. The 5'-phosphate recognition activity of these mutants was examined by UV cross-linking to a 5-nucleotide gap DNA where the 5' terminus in the gap was either phosphorylated or unphosphorylated. The results indicate that Lys35 is involved in 5'-phosphate recognition of DNA polymerase beta. Finally, the dRP lyase activity of these mutants was evaluated using a preincised apurinic/apyrimidinic DNA. Alanine mutants of Lys35 and Lys60 are significantly reduced in dRP lyase activity, consistent with the lower ssDNA binding activity. More importantly, alanine substitution for Lys72 resulted in a greater than 90% loss of dRP lyase activity, without affecting DNA binding. Alanine mutants of Lys68 and Lys84 had wild-type dRP lyase activity. The triple alanine mutant, K35A/K68A/K72A, was devoid of dRP lyase activity, suggesting that the effects of the alanine substitution at Lys72 and Lys35 were additive. The results suggest that Lys72 is directly involved in formation of a covalent imino intermediate and are consistent with Lys72 as the predominant Schiff base nucleophile in the dRP lyase beta-elimination catalytic reaction. JF - The Journal of biological chemistry AU - Prasad, R AU - Beard, W A AU - Chyan, J Y AU - Maciejewski, M W AU - Mullen, G P AU - Wilson, S H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 11121 EP - 11126 VL - 273 IS - 18 SN - 0021-9258, 0021-9258 KW - DNA, Single-Stranded KW - 0 KW - Recombinant Proteins KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Lyases KW - EC 4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Escherichia coli -- genetics KW - Circular Dichroism KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Catalysis KW - DNA, Single-Stranded -- metabolism KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- chemistry KW - DNA Polymerase beta -- metabolism KW - Lyases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79822765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+analysis+of+the+amino-terminal+8-kDa+domain+of+DNA+polymerase+beta+as+revealed+by+site-directed+mutagenesis.+DNA+binding+and+5%27-deoxyribose+phosphate+lyase+activities.&rft.au=Prasad%2C+R%3BBeard%2C+W+A%3BChyan%2C+J+Y%3BMaciejewski%2C+M+W%3BMullen%2C+G+P%3BWilson%2C+S+H&rft.aulast=Prasad&rft.aufirst=R&rft.date=1998-05-01&rft.volume=273&rft.issue=18&rft.spage=11121&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutations in the vnd/NK-2 homeodomain. Basis of variations in structure and sequence-specific DNA binding. AN - 79822095; 9556579 AB - Secondary structures, DNA binding properties, and thermal denaturation behavior of six site-directed mutant homeodomains encoded by the vnd/NK-2 gene from Drosophila melanogaster are described. Three single site H52R, Y54M, and T56W mutations, two double site H52R/T56W and Y54M/T56W mutations, and one triple site H52R/Y54M/T56W mutation were investigated. These positions were chosen based on their variability across homeodomains displaying differences in secondary structure and DNA binding specificity. Multidimensional NMR, electrophoretic mobility shift assays, and circular dichroism spectropolarimetry studies were carried out on recombinant 80-amino acid residue proteins containing the homeodomain. Position 56, but more importantly position 56 in combination with position 52, plays an important role in determining the length of the recognition helix. The H52R mutation alone does not affect the length of this helix but does increase the thermal stability. Introduction of site mutations at positions 52 and 56 in vnd/NK-2 does not modify their high affinity binding to the 18-base pair DNA fragment containing the vnd/NK-2 consensus binding sequence, CAAGTG. Site mutations involving position 54 (Y54M, Y54M/T56W, and H52R/Y54M/T56W) all show a decrease of 1 order of magnitude in their binding affinity. The roles in structure and sequence specificity of individual atom-atom interactions are described. JF - The Journal of biological chemistry AU - Weiler, S AU - Gruschus, J M AU - Tsao, D H AU - Yu, L AU - Wang, L H AU - Nirenberg, M AU - Ferretti, J A AD - Laboratory of Biophysical Chemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-0380, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 10994 EP - 11000 VL - 273 IS - 18 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Drosophila Proteins KW - Homeodomain Proteins KW - Transcription Factors KW - vnd protein, Drosophila KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Circular Dichroism KW - Amino Acid Sequence KW - Protein Binding KW - Magnetic Resonance Spectroscopy KW - Homeodomain Proteins -- genetics KW - DNA-Binding Proteins -- chemistry KW - Homeodomain Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Homeodomain Proteins -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79822095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mutations+in+the+vnd%2FNK-2+homeodomain.+Basis+of+variations+in+structure+and+sequence-specific+DNA+binding.&rft.au=Weiler%2C+S%3BGruschus%2C+J+M%3BTsao%2C+D+H%3BYu%2C+L%3BWang%2C+L+H%3BNirenberg%2C+M%3BFerretti%2C+J+A&rft.aulast=Weiler&rft.aufirst=S&rft.date=1998-05-01&rft.volume=273&rft.issue=18&rft.spage=10994&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The N-terminal domain of IkappaB alpha masks the nuclear localization signal(s) of p50 and c-Rel homodimers. AN - 79820089; 9566883 AB - Members of the Rel/NF-kappaB family of transcription factors are related to each other over a region of about 300 amino acids called the Rel Homology Domain (RHD), which governs DNA binding, dimerization, and binding to inhibitor. At the C-terminal end of the RHD, each protein has a nuclear localization signal (NLS). The crystal structures of the p50 and RelA family members show that the RHD consists of two regions: an N-terminal section which contains some of the DNA contacts and a C-terminal section which contains the remaining DNA contacts and controls dimerization. In unstimulated cells, the homo- or heterodimeric Rel/NF-kappaB proteins are cytoplasmic by virtue of binding to an inhibitor protein (IkappaB) which somehow masks the NLS of each member of the dimer. The IkappaB proteins consist of an ankyrin-repeat-containing domain that is required for binding to dimers and N- and C-terminal domains that are dispensable for binding to most dimers. In this study, we examined the interaction between IkappaB alpha and Rel family homodimers by mutational analysis. We show that (i) the dimerization regions of p50, RelA, and c-Rel are sufficient for binding to IkappaB alpha, (ii) the NLSs of RelA and c-Rel are not required for binding to IkappaB alpha but do stabilize the interaction, (iii) the NLS of p50 is required for binding to IkappaB alpha, (iv) only certain residues within the p50 NLS are required for binding, and (v) in a p50-IkappaB alpha complex or a c-Rel-IkappaB alpha complex, the N terminus of IkappaB alpha either directly or indirectly masks one or both of the dimer NLSs. JF - Molecular and cellular biology AU - Latimer, M AU - Ernst, M K AU - Dunn, L L AU - Drutskaya, M AU - Rice, N R AD - Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 2640 EP - 2649 VL - 18 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - I-kappa B Proteins KW - NF-kappa B KW - NF-kappa B p50 Subunit KW - NFKBIA protein, human KW - Nuclear Localization Signals KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-rel KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Index Medicus KW - Cytoplasm -- metabolism KW - Humans KW - Dimerization KW - Cell Compartmentation KW - Protein Binding KW - Mutation KW - Binding Sites KW - Proto-Oncogene Proteins -- metabolism KW - NF-kappa B -- genetics KW - NF-kappa B -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79820089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+N-terminal+domain+of+IkappaB+alpha+masks+the+nuclear+localization+signal%28s%29+of+p50+and+c-Rel+homodimers.&rft.au=Latimer%2C+M%3BErnst%2C+M+K%3BDunn%2C+L+L%3BDrutskaya%2C+M%3BRice%2C+N+R&rft.aulast=Latimer&rft.aufirst=M&rft.date=1998-05-01&rft.volume=18&rft.issue=5&rft.spage=2640&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1986 Oct 17;234(4774):364-8 [2876518] Nature. 1998 Jan 22;391(6665):410-3 [9450761] Mol Cell Biol. 1992 Sep;12(9):4067-75 [1508203] Genes Dev. 1992 Oct;6(10):1899-913 [1340770] Cell. 1992 Oct 16;71(2):243-53 [1423592] J Virol. 1993 Feb;67(2):832-42 [8419648] Mol Biol Cell. 1992 Dec;3(12):1339-52 [1493333] EMBO J. 1993 Jul;12(7):2781-8 [8334994] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8962-6 [8415639] J Biol Chem. 1993 Oct 25;268(30):22703-9 [8226780] Gene Expr. 1993;3(2):135-50 [8268718] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5350-4 [8202491] Mol Cell Biol. 1995 Feb;15(2):872-82 [7823953] Nature. 1995 Jan 26;373(6512):303-10 [7530332] Nature. 1995 Jan 26;373(6512):311-7 [7830764] Cell. 1995 Feb 24;80(4):573-82 [7867065] Science. 1995 Mar 10;267(5203):1485-8 [7878466] Mol Cell Biol. 1995 May;15(5):2809-18 [7739562] Mol Cell Biol. 1995 Jul;15(7):3627-34 [7791770] Adv Cancer Res. 1995;66:255-92 [7793317] EMBO J. 1995 Jun 15;14(12):2876-83 [7796813] Genes Dev. 1995 Jul 1;9(13):1586-97 [7628694] Mol Cell Biol. 1995 Oct;15(10):5339-45 [7565683] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10242-6 [7479760] Mol Cell Biol. 1996 Mar;16(3):1103-14 [8622655] J Virol. 1996 May;70(5):3176-88 [8627798] Annu Rev Immunol. 1996;14:649-83 [8717528] J Virol. 1997 Apr;71(4):3161-7 [9060679] EMBO J. 1997 Mar 17;16(6):1413-26 [9135156] Nat Struct Biol. 1998 Jan;5(1):67-73 [9437432] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333-7 [1533932] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle. AN - 79810983; 9557701 AB - The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been reported to play a crucial role in the targeting of the Gag polyprotein precursor to the plasma membrane and in the incorporation of viral envelope glycoproteins into budding virions. In this report, we present evidence that mutation of a highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus replication in a range of cell types, including T-cell lines, primary human peripheral blood mononuclear cells, and monocyte-derived macrophages. These mutations do not impair virus assembly and release, RNA encapsidation, or envelope glycoprotein incorporation into virions but rather cause significant defects in an early step in the virus life cycle, as measured by single-cycle infectivity assays and the analysis of viral DNA synthesis early postinfection. This infectivity defect is independent of the type of envelope glycoprotein carried on mutant virions; similar results are obtained in pseudotyping experiments using wild-type or truncated HIV-1 envelope glycoproteins, the amphotropic murine leukemia virus envelope, or the vesicular stomatitis G protein. Intriguingly, matrix residue 20 mutations also increase the apparent binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce defects in endogenous reverse transcriptase activity without affecting virion density or morphology. These results help elucidate the function of matrix in HIV-1 replication. JF - Journal of virology AU - Kiernan, R E AU - Ono, A AU - Englund, G 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 - 1998/05// PY - 1998 DA - May 1998 SP - 4116 EP - 4126 VL - 72 IS - 5 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Gene Products, gag KW - HIV Envelope Protein gp41 KW - RNA, Viral KW - Viral Envelope Proteins KW - Viral Matrix Proteins KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Virion KW - HeLa Cells KW - Humans KW - HIV Envelope Protein gp41 -- metabolism KW - Jurkat Cells KW - Amino Acid Sequence KW - Gene Products, gag -- metabolism KW - Mutagenesis, Site-Directed KW - DNA, Viral -- biosynthesis KW - Tumor Cells, Cultured KW - HIV Envelope Protein gp41 -- genetics KW - HIV Reverse Transcriptase -- metabolism KW - Molecular Sequence Data KW - Viral Envelope Proteins -- metabolism KW - Cell Membrane -- metabolism KW - RNA, Viral -- metabolism KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Viral Matrix Proteins -- genetics KW - Virus Replication -- physiology KW - HIV-1 -- physiology KW - Viral Matrix Proteins -- physiology KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79810983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+matrix+in+an+early+postentry+step+in+the+human+immunodeficiency+virus+type+1+life+cycle.&rft.au=Kiernan%2C+R+E%3BOno%2C+A%3BEnglund%2C+G%3BFreed%2C+E+O&rft.aulast=Kiernan&rft.aufirst=R&rft.date=1998-05-01&rft.volume=72&rft.issue=5&rft.spage=4116&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 - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1996 Nov 1;15(21):5783-8 [8918455] J Virol. 1996 Dec;70(12):8540-8 [8970978] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Virol. 1996 May;70(5):2809-24 [8627755] J Virol. 1996 May;70(5):2963-73 [8627772] J Virol. 1996 Jun;70(6):3551-60 [8648689] J Virol. 1996 Aug;70(8):5297-305 [8764040] Virology. 1973 Dec;56(2):549-64 [4127970] J Mol Biol. 1982 Apr 15;156(3):609-31 [6288961] Virology. 1983 Oct 30;130(2):415-26 [6196908] J Virol. 1984 Mar;49(3):909-17 [6608006] J Virol. 1996 Dec;70(12):8645-52 [8970990] J Virol. 1996 Dec;70(12):8701-9 [8970997] Cell. 1997 Jan 24;88(2):171-3; discussion 173-4 [9008157] Virology. 1997 Feb 17;228(2):294-306 [9123837] J Virol. 1997 Jun;71(6):4409-18 [9151831] J Virol. 1997 Jul;71(7):5382-90 [9188609] J Virol. 1997 Aug;71(8):5871-7 [9223476] J Virol. 1997 Sep;71(9):6582-92 [9261380] J Virol. 1997 Sep;71(9):6973-81 [9261426] EMBO J. 1997 Aug 1;16(15):4531-9 [9303297] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):367-71 [8552640] J Virol. 1996 Feb;70(2):1016-26 [8551559] J Virol. 1986 Aug;59(2):284-91 [3016298] Virology. 1987 Jan;156(1):171-6 [3643678] Science. 1988 Jan 29;239(4839):487-91 [2448875] Annu Rev Cell Biol. 1988;4:611-47 [3058168] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Nature. 1989 Aug 3;340(6232):397-400 [2666861] 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] J Virol. 1991 Jan;65(1):162-9 [1845882] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 [1729720] J Virol. 1992 Apr;66(4):2232-9 [1548759] Virology. 1992 Jul;189(1):167-77 [1604808] J Virol. 1992 Aug;66(8):4893-900 [1378513] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Aug;66(8):5067-74 [1378514] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1993 Jul;67(7):4264-73 [7685414] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] J Virol. 1993 Aug;67(8):4945-55 [8331734] J Virol. 1993 Aug;67(8):4972-80 [8331736] J Virol. 1993 Oct;67(10):6322-6 [8371360] J Virol. 1993 Nov;67(11):6387-94 [8411340] Nature. 1993 Oct 14;365(6447):666-9 [8105392] 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] Nature. 1994 May 12;369(6476):107-8 [8192816] Virology. 1994 Jun;201(2):349-55 [8184544] J Virol. 1994 Aug;68(8):5311-20 [8035531] 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] J Virol. 1994 Oct;68(10):6644-54 [7521919] Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9564-8 [7937806] J Virol. 1994 Dec;68(12):8180-7 [7966609] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1031-8 [7980574] J Virol. 1995 Mar;69(3):1984-9 [7853546] Virology. 1995 Feb 1;206(2):935-44 [7531918] Cell. 1995 Feb 10;80(3):379-88 [7859280] J Virol. 1995 May;69(5):2729-36 [7535863] J Virol. 1995 Jun;69(6):3824-30 [7745730] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1995 Jul;69(7):4053-9 [7539505] J Virol. 1995 Aug;69(8):5048-56 [7541845] Virology. 1995 Oct 1;212(2):451-7 [7571414] J Virol. 1995 Nov;69(11):6810-8 [7474093] Cell. 1995 Nov 17;83(4):569-76 [7585960] J Virol. 1996 Jan;70(1):341-51 [8523546] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12519-24 [8901614] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phylogenetic and functional classification of mitogen- and stress-activated protein kinases. AN - 79809653; 9545468 AB - All currently sequenced stress-activated protein kinases (SAPKs), extracellular signal-regulated kinases (ERKs), and other mitogen-activated protein kinases (MAPKs) were analyzed by sequence alignment, phylogenetic tree construction, and three-dimensional structure modeling in order to classify members of the MAPK family. Based on this analysis the MAPK family was divided into three subgroups (SAPKs, ERKs, and MAPK3) that consist of at least nine subfamilies. Members of a given subfamily were exclusively from animals, plants, or yeast/fungi. A single signature sequence, [LIVM][TS]XX[LIVM]XT[RK][WY]YRXPX[LIVM] [LIVM], was identified that is characteristic for all MAPKs and sufficient to distinguish MAPKs from other members of the protein kinase superfamily. This signature sequence contains the phosphorylation site and is located on loop 12 of the three-dimensional structure of MAPKs. I also identified signature sequences that are characteristic for each of the nine subfamilies of MAPKs. By modeling the three-dimensional structure of three proteins for each MAPK subfamily based on the resolved atomic structures of rat ERK2 and murine p38, it is demonstrated that amino acids conserved in all MAPKs are located primarily in the center of the protein around the catalytic cleft. I conclude that these residues are important for maintaining proper folding into the gross structure common to all MAPKs. On the other hand, amino acids conserved in a given subfamily are located mainly in the periphery of MAPKs, indicating their possible importance for defining interactions with substrates, activators, and inhibitors. Within these subfamily-specific regions, amino acids were identified that represent unique residues occurring in only a single subfamily and their location was mapped in three-dimensional structure models. These unique residues are likely to be crucial for subfamily-specific interactions of MAPKs with substrates, inhibitors, or activators and, therefore, represent excellent targets for site-directed mutagenesis experiments. JF - Journal of molecular evolution AU - Kültz, D AD - Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, 10 Center Drive, MSC 1603, Building 10/Room 6N260, Bethesda, MD 20892-1603, USA. kultzd@gwgate.nhlbi.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 571 EP - 588 VL - 46 IS - 5 SN - 0022-2844, 0022-2844 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Rats KW - Animals KW - Sequence Alignment KW - Conserved Sequence KW - Models, Molecular KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Protein Conformation KW - Mutagenesis KW - Phylogeny KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- chemistry KW - Calcium-Calmodulin-Dependent Protein Kinases -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+evolution&rft.atitle=Phylogenetic+and+functional+classification+of+mitogen-+and+stress-activated+protein+kinases.&rft.au=K%C3%BCltz%2C+D&rft.aulast=K%C3%BCltz&rft.aufirst=D&rft.date=1998-05-01&rft.volume=46&rft.issue=5&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-29 N1 - Date created - 1998-05-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient in vitro repair of 7-hydro-8-oxodeoxyguanosine by human cell extracts: involvement of multiple pathways. AN - 79807250; 9547279 AB - To investigate the repair of oxidative damage in DNA, we have established an in vitro assay utilizing human lymphoblastoid whole cell extracts and plasmid DNA damaged by exposure to methylene blue and visible light. This treatment has been shown to produce predominantly 7-hydro-8-oxodeoxyguanosine (8-oxodG) in double-stranded DNA at low levels of modification. DNA containing 1. 6 lesions per plasmid is substrate for efficient repair synthesis by cell extracts. The incorporation of dGMP is 2.7 +/- 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleotides. Damage-specific nicking occurs within 15 min, while resynthesis is slower. The incorporation of dGMP increases linearly, while the incorporation of dCMP exhibits a distinct lag. Extracts from xeroderma pigmentosum (XP) complementation groups A and B exhibit 25 and 40%, respectively, of the incorporation of dCMP compared with normal extracts, but extracts from an XP-D cell line exhibit twice the activity. These data suggest that the efficient repair of 8-oxodG lesions observed in human cell extracts involves more than one pathway of base excision repair. JF - Nucleic acids research AU - Jaiswal, M AU - Lipinski, L J AU - Bohr, V A AU - Mazur, S J AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 2184 EP - 2191 VL - 26 IS - 9 SN - 0305-1048, 0305-1048 KW - Deoxyguanine Nucleotides KW - 0 KW - Radiation-Sensitizing Agents KW - Deoxycytidine Monophosphate KW - 1032-65-1 KW - 2'-deoxyguanosine 5'-phosphate KW - 7EAM4TG712 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Deoxyguanosine KW - G9481N71RO KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - DNA Damage KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Xeroderma Pigmentosum -- metabolism KW - Dose-Response Relationship, Radiation KW - Deoxycytidine Monophosphate -- metabolism KW - Deoxyguanine Nucleotides -- metabolism KW - Cockayne Syndrome -- metabolism KW - Lymphocytes -- radiation effects KW - Light KW - Lymphocytes -- cytology KW - Subcellular Fractions -- metabolism KW - Hematopoietic Stem Cells -- radiation effects KW - Cell Line KW - Cell-Free System KW - DNA Repair -- radiation effects KW - Deoxyguanosine -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79807250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+in+vitro+repair+of+7-hydro-8-oxodeoxyguanosine+by+human+cell+extracts%3A+involvement+of+multiple+pathways.&rft.au=Jaiswal%2C+M%3BLipinski%2C+L+J%3BBohr%2C+V+A%3BMazur%2C+S+J&rft.aulast=Jaiswal&rft.aufirst=M&rft.date=1998-05-01&rft.volume=26&rft.issue=9&rft.spage=2184&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 - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1989 Sep;9(9):3750-7 [2779565] J Biol Chem. 1997 Oct 24;272(43):27338-44 [9341184] Biochemistry. 1990 Jul 31;29(30):7024-32 [2223758] J Bacteriol. 1991 Jun;173(11):3419-24 [1710617] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4690-4 [2052552] Biochemistry. 1992 Jan 14;31(1):106-10 [1731864] Mol Cell Biol. 1992 Apr;12(4):1605-12 [1549115] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6866-70 [1495976] Mutat Res. 1992 Sep;275(3-6):331-42 [1383774] Nucleic Acids Res. 1992 Sep 11;20(17):4437-43 [1408745] J Biol Chem. 1993 Mar 5;268(7):4839-47 [8444862] Cancer Res. 1974 Dec;34(12):3318-25 [4371955] J Biol Chem. 1983 Aug 25;258(16):9990-4 [6411709] Arch Biochem Biophys. 1989 Aug 15;273(1):106-11 [2502945] Nature. 1993 Apr 22;362(6422):709-15 [8469282] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6335-9 [8327515] J Biol Chem. 1993 Sep 15;268(26):19416-21 [8366089] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-22 [8367443] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8901-4 [8415629] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499-503 [8248136] Biochim Biophys Acta. 1994 Jan 18;1217(1):9-15 [8286420] Mol Cell Biol. 1994 Sep;14(9):6187-97 [7915006] Annu Rev Biochem. 1994;63:915-48 [7979257] J Invest Dermatol. 1995 Jan;104(1):68-73 [7798643] Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):719-23 [7846041] Biochemistry. 1995 Apr 18;34(15):5011-7 [7711023] Chem Res Toxicol. 1995 Apr-May;8(3):379-88 [7578924] Nucleic Acids Res. 1996 Apr 15;24(8):1389-94 [8628669] J Biol Chem. 1996 Apr 19;271(16):9573-8 [8621631] EMBO J. 1996 May 1;15(9):2306-12 [8641296] Proc Natl Acad Sci U S A. 1996 May 28;93(11):5197-202 [8643552] Curr Biol. 1996 Aug 1;6(8):968-80 [8805338] Mutat Res. 1996 Dec 2;364(3):183-92 [8960130] Science. 1997 Feb 14;275(5302):990-3 [9020084] Carcinogenesis. 1997 Apr;18(4):605-10 [9111189] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-11 [9113985] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7429-34 [9207108] EMBO J. 1997 Jun 2;16(11):3341-8 [9214649] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8010-5 [9223305] Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016-20 [9223306] Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9463-8 [9256505] J Biol Chem. 1997 Aug 8;272(32):19633-6 [9289489] Biochemistry. 1989 Nov 28;28(24):9515-20 [2482074] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The utility of monitoring carcinoembyronic antigen during systemic therapy for advanced colorectal cancer. AN - 79788559; 9538153 AB - To determine if pre-treatment serum carcinoembryonic antigen (CEA) levels or changes in CEA values during treatment have prognostic value, we reviewed five prior fluorouracil/leucovorin-based trials and identified 125 colorectal cancer patients with no prior chemotherapy for metastatic disease in whom CEA values were available. Although pre-treatment serum CEA values did not predict for clinical response or time to progression, serial monitoring of CEA appeared to be useful in patients with an elevated pre-treatment CEA, particularly when a decrease in CEA occurred in concert with radiographic evidence of disease response. The CEA nadir was a strong prognostic variable with respect to time to disease progression. A consistent rise in CEA values over the minimum value signals the need for radiographic re-assessment of the patient's disease status to rule out disease progression. JF - Oncology reports AU - Grem, J L AU - Steinberg, S M AU - Chen, A P AU - McAtee, N AU - Cullen, E AU - Hamilton, J M AU - Allegra, C J AD - NCI-Medicine Branch, NNMC, Building 8, Room 5101, 8901 Wisconsin Ave., Bethesda, MD, 20889-5105, USA. PY - 1998 SP - 559 EP - 567 VL - 5 IS - 3 SN - 1021-335X, 1021-335X KW - Antidotes KW - 0 KW - Antimetabolites, Antineoplastic KW - Carcinoembryonic Antigen KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Sensitivity and Specificity KW - Antidotes -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Retrospective Studies KW - Prognosis KW - Clinical Trials as Topic KW - Disease Progression KW - Aged KW - Fluorouracil -- therapeutic use KW - Adult KW - Middle Aged KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Female KW - Male KW - Survival Analysis KW - Rectal Neoplasms -- drug therapy KW - Rectal Neoplasms -- blood KW - Colonic Neoplasms -- drug therapy KW - Rectal Neoplasms -- pathology KW - Carcinoembryonic Antigen -- blood KW - Colonic Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Colonic Neoplasms -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79788559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reports&rft.atitle=The+utility+of+monitoring+carcinoembyronic+antigen+during+systemic+therapy+for+advanced+colorectal+cancer.&rft.au=Grem%2C+J+L%3BSteinberg%2C+S+M%3BChen%2C+A+P%3BMcAtee%2C+N%3BCullen%2C+E%3BHamilton%2C+J+M%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1998-05-01&rft.volume=5&rft.issue=3&rft.spage=559&rft.isbn=&rft.btitle=&rft.title=Oncology+reports&rft.issn=1021335X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of transforming growth factor-beta1, -beta2, and -beta3 in androgen-responsive growth of NRP-152 rat prostatic epithelial cells. AN - 79756886; 9525477 AB - We have investigated the role of autocrine/paracrine TGF-beta secretion in the regulation of cell growth by androgens as demonstrated by its inhibition by two androgen response modifiers; the nonsteroidal antiandrogen hydroxyflutamide (OHF), believed to act by inhibiting androgen binding to androgen receptors, or finasteride, an inhibitor of 5alpha-reductase, the enzyme necessary for the conversion of testosterone to 5alpha-dihydrotestosterone (DHT), using the nontumorigenic rat prostatic epithelial cell line NRP-152. Growth of these cells was stimulated three- to sixfold over control by either testosterone or DHT under serum-free culture conditions. This was accompanied by a two- to threefold decrease in the secretion rate of TGF-beta1, -beta2, and -beta3. Finasteride reversed the ability of testosterone but not DHT to stimulate growth and downregulate expression of TGF-beta1, -beta2, and -beta3 in a dose-dependent fashion, suggesting that this activity of testosterone required its conversion to DHT. OHF antagonized the stimulatory effects of DHT on NRP-152 cell growth but could reverse the inhibitory effects of DHT only on TGF-beta2 and TGF-beta3 and not TGF-beta1 secretion. This suggests that either TGF-beta1 regulation by DHT or the androgen antagonism of OHF occurs independent of androgen receptor binding. Neutralizing antibodies to TGF-beta (pantropic and isoform-specific) were able to block the ability of finasteride to antagonize the effects of testosterone nearly completely while only partially inhibiting the antiandrogenic effects of OHF. Thus, the ability of androgens to stimulate growth of NRP-152 cells involves the downregulation of the production of TGF-beta1, -beta2, and -beta3 in addition to other growth-stimulatory mechanisms. JF - Journal of cellular physiology AU - Lucia, M S AU - Sporn, M B AU - Roberts, A B AU - Stewart, L V AU - Danielpour, D AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 184 EP - 192 VL - 175 IS - 2 SN - 0021-9541, 0021-9541 KW - Androgen Antagonists KW - 0 KW - Androgens KW - Antibodies KW - Transforming Growth Factor beta KW - Dihydrotestosterone KW - 08J2K08A3Y KW - hydroxyflutamide KW - 31D90UKP5Y KW - Testosterone KW - 3XMK78S47O KW - Finasteride KW - 57GNO57U7G KW - Flutamide KW - 76W6J0943E KW - Index Medicus KW - Animals KW - Antibodies -- immunology KW - Androgen Antagonists -- pharmacology KW - Finasteride -- pharmacology KW - Testosterone -- antagonists & inhibitors KW - Rats KW - Flutamide -- analogs & derivatives KW - Testosterone -- pharmacology KW - Dihydrotestosterone -- antagonists & inhibitors KW - Down-Regulation -- physiology KW - Dihydrotestosterone -- pharmacology KW - Antibodies -- pharmacology KW - Flutamide -- pharmacology KW - Cell Line KW - Male KW - Prostate -- drug effects KW - Cell Division -- drug effects KW - Androgens -- pharmacology KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79756886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+transforming+growth+factor-beta1%2C+-beta2%2C+and+-beta3+in+androgen-responsive+growth+of+NRP-152+rat+prostatic+epithelial+cells.&rft.au=Lucia%2C+M+S%3BSporn%2C+M+B%3BRoberts%2C+A+B%3BStewart%2C+L+V%3BDanielpour%2C+D&rft.aulast=Lucia&rft.aufirst=M&rft.date=1998-05-01&rft.volume=175&rft.issue=2&rft.spage=184&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 - 1998-04-16 N1 - Date created - 1998-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Frequency of lumbago in a cohort of nursing students]. TT - Frequenza della lombalgia in una coorte di allievi infermieri. AN - 73914734; 9734194 AB - The etiology and frequency of low back pain among health care personnel have been widely studied by means of cross sectional studies. The aim of our study was to calculate low back pain incidence in a prospective cohort of nursing students. A population of 344 subjects (72 males and 272 females) was involved in this investigation. Every student was submitted to a clinical and functional examination of the spine before beginning training and was checked in two following steps by a specific questionnaire for epidemiological studies of spinal disorders in working communities. 197 subjects (57.3%)(41 males and 156 females) completed follow-up. The low back pain incidence was similar at the end of two exposure periods (12.1% and 13.1%). The cumulative incidence was 22.5% throughout the study period. The longitudinal study allowed good control of selection bias and confounding factors; more over it showed that compared to other measurements of occurrence the cumulative incidence was between other occurrence measures, more informative, in our case, than prevalence and incidence rates. A cumulative incidence of low back pain over 20% after only two years of exposure in a young and healthy population of nursing students, requires implementation of ergonomic measures for patient handling tasks. JF - La Medicina del lavoro AU - Baldasseroni, A AU - Tartaglia, R AU - Sgarrella, C AU - Carnevale, F AD - U.O. Igiene e Salute nei Luoghi di Lavoro G. Pieraccini, Azienda Sanitaria di Firenze. PY - 1998 SP - 242 EP - 253 VL - 89 IS - 3 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Adult KW - Incidence KW - Middle Aged KW - Italy -- epidemiology KW - Longitudinal Studies KW - Male KW - Female KW - Students, Nursing -- statistics & numerical data KW - Low Back Pain -- epidemiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73914734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BFrequency+of+lumbago+in+a+cohort+of+nursing+students%5D.&rft.au=Baldasseroni%2C+A%3BTartaglia%2C+R%3BSgarrella%2C+C%3BCarnevale%2C+F&rft.aulast=Baldasseroni&rft.aufirst=A&rft.date=1998-05-01&rft.volume=89&rft.issue=3&rft.spage=242&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 - 1998-09-21 N1 - Date created - 1998-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rearrangements of archetypal regulatory regions in JC virus genomes from urine. AN - 73855838; 9711540 AB - The regulatory region of progressive multifocal leukoencephalopathy-type JC virus (JCV) is rearranged in each host by a process of deletion and duplication. Of the more than 40 that have been examined, no two regulatory regions have been rearranged identically in the brain. The substrate for this rearrangement appears to be a highly stable archetypal regulatory region excreted in the urine. Its role as the transmissible form of the virus, although inferred, has never been proven. We have now amplified by PCR and cycle-sequenced the regulatory regions from 48 urinary strains of the virus. We find that the urinary form of the regulatory region is not entirely stable. Short deletions and duplications in the range of 2-16 bp were observed in seven of these strains. One of these, an inverted repeat, is a pattern of rearrangement not yet found in the brain. Two others (#208 and 230) showed a 2-bp deletion at position nos. 221 and 222, and an unusual mutation at position no. 219. These two urines were collected in different states of the USA at different times and analysed months apart. It is very unlikely that these unusual changes represent sample contamination or that they arose independently. This finding indicates that archetypal forms of the JCV regulatory region are infectious, despite their relative inactivity in tissue culture. While changes in the archetypal structure can be found, it is clear that rearrangements in the kidney are rare or rarely infectious. JF - Research in virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1998 SP - 163 EP - 170 VL - 149 IS - 3 SN - 0923-2516, 0923-2516 KW - DNA, Viral KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - HIV Infections -- virology KW - HIV Infections -- urine KW - Humans KW - Leukoencephalopathy, Progressive Multifocal -- urine KW - Aged KW - Multiple Sclerosis -- urine KW - Polymerase Chain Reaction KW - Adult KW - Middle Aged KW - Multiple Sclerosis -- virology KW - Female KW - Male KW - Regulatory Sequences, Nucleic Acid KW - Tumor Virus Infections -- virology KW - JC Virus -- genetics KW - Papillomavirus Infections -- urine KW - Tumor Virus Infections -- urine KW - Recombination, Genetic KW - Papillomavirus Infections -- virology KW - DNA, Viral -- urine KW - DNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73855838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Research+in+virology&rft.atitle=Rearrangements+of+archetypal+regulatory+regions+in+JC+virus+genomes+from+urine.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=149&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Research+in+virology&rft.issn=09232516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-20 N1 - Date created - 1998-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of subcutaneous recombinant human erythropoietin (r-HuEPO) on anemia in cancer patients receiving platinum-based chemotherapy. AN - 70041409; 9813972 AB - Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy. JF - JPMA. The Journal of the Pakistan Medical Association AU - Malik, I A AU - Khan, Z K AU - Hakimali, A AU - Sabih, M AU - Rehman, G AD - National Cancer Institute, Clifton, Karachi. