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 improvemen