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 127 EP - 131 VL - 48 IS - 5 SN - 0030-9982, 0030-9982 KW - Antineoplastic Agents KW - 0 KW - Hemoglobins KW - Recombinant Proteins KW - Erythropoietin KW - 11096-26-7 KW - Ferritins KW - 9007-73-2 KW - Iron KW - E1UOL152H7 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Ferritins -- blood KW - Lung Neoplasms -- complications KW - Humans KW - Lung Neoplasms -- drug therapy KW - Quality of Life KW - Ovarian Neoplasms -- complications KW - Activities of Daily Living KW - Iron -- blood KW - Ovarian Neoplasms -- drug therapy KW - Hemoglobins -- analysis KW - Iron -- administration & dosage KW - Blood Transfusion KW - Injections, Subcutaneous KW - Reticulocyte Count KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Female KW - Iron -- therapeutic use KW - Neoplasms -- drug therapy KW - Erythropoietin -- blood KW - Neoplasms -- complications KW - Antineoplastic Agents -- administration & dosage KW - Anemia -- blood KW - Erythropoietin -- administration & dosage KW - Erythropoietin -- therapeutic use KW - Anemia -- drug therapy KW - Anemia -- etiology KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JPMA.+The+Journal+of+the+Pakistan+Medical+Association&rft.atitle=The+effect+of+subcutaneous+recombinant+human+erythropoietin+%28r-HuEPO%29+on+anemia+in+cancer+patients+receiving+platinum-based+chemotherapy.&rft.au=Malik%2C+I+A%3BKhan%2C+Z+K%3BHakimali%2C+A%3BSabih%2C+M%3BRehman%2C+G&rft.aulast=Malik&rft.aufirst=I&rft.date=1998-05-01&rft.volume=48&rft.issue=5&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=JPMA.+The+Journal+of+the+Pakistan+Medical+Association&rft.issn=00309982&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-12-03 N1 - Date created - 1998-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil. AN - 69976099; 9778647 AB - Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites. JF - Molecular and chemical neuropathology AU - Rabin, O AU - Drieu, K AU - Grange, E AU - Chang, M C AU - Rapoport, S I AU - Purdon, A D AD - Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD 20892-1582, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 79 EP - 101 VL - 34 IS - 1 SN - 1044-7393, 1044-7393 KW - Fatty Acids KW - 0 KW - Flavonoids KW - Membrane Lipids KW - Neuroprotective Agents KW - Phospholipids KW - Plant Extracts KW - Ginkgo biloba extract KW - 19FUJ2C58T KW - Arachidonic Acid KW - 27YG812J1I KW - Palmitic Acid KW - 2V16EO95H1 KW - Index Medicus KW - Gerbillinae KW - Animals KW - Palmitic Acid -- metabolism KW - Wakefulness KW - Male KW - Arachidonic Acid -- metabolism KW - Reperfusion Injury -- metabolism KW - Ischemic Attack, Transient -- metabolism KW - Reperfusion Injury -- prevention & control KW - Plants, Medicinal KW - Brain Chemistry -- drug effects KW - Phospholipids -- metabolism KW - Membrane Lipids -- metabolism KW - Neuroprotective Agents -- therapeutic use KW - Ginkgo biloba -- chemistry KW - Ischemic Attack, Transient -- drug therapy KW - Neuroprotective Agents -- pharmacology KW - Fatty Acids -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemical+neuropathology&rft.atitle=Effects+of+EGb+761+on+fatty+acid+reincorporation+during+reperfusion+following+ischemia+in+the+brain+of+the+awake+gerbil.&rft.au=Rabin%2C+O%3BDrieu%2C+K%3BGrange%2C+E%3BChang%2C+M+C%3BRapoport%2C+S+I%3BPurdon%2C+A+D&rft.aulast=Rabin&rft.aufirst=O&rft.date=1998-05-01&rft.volume=34&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Molecular+and+chemical+neuropathology&rft.issn=10447393&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-01-04 N1 - Date created - 1999-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential wire codes: reproducibility and relation with measured magnetic fields. AN - 69950033; 9764111 AB - To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States. Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code. The reproducibility of any of three different classifications of wire codes was excellent (kappa > or = 0.89). Mean and median magnetic fields, and the percentage of homes with high magnetic fields increased with increasing category for each of the wire code classification schemes. The size of the odds ratios for risk of leukaemia and high categories of wire code did not reflect the mean levels of the magnetic field in those categories in two study regions. Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area. JF - Occupational and environmental medicine AU - Tarone, R E AU - Kaune, W T AU - Linet, M S AU - Hatch, E E AU - Kleinerman, R A AU - Robison, L L AU - Boice, J D AU - Wacholder, S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 333 EP - 339 VL - 55 IS - 5 SN - 1351-0711, 1351-0711 KW - Index Medicus KW - Odds Ratio KW - Reproducibility of Results KW - Humans KW - Leukemia, Radiation-Induced -- etiology KW - Child KW - Child, Preschool KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- etiology KW - Risk Assessment KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- epidemiology KW - Leukemia, Radiation-Induced -- epidemiology KW - Risk Factors KW - Bias (Epidemiology) KW - United States -- epidemiology KW - Electric Wiring -- classification KW - Electromagnetic Fields -- adverse effects KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69950033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Residential+wire+codes%3A+reproducibility+and+relation+with+measured+magnetic+fields.&rft.au=Tarone%2C+R+E%3BKaune%2C+W+T%3BLinet%2C+M+S%3BHatch%2C+E+E%3BKleinerman%2C+R+A%3BRobison%2C+L+L%3BBoice%2C+J+D%3BWacholder%2C+S&rft.aulast=Tarone&rft.aufirst=R&rft.date=1998-05-01&rft.volume=55&rft.issue=5&rft.spage=333&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 completed - 1998-10-15 N1 - Date created - 1998-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Epidemiol. 1979 Mar;109(3):273-84 [453167] Bioelectromagnetics. 1997;18(2):99-110 [9084860] Am J Epidemiol. 1980 Mar;111(3):292-6 [7361752] Epidemiology. 1997 Sep;8(5):575-83 [9270962] Int J Epidemiol. 1982 Dec;11(4):345-55 [7152787] Bioelectromagnetics. 1987;8(4):315-35 [3426634] Am J Epidemiol. 1988 Jul;128(1):21-38 [3164167] Bioelectromagnetics. 1989;10(1):13-21 [2712837] Am J Epidemiol. 1991 Nov 1;134(9):923-37 [1843457] Comput Biomed Res. 1992 Feb;25(1):75-84 [1547628] Bioelectromagnetics. 1993;14(2):145-59 [8494556] J Clin Epidemiol. 1993 Jun;46(6):545-8 [8501481] Environ Health Perspect. 1993 Apr 22;101(1):76-80 [8513768] Am J Epidemiol. 1993 Oct 1;138(7):467-81 [8213751] Bioelectromagnetics. 1994;15(4):275-82 [7980656] Epidemiology. 1995 Jan;6(1):31-5 [7888441] Am J Epidemiol. 1996 Jan 15;143(2):105-19 [8546111] Am J Epidemiol. 1996 Jan 15;143(2):120-8 [8546112] Epidemiology. 1996 May;7(3):217-8 [8728430] Epidemiology. 1996 May;7(3):220-4 [8728432] N Engl J Med. 1997 Jul 3;337(1):1-7 [9203424] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complete genome of a JC virus genotype type 6 from the brain of an African American with progressive multifocal leukoencephalopathy. AN - 69196518; 10195251 AB - The major genotypes of the human polyomavirus JC (JCV) include type 1 (European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we report characterization of the complete genome of a genotype obtained from the brain of an African American with systemic lupus erythematosus (SLE) and progressive multifocal leukoencephalopathy (PML). DNA extracted from JCV-infected brain tissue was subjected to whole-genome polymerase chain reaction (PCR) amplification and direct cycle sequencing. Relations to other JCV genotypes and the predicted amino acid sequence were analyzed. This African-American type 6 strain (#601) differs from strains of all other genotypes in about 2% of its DNA sequence. The length of the total coding region of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in the large T-antigen intron. This strain, originally placed with the type 2 group on the basis of its sequence in the VT-intergenic region, is very closely related to strains recently identified in the urine of individuals from Ghana, West Africa. This is the first example of an African JCV genotype identified in the brain of an African-American PML patient. The extent of sequence divergence of JCV type 6 suggests a split of type 6 strains before the separation of types 2 and 3. These findings confirm that distinctive African genotypes of JCV have been maintained in the African-American population and that they are capable of causing PML. JF - Journal of human virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1998 SP - 267 EP - 272 VL - 1 IS - 4 SN - 1090-9508, 1090-9508 KW - Index Medicus KW - Phylogeny KW - Genotype KW - Base Sequence KW - Humans KW - Adult KW - Molecular Sequence Data KW - African Americans KW - Female KW - Lupus Erythematosus, Systemic -- complications KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - Leukoencephalopathy, Progressive Multifocal -- complications KW - Polyomavirus -- genetics KW - Genome, Viral KW - Brain -- virology KW - Polyomavirus -- isolation & purification KW - Lupus Erythematosus, Systemic -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69196518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Complete+genome+of+a+JC+virus+genotype+type+6+from+the+brain+of+an+African+American+with+progressive+multifocal+leukoencephalopathy.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-05-01&rft.volume=1&rft.issue=4&rft.spage=267&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 - 1999-04-29 N1 - Date created - 1999-04-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015538; GENBANK; AF015537 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Telephone Support Groups for HIV-Positive Mothers Whose Children Have Died of AIDS AN - 61445230; 199901455 AB - Describes a telephone support group for human immunodeficiency virus-positive (HIV+) mothers on the East Coast & in the Midwest whose children had died of acquired immune deficiency syndrome (AIDS), 1990-1992. The 12-session support group aimed to help participants counterbalance the impact of grief, confront the reality of death, bring feelings into the open, make use of available resources, acknowledge their own health care needs, find release from guilt & regrets through forgiveness, maintain a sense of inner integration, redefine the self, keep communication channels open in the family, assist the family's other children with their grief, & grant permission to cease grieving. This psychotherapeutic modality is recommended to all social workers involved in the HIV epidemic as a practical & cost-effective means of reaching people who may not be geographically or emotionally able to attend in-person groups. 11 References. M. Greenberg JF - Social Work AU - Wiener, Lori S AD - Pediatric HIV Psychosocial Support Program National Cancer Instit National Instits Health, Bethesda MD wienerl@pbmac.nci.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 279 EP - 285 VL - 43 IS - 3 SN - 0037-8046, 0037-8046 KW - Death KW - Psychotherapy KW - Mothers KW - Acquired Immune Deficiency Syndrome KW - Self Help Groups KW - Children KW - Telephone Communications KW - article KW - 6123: social welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61445230?accountid=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=Social+Work&rft.atitle=Telephone+Support+Groups+for+HIV-Positive+Mothers+Whose+Children+Have+Died+of+AIDS&rft.au=Wiener%2C+Lori+S&rft.aulast=Wiener&rft.aufirst=Lori&rft.date=1998-05-01&rft.volume=43&rft.issue=3&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Social+Work&rft.issn=00378046&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Acquired Immune Deficiency Syndrome; Mothers; Self Help Groups; Telephone Communications; Children; Death; Psychotherapy ER - TY - JOUR T1 - Dietary habits and stomach cancer in Shanghai, China AN - 17565975; 4352422 AB - Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population-based case-control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20-69) newly diagnosed in 1988-1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1-2.1) and 1.9 (95% CI 1.3-2.9) in the highest quartile of intake among men (p for trend = 0.02) and women (p = 0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p = 0.07) and women (p = 0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non-cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved. JF - International Journal of Cancer AU - Ji, B-T AU - Chow, W-H AU - Yang, G AU - McLaughlin, J K AU - Zheng, W AU - Shu, X-O AU - Jin, F AU - Gao, R-N AU - Gao, Y-T AU - Fraumeni, JF Jr AD - National Cancer Institute, 6130 Executive Blvd, EPN 415, Rockville, MD 20852, USA, jib@epndce.nci.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 659 EP - 664 VL - 76 IS - 5 SN - 0020-7136, 0020-7136 KW - China, Shanghai KW - starch KW - stomach KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Diets KW - Cancer KW - Public health KW - Carbohydrates KW - H 11000:Diseases/Injuries/Trauma KW - H 12000:Epidemiology and Public Health KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17565975?accountid=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=Dietary+habits+and+stomach+cancer+in+Shanghai%2C+China&rft.au=Ji%2C+B-T%3BChow%2C+W-H%3BYang%2C+G%3BMcLaughlin%2C+J+K%3BZheng%2C+W%3BShu%2C+X-O%3BJin%2C+F%3BGao%2C+R-N%3BGao%2C+Y-T%3BFraumeni%2C+JF+Jr&rft.aulast=Ji&rft.aufirst=B-T&rft.date=1998-05-01&rft.volume=76&rft.issue=5&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2F%28SICI%291097-0215%2819980529%2976%3A53.3.CO%3B2-M LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Diets; Carbohydrates; Public health; Risk assessment DO - http://dx.doi.org/10.1002/(SICI)1097-0215(19980529)76:5<659::AID-IJC8>3.3.CO;2-M ER - TY - JOUR T1 - Cooperative breeding and monogamy in prairie voles: influence of the sire and geographical variation AN - 17264164; 4331107 AB - Mammalian monogamy is characterized by pair bonding and a relative absence of sexual dimorphism in body size. Alloparental behaviour is a characteristic of mammalian cooperative breeding systems. Studies of prairie voles, Microtus ochrogaster, from stock captured in a resource-abundant habitat in Illinois have supported the assumption that this species is a monogamous, cooperative breeder, while other studies of prairie voles from a more arid habitat in Kansas have called this assumption into question. We hypothesized that reported differences between these populations represented true intraspecific variation. Patterns of sexual dimorphism in body size, partner preferences and parental contact behaviour were compared in prairie voles from stocks originating in Illinois or Kansas. Both Illinois and Kansas voles showed a strong preference for a familiar partner, which is suggestive of monogamy. Sexual dimorphism in body size was observed in Kansas, but not Illinois voles. Illinois voles displayed significantly higher levels of parental contact behaviour than did voles from Kansas. When animals from Illinois and Kansas were crossed, the expression of parental contact behaviour of the 'hybrid' offspring followed the pattern seen in the population of origin of the sire. Removal of the sire prior to the birth of the litter increased alloparenting in Kansas voles, but removal of the sire was associated with lower levels of alloparenting in Illinois voles. Thus, some traits associated with the social system may show intraspecific variation and can be influenced by the presence or absence of the sire during rearing. JF - Animal Behaviour AU - Roberts, R L AU - Williams, J R AU - Wang, A K AU - Carter, C S AD - Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, NIH Animal Center, P.O. Box 529, Poolesville, MD 20837, USA, robertl@lce.nichd.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1131 EP - 1140 PB - Academic Press Ltd. VL - 55 IS - 5 SN - 0003-3472, 0003-3472 KW - Prairie vole KW - USA, Illinois KW - USA, Kansas KW - Ecology Abstracts; Animal Behavior Abstracts KW - Sexual dimorphism KW - Paternity KW - Communal breeding KW - Microtus ochrogaster KW - Monogamy KW - Mate selection KW - Parental behavior KW - Geographical variations KW - Y 25427:Mammals (excluding primates) KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17264164?accountid=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=Animal+Behaviour&rft.atitle=Cooperative+breeding+and+monogamy+in+prairie+voles%3A+influence+of+the+sire+and+geographical+variation&rft.au=Roberts%2C+R+L%3BWilliams%2C+J+R%3BWang%2C+A+K%3BCarter%2C+C+S&rft.aulast=Roberts&rft.aufirst=R&rft.date=1998-05-01&rft.volume=55&rft.issue=5&rft.spage=1131&rft.isbn=&rft.btitle=&rft.title=Animal+Behaviour&rft.issn=00033472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Replaces previous citation with incorrect issue number. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Microtus ochrogaster; Geographical variations; Mate selection; Communal breeding; Monogamy; Paternity; Sexual dimorphism; Parental behavior ER - TY - JOUR T1 - Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions AN - 17094384; 4406834 AB - The incidence of acute lymphoblastic leukemia (ALL) in children has shown temporal and geographic variation during the 20th century, with higher rates in developed nations appearing in the first half of the century, but with persisting low rates in developing nations. We sought to assess the relation of childhood ALL with hygiene conditions, an aspect of socioeconomic development affecting rates of exposure to infectious agents. Infection patterns for hepatitis A virus (HAV), an agent with a fecal-oral route of transmission, were used to indicate hygiene conditions in different populations, with emphasis on instructive United States and Japanese data. A catalytic model was fit to these data, estimating the HAV force of infection and age-specific seroprevalence rates over time. These analyses were used to assess the temporal relationship of changes in HAV infection rates to changes in childhood leukemia mortality and incidence rates. We observed an inverse relationship between HAV infection prevalence and rates of childhood leukemia. Further, decreases in the HAV force of infection in the United States and Japan appear to have preceded increases in childhood leukemia rates. We describe a model based on a putative leukemia-inducing agent with a change in infection rate over time correlated with that of HAV that describes well the temporal trends in childhood leukemia rates for White children in the US and for Japanese children. The data suggest that improved public hygiene conditions, as measured by decreased prevalence of HAV infection, are associated with higher childhood ALL incidence rates. The model that we present supports the plausibility of the hypothesis that decreased childhood exposure to a leukemia-inducing agent associated with hygiene conditions leads to higher rates of ALL in children by increasing the frequency of in utero transmission caused by primary infection during pregnancy (or by increasing the number of individuals infected in early infancy because of lack of protective maternal antibodies). JF - Cancer Causes & Control AU - Smith, MA AU - Simon, R AU - Strickler, H D AU - McQuillan, G AU - Ries, LAG AU - Linet AD - Cancer Therapy Evaluation Program, NCI, Rm. 741, EPN, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 285 EP - 298 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - acute lymphatic leukemia KW - hepatitis A KW - hepatitis A virus KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Socioeconomics KW - Children KW - Pregnancy KW - Socio-economic aspects KW - Acute lymphatic leukemia KW - Hygiene KW - X 24240:Miscellaneous KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17094384?accountid=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=Evidence+that+childhood+acute+lymphoblastic+leukemia+is+associated+with+an+infectious+agent+linked+to+hygiene+conditions&rft.au=Smith%2C+MA%3BSimon%2C+R%3BStrickler%2C+H+D%3BMcQuillan%2C+G%3BRies%2C+LAG%3BLinet&rft.aulast=Smith&rft.aufirst=MA&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=285&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 - Children; Socioeconomics; Pregnancy; Hygiene; Acute lymphatic leukemia; Socio-economic aspects ER - TY - JOUR T1 - Risk factors for male breast cancer (United States) AN - 17091976; 4406832 AB - The etiology of male breast cancer is obscure, although an excess risk has been associated with Klinefelter syndrome, testicular disorders, benign breast disease including gynecomastia, use of exogenous estrogens, radiation, and a family history of male or female breast cancer. We conducted a case-control study to investigate risk factors further for breast cancer in men. Based on data from the 1986 National (United States) Mortality Followback Survey (NMFS) of almost 20,000 deceased adults (age 25 years or over), we compared information obtained from next-of-kin interviews of 178 men who died of breast cancer with that of 512 male controls who died of other causes. Information was obtained on selected demographic and other factors, including diet, exercise, occupation, height and weight, and use of tobacco and alcohol. Increased risks were found for men who were described by their next-of-kin as very overweight (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-5.0). The risks associated with the three upper quartiles of body mass index (BMI) (wt/ht super(2)) were 1.3, 1.6, and 2.3, respectively, with a significant dose-response relationship (P < 0.01). An excess risk was also associated with limited exercise (OR = 1.3, CI = 0.8-2.0). Consumption of red meat was associated with an increased risk, and consumption of fruits and vegetables with a decreased risk, although the trends were not significant. No association was found for tobacco or alcohol use, but an excess risk was associated with higher levels of socioeconomic status (SES) (OR = 1.8, CI = 1.1-3.0). Our study suggests that obesity increases the risk of male breast cancer, possibly through hormonal mechanisms, while dietary factors, physical activity, and SES indicators also deserve further investigation. JF - Cancer Causes & Control AU - Hsing, A W AU - McLaughlin, J K AU - Cocco, P AU - Chien, HTC AU - Fraumeni, JF Jr AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6130 Executive Blvd., Room 443, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 269 EP - 275 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - USA KW - males KW - obesity KW - physical activity KW - Risk Abstracts KW - Diets KW - Breast cancer KW - Socioeconomics KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17091976?accountid=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=Risk+factors+for+male+breast+cancer+%28United+States%29&rft.au=Hsing%2C+A+W%3BMcLaughlin%2C+J+K%3BCocco%2C+P%3BChien%2C+HTC%3BFraumeni%2C+JF+Jr&rft.aulast=Hsing&rft.aufirst=A&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=269&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 - Diets; Socioeconomics; Breast cancer; Cancer ER - TY - JOUR T1 - Fertility problems and breast cancer risk in young women: a case-control study in the United States AN - 17091622; 4406838 AB - Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored. Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States. Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR] = 1.05). Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems, but a relatively strong association among women with fertility problems. Among women with a first full-term birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. JF - Cancer Causes & Control AU - Weiss, HA AU - Troisi, R AU - Rossing, MA AU - Brogan, D AU - Coates, R J AU - Gammon, MD AU - Potischman, N AU - Swanson, CA AU - Brinton, LA AD - Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North Rm. 443, 6130 Exec. Blvd., Bethesda, MD 20892-7374, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 331 EP - 339 VL - 9 IS - 3 SN - 0957-5243, 0957-5243 KW - USA KW - Risk Abstracts KW - Fertility KW - Statistical analysis KW - Cancer KW - Pregnancy KW - Breast cancer KW - Females KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17091622?accountid=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=Fertility+problems+and+breast+cancer+risk+in+young+women%3A+a+case-control+study+in+the+United+States&rft.au=Weiss%2C+HA%3BTroisi%2C+R%3BRossing%2C+MA%3BBrogan%2C+D%3BCoates%2C+R+J%3BGammon%2C+MD%3BPotischman%2C+N%3BSwanson%2C+CA%3BBrinton%2C+LA&rft.aulast=Weiss&rft.aufirst=HA&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=331&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 - Pregnancy; Fertility; Breast cancer; Females; Statistical analysis; Cancer ER - TY - JOUR T1 - Molecular properties of ClpAP protease of Escherichia coli: ATP-dependent association of ClpA and ClpP AN - 16553522; 4372875 AB - The ClpAP protease from Escherichia coli consists of the ATP-binding regulatory component, ClpA (subunit M sub(r) 84 165), and the proteolytic component, ClpP (subunit M sub(r) 21 563). Our hydrodynamic studies demonstrate that the predominant forms of these proteins in solution correspond to those observed by electron microscopy. ClpP and proClpP(SA), which in electron micrographs appear to have subunits arranged in rings of seven subunits, were found by ultracentrifugation to have s sub(20,w) values of 12.2 and 13.2 S and molecular weights of 300 000 and 324 000 plus or minus 3000, respectively, indicating that the native form of each consists of two such rings. The two intact rings of ClpP were separated in the presence of greater than or equal to 0.1 M sulfate at low temperatures, suggesting that ring-ring contacts are polar in nature and more easily disrupted than subunit contacts within individual rings. Sedimentation equilibrium analysis indicated that ClpA purified without nucleotide exists as an equilibrium mixture of monomers and dimers with K sub(a) = (1.0 plus or minus 0.2) x 10 super(5) M super(-1) and that, upon addition of MgATP or adenosine 5'-O-(3-thiotriphosphate), ClpA subunits associated to a form with M sub(r) 505 000 plus or minus 5000, consistent with the hexameric structure seen by electron microscopy. Sedimentation velocity and gel-filtration analysis showed that the nucleotide-promoted hexamer of ClpA (s sub(20,w) = 17.2 S) binds tightly to ClpP producing species with s sub(20,w) values of 21 and 27 S (f/f sub(0) = 1.5 and 1.8, respectively), consistent with electron micrographs of ClpAP that show a single tetradecamer of ClpP associated with either one or two ClpA hexamers. Under assay conditions in the presence of ATP and Mg super(2+), the apparent dissociation constant of hexameric ClpA and tetradecameric ClpP was similar to 4 plus or minus 2 nM. By the method of continuous variation, the optimal ratio of ClpA to ClpP in the active complex was 2:1. The specific activities of limiting ClpA and ClpP determined in the presence of an excess of the other component indicated that the second molecule of ClpA provides very little additional activation of ClpP. JF - Biochemistry (Washington) AU - Maurizi, M R AU - Singh, S K AU - Thompson, M W AU - Kessel, M AU - Ginsburg, A AD - Laboratory of Cell Biology, National Cancer Institute, Bldg. 37, Room 1B09, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 7778 EP - 7786 VL - 37 IS - 21 SN - 0006-2960, 0006-2960 KW - ClpA protein KW - ClpP protein KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Proteinase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16553522?accountid=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=Molecular+properties+of+ClpAP+protease+of+Escherichia+coli%3A+ATP-dependent+association+of+ClpA+and+ClpP&rft.au=Maurizi%2C+M+R%3BSingh%2C+S+K%3BThompson%2C+M+W%3BKessel%2C+M%3BGinsburg%2C+A&rft.aulast=Maurizi&rft.aufirst=M&rft.date=1998-05-01&rft.volume=37&rft.issue=21&rft.spage=7778&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; Proteinase ER - TY - JOUR T1 - Evaluating health risks from groundwater contaminants AN - 16547550; 4374996 AB - A method is proposed to evaluate changes in health risks from ground water drawn from specified locations in the subsurface as a result of the transport of contaminant chemicals from buried waste sites. To evaluate the health risk, a stochastic one-dimensional contaminant transport model is solved with Monte Carlo simulation. The risk at a specified location is equal to the number of times that contaminant concentrations exceed the health standard concentration divided by the number of iterations in the Monte Carlo simulation. The method is used on a simulated aquifer to demonstrate how health risks vary with time and location in the subsurface. JF - Journal of Environmental Engineering AU - Piver, W T AU - Duval, LA AU - Schreifer, JA AD - Nat. Inst. of Envir. Health Sci., Research Triangle Park, NC 27709, USA, piveriehs.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 475 EP - 479 VL - 124 IS - 5 SN - 0733-9372, 0733-9372 KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Water Resources Abstracts KW - Risk assessment KW - Aquifers KW - Spatial distribution KW - Contamination KW - Environmental health KW - Public health KW - Evaluation KW - Waste disposal sites KW - Monte carlo method KW - Temporal distribution KW - Simulation KW - Stochastic process KW - Risk KW - Chemical wastes KW - Groundwater pollution KW - Model studies KW - P 2000:FRESHWATER POLLUTION KW - SW 0840:Groundwater KW - SW 3030:Effects of 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/16547550?accountid=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+Environmental+Engineering&rft.atitle=Evaluating+health+risks+from+groundwater+contaminants&rft.au=Piver%2C+W+T%3BDuval%2C+LA%3BSchreifer%2C+JA&rft.aulast=Piver&rft.aufirst=W&rft.date=1998-05-01&rft.volume=124&rft.issue=5&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Engineering&rft.issn=07339372&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 - Aquifers; Risk assessment; Contamination; Spatial distribution; Temporal distribution; Waste disposal sites; Chemical wastes; Simulation; Groundwater pollution; Environmental health; Public health; Stochastic process; Evaluation; Risk; Monte carlo method; Model studies ER - TY - JOUR T1 - The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women AN - 16525347; 4352055 AB - Background. Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. Methods. The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at similar to 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. Results. Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM sub(197) mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 mu g/ml) than among uninfected children (2.70 mu g/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P greater than or equal to 0.48). The proportion of children with antibody concentrations greater than or equal to 1.0 mu g/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P = 0.81). Conclusions. These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued. JF - Pediatric Infectious Disease Journal AU - Read, J S AU - Frasch, CE AU - Rich, K AU - Fitzgerald, G A AU - Clemens, J D AU - Pitt, J AU - Pelton, SI AU - Hanson, I C AU - Handelsman, E AU - Diaz, C AU - Fowler, M G AD - Pediatric, Adolescent, and Maternal (PAMA) Branch, National Institute of Child Health and Human Development, National Institutes of Health, Executive Building, Room 4B11F, 6100 Executive Boulevard MSC 7510, Bethesda, MD 20892-7510, USA, jr92o@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 391 EP - 397 VL - 17 IS - 5 SN - 0891-3668, 0891-3668 KW - HIV KW - Haemophilus influenzae type B disease KW - man KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - V 22003:AIDS: Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16525347?accountid=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=Pediatric+Infectious+Disease+Journal&rft.atitle=The+immunogenicity+of+Haemophilus+influenzae+type+b+conjugate+vaccines+in+children+born+to+human+immunodeficiency+virus-infected+women&rft.au=Read%2C+J+S%3BFrasch%2C+CE%3BRich%2C+K%3BFitzgerald%2C+G+A%3BClemens%2C+J+D%3BPitt%2C+J%3BPelton%2C+SI%3BHanson%2C+I+C%3BHandelsman%2C+E%3BDiaz%2C+C%3BFowler%2C+M+G&rft.aulast=Read&rft.aufirst=J&rft.date=1998-05-01&rft.volume=17&rft.issue=5&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Pediatric+Infectious+Disease+Journal&rft.issn=08913668&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 - Mutations affecting the alpha subunit of Bordetella pertussis RNA polymerase suppress growth inhibition conferred by short C-terminal deletions of the response regulator BvgA AN - 16524910; 4358056 AB - The effects of short deletions of the C terminus of the BvgA response regulator protein of the BvgAS two-component system were examined in Bordetella pertussis. When present as a single copy in the chromosome, deletions removing as few as two amino acids conferred a completely Bvg super(-) phenotype. When provided in trans, on the broad-host-range plasmid pRK290, under the control of the native bvgAS promoter, deletions of two or three amino acids conferred a profound growth inhibition which was dependent on the integrity and activity of the wild-type chromosomal bvgAS locus. It is proposed that this phenotype was the result of an inappropriate interaction of the mutant BvgA protein with the RNA polymerase enzyme, specifically the alpha subunit. Mutant strains in which this growth inhibition was relieved were isolated and characterized. Although most of the suppressor mutations affected either the mutant plasmid copy or the wild-type chromosomal bvg locus, three mutations which affected the alpha subunit of B. pertussis RNA polymerase were also isolated. Two of these resulted in increased levels of the alpha subunit, and one caused a substitution of glycine for the aspartic acid residue at position 171, in the N-terminal domain. All three mutations also resulted in a differential phenotype in that expression of fha was essentially normal, but expression of ptx was greatly reduced. JF - Journal of Bacteriology AU - Stibitz, S AD - Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA, stibitz@helix.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 2484 EP - 2492 VL - 180 IS - 9 SN - 0021-9193, 0021-9193 KW - BvgA protein KW - C-terminus KW - DNA-directed RNA polymerase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16524910?accountid=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=Mutations+affecting+the+alpha+subunit+of+Bordetella+pertussis+RNA+polymerase+suppress+growth+inhibition+conferred+by+short+C-terminal+deletions+of+the+response+regulator+BvgA&rft.au=Stibitz%2C+S&rft.aulast=Stibitz&rft.aufirst=S&rft.date=1998-05-01&rft.volume=180&rft.issue=9&rft.spage=2484&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 ER - TY - JOUR T1 - Targeting RNase L to human immunodeficiency virus RNA with 2-5A-antisense AN - 16520960; 4331051 AB - In an attempt to develop a lead for the application of 2-5A-antisense to the targeted destruction of human immunodeficiency virus (HIV) RNA, specific target sequences within the HIV mRNAs were identified by analysis of the theoretical secondary structure. 2-5A-antisense chimeras were chosen against a total of 11 different sequences: three in the gag mRNA, three in the rev mRNA and five in the tat mRNA. 2-5A-antisense chimera synthesis was accomplished using solid-phase phosphoramidite chemistry. These chimeras were evaluated for their activity in a cell-free assay system using purified recombinant human RNase L to effect cleavage of super(32)P-labelled RNA transcripts of plasmids derived from HIV NL4-3. This screening revealed that of the three 2-5A-antisense chimeras targeted against gag mRNA, only one had significant HIV RNA cleavage activity, approximately 10-fold-reduced compared to the parent 2-5A tetramer and comparable to that reported for the prototypical 2-5A-anti-PKR chimera, targeted against PKR mRNA. The cleavage activity of this chimera was specific, since a scrambled antisense domain chimera and a chimera without the key 5'-monophosphate moiety were both inactive. The 10 other 2-5A-antisense chimeras against tat and rev had significantly less activity. These results imply that HIV gag RNA, like PKR RNA and a model HIV tat-oligoA-vif RNA, can be cleaved using the 2-5A-antisense approach. The results further imply that not all regions of a potential RNA target are accessible to the 2-5A-antisense approach. JF - Antiviral Chemistry & Chemotherapy AU - Player, M R AU - Maitra, R K AU - Silverman, R H 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, torrence@helix.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 225 EP - 231 VL - 9 IS - 3 SN - 0956-3202, 0956-3202 KW - Chimeras KW - HIV-1 KW - Human immunodeficiency virus 1 KW - chimeras KW - ribonuclease L KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - A 01068:Antiviral & viricidal KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16520960?accountid=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+Chemistry+%26+Chemotherapy&rft.atitle=Targeting+RNase+L+to+human+immunodeficiency+virus+RNA+with+2-5A-antisense&rft.au=Player%2C+M+R%3BMaitra%2C+R+K%3BSilverman%2C+R+H%3BTorrence%2C+P+F&rft.aulast=Player&rft.aufirst=M&rft.date=1998-05-01&rft.volume=9&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Antiviral+Chemistry+%26+Chemotherapy&rft.issn=09563202&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 - Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells AN - 16517638; 4342357 AB - We have reported the tumor suppressive effects of manganese-containing superoxide dismutase (MnSOD) in human breast cancer cells. In order to understand the molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor gene(s), especially the ones inhibiting tumor invasion and motility, are involved in MnSOD-induced tumor suppression. Maspin is one of the serpin family of protease inhibitors that has been shown to function as a tumor-suppressor in human breast epithelium. In the present study, we demonstrated that maspin expression was up-regulated in human breast cancer MCF-7 cells that overexpress a normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and Northern blot and identified by sequencing. Maspin gene expression was induced in parallel with the level of exogenous MnSOD protein, which was induced by transfection with varied amounts of cDNA. In order to analyze cell invasion ability, which may be related to the induced maspin gene expression, MnSOD stable transfectants were tested using a matrigel invasion chamber. The invasion ability was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD-transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell line. In conclusion, these results suggest that overexpression of a normal MnSOD cDNA in human breast cancer cells up-regulates the gene expression of the protease inhibitor, maspin, which may play a role in the inhibitory function of MnSOD on tumor invasion. JF - Carcinogenesis AU - Li, J-J AU - Colburn, N H AU - Oberley, L W AD - Gene Regulation Section, Laboratory of Biochemical Physiology, National Cancer Institute, NCI-FCRDC, Frederick, MD 21702-1201, USA, Lij@ncifcrf.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 833 EP - 839 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - DNA KW - MCF-7 cells KW - breast carcinoma KW - man KW - manganese KW - maspin KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - X 24240:Miscellaneous KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16517638?accountid=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=Maspin+gene+expression+in+tumor+suppression+induced+by+overexpressing+manganese-containing+superoxide+dismutase+cDNA+in+human+breast+cancer+cells&rft.au=Li%2C+J-J%3BColburn%2C+N+H%3BOberley%2C+L+W&rft.aulast=Li&rft.aufirst=J-J&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=833&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 ER - TY - JOUR T1 - Phosphorylation destabilizes the amino-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system AN - 16470843; 4335543 AB - Thermal stabilities of enzyme I (63 562 M sub(r) subunit), in the Escherichia coli phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), and a cloned amino-terminal domain of enzyme I (EIN; 28 346 M sub(r)) were investigated by differential scanning calorimetry (DSC) and far-UV circular dichroism (CD) at pH 7.5. EIN expressed in a Delta pts E. coli strain showed a single, reversible, two-state transition with T sub(m) = 57 degree C and an unfolding enthalpy of similar to 140 kcal/mol. In contrast, monomeric EIN expressed in a wild-type strain (pts super(+)) had two endotherms with T sub(m) approximately equal to 50 and 57 degree C and overall Delta H = 140 kcal/mol and was converted completely to the more stable form after five DSC scans from 10 to 75 degree C (without changes in CD: similar to 58% alpha -helices). Thermal conversion to a more stable form was correlated with dephosphorylation of EIN by mass spectral analysis. Dephospho-enzyme I (monomer reversible reaction dimer) exhibited endotherms for C- and N-terminal domain unfolding with T sub(m) = 41 and 54 degree C, respectively. Thermal unfolding of the C-terminal domain occurred over a broad temperature range ( similar to 30-50 degree C), was scan rate- and concentration-dependent, coincident with a light scattering decrease and Trp residue exposure, and independent of phosphorylation. Reversible thermal unfolding of the nonphosphorylated N-terminal domain was more cooperative, occurring from 50 to 60 degree C. DSC of partially phosphorylated enzyme I indicated that the amino-terminal domain was destabilized by phosphorylation (from T sub(m) = 54 to similar to 48 degree C). A decrease in conformational stability of the amino-terminal domain of enzyme I produced by phosphorylation of the active-site His 189 has the physiological consequence of promoting phosphotransfer to the phosphocarrier protein, HPr. JF - Biochemistry (Washington) AU - Nosworthy, N J AU - Peterkofsky, A AU - Koenig, S AU - Seok, Yeong-Jae AU - Szczepanowski, R H AU - Ginsburg, A AD - National Institutes of Health, Building 3, Room 208, Bethesda, MD 20892-0340, USA, aog@cu.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 6718 EP - 6726 VL - 37 IS - 19 SN - 0006-2960, 0006-2960 KW - enzyme I KW - phosphoenolpyruvate-sugar phosphotransferase KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16470843?accountid=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=Phosphorylation+destabilizes+the+amino-terminal+domain+of+enzyme+I+of+the+Escherichia+coli+phosphoenolpyruvate%3Asugar+phosphotransferase+system&rft.au=Nosworthy%2C+N+J%3BPeterkofsky%2C+A%3BKoenig%2C+S%3BSeok%2C+Yeong-Jae%3BSzczepanowski%2C+R+H%3BGinsburg%2C+A&rft.aulast=Nosworthy&rft.aufirst=N&rft.date=1998-05-01&rft.volume=37&rft.issue=19&rft.spage=6718&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 ER - TY - JOUR T1 - Enzymatic and structural similarities between the Escherichia coli ATP-dependent proteases, ClpXP and ClpAP AN - 16445139; 4344787 AB - Escherichia coli ClpX, a member of the Clp family of ATPases, has ATP-dependent chaperone activity and is required for specific ATP-dependent proteolytic activities expressed by ClpP. Gel filtration and electron microscopy showed that ClpX subunits (M sub(r) 46,000) associate to form a six-membered ring (M sub(r) similar to 280,000) that is stabilized by binding of ATP or nonhydrolyzable analogs of ATP. ClpP, which is composed of two seven-membered rings stacked face-to-face, interacts with the nucleotide-stabilized hexamer of ClpX to form a complex that could be isolated by gel filtration. Electron micrographs of negatively stained ClpXP preparations showed side views of 1:1 and 2:1 ClpXP complexes in which ClpP was flanked on either one or both sides by a ring of ClpX. Thus, as was seen for ClpAP, a symmetry mismatch exists in the bonding interactions between the seven-membered rings of ClpP and the six-membered rings of ClpX. Competition studies showed that ClpA may have a slightly higher affinity ( similar to 2-fold) for binding to ClpP. Mixed complexes of ClpA, ClpX, and ClpP with the two ATPases bound simultaneously to opposite faces of a single ClpP molecule were seen by electron microscopy. In the presence of ATP or nonhydrolyzable analogs of ATP, ClpXP had nearly the same activity as ClpAP against oligopeptide substrates (> 10,000 min super(-1) /tetradecamer of ClpP). Thus, ClpX and ClpA interactions with ClpP result in structurally analogous complexes and induce similar conformational changes that affect the accessibility and the catalytic efficiency of ClpP active sites. JF - Journal of Biological Chemistry AU - Grimaud, R AU - Kessel, M AU - Beuron, F AU - Steven, A C AU - Maurizi, M R AD - NCI, Natl. Inst. Health, Bldg. 37, 1B07, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-2755, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 12476 EP - 12481 VL - 273 IS - 20 SN - 0021-9258, 0021-9258 KW - ClpAP protein KW - ClpX protein KW - ClpXP protein KW - structure-activity relationships KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16445139?accountid=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=Enzymatic+and+structural+similarities+between+the+Escherichia+coli+ATP-dependent+proteases%2C+ClpXP+and+ClpAP&rft.au=Grimaud%2C+R%3BKessel%2C+M%3BBeuron%2C+F%3BSteven%2C+A+C%3BMaurizi%2C+M+R&rft.aulast=Grimaud&rft.aufirst=R&rft.date=1998-05-01&rft.volume=273&rft.issue=20&rft.spage=12476&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 ER - TY - JOUR T1 - Caffeine-derived N-nitroso compounds. V. Carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats AN - 16439588; 4342370 AB - Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product of caffeine present in a typically made and widely consumed tea from Kashmir (India), a high incidence area of esophageal and stomach cancer. The chemical synthesis, in vitro metabolic studies and mutagenicity of the compounds has been previously reported. DNC, a nitrosamide is highly mutagenic both with and without metabolic activation whereas MNC, like several other aromatic asymmetric nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report the results of the first carcinogenicity experiments on chronic oral administration of these compounds in BD-IX rats. The acute LD sub(50) of MNC and DNC were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and gastrointestinal haemorrhages were the first symptoms of intoxication observed after 2 days for both the compounds. All three dose groups of MNC treated rats showed localization of tumours in nasal cavity (93.9-100% of all malignant tumours). The tumours were histologically diagnosed as neuroepitheliomas of the olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity were observed in the untreated controls. DNC, in contrast, induced squamous cell carcinoma of forestomach in 100% animals at low and high doses, of which nearly half the tumours metastasized predominantly into the peritoneum. No forestomach tumours were seen in the untreated controls. The data presented here clearly show the potential for induction of malignant tumours and distinct organ-specificity by MNC and DNC in rats, and support the postulate that a chronic exposure to these compounds may provide a carcinogenic risk for high incidence of gastrointestinal cancers in Kashmir. JF - Carcinogenesis AU - Ivankovic, S AU - Seibel, J AU - Komitowski, D AU - Spiegelhalder, B AU - Preussmann, R AU - Siddiqi, M AD - Chittaranjan National Cancer Institute, 37, S.P.Mukherjee Road, Calcutta-700026, India, cncinst@giasc101.vsnl.net.in Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 933 EP - 937 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - dinitrosocaffeidine KW - mononitrosocaffeidine KW - rats KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants KW - X 24200:Nitrosamines & related compounds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16439588?accountid=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=Caffeine-derived+N-nitroso+compounds.+V.+Carcinogenicity+of+mononitrosocaffeidine+and+dinitrosocaffeidine+in+bd-ix+rats&rft.au=Ivankovic%2C+S%3BSeibel%2C+J%3BKomitowski%2C+D%3BSpiegelhalder%2C+B%3BPreussmann%2C+R%3BSiddiqi%2C+M&rft.aulast=Ivankovic&rft.aufirst=S&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=933&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 ER - TY - JOUR T1 - The multifaceted roles of nitric oxide in cancer AN - 16436359; 4342342 AB - The roles of nitric oxide (NO) in numerous disease states have generated considerable discussion over the past several years. NO has been labeled as the causative agent in different pathophysiological mechanisms, yet appears to protect against various chemical species such as those generated under oxidative stress. Similarly, NO appears to exert a dichotomy of effects within the multistage model of cancer. Chronic inflammation can lead to the production of chemical intermediates, among them NO, which in turn can mediate damage to DNA. Yet, NO also appears to be critical for the tumoricidal activity of the immune system. Furthermore, NO can also have a multitude of effects on other aspects of tumor biology, including angiogenesis and metastasis. This report will discuss how the chemistry of NO may impact the initiation and progression stages of cancer. JF - Carcinogenesis AU - Wink, DA AU - Vodovotz, Y AU - Laval, J AU - Laval, F AU - Dewhirst, M W AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bldg. 10, Room B3-B69, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 711 EP - 721 VL - 19 IS - 5 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16436359?accountid=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=The+multifaceted+roles+of+nitric+oxide+in+cancer&rft.au=Wink%2C+DA%3BVodovotz%2C+Y%3BLaval%2C+J%3BLaval%2C+F%3BDewhirst%2C+M+W%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=DA&rft.date=1998-05-01&rft.volume=19&rft.issue=5&rft.spage=711&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 ER - TY - JOUR T1 - An RNA pseudoknot as the molecular switch for translation of the repZ-gene encoding the replication initiator of IncI alpha plasmid ColIb-P9 AN - 16430545; 4339040 AB - Translation initiation of the repZ gene encoding the replication initiator of plasmid ColIb-P9 is not only negatively regulated by the action of the antisense Inc RNA encoded in the leader region, but is also coupled to the translation and termination of a transcribed leader sequence, repY, a positive regulatory element for repZ gene expression. This translational coupling depends on base pairing between two complementary sequences, 5'-rGGCG-3' and 5'-rCGCC-3', which are located upstream of and in the middle of repY, respectively, and have the potential to form a pseudoknot with the stem-loop structure I. Another stem-loop called structure III near the 3'-end of repY sequesters both the 5'-rCGCC-3' sequence and the repZ ribosome-binding site. Here we show that the RepZ mRNA leader sequence synthesized in vitro indeed contains several stem-loop structures including structures I and III, but not the pseudoknot. However, disruption of structure III, without changing the repZ ribosome-binding site, by means of base substitution and deletion induces base pairing between the two short complementary sequences distantly separated, resulting in the formation of a pseudoknot. When the pseudoknot is allowed to form in vivo due to the same mutations, a maximum level of repZ expression is obtained comparable to one observed in the absence of Inc RNA. These results strengthen our previously proposed model that the pseudoknot induced by the translation and termination of the repY reading frame functions as the molecular switch for translational initiation of the repZ gene. JF - Journal of Biological Chemistry AU - Asano, K AU - Mizobuchi, K AD - Lab. Eukaryotic Gene Regulation, NICHD, Natl. Institutes Health, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 11815 EP - 11825 VL - 273 IS - 19 SN - 0021-9258, 0021-9258 KW - plasmid ColIb-P9 KW - pseudoknots KW - psudoknots KW - repY regulatory element KW - repZ gene KW - translation initiation KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02760:Plasmids KW - N 14430:Translation initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16430545?accountid=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=An+RNA+pseudoknot+as+the+molecular+switch+for+translation+of+the+repZ-gene+encoding+the+replication+initiator+of+IncI+alpha+plasmid+ColIb-P9&rft.au=Asano%2C+K%3BMizobuchi%2C+K&rft.aulast=Asano&rft.aufirst=K&rft.date=1998-05-01&rft.volume=273&rft.issue=19&rft.spage=11815&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 ER - TY - JOUR T1 - Characterization of an MDR1 retroviral bicistronic vector for correction of X-linked severe combined immunodeficiency AN - 16416014; 4324765 AB - X-linked severe combined immunodeficiency (XSCID) is a hereditary disorder characterized by severe T cell lymphopenia and abnormal B cell function. The disease is caused by mutations in IL2RG, the gene encoding the interleukin-2 receptor common gamma chain ( gamma c) shared by several interleukin receptors. A Harvey retroviral bicistronic vector containing an IL2RG cDNA and cDNA encoding the multidrug transporter (MDR1) was constructed to investigate the correction of XSCID. Translation of the MDR1 cDNA is achieved from an internal ribosome entry site (IRES). Mouse fibroblasts transfected or transduced with the vector expressed both membrane proteins as detected with specific monoclonal antibodies by fluorescence activated cell sorting. Two human XSCID B cell lines were transduced using a filter concentration method in combination with phosphate depletion. Significant expression of both proteins was detected by Western blot analysis. This construct might be particularly useful if high expression of gamma c is required, as might be achievable through in vivo selection for drug resistance of recipient lymphocytes. JF - Gene Therapy AU - Kleiman, SE AU - Pastan, I AU - Puck, J M AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Institutes of Health, Building 37, Room 1A09, 37 Convent Drive MSC4255, Bethesda, MD 20892-4255, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 671 EP - 676 VL - 5 IS - 5 SN - 0969-7128, 0969-7128 KW - Mdr-1 protein KW - bicistronic vectors KW - interleukin 2 receptors KW - mice KW - multidrug resistance KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416014?accountid=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=Characterization+of+an+MDR1+retroviral+bicistronic+vector+for+correction+of+X-linked+severe+combined+immunodeficiency&rft.au=Kleiman%2C+SE%3BPastan%2C+I%3BPuck%2C+J+M%3BGottesman%2C+M+M&rft.aulast=Kleiman&rft.aufirst=SE&rft.date=1998-05-01&rft.volume=5&rft.issue=5&rft.spage=671&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 ER - TY - JOUR T1 - Research toward vaccines against malaria AN - 16415938; 4311197 AB - Malaria is one of the major causes of disease and death between the Tropic of Cancer and Tropic of Capricorn. Plasmodium falciparum has an especially profound impact on infants and children in sub-Saharan Africa, where its effect on health is increasing as chloroquine resistance spreads across the continent. We believe that vaccination against P. falciparum is the intervention with the greatest potential to reduce malaria-associated severe morbidity and mortality in areas with the most intense transmission and that it may do so without necessarily preventing blood stage infection. Malaria vaccines also would be the optimal method for preventing malaria in travelers to countries where malaria is transmitted. Such vaccines will have to entirely prevent the development of any clinical manifestations of infection with P. falciparum and of the second most common human malaria parasite, P. vivax. This will require preventing blood stage infection. Infants and young children at risk from P. falciparum in Africa and nonimmune travelers to areas endemic for P. falciparum and P. vivax represent the extremes of target groups in whom malaria vaccines would be useful. Even in countries where the overall numbers of afflicted individuals are not as great as in Africa, malaria wreaks its havoc in many epidemiologic settings and population groups, dramatically undermines the productivity of workers, and drains national budgets. From the Amazon basin to the Indian subcontinent, Southeast Asia, and Oceania, malaria is often a major national public health problem. In these settings, vaccines offer the greatest potential for reducing malaria's debilitating effects. The spread of drug-resistant P. falciparum and the recent emergence and spread of chloroquine-resistant P. vivax have created an increasing urgency for effective malaria vaccines. JF - Nature Medicine AU - Miller, L H AU - Hoffman, S L AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, louis_miller@nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 520 EP - 524 VL - 4 IS - 5 SN - 1078-8956, 1078-8956 KW - Plasmodium falciparum KW - Plasmodium vivax KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33365:Vaccines (other) KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16415938?accountid=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=Research+toward+vaccines+against+malaria&rft.au=Miller%2C+L+H%3BHoffman%2C+S+L&rft.aulast=Miller&rft.aufirst=L&rft.date=1998-05-01&rft.volume=4&rft.issue=5&rft.spage=520&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 ER - TY - JOUR T1 - Efficacy of multiple administrations of a recombinant adenovirus expressing wild-type p53 in an immune-competent mouse tumor model AN - 16410546; 4324757 AB - Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene beta -galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors lasted for about 7 days, however, administration of another dose of Ad- beta gal, on day 7 produced beta -galactosidase expression. To investigate the effect of antibodies to adenovirus, animals were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Ad beta -gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (10 super(9) plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 x 10 super(8) plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals. JF - Gene Therapy AU - Li, Z AU - Rakkar, A AU - Katayose, Y AU - Kim, M AU - Shanmugam, N AU - Srivastava, S AU - Moul, J W AU - McLeod, D G AU - Cowan, KH AU - Seth, P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, Bethesda, MD 20892, USA Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 605 EP - 613 VL - 5 IS - 5 SN - 0969-7128, 0969-7128 KW - Adenovirus KW - beta -galactosidase KW - mice KW - p53 protein KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07397:Rodentia (mice) 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/16410546?accountid=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=Efficacy+of+multiple+administrations+of+a+recombinant+adenovirus+expressing+wild-type+p53+in+an+immune-competent+mouse+tumor+model&rft.au=Li%2C+Z%3BRakkar%2C+A%3BKatayose%2C+Y%3BKim%2C+M%3BShanmugam%2C+N%3BSrivastava%2C+S%3BMoul%2C+J+W%3BMcLeod%2C+D+G%3BCowan%2C+KH%3BSeth%2C+P&rft.aulast=Li&rft.aufirst=Z&rft.date=1998-05-01&rft.volume=5&rft.issue=5&rft.spage=605&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 ER - TY - JOUR T1 - Generation of polyclonal rabbit antisera to mouse melanoma associated antigens using gene gun immunization AN - 16404929; 4313935 AB - Lymphocytes from patients with melanoma have been used to clone melanoma associated antigens which are, for the most part, nonmutated melanocyte tissue differentiation antigens. To establish a mouse model for the use of these `self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1. We sought to generate antisera against these proteins for use in the construction of experimental recombinant and synthetic anti-cancer vaccines, and for use in biologic studies. Using genes cloned from the B16 mouse melanoma or from murine melanocytes, we immunized rabbits with plasmid DNAs coated onto microscopic gold beads that were then delivered using a hand-held, helium-driven `gene gun'. This strategy enabled us to generate polyclonal rabbit sera containing antibodies that specifically recognized each antigen, as measured by immunostaining of vaccinia virus infected cells. The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16. The identities of the recognized proteins was confirmed by Western blot analysis. The titers and specificities of these antisera were determined using ELISA. Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues. Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens. These anti-sera may be useful in the detection, purification and characterization of the mouse homologues of recently cloned human tumor associated antigens and may enable the establishment of an animal model of the immune consequences of vaccination against `self' antigens. JF - Journal of Immunological Methods AU - Surman AU - Irvine, K R AU - Shulman, E P AU - Allweis, T M AU - Rosenberg, SA AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 51 EP - 62 PB - Elsevier Science B.V. VL - 214 IS - 1-2 SN - 0022-1759, 0022-1759 KW - MART-1 antigen KW - glycoprotein gp100 KW - tyrosinase related protein 1 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts 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/16404929?accountid=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=Generation+of+polyclonal+rabbit+antisera+to+mouse+melanoma+associated+antigens+using+gene+gun+immunization&rft.au=Surman%3BIrvine%2C+K+R%3BShulman%2C+E+P%3BAllweis%2C+T+M%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Surman&rft.aufirst=&rft.date=1998-05-01&rft.volume=214&rft.issue=1-2&rft.spage=51&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 ER - TY - JOUR T1 - Synthesis and Characterization of Lipooligosaccharide-Based Conjugates as Vaccine Candidates for Moraxella (Branhamella) catarrhalis AN - 16387220; 4307565 AB - Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. JF - Infection and Immunity AU - Gu, Xin-Xing AU - Chen, Jing AU - Barenkamp, S J AU - Robbins, J B AU - Tsai, Chao-Ming AU - Lim, D J AU - Battey, J AD - NIDCD, NIH, 5 Research Court, 2A31, Rockville, MD 20850, USA, xgu@pop.nidcd.nih.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 1891 EP - 1897 VL - 66 IS - 5 SN - 0019-9567, 0019-9567 KW - Moraxella catarrhalis KW - children KW - lipooligosaccharides KW - man KW - monophosphoryl lipid A KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16387220?accountid=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=Synthesis+and+Characterization+of+Lipooligosaccharide-Based+Conjugates+as+Vaccine+Candidates+for+Moraxella+%28Branhamella%29+catarrhalis&rft.au=Gu%2C+Xin-Xing%3BChen%2C+Jing%3BBarenkamp%2C+S+J%3BRobbins%2C+J+B%3BTsai%2C+Chao-Ming%3BLim%2C+D+J%3BBattey%2C+J&rft.aulast=Gu&rft.aufirst=Xin-Xing&rft.date=1998-05-01&rft.volume=66&rft.issue=5&rft.spage=1891&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 ER - TY - JOUR T1 - The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system AN - 16349489; 4316731 AB - Interruption of translation in Escherichia coli can lead to the addition of an 11-residue carboxy-terminal peptide tail to the nascent chain. This modification is mediated by SsrA RNA (also called 10Sa RNA and tmRNA) and marks the tagged polypeptide for proteolysis. Degradation in vivo of lambda repressor amino-terminal domain variants bearing this carboxy-terminal SsrA peptide tag is shown here to depend on the cytoplasmic proteases ClpXP and ClpAP. Degradation in vitro of SsrA-tagged substrates was reproduced with purified components and required a substrate with a wild-type SsrA tail, the presence of both ClpP and either ClpA or ClpX, and ATP. Clp-dependent proteolysis accounts for most degradation of SsrA-tagged amino-domain substrates at 32 degree C, but additional proteases contribute to the degradation of some of these SsrA-tagged substrates at 39 degree C. The existence of multiple cytoplasmic proteases that function in SsrA quality-control surveillance suggests that the SsrA tag is designed to serve as a relatively promiscuous signal for proteolysis. Having diverse degradation systems able to recognize this tag may increase degradation capacity, permit degradation of a wide variety of different tagged proteins, or allow SsrA-tagged proteins to be degraded under different growth conditions. JF - Genes & Development AU - Gottesman, S AU - Roche, E AU - Zhou, YanNing AU - Sauer, R T AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 1998/05/01/ PY - 1998 DA - 1998 May 01 SP - 1338 EP - 1347 VL - 12 IS - 9 SN - 0890-9369, 0890-9369 KW - ClpAP protein KW - ClpXP protein KW - protein degradation KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02728:Enzymes KW - N 14400:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16349489?accountid=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=Genes+%26+Development&rft.atitle=The+ClpXP+and+ClpAP+proteases+degrade+proteins+with+carboxy-terminal+peptide+tails+added+by+the+SsrA-tagging+system&rft.au=Gottesman%2C+S%3BRoche%2C+E%3BZhou%2C+YanNing%3BSauer%2C+R+T&rft.aulast=Gottesman&rft.aufirst=S&rft.date=1998-05-01&rft.volume=12&rft.issue=9&rft.spage=1338&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the Escherichia coli endoribonuclease RNase III - the effect of dsRNA binding on gene expression AN - 16347403; 4315626 AB - RNase III, a double-stranded RNA-specific endonuclease, is proposed to be one of Escherichia coli's global regulators because of its ability to affect the expression of a large number of unrelated genes by influencing post-transcriptional control of mRNA stability or mRNA translational efficiency. Here, we describe the phenotypes of bacteria carrying point mutations in rnc, the gene encoding RNase III. The substrate recognition and RNA-processing properties of mutant proteins were analysed in vivo by measuring expression from known RNase III-modulated genes and in vitro from the proteins' binding and cleavage activities on known double-stranded RNA substrates. Our results show that although the point mutation rnc70 exhibited all the usual rnc null-like phenotypes, unlike other mutations, it was dominant over the wild-type allele. Multicopy expression of rnc70 could suppress a lethal phenotype of the wild-type rnc allele in a certain genetic background; it could also inhibit the RNase III-mediated activation of lambda N gene translation by competing for the RNA-binding site of the wild-type endonuclease. The mutant protein failed to cleave the standard RNase III substrates in vitro but exhibited an affinity for double-stranded RNA when passed through poly(rI):poly(rC) columns. Filter binding and gel-shift assays with purified Rnc70 showed that the mutant protein binds to known RNase III mRNA substrates in a site-specific manner. In vitro processing reactions with purified enzyme and labelled RNA showed that the in vivo dominant effect of the mutant enzyme over the wild-type was not necessarily caused by formation of mixed dimers. Thus, the rnc70 mutation generates a mutant RNase III with impaired endonucleolytic activity but without blocking its ability to recognize and bind double-stranded RNA substrates. JF - Molecular Microbiology AU - Dasgupta, S AU - Fernandez, L AU - Kameyama, L AU - Inada, T AU - Nakamura, Y AU - Pappas, A AU - Court, D L AD - Gene Regulation and Chromosome Biology Laboratory, ABL-Basic Research Program, NCI-FCRDC, PO Box B, Frederick, MD 21702, USA, court@ncifcrf.gov Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 629 EP - 640 VL - 28 IS - 3 SN - 0950-382X, 0950-382X KW - RNA KW - point mutation KW - rnc gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14711:RNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16347403?accountid=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=Genetic+uncoupling+of+the+dsRNA-binding+and+RNA+cleavage+activities+of+the+Escherichia+coli+endoribonuclease+RNase+III+-+the+effect+of+dsRNA+binding+on+gene+expression&rft.au=Dasgupta%2C+S%3BFernandez%2C+L%3BKameyama%2C+L%3BInada%2C+T%3BNakamura%2C+Y%3BPappas%2C+A%3BCourt%2C+D+L&rft.aulast=Dasgupta&rft.aufirst=S&rft.date=1998-05-01&rft.volume=28&rft.issue=3&rft.spage=629&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 ER - TY - JOUR T1 - Antisense depletion of RI alpha subunit of protein kinase A induces apoptosis and growth arrest in human breast cancer cells AN - 1496897241; 16923064 AB - In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RI alpha subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RI alpha subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RI alpha antisense oligodeoxynucleotide correlated with a decrease in the RI alpha mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RI alpha antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RI alpha and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment. JF - Breast Cancer Research and Treatment AU - Srivastava, Rakesh K AU - Srivastava, Aparna R AU - Park, Yun Gyu AU - Agrawal, Sudhir AU - Cho-Chung, Yoon S AD - Cellular Biochemistry Section, Laboratory of Tumor and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 1998/05// PY - 1998 DA - May 1998 SP - 97 EP - 107 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 49 IS - 2 SN - 0167-6806, 0167-6806 KW - Biotechnology and Bioengineering Abstracts KW - Antisense oligonucleotides KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1496897241?accountid=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=Breast+Cancer+Research+and+Treatment&rft.atitle=Antisense+depletion+of+RI+alpha+subunit+of+protein+kinase+A+induces+apoptosis+and+growth+arrest+in+human+breast+cancer+cells&rft.au=Srivastava%2C+Rakesh+K%3BSrivastava%2C+Aparna+R%3BPark%2C+Yun+Gyu%3BAgrawal%2C+Sudhir%3BCho-Chung%2C+Yoon+S&rft.aulast=Srivastava&rft.aufirst=Rakesh&rft.date=1998-05-01&rft.volume=49&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Breast+Cancer+Research+and+Treatment&rft.issn=01676806&rft_id=info:doi/10.1023%2FA%3A1005905723550 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-02-11 N1 - SubjectsTermNotLitGenreText - Antisense oligonucleotides DO - http://dx.doi.org/10.1023/A:1005905723550 ER - TY - JOUR T1 - Identification of amino acid residues associated with modulation of flavin-containing monooxygenase (FMO) activity by imipramine: structure/function studies with FMO1 from pig and rabbit. AN - 79822717; 9558327 AB - The activity of the flavin-containing monooxygenase (FMO) can be modulated by a number of nitrogen-containing compounds in a manner that is both isoform and modulator-dependent. We now show that the direction (activation or inhibition) and extent of modulation can also be dependent on substrate concentration. Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at methimazole concentrations greater than 50 or 100 microM, respectively, and inhibits at lower methimazole concentrations. The extent of the activation increases as the substrate concentration increases, and the extent of inhibition increases as the substrate concentration decreases. With either inhibition or activation, the magnitude of the effect shows a similar, direct dependency on imipramine concentration. In contrast, imipramine inhibits the metabolism of methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural basis for this unique ortholog difference between the responses of rabbit and pig FMO1 to imipramine was studied by random chimeragenesis and site-directed mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by imipramine is controlled to a great extent by two areas of the FMO primary structure (residues 381-432 and 433-465). Four amino acids in these regions (positions 381, 400, 420 and 433) and one additional residue (position 186) were identified by site-directed mutagenesis as primary determinants of the imipramine response. When the residues at these positions in rabbit FMO1 are exchanged for the corresponding residues of pig FMO1, a mutant with the functional properties of pig FMO1 is produced. Our results suggest that the response of FMO1 to imipramine involves a distribution between two sites that is regulated by structural features that do not alter the overall binding. The inhibition observed, although it appears to be competitive, likely does not involve competition for a binding site since alteration of imipramine metabolism has no effect on the parameters of methimazole metabolism. JF - Biochemistry AU - Wyatt, M K AU - Overby, L H AU - Lawton, M P AU - Philpot, R M AD - Molecular Pharmacology Section, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04/28/ PY - 1998 DA - 1998 Apr 28 SP - 5930 EP - 5938 VL - 37 IS - 17 SN - 0006-2960, 0006-2960 KW - Amino Acids KW - 0 KW - Recombinant Fusion Proteins KW - Methimazole KW - 554Z48XN5E KW - Oxygenases KW - EC 1.13.- KW - dimethylaniline monooxygenase (N-oxide forming) KW - EC 1.14.13.8 KW - Imipramine KW - OGG85SX4E4 KW - Index Medicus KW - Swine KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Genetic Vectors -- biosynthesis KW - Rabbits KW - Enzyme Activation -- genetics KW - Recombinant Fusion Proteins -- chemistry KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Methimazole -- metabolism KW - Amino Acid Substitution -- genetics KW - Enzyme Activation -- drug effects KW - Catalysis KW - Oxygenases -- biosynthesis KW - Oxygenases -- metabolism KW - Amino Acids -- chemistry KW - Amino Acids -- genetics KW - Imipramine -- pharmacology KW - Oxygenases -- genetics KW - Imipramine -- metabolism KW - Amino Acids -- metabolism KW - Oxygenases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79822717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+amino+acid+residues+associated+with+modulation+of+flavin-containing+monooxygenase+%28FMO%29+activity+by+imipramine%3A+structure%2Ffunction+studies+with+FMO1+from+pig+and+rabbit.&rft.au=Wyatt%2C+M+K%3BOverby%2C+L+H%3BLawton%2C+M+P%3BPhilpot%2C+R+M&rft.aulast=Wyatt&rft.aufirst=M&rft.date=1998-04-28&rft.volume=37&rft.issue=17&rft.spage=5930&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins. AN - 79821850; 9560204 AB - The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity in cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitination in vitro. A regulatory pathway is described in which excess iron is sensed by its ability to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequently is degraded by the proteasome. Selective targeting and removal of oxidatively modified proteins may contribute to the turnover of many proteins that are degraded by the proteasome. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Iwai, K AU - Drake, S K AU - Wehr, N B AU - Weissman, A M AU - LaVaute, T AU - Minato, N AU - Klausner, R D AU - Levine, R L AU - Rouault, T A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA. Y1 - 1998/04/28/ PY - 1998 DA - 1998 Apr 28 SP - 4924 EP - 4928 VL - 95 IS - 9 SN - 0027-8424, 0027-8424 KW - Iron-Regulatory Proteins KW - 0 KW - Iron-Sulfur Proteins KW - Multienzyme Complexes KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Ubiquitins KW - Iron KW - E1UOL152H7 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Iron Regulatory Protein 2 KW - EC 4.2.1.3 KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Ubiquitins -- metabolism KW - COS Cells KW - Recombinant Proteins -- metabolism KW - Iron -- metabolism KW - Cell-Free System KW - Multienzyme Complexes -- metabolism KW - RNA-Binding Proteins -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Iron-Sulfur Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79821850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Iron-dependent+oxidation%2C+ubiquitination%2C+and+degradation+of+iron+regulatory+protein+2%3A+implications+for+degradation+of+oxidized+proteins.&rft.au=Iwai%2C+K%3BDrake%2C+S+K%3BWehr%2C+N+B%3BWeissman%2C+A+M%3BLaVaute%2C+T%3BMinato%2C+N%3BKlausner%2C+R+D%3BLevine%2C+R+L%3BRouault%2C+T+A&rft.aulast=Iwai&rft.aufirst=K&rft.date=1998-04-28&rft.volume=95&rft.issue=9&rft.spage=4924&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 - 1998-06-04 N1 - Date created - 1998-06-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1985 Dec 15;260(29):15394-7 [2866184] J Biol Chem. 1997 Sep 5;272(36):22642-7 [9278421] Arch Biochem Biophys. 1991 Sep;289(2):371-5 [1680314] Cell. 1993 Jan 15;72(1):19-28 [8380757] Annu Rev Biochem. 1993;62:797-821 [8352601] J Biol Chem. 1994 Jan 28;269(4):2405-10 [8300566] Methods Enzymol. 1994;233:346-57 [8015469] Science. 1994 Sep 2;265(5177):1454-8 [8073290] Cell. 1994 Sep 9;78(5):761-71 [8087844] Cell. 1994 Oct 7;79(1):13-21 [7923371] J Biol Chem. 1994 Dec 9;269(49):30904-10 [7983023] Science. 1995 May 5;268(5211):726-31 [7732382] Genes Dev. 1995 Jul 1;9(13):1586-97 [7628694] J Biol Chem. 1995 Sep 15;270(37):21645-51 [7665579] Curr Biol. 1995 Aug 1;5(8):854-8 [7583140] J Biol Chem. 1995 Oct 13;270(41):24209-15 [7592626] EMBO J. 1995 Nov 1;14(21):5350-7 [7489724] Cell. 1996 Mar 22;84(6):853-62 [8601309] J Biol Chem. 1996 Apr 12;271(15):8709-13 [8621503] J Biol Chem. 1996 Jun 28;271(26):15504-9 [8663134] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8175-82 [8710843] Annu Rev Biochem. 1996;65:801-47 [8811196] Annu Rev Genet. 1996;30:405-39 [8982460] Immunol Today. 1997 Apr;18(4):189-98 [9136456] J Biol Chem. 1997 Aug 15;272(33):20313-6 [9252331] Arch Biochem Biophys. 1990 Apr;278(1):26-34 [1969723] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Corticosterone attenuates zinc-induced neurotoxicity in primary hippocampal cultures. AN - 79873639; 9593952 AB - Primary hippocampal cultures derived from newborn rats were exposed to zinc chloride at 50, 75, 100, 150 and 200 microM concentrations. Neuronal injury was assessed morphologically and by the lactate dehydrogenase (LDH) efflux assay. Zinc exposure increased LDH efflux in a concentration-dependent manner. Exposure to 100 microM zinc for 24 h resulted in beading of neurites and swelling of neuronal soma. When cultures were co-exposed to zinc at 100 microM and corticosterone in the range of 10-5 to 10-7 M, degeneration of neurons caused by zinc was attenuated. Our study suggests that corticosterone can protect neurons from zinc-induced neurotoxicity at low doses. Copyright 1998 Elsevier Science B.V. JF - Brain research AU - Sunanda AU - Rao, B S AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore 560 029, India. Y1 - 1998/04/27/ PY - 1998 DA - 1998 Apr 27 SP - 295 EP - 298 VL - 791 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Neuroprotective Agents KW - 0 KW - Neurotoxins KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Zinc KW - J41CSQ7QDS KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Analysis of Variance KW - Cells, Cultured KW - Rats, Wistar KW - L-Lactate Dehydrogenase -- metabolism KW - Zinc -- antagonists & inhibitors KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Neurons -- enzymology KW - Hippocampus -- enzymology KW - Corticosterone -- pharmacology KW - Neurotoxins -- antagonists & inhibitors KW - Neuroprotective Agents -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79873639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Corticosterone+attenuates+zinc-induced+neurotoxicity+in+primary+hippocampal+cultures.&rft.au=Sunanda%3BRao%2C+B+S%3BRaju%2C+T+R&rft.aulast=Sunanda&rft.aufirst=&rft.date=1998-04-27&rft.volume=791&rft.issue=1-2&rft.spage=295&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 - 1998-08-03 N1 - Date created - 1998-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyamine-like actions of aminoglycosides and aminoglycoside derivatives at NMDA receptors. AN - 79983093; 9653898 AB - Recent pharmacological studies indicate that aminoglycoside-induced hearing loss may be an excitotoxic process modulated by a polyamine-like activation of cochlear NMDA receptors. Aminoglycoside antibiotics are constituted by a series of glycosidically linked aminocyclitols and aminosugars. We report here on the actions of these individual aminocyclitols and aminosugars on wild type NMDA receptors from rat brain. Compared to the parent molecules, neither aminocyclitols (e.g., 2-deoxystreptamine, streptamine, and streptidine) nor aminosugars (e.g., D-glucosamine and kanosamine) were effective at enhancing [3H]dizocilpine ([3H]MK-801) binding or inhibiting [3H]ifenprodil at NMDA receptors. Moreover, the appropriate combinations of aminosugars and aminocyclitols did not reconstitute the activity of the parent aminoglycoside at NMDA receptors. These data indicate that the polyamine-like actions of aminoglycosides are attributable to the conformation of the parent molecule rather than a particular amine containing constituent. Thus, it may be possible to synthesize or isolate aminoglycoside antibiotics devoid of ototoxicity. JF - European journal of pharmacology AU - Segal, J A AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. segalj@lilly.com Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 311 EP - 317 VL - 347 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Adrenergic alpha-Antagonists KW - 0 KW - Anti-Bacterial Agents KW - Excitatory Amino Acid Antagonists KW - Piperidines KW - Polyamines KW - Receptors, N-Methyl-D-Aspartate KW - Neomycin KW - 1404-04-2 KW - Spermine KW - 2FZ7Y3VOQX KW - Kanamycin KW - 59-01-8 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - ifenprodil KW - R8OE3P6O5S KW - Index Medicus KW - Animals KW - Dizocilpine Maleate -- metabolism KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Piperidines -- metabolism KW - Neomycin -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Kanamycin -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Spermine -- pharmacology KW - In Vitro Techniques KW - Carbohydrate Sequence KW - Molecular Sequence Data KW - Male KW - Adrenergic alpha-Antagonists -- pharmacology KW - Polyamines -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Anti-Bacterial Agents -- pharmacology KW - Polyamines -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79983093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmacology&rft.atitle=Polyamine-like+actions+of+aminoglycosides+and+aminoglycoside+derivatives+at+NMDA+receptors.&rft.au=Segal%2C+J+A%3BSkolnick%2C+P&rft.aulast=Segal&rft.aufirst=J&rft.date=1998-04-24&rft.volume=347&rft.issue=2-3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-09-17 N1 - Date created - 1998-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of accessory proteins on T4 DNA polymerase replication fidelity. AN - 79840996; 9571039 AB - The influence of replication accessory proteins on the fidelity of T4 DNA polymerase has been examined. Steady-state kinetic measurements showed that exonuclease-deficient T4 DNA polymerase, alone or with clamp loaders gp44/gp62 and polymerase clamp gp45, displays decreased binding affinity for incorrect as compared to correct dNTPs and a deceased kcat for misinsertion as compared to correct insertion. Kinetic constants were similar with and without accessory proteins, indicating that accessory proteins had little effect on misinsertion. They also had little effect on the Km value for extension of a T.T mismatch. However, the kcat value for T.T mismatch extension was fivefold higher in the presence of the clamp loader and clamp proteins. Thus, in the absence of proofreading, these accessory proteins may promote stable misincorporation. The kinetic analysis is supported by error rate determinations during gap-filling synthesis, which require both misinsertion and mispair extension. For some mispairs, the accuracy of exonuclease-deficient polymerase alone is similar to that in the presence of clamp loader, clamp and single-stranded DNA binding protein (gp32). However, exonuclease-deficient holoenzyme complex is actually less accurate than the polymerase alone for some base substitutions. We suggest that gp45 promotes extension of mismatches by tethering the polymerase to DNA, a process that may be relevant to replication past lesions or other blocks to DNA synthesis. The error rate for one-nucleotide deletions in homopolymeric runs was similar for the polymerase with or without its accessory proteins. This implies that strand misalignment errors arise during highly processive replication. Thus, either unpaired bases can migrate through the run while the DNA polymerase is bound to the template-primer, or the DNA polymerase dissociates from the DNA to allow misalignment but remains tethered to the template through interactions with the clamp. Finally, the T4 replication accessory proteins reduced by >/=10-fold the rate at which exonuclease-deficient T4 DNA polymerase generated deletions of larger numbers of nucleotides, indicating that these proteins influence replication fidelity for other than single base mutations. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Kroutil, L C AU - Frey, M W AU - Kaboord, B F AU - Kunkel, T A AU - Benkovic, S J AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 135 EP - 146 VL - 278 IS - 1 SN - 0022-2836, 0022-2836 KW - DNA, Viral KW - 0 KW - DNA-Binding Proteins KW - Oligodeoxyribonucleotides KW - Trans-Activators KW - Viral Proteins KW - gene 43 protein, Enterobacteria phage T4 KW - gene 44 protein, Enterobacteria phage T4 KW - gene 45 protein, Enterobacteria phage T4 KW - gp32 protein, Enterobacteria phage T4 KW - gp62 protein, bacteriophage T4 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Frameshift Mutation KW - DNA, Viral -- biosynthesis KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Mutagenesis KW - Trans-Activators -- metabolism KW - Bacteriophage T4 -- metabolism KW - Viral Proteins -- metabolism KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+accessory+proteins+on+T4+DNA+polymerase+replication+fidelity.&rft.au=Kroutil%2C+L+C%3BFrey%2C+M+W%3BKaboord%2C+B+F%3BKunkel%2C+T+A%3BBenkovic%2C+S+J&rft.aulast=Kroutil&rft.aufirst=L&rft.date=1998-04-24&rft.volume=278&rft.issue=1&rft.spage=135&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 - 1998-06-25 N1 - Date created - 1998-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta. AN - 79818923; 9553136 AB - Interleukin-2 (IL-2) induces heterodimerization of the IL-2 receptor beta (IL-2Rbeta) and gammac chains of its receptor and activates the Janus family tyrosine kinases, Jak1 and Jak3. Whereas Jak1 associates with IL-2Rbeta, Jak3 associates primarily with gammac but also with IL-2Rbeta. We analyzed four IL-2Rbeta mutations that diminish IL-2-induced proliferation and found that each also decreased IL-2-induced signal transducer and activator of transcription (STAT) activation. For this reason, and because the mutations were in the IL-2Rbeta membrane-proximal region, we investigated and found that each mutation diminished IL-2Rbeta association with both Jak1 and Jak3. This suggested that these Jaks might interact with the same region of IL-2Rbeta; however, certain IL-2Rbeta internal deletions and C-terminal truncations differentially affected the association of Jak1 and Jak3. Interestingly, just as Jak1-IL-2Rbeta association is Jak3-independent and functionally important, we show that Jak3-IL-2Rbeta association is Jak1-independent and implicate this association as being important for IL-2-induced Stat5 activation. Moreover, Jak1 and Jak3 could associate only in the presence of IL-2Rbeta, suggesting that these kinases can simultaneously bind to IL-2Rbeta. Thus, our data not only demonstrate that somewhat more distal as well as membrane-proximal cytoplasmic regions of a type I cytokine receptor are important for Jak kinase association but also suggest that two IL-2Rbeta-Jak kinase interactions are important for IL-2 signaling. JF - The Journal of biological chemistry AU - Zhu, M H AU - Berry, J A AU - Russell, S M AU - Leonard, W J AD - Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/24/ PY - 1998 DA - 1998 Apr 24 SP - 10719 EP - 10725 VL - 273 IS - 17 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-2 KW - Milk Proteins KW - Receptors, Interleukin-2 KW - STAT5 Transcription Factor KW - Trans-Activators KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - JAK1 protein, human KW - EC 2.7.10.2 KW - JAK3 protein, human KW - Jak1 protein, mouse KW - Jak3 protein, mouse KW - Janus Kinase 1 KW - Janus Kinase 3 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Interleukin-2 -- metabolism KW - COS Cells KW - HeLa Cells KW - Humans KW - Mice KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Signal Transduction KW - DNA-Binding Proteins -- metabolism KW - Receptors, Interleukin-2 -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - Receptors, Interleukin-2 -- genetics KW - Receptors, Interleukin-2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79818923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Delineation+of+the+regions+of+interleukin-2+%28IL-2%29+receptor+beta+chain+important+for+association+of+Jak1+and+Jak3.+Jak1-independent+functional+recruitment+of+Jak3+to+Il-2Rbeta.&rft.au=Zhu%2C+M+H%3BBerry%2C+J+A%3BRussell%2C+S+M%3BLeonard%2C+W+J&rft.aulast=Zhu&rft.aufirst=M&rft.date=1998-04-24&rft.volume=273&rft.issue=17&rft.spage=10719&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 - 1998-05-22 N1 - Date created - 1998-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites. AN - 79820512; 9554879 AB - The molecular basis for recognition by human P2Y1 receptors of the novel, competitive antagonist 2'-deoxy-N6-methyladenosine 3', 5'-bisphosphate (MRS 2179) was probed using site-directed mutagenesis and molecular modeling. The potency of this antagonist was measured in mutant receptors in which key residues in the transmembrane helical domains (TMs) 3, 5, 6, and 7 were replaced by Ala or other amino acids. The capacity of MRS 2179 to block stimulation of phospholipase C promoted by 2-methylthioadenosine 5'-diphosphate (2-MeSADP) was lost in P2Y1 receptors having F226A, K280A, or Q307A mutations, indicating that these residues are critical for the binding of the antagonist molecule. Mutation of the residues His132, Thr222, and Tyr136 had an intermediate effect on the capacity of MRS 2179 to block the P2Y1 receptor. These positions therefore appear to have a modulatory role in recognition of this antagonist. F131A, H277A, T221A, R310K, or S317A mutant receptors exhibited an apparent affinity for MRS 2179 that was similar to that observed with the wild-type receptor. Thus, Phe131, Thr221, His277, and Ser317 are not essential for antagonist recognition. A computer-generated model of the human P2Y1 receptor was built and analyzed to help interpret these results. The model was derived through primary sequence comparison, secondary structure prediction, and three-dimensional homology building, using rhodopsin as a template, and was consistent with data obtained from mutagenesis studies. We have introduced a "cross-docking" procedure to obtain energetically refined 3D structures of the ligand-receptor complexes. Cross-docking simulates the reorganization of the native receptor structure induced by a ligand. A putative nucleotide binding site was localized and used to predict which residues are likely to be in proximity to agonists and antagonists. According to our model TM6 and TM7 are close to the adenine ring, TM3 and TM6 are close to the ribose moiety, and TM3, TM6, and TM7 are near the triphosphate chain. JF - Journal of medicinal chemistry AU - Moro, S AU - Guo, D AU - Camaioni, E AU - Boyer, J L AU - Harden, T K AU - Jacobson, K A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. Y1 - 1998/04/23/ PY - 1998 DA - 1998 Apr 23 SP - 1456 EP - 1466 VL - 41 IS - 9 SN - 0022-2623, 0022-2623 KW - Enzyme Inhibitors KW - 0 KW - Ligands KW - N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate KW - P2RY1 protein, human KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Type C Phospholipases -- antagonists & inhibitors KW - COS Cells KW - Humans KW - Receptors, Purinergic P2 -- chemistry KW - Enzyme Inhibitors -- chemistry KW - Amino Acid Sequence KW - Receptors, Purinergic P2 -- genetics KW - Molecular Sequence Data KW - Point Mutation KW - Enzyme Inhibitors -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Enzyme Inhibitors -- metabolism KW - Protein Conformation KW - Mutagenesis, Site-Directed KW - Adenosine Diphosphate -- analogs & derivatives KW - Models, Molecular KW - Adenosine Diphosphate -- chemistry KW - Adenosine Diphosphate -- pharmacology KW - Adenosine Diphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79820512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+P2Y1+receptor%3A+molecular+modeling+and+site-directed+mutagenesis+as+tools+to+identify+agonist+and+antagonist+recognition+sites.&rft.au=Moro%2C+S%3BGuo%2C+D%3BCamaioni%2C+E%3BBoyer%2C+J+L%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Moro&rft.aufirst=S&rft.date=1998-04-23&rft.volume=41&rft.issue=9&rft.spage=1456&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Mol Biol. 1981 Jan 5;145(1):215-50 [7265198] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Biochem J. 1983 May 15;212(2):473-82 [6309146] EMBO J. 1982;1(12):1635-40 [6765200] Methods Enzymol. 1987;152:684-704 [3657593] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] Nature. 1993 Apr 22;362(6422):770-2 [8469290] FEBS Lett. 1993 Jun 14;324(2):219-25 [8508924] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] J Biol Chem. 1995 Mar 3;270(9):4185-8 [7876172] J Biol Chem. 1995 Jun 9;270(23):13987-97 [7775460] Biochem Pharmacol. 1996 Feb 23;51(4):545-55 [8619901] Br J Pharmacol. 1996 May;118(1):167-73 [8733591] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Mol Pharmacol. 1997 Sep;52(3):499-507 [9281613] Nature. 1997 Sep 11;389(6647):203-6 [9296501] J Med Chem. 1997 Nov 21;40(24):3871-86 [9397168] J Med Chem. 1998 Jan 15;41(2):183-90 [9457242] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation. AN - 79812693; 9548940 AB - Studies utilizing the overexpression of individual isoforms indicated that both PKC-alpha and -delta promote a number of biological effects, including inhibition of DNA synthesis associated with rearrangements of the actin cytoskeleton in the murine B-cell lymphoma (Baf3), differentiation of the murine promyelocyte line 32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these results reflect some form of cross-regulation between PKC-alpha and -delta rather than their functional redundancy. In this report, we show that overexpression of PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA and protein levels. The elevated steady-state PKC-delta mRNA level results from a combination of increased PKC-delta transcription and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In addition, phorbol ester-induced elevation of PKC-delta mRNA and protein levels can be prevented by the PKC inhibitor GF109203X, an indication of the requirement for PKC kinase activity. Inhibition of new protein synthesis by cycloheximide showed that upregulation of PKC-delta mRNA, as opposed to delayed downregulation of the PKC-delta protein, is primarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross-regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not. JF - Biochemistry AU - Romanova, L Y AU - Alexandrov, I A AU - Nordan, R P AU - Blagosklonny, M V AU - Mushinski, J F AD - Laboratory of Genetics and Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1998/04/21/ PY - 1998 DA - 1998 Apr 21 SP - 5558 EP - 5565 VL - 37 IS - 16 SN - 0006-2960, 0006-2960 KW - Indoles KW - 0 KW - Isoenzymes KW - Maleimides KW - RNA, Messenger KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Enzyme Stability -- genetics KW - Up-Regulation -- genetics KW - Mice KW - Enzyme Activation -- genetics KW - Lymphoma, B-Cell KW - Tumor Cells, Cultured KW - Up-Regulation -- drug effects KW - Enzyme Activation -- drug effects KW - Leukemia, Promyelocytic, Acute KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Stability -- drug effects KW - Indoles -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Transcription, Genetic -- drug effects KW - RNA, Messenger -- metabolism KW - Isoenzymes -- physiology KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- genetics KW - Protein Kinase C -- biosynthesis KW - Protein Kinase C -- physiology KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79812693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cross-talk+between+protein+kinase+C-alpha+%28PKC-alpha%29+and+-delta+%28PKC-delta%29%3A+PKC-alpha+elevates+the+PKC-delta+protein+level%2C+altering+its+mRNA+transcription+and+degradation.&rft.au=Romanova%2C+L+Y%3BAlexandrov%2C+I+A%3BNordan%2C+R+P%3BBlagosklonny%2C+M+V%3BMushinski%2C+J+F&rft.aulast=Romanova&rft.aufirst=L&rft.date=1998-04-21&rft.volume=37&rft.issue=16&rft.spage=5558&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BSE: the final resting place. AN - 79964269; 9643681 JF - Lancet (London, England) AU - Brown, P AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA. Y1 - 1998/04/18/ PY - 1998 DA - 1998 Apr 18 SP - 1146 EP - 1147 VL - 351 IS - 9110 SN - 0140-6736, 0140-6736 KW - Hazardous Waste KW - 0 KW - Medical Waste KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Animals KW - Cattle KW - Risk Factors KW - Humans KW - Ireland KW - Hazardous Waste -- legislation & jurisprudence KW - Creutzfeldt-Jakob Syndrome -- transmission KW - Prion Diseases -- prevention & control KW - Encephalopathy, Bovine Spongiform -- transmission KW - Medical Waste -- legislation & jurisprudence KW - Prion Diseases -- transmission KW - Creutzfeldt-Jakob Syndrome -- prevention & control KW - Encephalopathy, Bovine Spongiform -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79964269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=BSE%3A+the+final+resting+place.&rft.au=Brown%2C+P&rft.aulast=Brown&rft.aufirst=P&rft.date=1998-04-18&rft.volume=351&rft.issue=9110&rft.spage=1146&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 - 1998-07-01 N1 - Date created - 1998-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recognition of core binding sites by bacteriophage integrases. AN - 79839431; 9571022 AB - Bacteriophage integrases promote recombination between DNA molecules that carry attachment sites. They are members of a large and widely distributed family of site-specific recombinases with diverse biological roles. The integrases of phages lambda and HK022 are closely related members of this family, but neither protein efficiently recombines the attachment sites of the other phage. The nucleotides responsible for this specificity difference are located close to the points of recombinational strand exchange, within an integrase binding motif called the extended core binding site. There are four imperfectly repeated copies of this motif in each set of phage attachment sites, but only two, B' and C, contain major specificity determinants. When these specificity determinants were replaced by the corresponding nucleotides from a site with the alternative specificity, the resulting mutant was recombined by both integrases. Thus, the determinants act by impeding recombination promoted by the non-cognate integrase. We found that identical nucleotide substitutions within different core site copies had different effects on recombination, suggesting that integrase does not recognize each of the extended core binding sites in the same way. Finally, substitution at several positions in lambda integrase with the corresponding HK022-specific amino acids prevents recombination of lambda attachment sites, and this defect can be suppressed in an allele-specific manner by appropriate substitutions of HK022-specific nucleotides in the extended core binding sites. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Dorgai, L AU - Sloan, S AU - Weisberg, R A AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 1059 EP - 1070 VL - 277 IS - 5 SN - 0022-2836, 0022-2836 KW - Viral Proteins KW - 0 KW - Integrases KW - EC 2.7.7.- KW - Index Medicus KW - Coliphages -- enzymology KW - Sequence Alignment KW - Plasmids -- genetics KW - Recombination, Genetic -- genetics KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Amino Acid Sequence KW - Mutagenesis -- genetics KW - Binding Sites -- genetics KW - Bacteriophages -- enzymology KW - Integrases -- chemistry KW - Integrases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79839431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recognition+of+core+binding+sites+by+bacteriophage+integrases.&rft.au=Dorgai%2C+L%3BSloan%2C+S%3BWeisberg%2C+R+A&rft.aulast=Dorgai&rft.aufirst=L&rft.date=1998-04-17&rft.volume=277&rft.issue=5&rft.spage=1059&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming G protein-coupled receptors block insulin and ras-induced adipocytic differentiation in 3T3-L1 cells: evidence for a PKC and MAP kinase independent pathway. AN - 79837969; 9571194 AB - We have used the expression of muscarinic m1 receptors in the preadipocytic 3T3-L1 cell line for dissecting the nature of the G protein-linked pathways governing adipocytic differentiation, a complex process controlled by many stimuli and their downstream targets. 3T3-L1 cells can be differentiated by insulin or by ras oncogenes, and MAP kinase has been implicated in this process. However, m1 stimulation failed to induce differentiation of 3T3-L1 cells. Furthermore, it prevented insulin or v-ras-induced adipocytic differentiation, utilizing a protein kinase C-independent pathway. m1 stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS-1 and SHC, nor the recruitment of Grb-2. Interestingly, whereas m1 receptors potently activated MAP kinase, another differentiation-inhibitor, TNF alpha, did not affect it. These results suggest that the control of adipocytic differentiation can occur utilizing a biochemical route independent of protein kinase C, and acting downstream, or independently from the Ras-MAP kinase pathway. JF - Biochemical and biophysical research communications AU - Crespo, P AU - Font de Mora, J AU - Aaronson, D S AU - Santos, E AU - Gutkind, J S AD - Molecular Signaling Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. crespop@medi.unican.es Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 554 EP - 561 VL - 245 IS - 2 SN - 0006-291X, 0006-291X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - Indoles KW - Insulin KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, mouse KW - Maleimides KW - Phosphoproteins KW - Proteins KW - Receptors, Muscarinic KW - Shc Signaling Adaptor Proteins KW - Shc1 protein, mouse KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - Tumor Necrosis Factor-alpha KW - Carbachol KW - 8Y164V895Y KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ras Proteins KW - EC 3.6.5.2 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Mice KW - Histocytochemistry KW - Proteins -- metabolism KW - Signal Transduction -- physiology KW - Phosphorylation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Protein Kinase C -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Carbachol -- pharmacology KW - Maleimides -- pharmacology KW - Phosphoproteins -- metabolism KW - Cell Differentiation -- physiology KW - GTP-Binding Proteins -- metabolism KW - Insulin -- pharmacology KW - Adipocytes -- metabolism KW - ras Proteins -- pharmacology KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79837969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+G+protein-coupled+receptors+block+insulin+and+ras-induced+adipocytic+differentiation+in+3T3-L1+cells%3A+evidence+for+a+PKC+and+MAP+kinase+independent+pathway.&rft.au=Crespo%2C+P%3BFont+de+Mora%2C+J%3BAaronson%2C+D+S%3BSantos%2C+E%3BGutkind%2C+J+S&rft.aulast=Crespo&rft.aufirst=P&rft.date=1998-04-17&rft.volume=245&rft.issue=2&rft.spage=554&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues. AN - 79809920; 9545315 AB - Helodermin and exendin-4, two peptides isolated from the salivary gland of the Gila monster, Heloderma suspectum, are approximately 50% homologous to vasoactive intestinal peptide (VIP) and glucagon-like peptide-1 (GLP-1), respectively, and interact with the mammalian receptors for VIP and GLP-1 with equal or higher affinity and efficacy. Immunohistochemical studies suggested the presence of helodermin-like peptides in mammals. To determine whether helodermin and exendin-4 are present in mammals and their evolutionary relationship to VIP and GLP-1, their cDNAs were first cloned from Gila monster salivary gland. Northern blots and reverse transcription-polymerase chain reaction of multiple Gila monster tissues identified approximately 500-base pair transcripts only from salivary gland. Both helodermin and exendin-4 full-length cDNAs were approximately 500 base pairs long, and they encoded precursor proteins containing the entire amino acid sequence of helodermin and exendin-4, as well as a 44- or 45-amino acid N-terminal extension peptide, respectively, having approximately 60% homology. The size and structural organization of these cDNAs indicated that they were closely related to one another but markedly different from known cDNAs for the VIP/GLP-1 peptide family previously identified in both lower and higher evolved species. Cloning of the Gila monster VIP/peptide histidine isoleucine, pituitary adenylate cyclase activating polypeptide, and glucagon/GLP-1 cDNAs and Southern blotting of Gila monster DNA demonstrate the coexistence of separate genes for these peptides and suggests, along with the restricted salivary gland expression, that helodermin and exendin-4 coevolved to serve a separate specialized function. Probing of a variety of rat and human tissues on Northern blots, human and rat Southern blots, and genomic and cDNA libraries with either helodermin- or exendin-4-specific cDNAs failed to identify evidence for mammalian homologues. These data indicate that helodermin and exendin-4 are not the precursors to VIP and GLP-1 and that they belong to a separate peptide family encoded by separate genes. Furthermore, the existence of as yet undiscovered mammalian homologues to helodermin and exendin-4 seems unlikely. JF - The Journal of biological chemistry AU - Pohl, M AU - Wank, S A AD - Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9778 EP - 9784 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - ADCYAP1 protein, human KW - 0 KW - Adcyap1 protein, rat KW - DNA Primers KW - DNA, Complementary KW - Neuropeptides KW - Peptide Fragments KW - Peptides KW - Pituitary Adenylate Cyclase-Activating Polypeptide KW - Protein Precursors KW - Recombinant Proteins KW - Venoms KW - glucagon-like peptide 1 (7-36) KW - 107444-51-9 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Glucagon-Like Peptides KW - 62340-29-8 KW - heliodermin KW - 89468-62-2 KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Mammals KW - Humans KW - Lizards KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Polymerase Chain Reaction KW - Base Sequence KW - Chickens KW - Peptide Fragments -- chemistry KW - Sequence Alignment KW - Trout KW - Protein Precursors -- chemistry KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Vasoactive Intestinal Peptide -- chemistry KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Peptides -- genetics KW - Neuropeptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cloning+of+the+helodermin+and+exendin-4+cDNAs+in+the+lizard.+Relationship+to+vasoactive+intestinal+polypeptide%2Fpituitary+adenylate+cyclase+activating+polypeptide+and+glucagon-like+peptide+1+and+evidence+against+the+existence+of+mammalian+homologues.&rft.au=Pohl%2C+M%3BWank%2C+S+A&rft.aulast=Pohl&rft.aufirst=M&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9778&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of V3 loop-Pseudomonas exotoxin chimeras. Candidate vaccines for human immunodeficiency virus-1. AN - 79809524; 9545339 AB - To develop a candidate vaccine for human immunodeficiency virus, type 1 (HIV-1), chimeric proteins were constructed by inserting sequences derived from the V3 loop of gp120 into a nontoxic form of Pseudomonas exotoxin (PE). Inserts of 14 or 26 amino acids, constrained by a disulfide bond, were introduced between domains II and III of PE. V3 loop-toxin proteins expressed in Escherichia coli and corresponding to either MN (subtype B) or Thai (subtype E) strains, were recognized by strain-specific monoclonal anti-gp120 antibodies. When loop sequences were introduced into an enzymatically active form of the toxin, there was no loss of toxin-mediated cell killing, suggesting that these sequences were co-transported to the cytosol. Sera from rabbits injected with nontoxic PE-V3 loop chimeras were reactive for strain-specific gp120s in Western blots, immunocapture assays, enzyme-linked immunosorbent assays, and neutralized HIV-1 infectivity. Since toxin vectors were designed to receive oligonucleotide duplexes encoding any V3 loop sequence, this approach should allow for the production of V3 loop-toxin chimeras corresponding to multiple HIV isolates. JF - The Journal of biological chemistry AU - FitzGerald, D J AU - Fryling, C M AU - McKee, M L AU - Vennari, J C AU - Wrin, T AU - Cromwell, M E AU - Daugherty, A L AU - Mrsny, R J AD - Biotherapy Section, Laboratory of Molecular Biology, Division of Basic Science, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9951 EP - 9958 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - AIDS Vaccines KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - HIV Antibodies KW - HIV Envelope Protein gp120 KW - Recombinant Fusion Proteins KW - Vaccines, Synthetic 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 - AIDS/HIV KW - Animals KW - Recombinant Fusion Proteins -- immunology KW - Humans KW - Rabbits KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- chemistry KW - Tumor Cells, Cultured KW - Acquired Immunodeficiency Syndrome -- blood KW - Cell Survival -- drug effects KW - HIV Antibodies -- blood KW - HIV Antibodies -- immunology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Neutralization Tests KW - Escherichia coli KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Carcinoma, Squamous Cell KW - Protein Conformation KW - HIV-1 -- isolation & purification KW - HIV Envelope Protein gp120 -- chemistry KW - Exotoxins -- chemistry KW - Exotoxins -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - Exotoxins -- toxicity KW - HIV Envelope Protein gp120 -- toxicity KW - Pseudomonas aeruginosa KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79809524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+V3+loop-Pseudomonas+exotoxin+chimeras.+Candidate+vaccines+for+human+immunodeficiency+virus-1.&rft.au=FitzGerald%2C+D+J%3BFryling%2C+C+M%3BMcKee%2C+M+L%3BVennari%2C+J+C%3BWrin%2C+T%3BCromwell%2C+M+E%3BDaugherty%2C+A+L%3BMrsny%2C+R+J&rft.aulast=FitzGerald&rft.aufirst=D&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9951&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes. AN - 79804862; 9545284 AB - Proliferating human medullary thymocytes can exhibit characteristic T helper cell type 1 cytokine responses exemplified by the immediate early expression of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin-beta. Here we report that cAMP-mediated attenuation of the transcription of T helper-1-specific cytokine genes in human medullary thymocytes correlates with the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP early repressor). We show that ICER binds specifically to several NFAT/AP-1 (nuclear factor of activated T cells/activating protein-1) composite DNA sites essential for the activation of the interleukin (IL)-2 promoter as well as to a homologous DNA motif present in the proximal segment of the interferon-gamma promoter. In the presence of the minimal NFAT DNA-binding domain, which is sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously identified as essential for the expression of the immunoregulatory cytokines such as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha. In extracts prepared from human medullary thymocytes treated with forskolin and ionomycin, these composite sites bind endogenously expressed ICER either singly or in complexes. Moreover, in Jurkat cells, ectopically expressed ICER represses transcription from NFAT-mediated, phorbol ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha promoters. We present evidence that ICER interactions with NFAT/AP-1 composite DNA sites correlate with its ability to repress transcription. These findings provide further insight into the mechanisms involved in cAMP-mediated transcriptional attenuation of cytokine expression. JF - The Journal of biological chemistry AU - Bodor, J AU - Habener, J F AD - Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA. Bodorj@exchange.nih.gov Y1 - 1998/04/17/ PY - 1998 DA - 1998 Apr 17 SP - 9544 EP - 9551 VL - 273 IS - 16 SN - 0021-9258, 0021-9258 KW - Cytokines KW - 0 KW - DNA-Binding Proteins KW - Interleukin-2 KW - LTB protein, human KW - Lymphotoxin-alpha KW - Lymphotoxin-beta KW - Membrane Proteins KW - NFATC Transcription Factors KW - Nuclear Proteins KW - RNA, Messenger KW - Recombinant Proteins KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Cyclic AMP KW - E0399OZS9N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Lymphotoxin-alpha -- biosynthesis KW - Transcription, Genetic -- drug effects KW - Recombinant Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Interferon-gamma -- biosynthesis KW - Interleukin-2 -- biosynthesis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Ionomycin -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Binding Sites KW - Child, Preschool KW - Infant KW - Lymphocyte Activation KW - Base Sequence KW - Cells, Cultured KW - Membrane Proteins -- biosynthesis KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Thymus Gland -- immunology KW - Cytokines -- genetics KW - Gene Expression Regulation -- immunology KW - Cytokines -- biosynthesis KW - Repressor Proteins -- metabolism KW - Cyclic AMP -- metabolism KW - T-Lymphocytes -- drug effects KW - Thymus Gland -- drug effects KW - T-Lymphocytes -- immunology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79804862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+transcriptional+repressor+ICER+in+cyclic+AMP-mediated+attenuation+of+cytokine+gene+expression+in+human+thymocytes.&rft.au=Bodor%2C+J%3BHabener%2C+J+F&rft.aulast=Bodor&rft.aufirst=J&rft.date=1998-04-17&rft.volume=273&rft.issue=16&rft.spage=9544&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired salivary dysfunction. Drugs and radiation. AN - 79892306; 9599303 AB - When considering the effects of drugs on salivary glands, a distinction should be drawn between the complaint of oral dryness (xerostomia), a symptom, and measurable secretory hypofunction, a sign. In general, the symptom of xerostomia is often not accompanied by objective reductions in salivary output, and xerostomia is not a reliable indicator of secretory hypofunction. Whereas therapeutic pharmaceutical side effects represent the most prominent cause of xerostomia, with over 500 drugs associated with this symptom, only a small number of drugs have been demonstrated to reduce salivary output substantially. There are examples in which drugs with a high prevalence of xerostomia complaints do not affect secretory function. The mechanisms responsible for this discrepancy between subjective and objective findings have not been fully identified. It is hypothesized that alterations in systemic or mucosal hydration may play a role. Of the drugs with true salivary hypofunctional actions, most have direct anticholinergic properties. In almost all cases, the salivary effects of pharmaceuticals are not permanent, and function returns to pretreatment levels when the medication is stopped. By contrast, the effects of irradiation on the salivary glands are permanent when exposures exceed 50 Gy. About 40,000 individuals per year receive irradiation that involves the salivary glands (by external beam or internal sources--radon implants and 1311) for treatment of cancers of the head and neck region. Although these radiation effects have been recognized as a significant clinical problem for more than 80 years, the specific mechanisms responsible for radiation-induced salivary gland dysfunction are still not understood. With the exception of studies documenting the secretory functional deficits following head and neck irradiation, limited studies have been done in humans. The majority of experimental work has been done in rodents. A variety of mechanisms, including mitotic and interphase cell death, direct DNA damage or effects of secondary metabolites, damage to progenitor cells, or altered gene expression, have all been proposed to explain the salivary epithelial cell death observed. Recent experimental studies with models of radiation-induced salivary damage in rats and a human salivary cell line suggest that the small percentage of surviving epithelial cells are capable of performing functions such as signal transduction and ion transport normally. Apoptotic cell death following irradiation has not been a prominent feature in these model systems. The effects of head and neck radiation on the salivary glands and oral cavity continue to present multiple significant clinical problems both during and after radiotherapy. In recent years, there has been some progress in minimizing these effects through more careful shielding and pretreatment planning. Additionally, there are preliminary results from a clinical trial suggesting that the use of a secretagogue, pilocarpine HCl, given during the course of radiotherapy, may reduce the secretory hypofunctional effects. A multicenter trial is now underway to test this hypothesis. There is still a real need to develop more effective treatments for this condition. JF - Annals of the New York Academy of Sciences AU - Fox, P C AD - Clinical Investigations Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892-1190, USA. pfox@yoda.nidr.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 132 EP - 137 VL - 842 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Xerostomia -- etiology KW - Salivary Glands -- radiation effects KW - Salivary Glands -- physiopathology KW - Animals KW - Salivary Glands -- drug effects KW - Xerostomia -- chemically induced KW - Humans KW - Cranial Irradiation -- adverse effects KW - Salivation -- radiation effects KW - Salivation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79892306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acquired+salivary+dysfunction.+Drugs+and+radiation.&rft.au=Fox%2C+P+C&rft.aulast=Fox&rft.aufirst=P&rft.date=1998-04-15&rft.volume=842&rft.issue=&rft.spage=132&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 - 1998-06-18 N1 - Date created - 1998-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. AN - 79817356; 9563489 AB - Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia. JF - Cancer research AU - Schmidt, L AU - Junker, K AU - Weirich, G AU - Glenn, G AU - Choyke, P AU - Lubensky, I AU - Zhuang, Z AU - Jeffers, M AU - Vande Woude, G AU - Neumann, H AU - Walther, M AU - Linehan, W M AU - Zbar, B AD - Intramural Research Support Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702, USA. Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1719 EP - 1722 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Pedigree KW - North America KW - 3T3 Cells KW - Animals KW - Humans KW - Aged KW - Amino Acid Sequence KW - Mice KW - Mice, Nude KW - Base Sequence KW - Penetrance KW - Transfection KW - Adult KW - Molecular Sequence Data KW - Carcinogenicity Tests KW - Middle Aged KW - Neoplasms, Multiple Primary -- genetics KW - Female KW - Male KW - Kidney Neoplasms -- genetics KW - Proto-Oncogene Proteins c-met -- genetics KW - Mutation KW - Carcinoma, Papillary -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79817356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Two+North+American+families+with+hereditary+papillary+renal+carcinoma+and+identical+novel+mutations+in+the+MET+proto-oncogene.&rft.au=Schmidt%2C+L%3BJunker%2C+K%3BWeirich%2C+G%3BGlenn%2C+G%3BChoyke%2C+P%3BLubensky%2C+I%3BZhuang%2C+Z%3BJeffers%2C+M%3BVande+Woude%2C+G%3BNeumann%2C+H%3BWalther%2C+M%3BLinehan%2C+W+M%3BZbar%2C+B&rft.aulast=Schmidt&rft.aufirst=L&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1719&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02958; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of elevated mutagenesis in the spleen with genetic susceptibility to induced plasmacytoma development in mice. AN - 79816905; 9563470 AB - Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice. This finding suggests a correlation between the genetic susceptibility to inflammation-induced peritoneal plasmacytomagenesis and the phenotype of increased mutagenesis in lymphoid tissues, raising the possibility that plasmacytoma resistance genes may inhibit tumor development by minimizing oxidative mutagenesis in B cells. JF - Cancer research AU - Felix, K AU - Kelliher, K AU - Bornkamm, G W AU - Janz, S AD - Laboratory of Genetics, DBS, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. felixk@dc37a.nci.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1616 EP - 1619 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Mice, Inbred Strains KW - Carcinogens -- pharmacology KW - Animals KW - Disease Susceptibility KW - Glutathione -- metabolism KW - Mice KW - Terpenes -- pharmacology KW - Buthionine Sulfoximine -- pharmacology KW - Mice, Inbred BALB C KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Spleen -- pathology KW - Oxidative Stress -- genetics KW - Mutagenesis -- genetics KW - Spleen -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+of+elevated+mutagenesis+in+the+spleen+with+genetic+susceptibility+to+induced+plasmacytoma+development+in+mice.&rft.au=Felix%2C+K%3BKelliher%2C+K%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1616&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha. AN - 79816678; 9563466 AB - The death receptor (DR) KILLER/DR5 gene has recently been identified as a doxorubicin-regulated transcript that was also induced by exogenous wild-type p53 in p53-negative cells. KILLER/DR5 gene encodes a DR containing cell surface protein that is highly homologous to DR4, another DR of the tumor necrosis factor (TNF) receptor family. Both DR4 and KILLER/DR5 independently bind to their specific ligand TRAIL and engage the caspase cascade to induce apoptosis. TRID (also known as TRAIL-R3) is an antiapoptotic decoy receptor that lacks the cytoplasmic death domain and competes with KILLER/DR5 and DR4 for binding to TRAIL. In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis. Just like other p53-regulated genes, ionizing radiation induction of KILLER/DR5 occurs in p53 wild-type cells, whereas methyl methanesulfonate regulation of KILLER/DR5 occurs in a p53-dependent and -independent manner. However, unlike other p53-regulated genes, KILLER/DR5 is not regulated following UV irradiation. TNF-alpha, a nongenotoxic cytokine, also induced the expression of KILLER/DR5 in a number of cancer cell lines, irrespective of p53 status. TNF-alpha did not alter the KILLER/DR5 mRNA stability, suggesting that the TNF-alpha regulation of KILLER/DRS expression appears transcriptional. We also provide evidence that KILLER/DR5 is regulated in a trigger and cell type-specific manner and that its induction by TNF-alpha, p53, or DNA damage is not the consequence of apoptosis induced by these agents. Unlike KILLER/DR5, none of the other KILLER/DR5 family members, including DR4, TRID, or the ligand TRAIL, displayed genotoxic stress or TNF-alpha regulation in a p53 transcription-dependent manner. Thus, KILLER/DR5 appears a bona fide downstream target of p53 that is also regulated in a cell type-specific, trigger-dependent, and p53-independent manner. JF - Cancer research AU - Sheikh, M S AU - Burns, T F AU - Huang, Y AU - Wu, G S AU - Amundson, S AU - Brooks, K S AU - Fornace, A J AU - el-Deiry, W S AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. mssheikh@box-m.nih.gov Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 1593 EP - 1598 VL - 58 IS - 8 SN - 0008-5472, 0008-5472 KW - Apoptosis Regulatory Proteins KW - 0 KW - GPI-Linked Proteins KW - Membrane Glycoproteins KW - RNA, Messenger KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Member 10c KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10A protein, human KW - TNFRSF10B protein, human 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 - Doxorubicin KW - 80168379AG KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Immunoblotting KW - Ultraviolet Rays KW - Blotting, Northern KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - RNA, Messenger -- analysis KW - Tumor Cells, Cultured -- radiation effects KW - Methyl Methanesulfonate -- pharmacology KW - Doxorubicin -- pharmacology KW - Transfection KW - Time Factors KW - Membrane Glycoproteins -- metabolism KW - Radiation, Ionizing KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79816678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53-dependent+and+-independent+regulation+of+the+death+receptor+KILLER%2FDR5+gene+expression+in+response+to+genotoxic+stress+and+tumor+necrosis+factor+alpha.&rft.au=Sheikh%2C+M+S%3BBurns%2C+T+F%3BHuang%2C+Y%3BWu%2C+G+S%3BAmundson%2C+S%3BBrooks%2C+K+S%3BFornace%2C+A+J%3Bel-Deiry%2C+W+S&rft.aulast=Sheikh&rft.aufirst=M&rft.date=1998-04-15&rft.volume=58&rft.issue=8&rft.spage=1593&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A subtractive PCR-based cDNA library made from fetal thymic stromal cells AN - 16413031; 4313926 AB - We describe our initial approach to clone and characterize genes expressed preferentially in thymic stromal cells, in an attempt to generate molecular reagents to study the role of these cells in thymopoiesis and thymic function. Thymic stromal cells were prepared from fetal thymic organ cultures by treating them with 2-deoxyguanosine and depleting the remaining hematopoietic cells with anti-CD45 antibody. A cDNA library was then prepared after subtraction and amplification by PCR. The cloned inserts were sequenced and compared for homology with known genes in the data base. Unidentified cDNAs were then examined for expression in normal and SCID thymus and in a set of SV40-transformed thymic epithelial cell lines, by Northern blotting and a dot blot assay. In this report we describe the development of the library and present a general description of the genes identified from the initial 249 cDNAs sequenced. Among these, a relatively high percentage (55%) do not show any homology to previously identified genes. Several genes with a limited expression pattern were selected for further study. JF - Journal of Immunological Methods AU - Kim, M G AU - Chen, C AU - Flomerfelt, F AU - Germain, R N AU - Schwartz, R H AD - Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA Y1 - 1998/04/15/ PY - 1998 DA - 1998 Apr 15 SP - 163 EP - 176 PB - Elsevier Science B.V. VL - 213 IS - 2 SN - 0022-1759, 0022-1759 KW - 2-deoxyguanosine KW - CD45 antigen KW - Polymerase chain reaction KW - SV40 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06713:Physicochemical methods KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16413031?accountid=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=A+subtractive+PCR-based+cDNA+library+made+from+fetal+thymic+stromal+cells&rft.au=Kim%2C+M+G%3BChen%2C+C%3BFlomerfelt%2C+F%3BGermain%2C+R+N%3BSchwartz%2C+R+H&rft.aulast=Kim&rft.aufirst=M&rft.date=1998-04-15&rft.volume=213&rft.issue=2&rft.spage=163&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 ER - TY - JOUR T1 - Effect of mutating the regulatory phosphoserine and conserved threonine on the activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain kinase. AN - 79801262; 9539704 AB - Phosphorylation of Ser-627 is both necessary and sufficient for full activity of the expressed 35-kDa catalytic domain of myosin I heavy chain kinase (MIHCK). Ser-627 lies in the variable loop between highly conserved residues DFG and APE at a position at which a phosphorylated Ser/Thr also occurs in many other Ser/Thr protein kinases. The variable loop of MIHCK contains two other hydroxyamino acids: Thr-631, which is conserved in almost all Ser/Thr kinases, and Thr-632, which is not conserved. We determined the effects on the kinase activity of the expressed catalytic domain of mutating Ser-627, Thr-631, and Thr-632 individually to Ala, Asp, and Glu. The S627A mutant was substantially less active than wild type (wt), with a lower kcat and higher Km for both peptide substrate and ATP, but was more active than unphosphorylated wt. The S627D and S627E mutants were also less active than phosphorylated wt, i.e., acidic amino acids cannot substitute for phospho-Ser-627. The activity of the T631A mutant was as low as that of the S627A mutant, whereas the T632A mutant was as active as phosphorylated wt, indicating that highly conserved Thr-631, although not phosphorylated, is essential for catalytic activity. Asp and Glu substitutions for Thr-631 and Thr-632 were inhibitory to various degrees. Molecular modeling indicated that Thr-631 can hydrogen bond with conserved residue Asp-591 in the catalytic loop and that similar interactions are possible for other kinases whose activities also are regulated by phosphorylation in the variable loop. Thus, this conserved Thr residue may be essential for the activities of other Ser/Thr protein kinases as well as for the activity of MIHCK. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Szczepanowska, J AU - Ramachandran, U AU - Herring, C J AU - Gruschus, J M AU - Qin, J AU - Korn, E D AU - Brzeska, H AD - Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/04/14/ PY - 1998 DA - 1998 Apr 14 SP - 4146 EP - 4151 VL - 95 IS - 8 SN - 0027-8424, 0027-8424 KW - Protozoan Proteins KW - 0 KW - Recombinant Proteins KW - Phosphoserine KW - 17885-08-4 KW - Threonine KW - 2ZD004190S KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - myosin-heavy-chain kinase KW - EC 2.7.11.7 KW - Index Medicus KW - Animals KW - Spodoptera KW - Models, Molecular KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Point Mutation KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Cell Line KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Protein Structure, Secondary KW - Acanthamoeba -- enzymology KW - Calcium-Calmodulin-Dependent Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79801262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+mutating+the+regulatory+phosphoserine+and+conserved+threonine+on+the+activity+of+the+expressed+catalytic+domain+of+Acanthamoeba+myosin+I+heavy+chain+kinase.&rft.au=Szczepanowska%2C+J%3BRamachandran%2C+U%3BHerring%2C+C+J%3BGruschus%2C+J+M%3BQin%2C+J%3BKorn%2C+E+D%3BBrzeska%2C+H&rft.aulast=Szczepanowska&rft.aufirst=J&rft.date=1998-04-14&rft.volume=95&rft.issue=8&rft.spage=4146&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 - 1998-05-13 N1 - Date created - 1998-05-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1973 Jul 10;248(13):4691-7 [4268864] J Biol Chem. 1996 Jul 19;271(29):16983-6 [8707782] J Biol Chem. 1996 Oct 25;271(43):27044-8 [8900194] J Biol Chem. 1996 Oct 25;271(43):27049-55 [8900195] J Biol Chem. 1996 Oct 25;271(43):27056-62 [8900196] J Biol Chem. 1996 Dec 13;271(50):31787-90 [8943216] Eur J Biochem. 1996 Dec 1;242(2):171-85 [8973630] EMBO J. 1996 Dec 16;15(24):6810-21 [9003756] Mol Cell Biol. 1997 Mar;17(3):1129-43 [9032240] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1092-5 [9037011] J Biol Chem. 1997 Mar 21;272(12):7586-94 [9065412] J Biol Chem. 1997 Apr 18;272(16):10514-21 [9099695] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8503-8 [9238006] J Biol Chem. 1984 Mar 10;259(5):3224-9 [6321501] Science. 1988 Jul 1;241(4861):42-52 [3291115] J Biol Chem. 1989 Nov 15;264(32):19340-8 [2530230] J Biol Chem. 1990 Mar 5;265(7):3591-4 [2154483] J Biol Chem. 1990 Sep 25;265(27):16138-44 [2168881] J Biol Chem. 1992 Mar 5;267(7):4949-56 [1311323] Annu Rev Cell Biol. 1992;8:429-62 [1335745] Biochemistry. 1993 Mar 9;32(9):2154-61 [8443157] Mol Cell Biol. 1993 Apr;13(4):2332-41 [8455615] J Biol Chem. 1993 Aug 25;268(24):17995-8001 [8394357] Protein Sci. 1993 Oct;2(10):1559-73 [8251932] Nature. 1994 Feb 24;367(6465):704-11 [8107865] Protein Sci. 1994 Feb;3(2):176-87 [8003955] Structure. 1994 May 15;2(5):345-55 [8081750] Biochemistry. 1995 Feb 28;34(8):2447-54 [7873523] EMBO J. 1995 Mar 1;14(5):1015-23 [7889932] FASEB J. 1995 May;9(8):576-96 [7768349] J Biol Chem. 1995 Jul 7;270(27):15984-92 [7608157] Nature. 1995 Jul 27;376(6538):313-20 [7630397] Structure. 1995 May 15;3(5):467-82 [7663944] J Biol Chem. 1995 Sep 8;270(36):21121-8 [7673144] Proteins. 1995 Aug;22(4):378-91 [7479711] J Biol Chem. 1995 Nov 17;270(46):27969-76 [7499274] Cell. 1996 Apr 19;85(2):149-58 [8612268] Nat Struct Biol. 1996 Aug;3(8):696-700 [8756328] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from yeast Sec7 with yeast and mammalian ADP ribosylation factors. AN - 79800398; 9539714 AB - The Saccharomyces cerevisiae Sec7 protein (ySec7p), which is an important component of the yeast secretory pathway, contains a sequence of approximately 200 amino acids referred to as a Sec7 domain. Similar Sec7 domain sequences have been recognized in several guanine nucleotide-exchange proteins (GEPs) for ADP ribosylation factors (ARFs). ARFs are approximately 20-kDa GTPases that regulate intracellular vesicular membrane trafficking and activate phospholipase D. GEPs activate ARFs by catalyzing the replacement of bound GDP with GTP. We, therefore, undertook to determine whether a Sec7 domain itself could catalyze nucleotide exchange on ARF and found that it exhibited brefeldin A (BFA)-inhibitable ARF GEP activity. BFA is known to inhibit ARF GEP activity in Golgi membranes, thereby causing reversible apparent dissolution of the Golgi complex in many cells. The His6-tagged Sec7 domain from ySec7p (rySec7d) synthesized in Escherichia coli enhanced binding of guanosine 5'-[gamma-[35S]thio]triphosphate by recombinant yeast ARF1 (ryARF1) and ryARF2 but not by ryARF3. The effects of rySec7d on ryARF2 were inhibited by BFA in a concentration-dependent manner but not by inactive analogues of BFA (B-17, B-27, and B-36). rySec7d also promoted BFA-sensitive guanosine 5'-[gamma-thio]triphosphate binding by nonmyristoylated recombinant human ARF1 (rhARF1), rhARF5, and rhARF6, although the effect on rhARF6 was very small. These results are consistent with the conclusion that the yeast Sec7 domain itself contains the elements necessary for ARF GEP activity and its inhibition by BFA. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sata, M AU - Donaldson, J G AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1998/04/14/ PY - 1998 DA - 1998 Apr 14 SP - 4204 EP - 4208 VL - 95 IS - 8 SN - 0027-8424, 0027-8424 KW - Carrier Proteins KW - 0 KW - Cyclopentanes KW - DNA Primers KW - Fungal Proteins KW - Guanine Nucleotide Exchange Factors KW - Recombinant Proteins KW - Sec7 guanine nucleotide exchange factors KW - NAD KW - 0U46U6E8UK KW - Brefeldin A KW - 20350-15-6 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Recombinant Proteins -- drug effects KW - Carrier Proteins -- metabolism KW - Humans KW - Cholera Toxin -- pharmacology KW - Sequence Tagged Sites KW - Cloning, Molecular KW - NAD -- metabolism KW - Polymerase Chain Reaction KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Fungal Proteins -- metabolism KW - Cyclopentanes -- pharmacology KW - Saccharomyces cerevisiae -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Fungal Proteins -- drug effects KW - GTP-Binding Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79800398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Brefeldin+A-inhibited+guanine+nucleotide-exchange+activity+of+Sec7+domain+from+yeast+Sec7+with+yeast+and+mammalian+ADP+ribosylation+factors.&rft.au=Sata%2C+M%3BDonaldson%2C+J+G%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Sata&rft.aufirst=M&rft.date=1998-04-14&rft.volume=95&rft.issue=8&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 - 1998-05-13 N1 - Date created - 1998-05-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1989 Mar 10;56(5):801-13 [2647301] J Biol Chem. 1998 Jan 2;273(1):23-7 [9417041] EMBO J. 1989 Sep;8(9):2695-702 [2684655] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1238-42 [2105501] Mol Cell Biol. 1990 Dec;10(12):6690-9 [2123295] J Cell Biol. 1991 Jan;112(1):27-37 [1986005] J Biol Chem. 1991 Feb 15;266(5):2772-7 [1993656] Cell. 1991 Nov 1;67(3):449-51 [1934055] Nature. 1992 Jan 9;355(6356):173-5 [1729652] Biochim Biophys Acta. 1992 Aug 17;1132(1):75-8 [1511013] Nature. 1992 Nov 26;360(6402):350-2 [1448151] J Biol Chem. 1993 Mar 5;268(7):4863-72 [8444865] Cell. 1993 Dec 17;75(6):1137-44 [8261513] Science. 1994 Jan 28;263(5146):523-6 [8290961] Nature. 1994 Mar 3;368(6466):32-8 [7906398] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3063-6 [8159707] Cell. 1994 Jul 1;77(7):1051-62 [8020095] J Biol Chem. 1994 Aug 19;269(33):20931-7 [8063710] Nature. 1994 Nov 3;372(6501):55-63 [7969419] Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11718-22 [7972129] Curr Opin Cell Biol. 1994 Aug;6(4):527-32 [7986529] J Cell Biol. 1995 Mar;128(6):1003-17 [7896867] Mol Cell Biochem. 1994 Sep;138(1-2):157-66 [7898460] Mol Cell Biol. 1996 Jul;16(7):3275-84 [8668142] Cell. 1996 Jul 26;86(2):233-42 [8706128] J Biol Chem. 1996 Sep 6;271(36):21767-74 [8702973] Nature. 1996 Dec 5;384(6608):479-81 [8945477] Nature. 1996 Dec 5;384(6608):481-4 [8945478] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] J Biol Chem. 1986 Aug 25;261(24):11398-403 [2426273] J Biol Chem. 1988 Aug 25;263(24):11711-7 [3042778] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1745-8 [9050849] Science. 1997 Mar 28;275(5308):1927-30 [9072969] EMBO J. 1997 Sep 1;16(17):5445-54 [9312003] J Cell Biol. 1997 Oct 6;139(1):49-61 [9314528] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12926-31 [9371777] Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:629-36 [3151179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of replication-deficient vaccinia virus/T7 RNA polymerase hybrid expression: effect of T7 RNA polymerase levels and alpha-amanitin. AN - 79829826; 9568032 AB - Components of the eukaryotic vaccinia virus/T7 RNA polymerase hybrid expression system were assessed using recombinant and nonrecombinant forms of modified vaccinia Ankara (MVA), a replication-deficient vaccinia virus strain. Recombinant MVA virus expressing T7 RNA polymerase (Wyatt, L. S., Moss, B., and Rozenblatt, S. (1995). Virology 210, 202-205) stimulated high levels of expression from a T7 promoter-chloramphenicol acetyltransferase (CAT) reporter. Most, but not all, of the virally induced expression was T7 RNA polymerase and T7 promoter dependent, with no viral enhancement of translation of T7 transcripts. The efficacy of supplying T7 RNA polymerase expression from nonviral sources was evaluated using a self-amplifying T7 RNA polymerase autogene or an inducible T7 RNA polymerase expression vector. The latter modes yielded CAT activity dependent on T7 RNA polymerase expression; however, expression required viral factors independent of T7 RNA polymerase and did not reach that attained using the recombinant virus. In further experiments, MVA-induced T7 RNA polymerase expression was upregulated by alpha-amanitin, an inhibitor of eukaryotic polymerases. This indicates that MVA/T7 RNA polymerase hybrid expression may be rendered still more efficient by ameliorating transcriptional interference due to an alpha-amanitin-sensitive eukaryotic factor(s). JF - Virology AU - Engleka, K A AU - Lewis, E W AU - Howard, B H AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA. engleka1@jeflin.tju.edu Y1 - 1998/04/10/ PY - 1998 DA - 1998 Apr 10 SP - 331 EP - 339 VL - 243 IS - 2 SN - 0042-6822, 0042-6822 KW - Amanitins KW - 0 KW - Enzyme Inhibitors KW - Viral Proteins KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - bacteriophage T7 RNA polymerase KW - EC 2.7.7.- KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Virus Replication KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - HeLa Cells KW - Humans KW - Enzyme Induction KW - Enzyme Inhibitors -- metabolism KW - Vaccinia virus -- genetics KW - Vaccinia virus -- enzymology KW - Defective Viruses -- genetics KW - Vaccinia virus -- physiology KW - Genetic Vectors KW - DNA-Directed RNA Polymerases -- metabolism KW - Gene Expression KW - Defective Viruses -- enzymology KW - Amanitins -- metabolism KW - Amanitins -- genetics KW - Defective Viruses -- physiology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79829826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+replication-deficient+vaccinia+virus%2FT7+RNA+polymerase+hybrid+expression%3A+effect+of+T7+RNA+polymerase+levels+and+alpha-amanitin.&rft.au=Engleka%2C+K+A%3BLewis%2C+E+W%3BHoward%2C+B+H&rft.aulast=Engleka&rft.aufirst=K&rft.date=1998-04-10&rft.volume=243&rft.issue=2&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-27 N1 - Date created - 1998-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a mutant (alphaD60N) tryptophan synthase alpha2beta2 complex reveals the correct orientation of active site alphaGlu49. AN - 79795555; 9535826 AB - The reversible cleavage of indole-3-glycerol by the alpha-subunit of tryptophan synthase has been proposed to be catalyzed by alphaGlu49 and alphaAsp60. Although previous x-ray crystallographic structures of the tryptophan synthase alpha2beta2 complex showed an interaction between the carboxylate of alphaAsp60 and the bound inhibitor indole-3-propanol phosphate, the carboxylate of alphaGlu49 was too distant to play its proposed role. To clarify the structural and functional roles of alphaGlu49, we have determined crystal structures of a mutant (alphaD60N) alpha2beta2 complex in the presence and absence of the true substrate, indole-3-glycerol phosphate. The enzyme in the crystal cleaves indole-3-glycerol phosphate very slowly at room temperature but not under cryo-conditions of 95 K. The structure of the complex with the true substrate obtained by cryo-crystallography reveals that indole-3-glycerol phosphate and indole-3-propanol phosphate have similar binding modes but different torsion angles. Most importantly, the side chain of alphaGlu49 interacts with 3-hydroxyl group of indole-3-glycerol phosphate as proposed. The movement of the side chain of alphaGlu49 into an extended conformation upon binding the true substrate provides evidence for an induced fit mechanism. Our results demonstrate how cryo-crystallography and mutagenesis can provide insight into enzyme mechanism. JF - The Journal of biological chemistry AU - Rhee, S AU - Miles, E W AU - Davies, D R AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04/10/ PY - 1998 DA - 1998 Apr 10 SP - 8553 EP - 8555 VL - 273 IS - 15 SN - 0021-9258, 0021-9258 KW - Glycerophosphates KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - indoleglycerol phosphate KW - 4220-97-7 KW - Tryptophan Synthase KW - EC 4.2.1.20 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Point Mutation KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Binding Sites KW - Tryptophan Synthase -- isolation & purification KW - Tryptophan Synthase -- metabolism KW - Tryptophan Synthase -- chemistry KW - Glycerophosphates -- chemistry KW - Glycerophosphates -- metabolism KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79795555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cryo-crystallography+of+a+true+substrate%2C+indole-3-glycerol+phosphate%2C+bound+to+a+mutant+%28alphaD60N%29+tryptophan+synthase+alpha2beta2+complex+reveals+the+correct+orientation+of+active+site+alphaGlu49.&rft.au=Rhee%2C+S%3BMiles%2C+E+W%3BDavies%2C+D+R&rft.aulast=Rhee&rft.aufirst=S&rft.date=1998-04-10&rft.volume=273&rft.issue=15&rft.spage=8553&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 - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1A5A; PDB; 1A5B N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic domain, but not the C2 domain. AN - 79790603; 9538021 AB - The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC) is absolutely dependent on Ca2+. The PH domain truncated catalytic core of rat phospholipase C delta1 (PLC-delta1) has Ca2+ binding sites in its catalytic and C2 domains, and potential Ca2+ binding sites in two EF-hands. A catalytically inactive PLC-delta1 catalytic core bound with low affinity to PIP2-containing vesicles in the presence of Ca2+. A mutant PLC-delta1 has been engineered which lacks the C2 domain Ca2+ binding site and the surrounding loops known as the jaws. Isothermal calorimetric titration showed four Ca2+ ions bind to the wild-type PLC-delta1 catalytic core in solution but only one binds to the C2 domain jaws deletion mutant. The activity and Ca2+ dependence of wild-type and mutant phospholipase Cs were determined using substrate incorporated in detergent micelles and in large unilamellar vesicles. The activities of wild-type and mutant were identical to each other in both assay systems. Wild-type and the C2 jaws deletion mutant of PLC have Hill coefficients of 1.12-1.16 with respect to [Ca2+]. We conclude that a single Ca2+ bound to the catalytic domain is entirely responsible for the Ca2+ dependence of the basal activity of PLC-delta1. JF - Biochemistry AU - Grobler, J A AU - Hurley, J H AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0580, USA. Y1 - 1998/04/07/ PY - 1998 DA - 1998 Apr 07 SP - 5020 EP - 5028 VL - 37 IS - 14 SN - 0006-2960, 0006-2960 KW - Isoenzymes KW - 0 KW - Recombinant Proteins KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C delta KW - EC 3.1.4.11 KW - Plcd1 protein, rat KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Chromatography, Gel KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Calorimetry KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Hydrolysis KW - Mutagenesis KW - Catalysis KW - Isoenzymes -- chemistry KW - Calcium -- metabolism KW - Type C Phospholipases -- chemistry KW - Type C Phospholipases -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Catalysis+by+phospholipase+C+delta1+requires+that+Ca2%2B+bind+to+the+catalytic+domain%2C+but+not+the+C2+domain.&rft.au=Grobler%2C+J+A%3BHurley%2C+J+H&rft.aulast=Grobler&rft.aufirst=J&rft.date=1998-04-07&rft.volume=37&rft.issue=14&rft.spage=5020&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-14 N1 - Date created - 1998-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins for targeted cancer therapy. AN - 1859323924; 10837618 AB - Immunotoxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. Immunotoxins contain a ligand such as a growth factor, monoclonal antibody, or fragment of an antibody which is connected to a protein toxin. After the ligand subunit binds to the surface of the target cell, the molecule internalizes and the toxin kills the cell. Bacterial toxins which have been targeted to cancer cells include Pseudomonas exotoxin and diphtheria toxin, which are well suited to forming recombinant single-chain or double-chain fusion toxins. Plant toxins include ricin, abrin, pokeweed antiviral protein, saporin and gelonin, and have generally been connected to ligands by disulfide-bond chemistry. Immunotoxins have been produced to target hematologic malignancies and solid tumors via a wide variety of growth factor receptors and antigens. Challenges facing the clinical application of immunotoxins are discussed. JF - Advanced drug delivery reviews AU - Pastan AU - Kreitman AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892, USA Y1 - 1998/04/06/ PY - 1998 DA - 1998 Apr 06 SP - 53 EP - 88 VL - 31 IS - 1-2 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859323924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advanced+drug+delivery+reviews&rft.atitle=Immunotoxins+for+targeted+cancer+therapy.&rft.au=Pastan%3BKreitman&rft.aulast=Pastan&rft.aufirst=&rft.date=1998-04-06&rft.volume=31&rft.issue=1-2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Advanced+drug+delivery+reviews&rft.issn=1872-8294&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2000-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of carcinogenicity of cadmium chloride in female Syrian hamsters. AN - 80029671; 9674965 AB - Cadmium is very effective at inducing necrosis within the ovaries of rodents, and the Syrian hamster appears particularly sensitive. The extent of cadmium-induced necrosis depends on the stage of the estrous cycle and is most pronounced when injected on the day prior to ovulation (proestrous). In male rodents cadmium induces a similar necrosis within the testes, which given sufficient time can lead to the development of testicular tumors. In this study we tested the hypothesis that cadmium-induced ovarian necrosis could eventually lead to tumor formation. In sexually mature groups of female Syrian hamsters (> 8 weeks old; n = 50-59), the estrous cycle was determined by visual inspection of vaginal discharge for four consecutive cycles. The animals were then given cadmium (0, 30, 40 and 50 micromol/kg) subcutaneously as a single injection in the dorsal thoracic midline on cycle day 4 (proestrous). Based on prior work, these doses are sufficient to induce extensive acute ovarian damage. Animals were then observed over the next 78 weeks. Although survival and body weight were reduced by cadmium, treatment with the metal did not result in an enhanced incidence of tumors at any site including the ovaries. Non-neoplastic lesions such as amyloidosis and pancreatic hepatocytes were linked to cadmium exposure. These results indicate that the association of cadmium-induced testicular necrosis with tumor development seen in males does not occur in the Syrian hamster ovaries. JF - Toxicology AU - Waalkes, M P AU - Rehm, S AD - Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 173 EP - 178 VL - 126 IS - 3 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Pancreas -- pathology KW - Animals KW - Liver -- pathology KW - Dose-Response Relationship, Drug KW - Amyloidosis -- chemically induced KW - Pancreas -- drug effects KW - Necrosis KW - Estrus KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Injections, Subcutaneous KW - Mesocricetus KW - Female KW - Cricetinae KW - Cadmium Chloride -- administration & dosage KW - Carcinogens -- administration & dosage KW - Ovary -- pathology KW - Ovary -- drug effects KW - Cadmium Chloride -- toxicity KW - Carcinogens -- toxicity KW - Ovarian Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80029671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Lack+of+carcinogenicity+of+cadmium+chloride+in+female+Syrian+hamsters.&rft.au=Waalkes%2C+M+P%3BRehm%2C+S&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1998-04-03&rft.volume=126&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-06 N1 - Date created - 1998-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase. AN - 79785029; 9533880 AB - Based on structural analyses and on the behavior of mutants, we suggest that the polymerase domain of HIV-1 reverse transcriptase (RT) plays a critical role in holding and appropriately positioning the template-primer both at the polymerase active site and at the RNase H active site. For RT to successfully copy the viral RNA genome, RNase H must cleave the RNA with absolute precision. We believe that a combination of the structure of the template-primer and its precise positioning are responsible for the specific cleavages RNase H makes. We have proposed that resistance of HIV-1 RT to nucleoside analogs involves a subtle repositioning of the template-primer. This hypothesis is based on both structural and biochemical analyses. Mutations that confer resistance to nucleoside analogs do not cluster at the polymerase active site; however, they are in positions where they could alter the interaction between RT and the template-primer. If, as we have hypothesized, the polymerase domain is primarily responsible for positioning the template-primer and RNase H cleavage depends on this positioning, it should be possible to use RNase H cleavage to monitor at least some of the major changes in the position of the template-primer. We have used three assays (polymerase, RNase H, and strand transfer) to investigate the effects of mutations in the polymerase domain, including mutations that confer resistance to nucleotide analogs, on HIV-1 RT. All three assays involve RNA sequences derived from the viral genome. The data show that alterations in the polymerase domain, in particular, mutations that are in positions that would be expected to alter the interaction of RT with the template-primer, can alter both the efficiency and specificity of RNase H cleavage. These results are discussed in light of the structure of HIV-1 RT. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Gao, H Q AU - Boyer, P L AU - Arnold, E AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 559 EP - 572 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - RNA KW - 63231-63-0 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Structure-Activity Relationship KW - Protein Conformation KW - Binding Sites KW - HIV Reverse Transcriptase -- genetics KW - RNA -- metabolism KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- enzymology KW - HIV Reverse Transcriptase -- chemistry KW - Ribonuclease H -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79785029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+mutations+in+the+polymerase+domain+on+the+polymerase%2C+RNase+H+and+strand+transfer+activities+of+human+immunodeficiency+virus+type+1+reverse+transcriptase.&rft.au=Gao%2C+H+Q%3BBoyer%2C+P+L%3BArnold%2C+E%3BHughes%2C+S+H&rft.aulast=Gao&rft.aufirst=H&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=559&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The solution structure of a fungal AREA protein-DNA complex: an alternative binding mode for the basic carboxyl tail of GATA factors. AN - 79782532; 9533883 AB - The solution structure of a complex between the DNA binding domain of a fungal GATA factor and a 13 base-pair oligonucleotide containing its physiologically relevant CGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. The AREA DNA binding domain, from Aspergillus nidulans, possesses a single Cys2-Cys2 zinc finger module and a basic C-terminal tail, which recognize the CGATAG element via an extensive network of hydrophobic interactions with the bases in the major groove and numerous non-specific contacts along the sugar-phosphate backbone. The zinc finger core of the AREA DNA binding domain has the same global fold as that of the C-terminal DNA binding domain of chicken GATA-1. In contrast to the complex with the DNA binding domain of GATA-1 in which the basic C-terminal tail wraps around the DNA and lies in the minor groove, the structure of complex with the AREA DNA binding domain reveals that the C-terminal tail of the fungal domain runs parallel with the sugar phosphate backbone along the edge of the minor groove. This difference is principally attributed to amino acid substitutions at two positions of the AREA DNA binding domain (Val55, Asn62) relative to that of GATA-1 (Gly55, Lys62). The impact of the different C-terminal tail binding modes on the affinity and specificity of GATA factors is discussed. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Starich, M R AU - Wikström, M AU - Arst, H N AU - Clore, G M AU - Gronenborn, A M AD - National Institute of Diabetes and Digestive Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 605 EP - 620 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - AreA protein, Aspergillus nidulans KW - 0 KW - DNA-Binding Proteins KW - Erythroid-Specific DNA-Binding Factors KW - Fungal Proteins KW - GATA1 Transcription Factor KW - GATA1 protein, human KW - Solutions KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Nucleic Acid Conformation KW - Protein Conformation KW - Mutagenesis KW - Binding Sites KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Transcription Factors -- chemistry KW - DNA-Binding Proteins -- genetics KW - DNA -- chemistry KW - Aspergillus nidulans -- chemistry KW - Zinc Fingers KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+solution+structure+of+a+fungal+AREA+protein-DNA+complex%3A+an+alternative+binding+mode+for+the+basic+carboxyl+tail+of+GATA+factors.&rft.au=Starich%2C+M+R%3BWikstr%C3%B6m%2C+M%3BArst%2C+H+N%3BClore%2C+G+M%3BGronenborn%2C+A+M&rft.aulast=Starich&rft.aufirst=M&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=605&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity. AN - 79782315; 9533884 AB - The seemingly innocuous leucine-to-valine mutation at position 22 of the AREA DNA binding domain results in dramatic changes in the in vivo expression profile of genes controlled by this GATA transcription factor. This is associated with a preference of the Leu22-->Val mutant for TGATAG sites over (A/C)GATAG sites. Quantitative gel retardation assays confirm this observation and show that the Leu22-->Val mutant AREA DNA binding domain has a approximately 30-fold lower affinity than the wild-type domain for a 13 base-pair oligonucleotide containing the wild-type CGATAG target. To gain insight into the measured affinity data and further explore sequence specificity of the AREA protein, the solution structure of a complex between the Leu22-->Val mutant AREA DNA binding domain and a 13 base-pair oligonucleotide containing its physiologically relevant TGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. Comparison of this structure with that of the wild-type AREA DNA binding domain complexed to its cognate CGATAG target site shows how subtle changes in amino acid side-chain length and hydrophobic packing can affect affinity and specificity for GATA-containing sequences, and how changes in DNA sequence can be compensated for by changes in protein sequence. Copyright 1998 Academic Press Limited. JF - Journal of molecular biology AU - Starich, M R AU - Wikström, M AU - Schumacher, S AU - Arst, H N 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, Bethesda, MD 20892-0520, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 621 EP - 634 VL - 277 IS - 3 SN - 0022-2836, 0022-2836 KW - AreA protein, Aspergillus nidulans KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - Solutions KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Leucine KW - GMW67QNF9C KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Nucleic Acid Conformation KW - Protein Conformation KW - Binding Sites KW - Aspergillus nidulans -- metabolism KW - DNA-Binding Proteins -- chemistry KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Leucine -- genetics KW - DNA-Binding Proteins -- genetics KW - Leucine -- chemistry KW - Valine -- genetics KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - Fungal Proteins -- chemistry KW - Fungal Proteins -- metabolism KW - Aspergillus nidulans -- genetics KW - Leucine -- metabolism KW - Transcription Factors -- chemistry KW - Aspergillus nidulans -- chemistry KW - DNA -- chemistry KW - Zinc Fingers KW - Valine -- metabolism KW - Valine -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79782315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+solution+structure+of+the+Leu22--%26gt%3BVal+mutant+AREA+DNA+binding+domain+complexed+with+a+TGATAG+core+element+defines+a+role+for+hydrophobic+packing+in+the+determination+of+specificity.&rft.au=Starich%2C+M+R%3BWikstr%C3%B6m%2C+M%3BSchumacher%2C+S%3BArst%2C+H+N%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Starich&rft.aufirst=M&rft.date=1998-04-03&rft.volume=277&rft.issue=3&rft.spage=621&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic hydrolysis of organic cyclic carbonates. AN - 79766133; 9525873 AB - Ethylene carbonate, a cyclic organic carbonate widely used industrially, is toxic when metabolically converted to ethylene glycol. A rat liver enzyme active in catalyzing the ring opening has been purified to electrophoretic homogeneity and found to be active in the hydrolysis of ethylene, vinylene, and propylene carbonates to CO2 and the respective glycols. Neither thiocarbonates nor open chain carbonates served as substrate nor did a variety of esters, lactams, lactones, and related heterocycles. The enzyme was active, however, with imides and appears to be identical to rat liver imidase. The identification was confirmed by copurification of enzyme activities, by similarities in the pattern of inhibition, and by the reactivity with a polyclonal antibody directed against the enzyme purified here. JF - The Journal of biological chemistry AU - Yang, Y L AU - Ramaswamy, S G AU - Jakoby, W B AD - Laboratory of Biochemistry and Metabolism, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1812, USA. Y1 - 1998/04/03/ PY - 1998 DA - 1998 Apr 03 SP - 7814 EP - 7817 VL - 273 IS - 14 SN - 0021-9258, 0021-9258 KW - Dioxolanes KW - 0 KW - Amidohydrolases KW - EC 3.5.- KW - dihydropyrimidinase KW - EC 3.5.2.2 KW - ethylene carbonate KW - RGJ96TB7R7 KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Substrate Specificity KW - Hydrolysis KW - Amidohydrolases -- metabolism KW - Dioxolanes -- chemistry KW - Dioxolanes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79766133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enzymatic+hydrolysis+of+organic+cyclic+carbonates.&rft.au=Yang%2C+Y+L%3BRamaswamy%2C+S+G%3BJakoby%2C+W+B&rft.aulast=Yang&rft.aufirst=Y&rft.date=1998-04-03&rft.volume=273&rft.issue=14&rft.spage=7814&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 - 1998-05-07 N1 - Date created - 1998-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin transporter messenger RNA in the developing rat brain: early expression in serotonergic neurons and transient expression in non-serotonergic neurons. AN - 85264721; pmid-9502257 AB - Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general, the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such as cingulate and frontopolar cortex exhibited hybridization peri- and postnatally, respectively. Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA may reflect critical periods important for tight regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue. 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, USA. PY - 1998 SP - 1185 EP - 1201 VL - 83 IS - 4 SN - 0306-4522, 0306-4522 KW - Pituitary Gland KW - Carrier Proteins KW - Membrane Glycoproteins KW - Aging KW - Animal KW - Brain KW - Transcription, Genetic KW - Organ Specificity KW - Membrane Proteins KW - Serotonin KW - RNA Probes KW - Pineal Gland KW - Pregnancy KW - RNA, Messenger KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Tryptophan Hydroxylase KW - Neurons KW - Embryo and Fetal Development KW - Female KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264721?accountid=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+in+the+developing+rat+brain%3A+early+expression+in+serotonergic+neurons+and+transient+expression+in+non-serotonergic+neurons.&rft.au=Hansson%2C+S+R%3BMezey%2C+E%3BHoffman%2C+B+J&rft.aulast=Hansson&rft.aufirst=S&rft.date=1998-04-01&rft.volume=83&rft.issue=4&rft.spage=1185&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 - Respiratory tract carcinogenesis by mineral fibres and dusts: models and mechanisms. AN - 80041271; 9689803 AB - Experimental pathology studies in respiratory carcinogenesis by mineral fibres and dusts are reviewed. Animal models, analogous to the corresponding human pathology, were developed for carcinogenesis by polycyclic aromatic hydrocarbons carried on mineral particles, by N-nitroso compounds, by asbestos fibres and by crystalline silica (quartz). Species and organ susceptibility factors determine marked differences in the carcinogenic response to silica in different species and target organs, suggesting possible pathogenetic mechanisms, such as the role of surface oxygen radicals and the induction of related enzymes. Cellular models have been effectively used to study the induction of toxicity and neoplastic transformation by mineral fibres and dusts. Cell culture models have been developed for respiratory epithelial cells and for their transformation. These include not only models for the laryngotracheobronchial columnar epithelium, but also for the alveolar type II epithelium and its transformation by silica. Recent studies on simian virus (SV)40 carcinogenesis in animal and cellular models and on the detection of SV40-like sequences in the deoxyribonucleic acid of human tumours point to the need for much further research on the role of interactions of viral, chemical and physical factors in human respiratory carcinogenesis. JF - Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 160 EP - 167 VL - 53 IS - 2 SN - 1122-0643, 1122-0643 KW - Mineral Fibers KW - 0 KW - Asbestos KW - 1332-21-4 KW - Quartz KW - 14808-60-7 KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Animals KW - Cells, Cultured KW - Humans KW - Disease Models, Animal KW - Mice KW - Cricetinae KW - Mineral Fibers -- adverse effects KW - Respiratory Tract Neoplasms -- etiology KW - Cell Transformation, Neoplastic -- chemically induced KW - Quartz -- adverse effects KW - Asbestos -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/80041271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Monaldi+archives+for+chest+disease+%3D+Archivio+Monaldi+per+le+malattie+del+torace&rft.atitle=Respiratory+tract+carcinogenesis+by+mineral+fibres+and+dusts%3A+models+and+mechanisms.&rft.au=Saffiotti%2C+U&rft.aulast=Saffiotti&rft.aufirst=U&rft.date=1998-04-01&rft.volume=53&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Monaldi+archives+for+chest+disease+%3D+Archivio+Monaldi+per+le+malattie+del+torace&rft.issn=11220643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-08-26 N1 - Date created - 1998-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of EGF-dependent mitogenesis by prostaglandin E2 in Syrian hamster embryo fibroblasts. AN - 79984048; 9654400 AB - Lipid metabolism can play an important role in the development and progression of human cancers. We have used Syrian hamster embryo (SHE) fibroblasts as a model system to study how lipid metabolites can alter cell proliferation and apoptosis. For example, the linoleic acid metabolite 13(S)-HpODE enhances EGF-dependent growth by inhibiting de-phosphorylation of the EGFR which leads to activation of the MAP kinase pathway. In contrast, the arachidonic acid metabolite, PGE2, inhibits EGF-dependent mitogenesis and the expression of the proto-oncogenes c-myc, c-jun, and jun-B. In this study, we have investigated the mechanism by which PGE2 attenuates these responses by studying the EGF signaling cascade in SHE cells. PGE2 pretreatment caused a concentration-dependent decrease in EGF-dependent phosphorylation of MAP kinase and a corresponding inhibition of EGF-stimulated MAP kinase activity. Pretreatment of the SHE cells with PGE2 had little effect on the magnitude of EGF-dependent receptor auto-phosphorylation and the phosphorylation of GAP suggesting a down-stream target. Treatment of cells with forskolin and EGF causes similar inhibition of MAP kinase phosphorylation as observed with PGE2 and EGF. Since PGE2 elevates cAMP in these cells, it may act by altering cAMP accumulation. Raf-1 activity can be inhibited by a cAMP-dependent process. Raf-1 activity, measured by phosphorylation of Mek-1, was attenuated by the addition of PGE2. To determine if inhibition of Raf-1 activity causes inhibition of the MAP kinase pathway, cells were concomitantly incubated with PGE2 and EGF. Inhibition of MAP kinase phosphorylation was observed. From these data, we propose that in SHE cells PGE2 increases cAMP levels, which in turn causes inhibition of Raf-1 activity. The MAP kinase pathway is thus downregulated which decreases mitogenesis and proto-oncogene expression. This study demonstrates that an arachidonic acid metabolite can modulate phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Hsi, L C AU - Eling, T E AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Eicosanoid Biochemistry Section, Research Triangle Park, NC 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 271 EP - 281 VL - 58 IS - 4 SN - 0952-3278, 0952-3278 KW - GTPase-Activating Proteins KW - 0 KW - Oxytocics KW - Proteins KW - Colforsin KW - 1F7A44V6OU KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Receptor, Epidermal Growth Factor -- metabolism KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Proteins -- metabolism KW - Phosphorylation -- drug effects KW - Colforsin -- pharmacology KW - Embryo, Mammalian -- cytology KW - Proto-Oncogene Proteins c-raf -- drug effects KW - Mesocricetus KW - Embryo, Mammalian -- drug effects KW - Cell Line KW - Cricetinae KW - Oxytocics -- administration & dosage KW - Fibroblasts -- drug effects KW - Dinoprostone -- pharmacology KW - Oxytocics -- pharmacology KW - Mitosis -- drug effects KW - Fibroblasts -- cytology KW - Epidermal Growth Factor -- pharmacology KW - Dinoprostone -- administration & dosage KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79984048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+EGF-dependent+mitogenesis+by+prostaglandin+E2+in+Syrian+hamster+embryo+fibroblasts.&rft.au=Hsi%2C+L+C%3BEling%2C+T+E&rft.aulast=Hsi&rft.aufirst=L&rft.date=1998-04-01&rft.volume=58&rft.issue=4&rft.spage=271&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 - 1998-09-08 N1 - Date created - 1998-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU). AN - 79972359; 9650089 AB - Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation. JF - Journal of autoimmunity AU - Chan, C C AU - Li, Y AU - Sun, B AU - Li, Q AU - Matteson, D M AU - Shen, D F AU - Nussenblatt, R B AU - Zhai, Y AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA. ccc@helix.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 111 EP - 118 VL - 11 IS - 2 SN - 0896-8411, 0896-8411 KW - Cytokines KW - 0 KW - Eye Proteins KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - PMEL protein, human KW - RNA, Messenger KW - Recombinant Proteins KW - gp100 Melanoma Antigen KW - Interleukin-12 KW - 187348-17-0 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Rats, Inbred Lew KW - Choroid -- chemistry KW - Humans KW - T-Lymphocytes, Cytotoxic -- immunology KW - Recombinant Proteins -- genetics KW - Immunization Schedule KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Cytokines -- analysis KW - Rats KW - Cattle KW - Recombinant Proteins -- immunology KW - Gene Expression Regulation KW - Recombinant Proteins -- administration & dosage KW - Female KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Eye Proteins -- toxicity KW - Genetic Vectors -- administration & dosage KW - Defective Viruses -- genetics KW - Neoplasm Proteins -- immunology KW - Autoimmune Diseases -- etiology KW - Uveitis -- immunology KW - Desensitization, Immunologic KW - Uveitis -- etiology KW - Adenoviridae -- genetics KW - Membrane Glycoproteins -- toxicity KW - Eye Proteins -- immunology KW - Interleukin-12 -- biosynthesis KW - Neoplasm Proteins -- toxicity KW - Eye Proteins -- genetics KW - Neoplasm Proteins -- genetics KW - Genetic Vectors -- genetics KW - Eye Proteins -- biosynthesis KW - Interleukin-12 -- genetics KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- genetics KW - Autoimmune Diseases -- immunology KW - Eye Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79972359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+adenovirus+encoding+gp100+modulates+experimental+melanin-protein+induced+uveitis+%28EMIU%29.&rft.au=Chan%2C+C+C%3BLi%2C+Y%3BSun%2C+B%3BLi%2C+Q%3BMatteson%2C+D+M%3BShen%2C+D+F%3BNussenblatt%2C+R+B%3BZhai%2C+Y&rft.aulast=Chan&rft.aufirst=C&rft.date=1998-04-01&rft.volume=11&rft.issue=2&rft.spage=111&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 - 1998-10-22 N1 - Date created - 1998-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus excreted by multiple sclerosis patients and paired controls from Hungary. AN - 79893253; 9599332 AB - JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent, or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR. These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three were Type 1B. In five pairs of MS patients and controls, both were positive for JCV by PCR. Two of these were husband/wife pairs of which one pair was matched for subtype (both Type 1A), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type 1B). These findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest that parent/child pairs can be used to trace JCV transmission within the MS family. JF - Multiple sclerosis (Houndmills, Basingstoke, England) AU - Stoner, G L AU - Agostini, H T AU - Ryschkewitsch, C F AU - Komoly, S AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 45 EP - 48 VL - 4 IS - 2 SN - 1352-4585, 1352-4585 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Genotype KW - Genetic Variation KW - Hungary KW - DNA, Viral -- analysis KW - Humans KW - Adult KW - Middle Aged KW - DNA, Viral -- urine KW - Male KW - Female KW - Multiple Sclerosis -- urine KW - JC Virus -- genetics KW - Multiple Sclerosis -- virology KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79893253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.atitle=JC+virus+excreted+by+multiple+sclerosis+patients+and+paired+controls+from+Hungary.&rft.au=Stoner%2C+G+L%3BAgostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BKomoly%2C+S&rft.aulast=Stoner&rft.aufirst=G&rft.date=1998-04-01&rft.volume=4&rft.issue=2&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Multiple+sclerosis+%28Houndmills%2C+Basingstoke%2C+England%29&rft.issn=13524585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-10 N1 - Date created - 1998-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of lead on cytoskeletal proteins expressed in E14 mesencephalic primary cultures. AN - 79875419; 9596558 AB - Several lines of evidence indicated that Pb exposure in vivo and in vitro altered neurite morphology in central and peripheral neurons. The present report shows that neurite length in mesencephalic primary cultures, consisting of neurons and glia, was decreased by Pb exposure when serum factors, presumably essential for glial functions, were absent in the culture medium. We studied whether a serum factor might control the mechanisms involved in the uptake and accumulation of Pb and its effect on cytoskeleton proteins. The total amount of Pb taken up in cell cultures was measured by atomic absorption spectroscopy and appeared to be down-regulated by a non-albumin-like serum component. In presence of serum, Pb exposure failed to alter cytoskeletal proteins. Instead, in serum-free neurobasal medium, Pb uptake failed to reach saturation within 6 h. Western blot analysis showed that the tau, 280 kDa MAP-2b, 70 kDa MAP-2c and GAP-43 protein bands were decreased 24 h after a 3 h exposure to 3 or 6 microM Pb in absence of serum. However, if cultures were maintained in serum-containing media after a 3 h Pb exposure without serum, the immunoblots did not differ from those of controls. It can be inferred that a serum factor prevents cytoskeletal protein alterations by Pb. In serum free medium, Pb that is primarily scavenged by the metallothionein I/II isoforms present in glial cells, may bind to thiol residues of proteins involved in either oxidative stress response or transcriptional regulation of cytoskeletal proteins. JF - Neurochemistry international AU - Scortegagna, M AU - Chikhale, E AU - Hanbauer, I AD - Laboratory of Molecular Immunology, NHLBI, Bethesda, MD 20892-1674, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 353 EP - 359 VL - 32 IS - 4 SN - 0197-0186, 0197-0186 KW - Cytoskeletal Proteins KW - 0 KW - GAP-43 Protein KW - Microtubule-Associated Proteins KW - Tubulin KW - tau Proteins KW - Lead KW - 2P299V784P KW - Index Medicus KW - Rats KW - GAP-43 Protein -- metabolism KW - Animals KW - tau Proteins -- metabolism KW - Rats, Sprague-Dawley KW - Microtubule-Associated Proteins -- metabolism KW - Blotting, Western KW - Cells, Cultured KW - Tubulin -- metabolism KW - Spectrophotometry, Atomic KW - Female KW - Pregnancy KW - Mesencephalon -- metabolism KW - Mesencephalon -- drug effects KW - Lead -- toxicity KW - Cytoskeletal Proteins -- metabolism KW - Lead -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79875419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Effect+of+lead+on+cytoskeletal+proteins+expressed+in+E14+mesencephalic+primary+cultures.&rft.au=Scortegagna%2C+M%3BChikhale%2C+E%3BHanbauer%2C+I&rft.aulast=Scortegagna&rft.aufirst=M&rft.date=1998-04-01&rft.volume=32&rft.issue=4&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-07-29 N1 - Date created - 1998-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of transgene expression in Tg.AC(v-Ha-ras) transgenic mice concomitant with DNA hypomethylation. AN - 79870064; 9585254 AB - Tg.AC transgenic mice have a transgene composed of a zeta-globin transcriptional control region, a v-Ha-ras coding region, and a simian virus 40 3' polyadenylation signal sequence. Induced ectopic expression of the transgene by chemical treatment or full-skin-thickness wounding leads to the development of skin papillomas. Reverse transcription-polymerase chain reaction assays and protein blotting indicated that the transgene was expressed 16-28 d after full-skin-thickness surgical wounding. Normal unwounded skin did not express the transgene. DNA blotting indicated that the position of the transgene remained stable during wound-induced tumorigenesis. Concomitant with the v-Ha-ras mRNA and protein expression was the hypomethylation of specific MspI/HpaII sites within the transgene. These results are consistent with the hypothesis that hypomethylation is required for the induced and sustained expression of the Tg.AC v-Ha-ras transgene in spontaneous and induced tumors in Tg.AC mice. JF - Molecular carcinogenesis AU - Cannon, R E AU - Spalding, J W AU - Virgil, K M AU - Faircloth, R S AU - Humble, M C AU - Lacks, G D AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 244 EP - 250 VL - 21 IS - 4 SN - 0899-1987, 0899-1987 KW - Globins KW - 9004-22-2 KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Simian virus 40 -- genetics KW - Globins -- genetics KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Wounds and Injuries -- complications KW - Female KW - Skin -- injuries KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- biosynthesis KW - Skin Neoplasms -- etiology KW - Transgenes KW - Wound Healing -- genetics KW - Papilloma -- genetics KW - Genes, ras KW - Skin Neoplasms -- genetics KW - DNA Methylation KW - Papilloma -- etiology KW - Gene Expression Regulation KW - Oncogene Protein p21(ras) -- physiology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79870064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+transgene+expression+in+Tg.AC%28v-Ha-ras%29+transgenic+mice+concomitant+with+DNA+hypomethylation.&rft.au=Cannon%2C+R+E%3BSpalding%2C+J+W%3BVirgil%2C+K+M%3BFaircloth%2C+R+S%3BHumble%2C+M+C%3BLacks%2C+G+D%3BTennant%2C+R+W&rft.aulast=Cannon&rft.aufirst=R&rft.date=1998-04-01&rft.volume=21&rft.issue=4&rft.spage=244&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 - 1998-05-20 N1 - Date created - 1998-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N rats and B6C3F1 mice. AN - 79867475; 9579026 AB - Isobutyraldehyde (a chemical structurally related to formaldehyde and used as a flavoring agent) was studied for toxicity and carcinogenicity by exposing male and female F344/N rats and B6C3F1 mice. Animals were exposed to isobutyraldehyde vapors 6 h per day, 5 days per week for up to 13 weeks or 2 years. In the 13-week studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed to concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm. Chemical-related body weight depression and deaths occurred in rats and mice exposed to 4000 and 8000 ppm. Necrosis of the epithelium accompanied with acute inflammatory reaction was observed in the nasal turbinate, larynx, and trachea of rats exposed to 8000 ppm. Exposure of rats to 4000 ppm resulted in metaplasia of the nasal respiratory epithelium, inflammation, degeneration of the olfactory epithelium, and osteodystrophy of the nasal turbinate bone. In the 13-week mouse study, exposure to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000 ppm. Degeneration of the olfactory epithelium was noted in males exposed 2000 ppm and in females exposed to 4000 ppm. In the 2-year studies, groups of 50 male and 50 male F344/N rats and B6C3F1 were exposed to concentrations isobutyraldehyde vapors of 0, 500, 1000, or 2000 ppm 6 h per day, 5 days per week. There were no differences in survival rates or mean body weights between exposed groups and control rats. Survival of male mice exposed to 2000 ppm and mean body weights of female mice exposed to 1000 or 2000 ppm were lower than those of the of the controls. No increase in neoplasm incidence was observed in rats and mice in the 2-year studies that could be attributed to isobutyraldehyde exposure. Chemical-related nonneoplastic lesions were limited to the nose of rats and mice. They included squamous metaplasia of the respiratory epithelium (rats), suppurative inflammation (rats), and olfactory epithelial degeneration (rats and mice) at 1000 and 2000 ppm. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Abdo, K M AU - Haseman, J K AU - Nyska, A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 136 EP - 151 VL - 42 IS - 2 SN - 1096-6080, 1096-6080 KW - Aldehydes KW - 0 KW - isobutyraldehyde KW - C42E28168L KW - Index Medicus KW - Rats KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Metaplasia KW - Inhalation Exposure KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Mice KW - Male KW - Female KW - Aldehydes -- toxicity KW - Aldehydes -- administration & dosage KW - Respiratory System -- pathology KW - Respiratory System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79867475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isobutyraldehyde+administered+by+inhalation+%28whole+body+exposure%29+for+up+to+thirteen+weeks+or+two+years+was+a+respiratory+tract+toxicant+but+was+not+carcinogenic+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Abdo%2C+K+M%3BHaseman%2C+J+K%3BNyska%2C+A&rft.aulast=Abdo&rft.aufirst=K&rft.date=1998-04-01&rft.volume=42&rft.issue=2&rft.spage=136&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism and disposition of phenolphthalein in male and female F344 rats and B6C3F1 mice. AN - 79866762; 9579019 AB - A recent 2-year carcinogenicity/toxicology study determined that phenolphthalein (PHTH) is a multisite carcinogen in both mice and rats at all doses evaluated. In response to this finding the metabolism and disposition of PHTH has been evaluated in both F344 rats and B6C3F1 mice at a single oral dose of 800 mg/kg. This dose fell within the range previously found to be carcinogenic in rats and mice. Studies were also performed using 1 and 50 mg/kg doses. At 800 mg/kg recovery of [14C]PHTH after 72 h was near 100% in females but closer to 75% in males. Radioactivity was primarily recovered in the feces in rats (> 90%), while mice excreted 30-40% of administered activity in the urine. There was no significant retention of radioactivity in tissues by 72 h and no significant accumulation of radioactivity in any tissue at any time point. Covalent binding to protein in target tissues, bone marrow and ovary, was at or less than the pmol/mg protein range. The major metabolite was PHTH glucuronide. Three minor metabolites were detected. A sulfate conjugate and and a hydroxylated metabolite were identified by comparison of retention times and 1H NMR and/or mass spectra with synthetic standards. A diglucuronide conjugate was tentatively identified. Biliary elimination was extensive in rats (35% of dose within 6 h); the only product detected in bile was phenolphthalein glucuronide. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Griffin, R J AU - Godfrey, V B AU - Burka, L T AD - National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 73 EP - 81 VL - 42 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Phenolphthaleins KW - Phenolphthalein KW - 6QK969R2IF KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Radiometry KW - Injections, Intravenous KW - Mice KW - Bile -- metabolism KW - Tissue Distribution KW - Feces KW - Male KW - Female KW - Carcinogens -- metabolism KW - Carcinogens -- pharmacokinetics KW - Phenolphthaleins -- metabolism KW - Phenolphthaleins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79866762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolism+and+disposition+of+phenolphthalein+in+male+and+female+F344+rats+and+B6C3F1+mice.&rft.au=Griffin%2C+R+J%3BGodfrey%2C+V+B%3BBurka%2C+L+T&rft.aulast=Griffin&rft.aufirst=R&rft.date=1998-04-01&rft.volume=42&rft.issue=2&rft.spage=73&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 - 1998-06-19 N1 - Date created - 1998-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of chlorine substitution on the dermal absorption of polychlorinated biphenyls. AN - 79840598; 9571983 AB - The fate of selected mono-, di-, tetra-, and hexachlorobiphenyls was investigated following single dermal administration (0.4 mg/kg) to determine the effects of chlorine substitution on the dermal absorption and disposition of polychlorinated biphenyls (PCBs). Single dermal doses of 14C-labeled mono-, di-, tetra-, and hexachlorobiphenyls were administered to 1-cm2 areas on the backs of F-344 male rats. Unabsorbed radioactivity was removed from the dose site either at euthanasia or 48 h postdose. Distribution of radioactivity in the dose site and selected tissues was determined by serial sacrifice at time points up to 2 weeks. Dermal penetration varied inversely with degree of chlorination and at 48 h ranged from ca. 100% for monochlorobiphenyl to ca. 30% for the hexachlorobiphenyl. Penetration rate constants correlated well with log kow. PCBs were retained in the epidermis for up to 2 weeks postdose. The data from these studies suggest that systemic absorption of PCBs involves a combination of sequential processes including penetration across the stratum corneum, possibly metabolism in the epidermis and/or dermis, adsorption to proteins, and finally absorption into the systemic circulation. The skin favors the rapid absorption of less chlorinated PCBs, but the relatively rapid metabolism and elimination of these compounds would result in lower body burdens. More highly chlorinated PCBs penetrate less rapidly but remain in the site of exposure and slowly enter the systemic circulation. The dermal absorption of a commercial PCB mixture was modeled, and the results suggest that the net result of the differences in absorbance rates would be a greater body burden of higher chlorinated PCBs relative to those that have a lower chlorine content. JF - Toxicology and applied pharmacology AU - Garner, C E AU - Matthews, H B AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 150 EP - 158 VL - 149 IS - 2 SN - 0041-008X, 0041-008X KW - Carbon Radioisotopes KW - 0 KW - Chlorine KW - 4R7X1O2820 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Administration, Cutaneous KW - Body Burden KW - Epidermis -- metabolism KW - Environmental Exposure KW - Tissue Distribution KW - Chlorine -- chemistry KW - Male KW - Structure-Activity Relationship KW - Skin Absorption KW - Polychlorinated Biphenyls -- chemistry KW - Polychlorinated Biphenyls -- analysis KW - Polychlorinated Biphenyls -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+chlorine+substitution+on+the+dermal+absorption+of+polychlorinated+biphenyls.&rft.au=Garner%2C+C+E%3BMatthews%2C+H+B&rft.aulast=Garner&rft.aufirst=C&rft.date=1998-04-01&rft.volume=149&rft.issue=2&rft.spage=150&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas. AN - 79840435; 9578060 AB - We report the updated results of an intensive treatment protocol for children ( or = 18 years) with advanced B-cell lymphomas. The protocol consists of two chemotherapy regimens: A, consisting of cyclophosphamide, doxorubicin, vincristine and high-dose methotrexate (CODOX-M), and B, consisting of ifosfamide, etoposide, and high-dose cytarabine (IVAC). Both cycles included intrathecal chemotherapy (cytarabine or methotrexate). Patients received a total of four cycles in the following sequence: A, B, A, B. Sixty-six previously untreated patients, enrolled before October 1996, were included in the present analysis. Of these, 55 had Burkitt's or Burkitt's-like lymphoma and 11 had diffuse large B-cell lymphoma. There were 53 males ad 13 females; 40 were children and 26 were adults (age range, 3 to 57 years). To date, 61 patients have achieved a complete response to therapy. Two patients subsequently relapsed, but one of these is a long-term survivor after further therapy and a bone marrow transplant. The event-free survival rate is 85% at I year and beyond. The median potential follow-up period is 48 months (range, 12 to 96 months) for patients remaining in complete remission. Neutropenia occurred in 98% of cycles and infection in 46% of A cycles and 50% of B cycles, but the duration was shortened in B cycles by the administration of granulocyte colony-stimulating factor. Positive blood cultures were observed in 21% of A cycles and 28% of B cycles, and there have been three toxic deaths. These results are better than those achieved with an earlier version of CODOX-M, suggesting that the addition of the IVAC regimen is responsible for the improved results. The similarity of the outcome in children and adults, however, confirms our previous observation that, at least in adults younger than 60 years with Burkitt's or Burkitt's-like lymphomas, treatment with regimens similar to those used in children is warranted. JF - Seminars in oncology AU - Adde, M AU - Shad, A AU - Venzon, D AU - Arndt, C AU - Gootenberg, J AU - Neely, J AU - Nieder, M AU - Owen, W AU - Seibel, N AU - Wilson, W AU - Horak, I D AU - Magrath, I AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 33 EP - 9; discussion 45-8 VL - 25 IS - 2 Suppl 4 SN - 0093-7754, 0093-7754 KW - Cytarabine KW - 04079A1RDZ KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Ifosfamide KW - UM20QQM95Y KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Neoplasm Staging KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Child KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Child, Preschool KW - Survival Rate KW - Etoposide -- administration & dosage KW - Adult KW - Middle Aged KW - Adolescent KW - Methotrexate -- administration & dosage KW - Male KW - Female KW - Ifosfamide -- administration & dosage KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, B-Cell -- pathology KW - Lymphoma, B-Cell -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79840435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Additional+chemotherapy+agents+improve+treatment+outcome+for+children+and+adults+with+advanced+B-cell+lymphomas.&rft.au=Adde%2C+M%3BShad%2C+A%3BVenzon%2C+D%3BArndt%2C+C%3BGootenberg%2C+J%3BNeely%2C+J%3BNieder%2C+M%3BOwen%2C+W%3BSeibel%2C+N%3BWilson%2C+W%3BHorak%2C+I+D%3BMagrath%2C+I&rft.aulast=Adde&rft.aufirst=M&rft.date=1998-04-01&rft.volume=25&rft.issue=2+Suppl+4&rft.spage=33&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opposing effects of alpha 1-adrenergic receptor subtypes on Ca2+ and pH homeostasis in rat cardiac myocytes. AN - 79835416; 9575918 AB - We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that 1) nonselective alpha 1-AR stimulation increased twitch and [Ca2+]i transient amplitudes, myofilament response to Ca2+, and pHi; 2) alpha 1-AR plus CEC increased twitch and [Ca2+]i transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha 1-AR plus WB-4101 decreased twitch and [Ca2+]i transient amplitudes and also pHi; and 4) cytosolic acidification due to alpha 1-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of alpha 1-adrenergic stimulation on contraction, [Ca2+]i, and pHi are due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways. JF - The American journal of physiology AU - Gambassi, G AU - Spurgeon, H A AU - Ziman, B D AU - Lakatta, E G AU - Capogrossi, M C AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - H1152 EP - H1162 VL - 274 IS - 4 Pt 2 SN - 0002-9513, 0002-9513 KW - Adrenergic alpha-Agonists KW - 0 KW - Adrenergic alpha-Antagonists KW - Dioxanes KW - Drug Combinations KW - Fluorescent Dyes KW - Indoles KW - Receptors, Adrenergic, alpha-1 KW - Phenylephrine KW - 1WS297W6MV KW - chlorethylclonidine KW - 3X825O680H KW - (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane KW - 613-67-2 KW - Hydrogen KW - 7YNJ3PO35Z KW - Clonidine KW - MN3L5RMN02 KW - indo-1 KW - N18RMK75W1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Adrenergic alpha-Agonists -- pharmacology KW - Clonidine -- analogs & derivatives KW - Hydrogen-Ion Concentration KW - Myocardial Contraction -- drug effects KW - Rats KW - Rats, Wistar KW - Clonidine -- pharmacology KW - Dioxanes -- pharmacology KW - Drug Synergism KW - Male KW - Phenylephrine -- pharmacology KW - Adrenergic alpha-Antagonists -- pharmacology KW - Calcium -- metabolism KW - Myocardium -- cytology KW - Hydrogen -- metabolism KW - Homeostasis -- physiology KW - Myocardium -- metabolism KW - Receptors, Adrenergic, alpha-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79835416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Opposing+effects+of+alpha+1-adrenergic+receptor+subtypes+on+Ca2%2B+and+pH+homeostasis+in+rat+cardiac+myocytes.&rft.au=Gambassi%2C+G%3BSpurgeon%2C+H+A%3BZiman%2C+B+D%3BLakatta%2C+E+G%3BCapogrossi%2C+M+C&rft.aulast=Gambassi&rft.aufirst=G&rft.date=1998-04-01&rft.volume=274&rft.issue=4+Pt+2&rft.spage=H1152&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 - 1998-06-02 N1 - Date created - 1998-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An analytic model of pinhole aperture penetration for 3D pinhole SPECT image reconstruction. AN - 79828832; 9572502 AB - Photons penetrate the attenuating material close to the aperture of pinhole collimators in nuclear medicine, broadening the tails of point spread functions (PSFs) and degrading the resolution of planar and SPECT images. An analytic approximation has been developed that models this penetration contribution to the PSF for knife-edge point pinhole apertures. The approximation has the form exp(-gamma r), where r is the distance on the detector surface from the projection of the point source through the pinhole. The rolloff coefficient gamma is a function of the photon energy, point source location and the design parameters of the collimator. There was excellent agreement between measured values of gamma from photon transport simulations of I-131 point sources (364 keV emission only) and theoretical predictions from the analytic formula. Predicted gamma values from the analytic formula averaged 25% greater than measured values from experimental I-131 point source acquisitions. Photon transport simulations were performed that modelled the 364 keV and less abundant 637 and 723 keV emissions and scatter within the scintillation crystal. Measured gamma values from these simulations averaged 12% greater than the experimental values, indicating that about half of the error between the analytic formula and the experimental measurements was due to unmodelled 637 and 723 keV emissions. The remaining error may be due in part to scatter in the pinhole region and backscatter from gamma camera components behind the scintillation crystal. The analytic penetration model was used in designing Metz filters to compensate for penetration blur and these filters were applied to the projection data as part of 3D SPECT image reconstruction. Image resolution and contrast were improved in simulated and experimental I-131 tumour phantom studies. This analytic model of pinhole aperture penetration can be readily incorporated into iterative 3D SPECT pinhole reconstruction algorithms. JF - Physics in medicine and biology AU - Smith, M F AU - Jaszczak, R J AD - Department of Radiology, Duke University Medical Center, Durham, NC, USA. smith@nmdhst.cc.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 761 EP - 775 VL - 43 IS - 4 SN - 0031-9155, 0031-9155 KW - Index Medicus KW - Radiation Protection KW - Photons KW - Humans KW - Phantoms, Imaging KW - Image Processing, Computer-Assisted -- instrumentation KW - Tomography, Emission-Computed, Single-Photon KW - Neoplasms -- diagnostic imaging KW - Models, Theoretical KW - Image Processing, Computer-Assisted -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79828832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physics+in+medicine+and+biology&rft.atitle=An+analytic+model+of+pinhole+aperture+penetration+for+3D+pinhole+SPECT+image+reconstruction.&rft.au=Smith%2C+M+F%3BJaszczak%2C+R+J&rft.aulast=Smith&rft.aufirst=M&rft.date=1998-04-01&rft.volume=43&rft.issue=4&rft.spage=761&rft.isbn=&rft.btitle=&rft.title=Physics+in+medicine+and+biology&rft.issn=00319155&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-06-16 N1 - Date created - 1998-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - JC virus Type 1 has multiple subtypes: three new complete genomes. AN - 79825122; 9568975 AB - The complete genomes of three new Type 1 strains of JC virus (JCV) from urine have been analysed. These were subtype 1A, subtype 1B and Type 4 as assigned from a short typing fragment in the VP1 gene. They differ from Mad1 (subtype 1A) by less than 1.0% of the DNA sequence. Based on its complete genome, the JCV Type 4 strain falls into a Type 1 subgroup. Type 4, with several Type 3-like sites in the short typing fragment, is a possible recombinant strain. The consensus of Type 1 DNA sequences is distinguished within the coding region from both Type 2 (strain GS/B) and five Type 3 (African and African American) strains at 64 sites. Most mutations are silent, but at 21 positions amino acid changes occur. Our findings define the subtypes of JCV Type 1 and support the validity of genotyping within the short VP1 fragment. JF - The Journal of general virology AU - Agostini, H T AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 801 EP - 805 VL - 79 ( Pt 4) SN - 0022-1317, 0022-1317 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Phylogeny KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Virus Infections -- virology KW - Humans KW - Urine -- virology KW - Papillomavirus Infections -- virology KW - Molecular Sequence Data KW - Middle Aged KW - Consensus Sequence KW - DNA, Viral -- genetics KW - Male KW - JC Virus -- genetics KW - JC Virus -- classification KW - Genome, Viral KW - JC Virus -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79825122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+general+virology&rft.atitle=JC+virus+Type+1+has+multiple+subtypes%3A+three+new+complete+genomes.&rft.au=Agostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Agostini&rft.aufirst=H&rft.date=1998-04-01&rft.volume=79+%28+Pt+4%29&rft.issue=&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF015528; GENBANK; AF015527; AF015526 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluoroquinolone antimicrobials: singlet oxygen, superoxide and phototoxicity. AN - 79813911; 9559584 AB - The fluoroquinolone antibacterial agents possess photosensitizing properties that lead to phototoxic responses in both human and animal subjects. The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (phi delta) by detection of the singlet oxygen (1O2) luminescence at 1270 nm for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low phi delta values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5. We also determined the 1O2 quenching constants for these compounds and their values were on the order of 10(6) M-1 s-1, except for lomefloxacin whose rate constant was 1.8 x 10(7) M-1 s-1. The phi delta values were significantly decreased in a solvent of lower polarity such as methanol (0.007 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F8 atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties. JF - Photochemistry and photobiology AU - Martínez, L J AU - Sik, R H AU - Chignell, C F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 399 EP - 403 VL - 67 IS - 4 SN - 0031-8655, 0031-8655 KW - Anti-Infective Agents KW - 0 KW - Fluoroquinolones KW - Free Radicals KW - Photosensitizing Agents KW - Quinolones KW - Superoxides KW - 11062-77-4 KW - Singlet Oxygen KW - 17778-80-2 KW - Hydroxyl Radical KW - 3352-57-6 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Humans KW - Salmonella typhimurium -- drug effects KW - Mice KW - Structure-Activity Relationship KW - Quinolones -- toxicity KW - Photosensitizing Agents -- toxicity KW - Photosensitizing Agents -- chemistry KW - Anti-Infective Agents -- toxicity KW - Quinolones -- chemistry KW - Anti-Infective Agents -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79813911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fluoroquinolone+antimicrobials%3A+singlet+oxygen%2C+superoxide+and+phototoxicity.&rft.au=Mart%C3%ADnez%2C+L+J%3BSik%2C+R+H%3BChignell%2C+C+F&rft.aulast=Mart%C3%ADnez&rft.aufirst=L&rft.date=1998-04-01&rft.volume=67&rft.issue=4&rft.spage=399&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene. AN - 79813910; 9547348 AB - By extending previous studies of the phenobarbital (PB)-responsive 132-base pair (bp) enhancer sequence in the CYP2B10 gene, we have delimited a 51-bp enhancer element that is fully inducible by PB in mouse primary hepatocytes. Sixteen structurally unrelated phenobarbital-type inducers activated the 51-bp enhancer element in transient transfection assays. The results thus indicate that most PB-type inducers, if not all inducers, increase the transcription of the CYP2B10 gene by activating this 51-bp element, now designated PB-responsive enhancer module or PBREM. JF - Molecular pharmacology AU - Honkakoski, P AU - Moore, R AU - Washburn, K A AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 597 EP - 601 VL - 53 IS - 4 SN - 0026-895X, 0026-895X KW - Pesticides KW - 0 KW - Pyridines KW - Solvents KW - Xenobiotics KW - Camphor KW - 76-22-2 KW - 1,4-bis(2-(3,5-dichloropyridyloxy))benzene KW - 76150-91-9 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K 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 - Base Composition KW - Polychlorinated Biphenyls -- pharmacology KW - Liver -- metabolism KW - Mice KW - Pesticides -- pharmacology KW - Enzyme Activation -- genetics KW - Camphor -- pharmacology KW - Liver -- drug effects KW - Enzyme Activation -- drug effects KW - Mice, Inbred C57BL KW - Solvents -- pharmacology KW - Pyridines -- pharmacology KW - Male KW - Phenobarbital -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Xenobiotics -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Enhancer Elements, Genetic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79813910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+by+diverse+xenochemicals+of+the+51-base+pair+phenobarbital-responsive+enhancer+module+in+the+CYP2B10+gene.&rft.au=Honkakoski%2C+P%3BMoore%2C+R%3BWashburn%2C+K+A%3BNegishi%2C+M&rft.aulast=Honkakoski&rft.aufirst=P&rft.date=1998-04-01&rft.volume=53&rft.issue=4&rft.spage=597&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 - 1998-05-06 N1 - Date created - 1998-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Bacillus subtilis DinR binding site: redefinition of the consensus sequence. AN - 79810358; 9555905 AB - Recently, the DinR protein was established as the cellular repressor of the SOS response in the bacterium Bacillus subtilis. It is believed that DinR functions as the repressor by binding to a consensus sequence located in the promoter region of each SOS gene. The binding site for DinR is believed to be synonymous with the formerly identified Cheo box, a region of 12 bp displaying dyad symmetry (GAAC-N4-GTTC). Electrophoretic mobility shift assays revealed that highly purified DinR does bind to such sites located upstream of the dinA, dinB, dinC, and dinR genes. Furthermore, detailed mutational analysis of the B. subtilis recA operator indicates that some nucleotides are more important than others for maintaining efficient DinR binding. For example, nucleotide substitutions immediately 5' and 3' of the Cheo box as well as those in the N4 region appear to affect DinR binding. This data, combined with computational analyses of potential binding sites in other gram-positive organisms, yields a new consensus (DinR box) of 5'-CGAACRNRYGTTYC-3'. DNA footprint analysis of the B. subtilis dinR and recA DinR boxes revealed that the DinR box is centrally located within a DNA region of 31 bp that is protected from hydroxyl radical cleavage in the presence of DinR. Furthermore, while DinR is predominantly monomeric in solution, it apparently binds to the DinR box in a dimeric state. JF - Journal of bacteriology AU - Winterling, K W AU - Chafin, D AU - Hayes, J J AU - Sun, J AU - Levine, A S AU - Yasbin, R E 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 - 1998/04// PY - 1998 DA - April 1998 SP - 2201 EP - 2211 VL - 180 IS - 8 SN - 0021-9193, 0021-9193 KW - Bacterial Proteins KW - 0 KW - Repressor Proteins KW - dinR protein, Bacillus subtilis KW - 144591-95-7 KW - Hydroxyl Radical KW - 3352-57-6 KW - Rec A Recombinases KW - EC 2.7.7.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Rec A Recombinases -- genetics KW - Sequence Homology, Nucleic Acid KW - Models, Molecular KW - Transcription, Genetic KW - Amino Acid Sequence KW - Nucleic Acid Conformation KW - Binding Sites KW - Base Sequence KW - SOS Response (Genetics) -- genetics KW - Sequence Alignment KW - DNA Footprinting KW - Molecular Sequence Data KW - Hydroxyl Radical -- analysis KW - Consensus Sequence KW - beta-Galactosidase -- biosynthesis KW - Bacillus subtilis -- genetics KW - Promoter Regions, Genetic KW - Bacterial Proteins -- metabolism KW - Bacillus subtilis -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79810358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Bacillus+subtilis+DinR+binding+site%3A+redefinition+of+the+consensus+sequence.&rft.au=Winterling%2C+K+W%3BChafin%2C+D%3BHayes%2C+J+J%3BSun%2C+J%3BLevine%2C+A+S%3BYasbin%2C+R+E%3BWoodgate%2C+R&rft.aulast=Winterling&rft.aufirst=K&rft.date=1998-04-01&rft.volume=180&rft.issue=8&rft.spage=2201&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 - 1998-05-18 N1 - Date created - 1998-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1997 Nov;26(4):643-53 [9427395] Mol Microbiol. 1997 Apr;24(1):141-53 [9140972] Proc Natl Acad Sci U S A. 1984 Mar;81(5):1375-9 [6231641] J Bacteriol. 1985 Jul;163(1):376-84 [3891738] Biochemistry. 1985 May 21;24(11):2812-8 [3896306] Nature. 1987 Apr 30-May 6;326(6116):886-8 [3553960] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4633-7 [3387430] FEBS Lett. 1988 Jul 4;234(1):56-60 [2968919] Biochemistry. 1989 Nov 28;28(24):9521-7 [2611245] J Bacteriol. 1991 Mar;173(5):1696-703 [1847907] Biochimie. 1991 Apr;73(4):449-56 [1911945] J Bacteriol. 1991 Nov;173(22):7084-91 [1657879] Methods Enzymol. 1991;208:103-17 [1779832] Science. 1992 Jan 10;255(5041):203-6 [1553548] J Bacteriol. 1992 May;174(10):3171-6 [1577687] Mol Microbiol. 1992 May;6(10):1263-70 [1640829] Biochimie. 1992 Jul-Aug;74(7-8):755-62 [1391055] Nucleic Acids Res. 1993 Jul 11;21(14):3335-6 [8341617] J Mol Biol. 1994 Aug 26;241(4):507-23 [8057377] Proteins. 1995 Mar;21(3):226-36 [7784426] Mol Microbiol. 1996 Oct;22(1):75-85 [8899710] J Biol Chem. 1996 Dec 27;271(52):33502-8 [8969214] J Bacteriol. 1997 Mar;179(5):1698-703 [9045831] Microbiology. 1997 Mar;143 ( Pt 3):929-36 [9084177] Radiat Res. 1966;:Suppl 6:156+ [5334390] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver. AN - 79805241; 9552055 AB - To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver. Thirty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior vena cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the axillary vein using an external venoveno bypass circuit. Complete vascular isolation of the liver was confirmed by an I-131-labelled human serum albumin monitoring technique. There was no operative mortality. Seventy-five percent of patients had reversible grade III or IV (National Cancer Institute Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the overall response rate was 75% (complete response, one patient [3%]; partial response, 26 patients [72%]). With a median potential follow-up of 15 months, the mean duration of response was 9 months (range, 2 to 30 months). IHP with TNF and melphalan results in significant regression of bulky hepatic cancers confined to the liver in the majority of patients. Based on these initial results, further refinement of this treatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of unresectable cancers confined to liver. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Alexander, H R AU - Bartlett, D L AU - Libutti, S K AU - Fraker, D L AU - Moser, T AU - Rosenberg, S A AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. hra@pop.nci.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 1479 EP - 1489 VL - 16 IS - 4 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Transaminases KW - EC 2.6.1.- KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Transaminases -- metabolism KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Male KW - Female KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Liver Neoplasms -- therapy KW - Melphalan -- administration & dosage KW - Liver Neoplasms -- enzymology KW - Melphalan -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79805241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolated+hepatic+perfusion+with+tumor+necrosis+factor+and+melphalan+for+unresectable+cancers+confined+to+the+liver.&rft.au=Alexander%2C+H+R%3BBartlett%2C+D+L%3BLibutti%2C+S+K%3BFraker%2C+D+L%3BMoser%2C+T%3BRosenberg%2C+S+A&rft.aulast=Alexander&rft.aufirst=H&rft.date=1998-04-01&rft.volume=16&rft.issue=4&rft.spage=1479&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in locomotor activity during chronic cocaine administration: effect on dopamine receptors and interaction with opioids. AN - 79794215; 9536022 AB - Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist. JF - The Journal of pharmacology and experimental therapeutics AU - Kunko, P M AU - French, D AU - Izenwasser, S AD - Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 277 EP - 284 VL - 285 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics, Opioid KW - 0 KW - Dopamine Uptake Inhibitors KW - Receptors, Dopamine KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dopamine -- pharmacology KW - Enzyme Activation KW - Dose-Response Relationship, Drug KW - Nucleus Accumbens -- enzymology KW - Adenylyl Cyclases -- metabolism KW - Male KW - Receptors, Dopamine -- drug effects KW - Dopamine Uptake Inhibitors -- blood KW - Analgesics, Opioid -- pharmacology KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Cocaine -- blood KW - Receptors, Dopamine -- metabolism KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79794215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+locomotor+activity+during+chronic+cocaine+administration%3A+effect+on+dopamine+receptors+and+interaction+with+opioids.&rft.au=Kunko%2C+P+M%3BFrench%2C+D%3BIzenwasser%2C+S&rft.aulast=Kunko&rft.aufirst=P&rft.date=1998-04-01&rft.volume=285&rft.issue=1&rft.spage=277&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin-induced secretion is dependent on activation of a cholera toxin-sensitive and phosphatidylinositol-3-kinase-regulated phospholipase D in a mast cell line. AN - 79790343; 9536000 AB - Release of secretory granules by rat RBL-2H3 mast cells is mediated primarily through activation of protein kinase C (PKC) and elevation of cytosolic free calcium ([Ca++]I). Here, we show that secretion was also dependent on the activation of a cholera toxin-sensitive phospholipase (PL) D in cells stimulated with thapsigargin. Wortmannin, LY294002, butanol, propranolol and Ro31-7549 inhibited responses to variety of secretagogues in a manner consistent with the notion that secretion was regulated by both PLD and PKC in a phosphatidylinositol-3-kinase-dependent manner. The effects of these inhibitors, however, were especially pronounced in cells activated by thapsigargin. This stimulant induced minimal stimulation of PLC but measurable activation of PLD, as assessed by formation of phosphatidylethanol in the presence of ethanol. The activation of PLD was suppressed by inhibitors of phosphatidylinositol-3-kinase and was dependent on a rise in [Ca++]i because thapsigargin failed to activate PLD and secretion when elevation of [Ca++]i was blocked. Treatment of cells with cholera toxin resulted in selective and similar enhancements in the activation of PLD and secretion by thapsigargin, whereas stimulation of PLC and PLA2 was unaffected. A role for PKC was indicated by the blockade of secretory response to thapsigargin by the PKC inhibitor Ro31-7549 and by the ability of the PKC agonist phorbol-12-myristate-13-acetate to reverse the inhibition of secretion by inhibitors of PLD. Such results suggested that thapsigargin, by causing substantial increases in [Ca++]I, induced secondary signals via PLD and PKC that synergized a calcium signal for secretion. JF - The Journal of pharmacology and experimental therapeutics AU - Cissel, D S AU - Fraundorfer, P F AU - Beaven, M A AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1760, USA. cisseld@gwgate.nhlbi.nih.gov Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 110 EP - 118 VL - 285 IS - 1 SN - 0022-3565, 0022-3565 KW - Adrenergic beta-Antagonists KW - 0 KW - Androstadienes KW - Butanols KW - Chromones KW - Enzyme Inhibitors KW - Morpholines KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Thapsigargin KW - 67526-95-8 KW - Cholera Toxin KW - 9012-63-9 KW - Propranolol KW - 9Y8NXQ24VQ KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phospholipase D KW - EC 3.1.4.4 KW - Calcium KW - SY7Q814VUP KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Propranolol -- pharmacology KW - Morpholines -- pharmacology KW - Androstadienes -- pharmacology KW - Cholera Toxin -- pharmacology KW - Cells, Cultured -- drug effects KW - Rats KW - Calcium -- metabolism KW - Chromones -- pharmacology KW - Butanols -- pharmacology KW - Adrenergic beta-Antagonists -- pharmacology KW - Female KW - Male KW - Thapsigargin -- pharmacology KW - Phospholipase D -- metabolism KW - Phospholipase D -- drug effects KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Mast Cells -- enzymology KW - Enzyme Inhibitors -- pharmacology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Mast Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79790343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thapsigargin-induced+secretion+is+dependent+on+activation+of+a+cholera+toxin-sensitive+and+phosphatidylinositol-3-kinase-regulated+phospholipase+D+in+a+mast+cell+line.&rft.au=Cissel%2C+D+S%3BFraundorfer%2C+P+F%3BBeaven%2C+M+A&rft.aulast=Cissel&rft.aufirst=D&rft.date=1998-04-01&rft.volume=285&rft.issue=1&rft.spage=110&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 - 1998-05-12 N1 - Date created - 1998-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health hazards of radiation exposure in the context of brain imaging research: special consideration for children. AN - 79786973; 9544683 AB - This review provides information on health and biological effects of low-dose radiation to help institutional review boards and investigators make educated assessments of the risks of low-level radiation exposure involved in research, particularly in children. Studies of low-level radiation exposure with large sample sizes and long follow-up were reviewed. To help interpret the studies, we clarified the measures and measurement strategies of radiation exposure and of health risks. The few large studies of risks of low-level radiation in children have failed to detect an increased incidence of cancer. Most studies of low-level radiation involve adults. The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy. Compared to the frequency of daily spontaneous genetic mutations, the biological effect of low-level radiation at the cellular level seems extremely low. Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation. Studies approved by institutional review boards in the U.S. that involve the exposure of healthy normal children to ionizing radiation were reviewed. Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life. In addition, no data were found that demonstrated higher risks with younger age at low-level radiation exposure. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Ernst, M AU - Freed, M E AU - Zametkin, A J AD - Brain Imaging Center, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 689 EP - 698 VL - 39 IS - 4 SN - 0161-5505, 0161-5505 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Radiation Dosage KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Radiotherapy KW - Child KW - Radon -- adverse effects KW - Radionuclide Imaging KW - Brain -- radiation effects KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79786973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Health+hazards+of+radiation+exposure+in+the+context+of+brain+imaging+research%3A+special+consideration+for+children.&rft.au=Ernst%2C+M%3BFreed%2C+M+E%3BZametkin%2C+A+J&rft.aulast=Ernst&rft.aufirst=M&rft.date=1998-04-01&rft.volume=39&rft.issue=4&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-05-01 N1 - Date created - 1998-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2. AN - 79762551; 9528799 AB - The human double-stranded RNA-dependent protein kinase (PKR) is an important component of the interferon response to virus infection. The activation of PKR is accompanied by autophosphorylation at multiple sites, including one in the N-terminal regulatory region (Thr-258) that is required for full kinase activity. Several protein kinases are activated by phosphorylation in the region between kinase subdomains VII and VIII, referred to as the activation loop. We show that Thr-446 and Thr-451 in the PKR activation loop are required in vivo and in vitro for high-level kinase activity. Mutation of either residue to Ala impaired translational control by PKR in yeast cells and COS1 cells and led to tumor formation in mice. These mutations also impaired autophosphorylation and eukaryotic initiation factor 2 subunit alpha (eIF2alpha) phosphorylation by PKR in vitro. Whereas the Ala-446 substitution substantially reduced PKR function, the mutant kinase containing Ala-451 was completely inactive. PKR specifically phosphorylated Thr-446 and Thr-451 in synthetic peptides in vitro, and mass spectrometry analysis of PKR phosphopeptides confirmed that Thr-446 is an autophosphorylation site in vivo. Substitution of Glu-490 in subdomain X of PKR partially restored kinase activity when combined with the Ala-451 mutation. This finding suggests that the interaction between subdomain X and the activation loop, described previously for MAP kinase, is a regulatory feature conserved in PKR. We found that the yeast eIF2alpha kinase GCN2 autophosphorylates at Thr-882 and Thr-887, located in the activation loop at exactly the same positions as Thr-446 and Thr-451 in PKR. Thr-887 was more critically required than was Thr-882 for GCN2 kinase activity, paralleling the relative importance of Thr-446 and Thr-451 in PKR. These results indicate striking similarities between GCN2 and PKR in the importance of autophosphorylation and the conserved Thr residues in the activation loop. JF - Molecular and cellular biology AU - Romano, P R AU - Garcia-Barrio, M T AU - Zhang, X AU - Wang, Q AU - Taylor, D R AU - Zhang, F AU - Herring, C AU - Mathews, M B AU - Qin, J AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 2282 EP - 2297 VL - 18 IS - 4 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Peptide Initiation Factors KW - Peptides KW - Saccharomyces cerevisiae Proteins KW - Threonine KW - 2ZD004190S KW - Protein Kinases KW - EC 2.7.- KW - eIF-2 Kinase KW - EC 2.7.11.1 KW - Index Medicus KW - Peptides -- chemical synthesis KW - Protein Biosynthesis KW - 3T3 Cells KW - Animals KW - Mass Spectrometry KW - Threonine -- metabolism KW - COS Cells KW - Neoplasms, Experimental -- etiology KW - Enzyme Activation KW - Humans KW - Peptides -- metabolism KW - Mice, Nude KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Gene Expression Regulation, Enzymologic KW - Phosphorylation KW - Conserved Sequence KW - Molecular Sequence Data KW - Substrate Specificity KW - Amino Acid Substitution KW - Saccharomyces cerevisiae -- genetics KW - Protein Kinases -- metabolism KW - Peptide Initiation Factors -- metabolism KW - Peptide Initiation Factors -- genetics KW - Fungal Proteins -- metabolism KW - eIF-2 Kinase -- metabolism KW - Protein Kinases -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Fungal Proteins -- genetics KW - eIF-2 Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79762551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Autophosphorylation+in+the+activation+loop+is+required+for+full+kinase+activity+in+vivo+of+human+and+yeast+eukaryotic+initiation+factor+2alpha+kinases+PKR+and+GCN2.&rft.au=Romano%2C+P+R%3BGarcia-Barrio%2C+M+T%3BZhang%2C+X%3BWang%2C+Q%3BTaylor%2C+D+R%3BZhang%2C+F%3BHerring%2C+C%3BMathews%2C+M+B%3BQin%2C+J%3BHinnebusch%2C+A+G&rft.aulast=Romano&rft.aufirst=P&rft.date=1998-04-01&rft.volume=18&rft.issue=4&rft.spage=2282&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 - 1998-05-21 N1 - Date created - 1998-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1979 Jul 25;254(14):6211-4 [221492] Anal Chem. 1997 Oct 1;69(19):3995-4001 [9322436] J Biol Chem. 1987 Nov 15;262(32):15538-44 [3479429] Eur J Biochem. 1989 Jan 2;178(3):581-9 [2912723] Yeast. 1985 Dec;1(2):83-138 [3916863] Mol Cell Biol. 1989 Apr;9(4):1576-86 [2725516] Nucleic Acids Res. 1989 Jun 26;17(12):4895 [2748349] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Methods Enzymol. 1991;194:477-90 [2005804] Science. 1991 Jul 26;253(5018):407-14 [1862342] Methods Enzymol. 1991;201:110-49 [1943760] Methods Enzymol. 1991;201:21-7 [1719341] Cell. 1992 Feb 7;68(3):585-96 [1739968] EMBO J. 1992 Apr;11(4):1553-62 [1348691] J Biol Chem. 1992 May 25;267(15):10729-36 [1375230] Science. 1992 Sep 18;257(5077):1685-9 [1382315] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10837-41 [1279695] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):232-6 [7678339] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1978 Oct 25;253(20):7145-8 [212418] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4621-5 [8099444] Nature. 1993 Jun 17;363(6430):595-602 [8510751] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Genes Dev. 1992 Dec;6(12B):2478-90 [1364113] Nature. 1994 Feb 24;367(6465):704-11 [8107865] Gene. 1994 May 27;143(1):21-7 [8200534] Protein Sci. 1994 Feb;3(2):176-87 [8003955] Mol Biol Cell. 1994 Mar;5(3):297-312 [8049522] Mol Cell Biol. 1995 Jan;15(1):365-78 [7799945] Biochemistry. 1995 Feb 28;34(8):2447-54 [7873523] J Biol Chem. 1995 Jun 23;270(25):14843-6 [7797459] J Virol. 1995 Aug;69(8):5195-8 [7541849] Mol Cell Biol. 1995 Aug;15(8):4497-506 [7623840] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8283-7 [7545299] Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9445-9 [7568151] J Biol Chem. 1996 Jan 19;271(3):1756-63 [8576179] Cell. 1996 Apr 19;85(2):149-58 [8612268] J Biol Chem. 1996 Oct 4;271(40):24989-94 [8798780] J Biol Chem. 1996 Oct 11;271(41):25657-63 [8810342] Mol Cell Biol. 1996 Nov;16(11):6295-302 [8887659] J Biol Chem. 1997 Jan 10;272(2):1291-6 [8995434] Mol Cell Biol. 1997 Mar;17(3):1298-313 [9032257] J Biol Chem. 1997 May 9;272(19):12544-50 [9139706] J Biol Chem. 1997 May 30;272(22):14434-41 [9162083] Cell. 1997 Sep 5;90(5):859-69 [9298898] J Biol Chem. 1985 Jul 15;260(14):8237-9 [2409082] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cleavage of the feline calicivirus capsid precursor is mediated by a virus-encoded proteinase. AN - 79757158; 9525628 AB - Feline calicivirus (FCV), a member of the Caliciviridae, produces its major structural protein as a precursor polyprotein from a subgenomic-sized mRNA. In this study, we show that the proteinase responsible for processing this precursor into the mature capsid protein is encoded by the viral genome at the 3'-terminal portion of open reading frame 1 (ORF1). Protein expression studies of either the entire or partial ORF1 indicate that the proteinase is active when expressed either in in vitro translation or in bacterial cells. Site-directed mutagenesis was used to characterize the proteinase Glu-Ala cleavage site in the capsid precursor, utilizing an in vitro cleavage assay in which mutant precursor proteins translated from cDNA clones were used as substrates for trans cleavage by the proteinase. In general, amino acid substitutions in the P1 position (Glu) of the cleavage site were less well tolerated by the proteinase than those in the P1' position (Ala). The precursor cleavage site mutations were introduced into an infectious cDNA clone of the FCV genome, and transfection of RNA derived from these clones into feline kidney cells showed that efficient cleavage of the capsid precursor by the virus-encoded proteinase is a critical determinant in the growth of the virus. JF - Journal of virology AU - Sosnovtsev, S V AU - Sosnovtseva, S A AU - Green, K Y AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 3051 EP - 3059 VL - 72 IS - 4 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Protein Precursors KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Animals KW - Base Sequence KW - Protein Precursors -- metabolism KW - Cats KW - Molecular Sequence Data KW - Gene Expression KW - Transcription, Genetic KW - Chromosome Mapping KW - Cell Line KW - Endopeptidases -- genetics KW - Calicivirus, Feline -- enzymology KW - Calicivirus, Feline -- genetics KW - Endopeptidases -- metabolism KW - Capsid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79757158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cleavage+of+the+feline+calicivirus+capsid+precursor+is+mediated+by+a+virus-encoded+proteinase.&rft.au=Sosnovtsev%2C+S+V%3BSosnovtseva%2C+S+A%3BGreen%2C+K+Y&rft.aulast=Sosnovtsev&rft.aufirst=S&rft.date=1998-04-01&rft.volume=72&rft.issue=4&rft.spage=3051&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 - 1998-04-17 N1 - Date created - 1998-04-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L40021; GENBANK N1 - SuppNotes - Cited By: Virus Res. 1993 Mar;27(3):219-28 [8488721] J Biol Chem. 1991 Mar 25;266(9):5412-6 [1848550] Virus Res. 1993 Oct;30(1):17-26 [7505513] 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 Gen Virol. 1997 May;78 ( Pt 5):1033-40 [9152420] J Virol. 1977 May;22(2):572-6 [559106] Nature. 1978 Aug 10;274(5671):614-5 [672996] Virology. 1978 Aug;89(1):318-21 [687392] Virology. 1979 May;95(1):251-5 [571647] Virus Res. 1988 Aug;11(1):59-72 [3176687] FEBS Lett. 1989 Jan 30;243(2):103-14 [2645167] Arch Virol. 1989;108(1-2):69-79 [2596975] Curr Top Microbiol Immunol. 1990;161:49-87 [2169385] Virus Res. 1990 Nov;17(3):145-60 [2077782] Virology. 1991 Aug;183(2):810-4 [1853578] Virology. 1991 Oct;184(2):677-86 [1887589] J Virol. 1991 Oct;65(10):5440-7 [1716692] Arch Biochem Biophys. 1991 May 1;286(2):402-8 [1654789] Arch Virol. 1992;122(3-4):223-35 [1731695] Biochemistry. 1992 Sep 1;31(34):7862-9 [1510973] Science. 1993 Jan 22;259(5094):516-9 [8380940] Arch Virol. 1990;114(3-4):143-52 [2241572] Annu Rev Microbiol. 1990;44:603-23 [2252396] Virology. 1993 Jul;195(1):51-61 [8391187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smaller volume of prefrontal lobe in polysubstance abusers: a magnetic resonance imaging study. AN - 79732314; 9509492 AB - The present study was conducted to test the hypothesis that individuals with substance abuse disorder exhibit structural deficits in the prefrontal cortex. Volumes of the prefrontal lobe in subjects with histories of polysubstance abuse (n = 25) were measured and compared with those in normal volunteers (n = 14), using high-resolution volumetric magnetic resonance imaging (MRI). The research participants were men, 22 to 41 years of age. Polysubstance abusers were abstinent from drugs of abuse (except nicotine) for at least 15 days before MRI scanning. The total volumes of the prefrontal lobe (left and right hemispheres) were significantly smaller in the substance abuse group than in the control group. When the prefrontal lobe was segmented for gray and white matter, the deficit in the substance abusers was seen as significantly smaller volumes of gray but not of white matter. These results indicate that hypoplasia and/or atrophy in the prefrontal cortex accompany substance abuse and suggest that structural deficits in the prefrontal cortex may play an essential role in the neuropathological basis of functional impairments in substance abuse disorder, as demonstrated by functional brain imaging and cognitive studies. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Liu, X AU - Matochik, J A AU - Cadet, J L AU - London, E D AD - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 1998/04// PY - 1998 DA - April 1998 SP - 243 EP - 252 VL - 18 IS - 4 SN - 0893-133X, 0893-133X KW - Index Medicus KW - Magnetic Resonance Imaging KW - Image Interpretation, Computer-Assisted KW - Humans KW - Adult KW - Observer Variation KW - Time Factors KW - Male KW - Substance-Related Disorders -- pathology KW - Prefrontal Cortex -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79732314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.atitle=Smaller+volume+of+prefrontal+lobe+in+polysubstance+abusers%3A+a+magnetic+resonance+imaging+study.&rft.au=Liu%2C+X%3BMatochik%2C+J+A%3BCadet%2C+J+L%3BLondon%2C+E+D&rft.aulast=Liu&rft.aufirst=X&rft.date=1998-04-01&rft.volume=18&rft.issue=4&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology+%3A+official+publication+of+the+American+College+of+Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-04-30 N1 - Date created - 1998-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How asthma friendly is your school? AN - 215682593; 03813817 AB - Seven questions to determine how a school assists children with asthma are discussed, and resource organizations for parents and school staff are listed. Schools should be smoke-free and should have a policy on asthma treatment and training of staff in asthma treatment. JF - The Journal of School Health AU - National Heart, Lung, and Blood Institute AU - National Asthma Education and Prevention Program AU - School Asthma Education Subcommittee AD - National Heart, Lung, and Blood Institute ; National Asthma Education and Prevention Program Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 167 EP - 168 CY - Kent PB - Blackwell Publishing Ltd. VL - 68 IS - 4 SN - 00224391 KW - Physical Fitness And Hygiene KW - Schools KW - Asthma KW - Health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215682593?accountid=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=The+Journal+of+School+Health&rft.atitle=How+asthma+friendly+is+your+school%3F&rft.au=National+Heart%2C+Lung%2C+and+Blood+Institute%3BNational+Asthma+Education+and+Prevention+Program%3BSchool+Asthma+Education+Subcommittee&rft.aulast=National+Heart&rft.aufirst=Lung&rft.date=1998-04-01&rft.volume=68&rft.issue=4&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+School+Health&rft.issn=00224391&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright American School Health Association Apr 1998 N1 - Last updated - 2012-02-21 N1 - CODEN - JSHEAZ ER - TY - JOUR T1 - Development and preliminary validation of a forced-choice test of response bias for posttraumatic stress disorder AN - 16548564; 4351706 AB - This article describes the development and preliminary validation of the Morel Emotional Numbing Test for PTSD (MENT), a forced-choice test for detecting response bias in assessments for posttraumatic stress disorder (PTSD). The differences in MENT error rates among four groups of military veterans applying for monetary compensation for combat-related PTSD and two groups of hospitalized military veterans were investigated (N = 102): (a) disability claimants with veritable self-presentations, who were diagnosed with PTSD; (b) disability claimants with veritable self-presentations, who were not diagnosed with PTSD; (c) older disability claimants (age 63 or older) with veritable self-presentations; (d) disability claimants with suspect self-presentations; (e) chemical-dependent inpatients; and (f) schizophrenic inpatients. Veritable versus suspect grouping among disability claimants was determined by examining MMPI-2F-K dissimulation index scores. The results indicated that the suspect group produced more errors on the MENT than the credible groups or the hospitalized patient groups (p < .0001). Clinical decision rules were used to evaluate the relative effectiveness of the MENT to identify malingering in the claimant groups. The overall efficiency or hit rate on the MENT was 95.6%. JF - Journal of Personality Assessment AU - Morel, K R AD - National Institute of Mental Health, Neuropsychiatry Branch, Neuroscience Center at St. Elizabeth's Hospital, 2700 Martin Luther King Jr. Avenue, SE, Washington, DC 20032, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 299 EP - 314 VL - 70 IS - 2 SN - 0022-3891, 0022-3891 KW - mental disorders KW - post traumatic stress disorder KW - trauma KW - Health & Safety Science Abstracts KW - Psychology KW - Stress KW - Military KW - Occupational health KW - H 11000:Diseases/Injuries/Trauma KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16548564?accountid=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+Personality+Assessment&rft.atitle=Development+and+preliminary+validation+of+a+forced-choice+test+of+response+bias+for+posttraumatic+stress+disorder&rft.au=Morel%2C+K+R&rft.aulast=Morel&rft.aufirst=K&rft.date=1998-04-01&rft.volume=70&rft.issue=2&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+Personality+Assessment&rft.issn=00223891&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 health; Psychology; Stress; Military ER - TY - JOUR T1 - Oligopeptide permease in Borrelia burgdorferi: Putative peptide-binding components encoded by both chromosomal and plasmid loci AN - 16519342; 4330612 AB - To elucidate the importance of oligopeptide permease for Borrelia burgdorferi, the agent of Lyme disease, a chromosomal locus in B. burgdorferi that encodes homologues of all five subunits of oligopeptide permease has been identified and characterized. B. burgdorferi has multiple copies of the gene encoding the peptide-binding component, OppA; three reside at the chromosomal locus and two are on plasmids. Northern analyses indicate that each oppA gene is independently transcribed, although the three chromosomal oppA genes are also expressed as bi- and tri-cistronic messages. Induction of one of the plasmid-encoded oppA genes was observed following an increase in temperature, which appears to be an important cue for adaptive responses in vivo. The deduced amino acid sequences suggest that all five borrelial OppA homologues are lipoproteins, but the protease-resistance of at least one of them in intact bacteria is inconsistent with outer-surface localization. Insertional inactivation of a plasmid-encoded oppA gene demonstrates that it is not essential for growth in culture. JF - Microbiology AU - Bono, J L AU - Tilly, K AU - Stevenson, B AU - Hogan, D AU - Rosa, P AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South Fourth Street, Hamilton, MT 59840, USA, patricia_rosa@nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1033 EP - 1044 VL - 144 IS - 4 SN - 1350-0872, 1350-0872 KW - Lyme disease KW - oligopeptide permease KW - oppA gene KW - Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - N 14640:Structure & sequence KW - A 01006:Enzymes & cofactors KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16519342?accountid=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=Oligopeptide+permease+in+Borrelia+burgdorferi%3A+Putative+peptide-binding+components+encoded+by+both+chromosomal+and+plasmid+loci&rft.au=Bono%2C+J+L%3BTilly%2C+K%3BStevenson%2C+B%3BHogan%2C+D%3BRosa%2C+P&rft.aulast=Bono&rft.aufirst=J&rft.date=1998-04-01&rft.volume=144&rft.issue=4&rft.spage=1033&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 ER - TY - JOUR T1 - Engineering trimeric fibrous proteins based on bacteriophage T4 adhesins AN - 16517588; 4342206 AB - The adsorption specificity of bacteriophage T4 is determined by genes 12 and 37, encoding the short tail-fibers (STF) and the distal part of the long tail-fibers (LTF), respectively. Both are trimeric proteins with rod domains made up of similar tandem quasi-repeats, similar to 40 amino acids long. Their assembly requires the viral chaperones gp57A and gp38. Here we report that fusing fragments of gp12 and gp37 to another trimeric T4 fibrous protein, fibritin, facilitates correct assembly, thereby by-passing the chaperone requirement. Fibritin is an alpha -helical coiled coil protein whose C-terminal part (fibritin E, comprising the last 120 residues) has recently been solved to atomic resolution. Gp12 fragments of 109 and 70 amino acids, corresponding to three and two quasi-repeats respectively, were fused to the C-terminus of fibritin E. A similar chimera was designed for the last 63 residues of gp37, which contain four copies of the pentapeptide Gly-X-His-X-His and assume a narrow rigid structure in the LTF distal tip. Expressed from plasmids, all three chimeras form soluble trimers that are resistant to dissociation by SDS and digestion by trypsin, indicative of correct folding and oligomerization. JF - Protein Engineering AU - Miroshnikov, KA AU - Marusich, E I AU - Cerritelli, ME AU - Cheng, N AU - Hyde, C C AU - Steven, A C AU - Mesyanzhinov, V V AD - Laboratory of Structural Biology Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2717, USA, alasdair_steven@nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 329 EP - 332 VL - 11 IS - 4 SN - 0269-2139, 0269-2139 KW - Fibritin KW - Gene 12 KW - Gene 37 KW - Glycoprotein gp12 KW - Glycoprotein gp37 KW - Glycoprotein gp38 KW - Glycoprotein gp57A KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - V 22032:Viral proteins KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16517588?accountid=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=Protein+Engineering&rft.atitle=Engineering+trimeric+fibrous+proteins+based+on+bacteriophage+T4+adhesins&rft.au=Miroshnikov%2C+KA%3BMarusich%2C+E+I%3BCerritelli%2C+ME%3BCheng%2C+N%3BHyde%2C+C+C%3BSteven%2C+A+C%3BMesyanzhinov%2C+V+V&rft.aulast=Miroshnikov&rft.aufirst=KA&rft.date=1998-04-01&rft.volume=11&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&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 - Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography with mass selective detection AN - 16509426; 4413787 AB - Breflate is a water soluble prodrug developed to facilitate parenteral administration of the investigational antineoplastic agent brefeldin A (BFA). Previously, using analytical methods based upon reversed-phase high performance liquid chromatography (HPLC) with low wavelength UV detection or gas chromatography (GC) with electron capture detection following derivatization with heptafluorobutyrylimidazole, it was demonstrated that breflate undergoes rapid and efficient conversion to BFA following bolus i.v. injection in mice and dogs. However, plasma concentrations of the drug and prodrug achieved during the administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous i.v. infusion were undetectable (< 0.1 mu g ml super(-1)) by these methods. The sensitivity and specificity required for therapeutic drug level monitoring were achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA and 1-eicosanol, the latter added to the sample as an internal standard (IS), were extracted from plasma into tert-butyl methyl ether (TBME) and esterified with trifluoroacetic anhydride. Methanol was added to the reaction mixture to effect the convenient removal of excess reagent as the volatile methyl ester during evaporation of the solvent. The residual material was analyzed directly upon reconstitution by capillary GC with automated splitless injection. Electron-ionization (70 eV) MS detection was performed by sequentially scanning ions at m/z 58, 202 and 325. The lowest concentration of either analyte quantified with acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was near 10 ng ml super(-1) in plasma using a sample volume of 100 mu l. The assay has proven to be sufficiently sensitive, specific and reproducible for the routine analysis of pharmacokinetic specimens acquired during IND (investigational new drug)-directed toxicology studies in dogs. JF - Journal of Pharmaceutical and Biomedical Analysis AU - Phillips, L R AU - Wolfe, T L AU - Malspeis, L AU - Supko, J G AD - Laboratory of Pharmaceutical Chemistry, Division of Cancer Treatment, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD 21701, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1301 EP - 1309 VL - 16 IS - 8 SN - 0731-7085, 0731-7085 KW - antineoplastic drugs KW - brefeldin A KW - breflate KW - gas chromatography KW - man KW - pharmacokinetics KW - plasma KW - Toxicology Abstracts KW - X 24171:Microbial KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16509426?accountid=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+Pharmaceutical+and+Biomedical+Analysis&rft.atitle=Analysis+of+brefeldin+A+and+the+prodrug+breflate+in+plasma+by+gas+chromatography+with+mass+selective+detection&rft.au=Phillips%2C+L+R%3BWolfe%2C+T+L%3BMalspeis%2C+L%3BSupko%2C+J+G&rft.aulast=Phillips&rft.aufirst=L&rft.date=1998-04-01&rft.volume=16&rft.issue=8&rft.spage=1301&rft.isbn=&rft.btitle=&rft.title=Journal+of+Pharmaceutical+and+Biomedical+Analysis&rft.issn=07317085&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 - Differential immune responses to staphylococcal enterotoxin B mutations in a hydrophobic loop dominating the interface with major histocompatibility complex class II receptors AN - 16480072; 4355559 AB - Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can trigger acute pathologic effects in humans. A hydrophobic loop on the surface of SEB and other bacterial superantigens, centered around a conserved leucine (L45) residue, is essential for binding to class II major histocompatibility complex molecules. Single residue changes of wild type SEB, designated Q43P, F44P, or L45R, resulted in nonlethal proteins at a dose equivalent to 30 murine LD sub(50) of SEB. Relative to SEB, the mutant proteins did not elevate serum concentrations of proinflammatory cytokines in mice and caused minimal proliferation of human lymphocytes. Anti-SEB titers of mice immunized with Q43P, F44P, L45R, or SEB were similar and protected 77%-100% of animals against a lethal SEB challenge. Levels of toxin-specific IgG1, IgG2a, IgG2b, and IgG3 in mice immunized with SEB, Q43P, or F44P were equivalent, but animals immunized with L45R had significantly elevated levels of IgG2a and IgG2b. Vaccines against staphylococcal superantigens should focus on this critical leucine residue. JF - Journal of Infectious Diseases AU - Woody, MA AU - Krakauer, T AU - Ulrich, R G AU - Stiles, B G AD - Laboratory of Leukocyte Biology, National Cancer Institute - Frederick Cancer Research and Development Center, Bldg. 567, Rm. 210, Frederick, MD 21702-1201, USA, mawoody@mail.ncifcrf.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1013 EP - 1012 VL - 177 IS - 4 SN - 0022-1899, 0022-1899 KW - Staphylococcus KW - class II molecule receptors KW - class II molecules receptors KW - enterotoxin B KW - mice KW - receptors KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - X 24171:Microbial 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/16480072?accountid=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=Differential+immune+responses+to+staphylococcal+enterotoxin+B+mutations+in+a+hydrophobic+loop+dominating+the+interface+with+major+histocompatibility+complex+class+II+receptors&rft.au=Woody%2C+MA%3BKrakauer%2C+T%3BUlrich%2C+R+G%3BStiles%2C+B+G&rft.aulast=Woody&rft.aufirst=MA&rft.date=1998-04-01&rft.volume=177&rft.issue=4&rft.spage=1013&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 ER - TY - JOUR T1 - Biology and potential strategies for the treatment of G sub(M2) gangliosidoses AN - 16439887; 4342767 AB - The G sub(M2) gangliosidoses are a group of heritable neurodegenerative disorders caused by excessive accumulation of the ganglioside G sub(M2) owing to deficiency in beta -hexosaminidase activity. Tay-Sachs and Sandhoff diseases have similar clinical phenotypes resulting from a deficiency in human hexosaminidase alpha and beta subunits, respectively. The lack of treatment for G sub(M2) gangliosidoses stimulated interest in developing animal models to understand the molecular mechanisms underlying the various forms of this disease and to test new potential therapies. In this review, we discuss the molecular biology of G sub(M2) gangliosidoses and the different strategies that have been tested in animal models for the treatment of this genetic disorder, including gene transfer and cell engraftment of neural stem cells engineered to express the hexosaminidase isoenzymes. JF - Molecular Medicine Today AU - Chavany, C AU - Jendoubi, M AD - Genetics and Molecular Immunology Section, LI, Bldg 9, Room 1W101, National Institutes of Health, 9 Memorial Drive, Bethesda, MD 20892, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 158 EP - 165 VL - 4 IS - 4 SN - 1357-4310, 1357-4310 KW - ganglioside GM2 KW - gangliosidosis KW - reviews KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/16439887?accountid=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=Biology+and+potential+strategies+for+the+treatment+of+G+sub%28M2%29+gangliosidoses&rft.au=Chavany%2C+C%3BJendoubi%2C+M&rft.aulast=Chavany&rft.aufirst=C&rft.date=1998-04-01&rft.volume=4&rft.issue=4&rft.spage=158&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Characterization of the bvgR locus of Bordetella pertussis AN - 16416092; 4318178 AB - Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. JF - Journal of Bacteriology AU - Merkel, T J AU - Barros, C AU - Stibitz, S AD - OIIB/NIDR/NIH, Building 30, Rm. 303, 30 Convent Dr. MSC 4350, Bethesda, MD 20892-4350, USA, merkel@yoda.nidr.nih.gov Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 1682 EP - 1690 VL - 180 IS - 7 KW - BvgA protein KW - BvgS protein KW - bvgR locus KW - nucleotide sequence KW - vir gene KW - virulence factors KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14640:Structure & sequence KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16416092?accountid=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=Characterization+of+the+bvgR+locus+of+Bordetella+pertussis&rft.au=Merkel%2C+T+J%3BBarros%2C+C%3BStibitz%2C+S&rft.aulast=Merkel&rft.aufirst=T&rft.date=1998-04-01&rft.volume=180&rft.issue=7&rft.spage=1682&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=&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 - The genetic effects of environmental lead AN - 16350372; 4294032 AB - This article reviews the effects of lead on genetic systems in the context of lead's various other toxic effects and its abundance and distribution in the environment. Lead is perhaps the longest used and best recognized toxic environmental chemical, yet it continued be used recklessly until only very recently. Lead is thus a lesson in the limitations and strengths of science, human conscience and common sense. Lead has been tested and found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts or complexes with many biomolecules and adversely affects the reproductive, nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and hematopoietic systems as well as developmental processes. It is likely that lead is a selective agent that continues to act on and influence the genetic structure and future evolution of exposed plant and animal populations. JF - Mutation Research--Reviews in Mutation Research AU - Johnson, F M AD - Toxicology Operations Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1998/04/01/ PY - 1998 DA - 1998 Apr 01 SP - 123 EP - 140 PB - Elsevier Science B.V. VL - 410 IS - 2 SN - 1383-5742, 1383-5742 KW - animals KW - plants KW - Genetics Abstracts; Toxicology Abstracts KW - X 24166:Environmental impact KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16350372?accountid=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=The+genetic+effects+of+environmental+lead&rft.au=Johnson%2C+F+M&rft.aulast=Johnson&rft.aufirst=F&rft.date=1998-04-01&rft.volume=410&rft.issue=2&rft.spage=123&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 ER - TY - JOUR T1 - Liposomal formulation of a self lymphoma antigen induces potent protective antitumor immunity AN - 16277753; 4294232 AB - We developed a liposome carrier for a model nonimmunogenic, self Ag. This carrier reproducibly converted lymphoma Ig into a potent tumor rejection Ag in mice. A single immunization induced protection against challenges representing 20 to 100 times the minimum lethal dose of parental tumor. This protective effect required minimal amounts of incorporated Ag and IL-2 and elicited specific Abs (compared with free Ag or liposomal control Ig which did not elicit any specific Abs); depletion experiments demonstrated a requirement for effector CD4 super(+) and CD8 super(+) T cells. Head-to-head comparisons, indicating superior potency and induction of specific T cell activation, distinguished liposomal from prototype, carrier-conjugated Ag. These results provide a strategy for formulating weak tumor or other clinically important Ags into vaccines. JF - Journal of Immunology AU - Kwak, L W AU - Pennington, R AU - Boni, L AU - Ochoa, A C AU - Robb, R J AU - Popescu, M C AD - National Cancer Institute, Frederick Cancer Research and Development Center, Bldg. 567, Rm. 205, Frederick, MD 21702, USA Y1 - 1998/04// PY - 1998 DA - Apr 1998 SP - 3637 EP - 3641 VL - 160 IS - 8 SN - 0022-1767, 0022-1767 KW - antigen (tumor-associated) KW - liposomes KW - lymphocytes T KW - lymphoma KW - mice KW - tumors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33388:Drug delivery vehicles (liposomes, cochleates, microspheres) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16277753?accountid=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=Liposomal+formulation+of+a+self+lymphoma+antigen+induces+potent+protective+antitumor+immunity&rft.au=Kwak%2C+L+W%3BPennington%2C+R%3BBoni%2C+L%3BOchoa%2C+A+C%3BRobb%2C+R+J%3BPopescu%2C+M+C&rft.aulast=Kwak&rft.aufirst=L&rft.date=1998-04-01&rft.volume=160&rft.issue=8&rft.spage=3637&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 ER -