TY - JOUR T1 - beta-Amyloid polypeptide increases calcium-uptake in PC12 cells: a possible mechanism for its cellular toxicity in Alzheimer's disease. AN - 77790128; 7697365 AB - Calcium-uptake into PC12 cells was measured by incubation with 45Ca after the cells were exposed for 24 h to beta-amyloid peptide(1-40) at concentrations between 0 and 46 microM. The rate of influx of 45Ca into PC12 cells was constant for the first 10 min. For 46 microM beta-amyloid peptide(1-40), the rate of influx was about 1,300 ions/s/microns 2 and the number of cells decreased significantly. There was no significant decrease in cell number when cells were exposed to beta-amyloid in calcium-free medium. These results indicate that beta-amyloid increases calcium uptake into PC12 cells, and suggest that the increased uptake is responsible for the toxicity of beta-amyloid in PC12 cells. JF - Brain research AU - Fukuyama, R AU - Wadhwani, K C AU - Galdzicki, Z AU - Rapoport, S I AU - Ehrenstein, G AD - Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892. Y1 - 1994/12/26/ PY - 1994 DA - 1994 Dec 26 SP - 269 EP - 272 VL - 667 IS - 2 SN - 0006-8993, 0006-8993 KW - Amyloid beta-Peptides KW - 0 KW - Calcium Isotopes KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Cell Membrane Permeability -- drug effects KW - Biological Transport KW - Alzheimer Disease -- metabolism KW - PC12 Cells KW - Alzheimer Disease -- pathology KW - Calcium -- metabolism KW - Amyloid beta-Peptides -- adverse effects KW - Amyloid beta-Peptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77790128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=beta-Amyloid+polypeptide+increases+calcium-uptake+in+PC12+cells%3A+a+possible+mechanism+for+its+cellular+toxicity+in+Alzheimer%27s+disease.&rft.au=Fukuyama%2C+R%3BWadhwani%2C+K+C%3BGaldzicki%2C+Z%3BRapoport%2C+S+I%3BEhrenstein%2C+G&rft.aulast=Fukuyama&rft.aufirst=R&rft.date=1994-12-26&rft.volume=667&rft.issue=2&rft.spage=269&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 - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a DNA binding site for the nuclear factor YY1 in the human GM-CSF core promoter. AN - 77712872; 7838721 AB - It has been well documented that the repeated CATT(A/T) sequence, localized between -64 and -35 in the human GM-CSF promoter, is required for the promoter activity, and this region likely serves as a core recognition sequence for a cellular transcription factor. However, the transcription factor that interacts with this site was not identified. Here, we report that this element contains a binding site for the nuclear factor YY1, which has not been reported to play a role in the regulation of cytokine gene transcription. Results from transient transfection assays of the Jurkat T cell line revealed that this repeated CATT(A/T) element exhibited enhancer activity when linked to both the human IFN-gamma promoter and the TK promoter. Mutation of the YY1 binding site eliminated about 60% of the enhancer activity of the element. We have found that the YY1 binding site could form two specific DNA-protein complexes, A and B, with Jurkat nuclear proteins in the electrophoretic mobility shift assay and that the binding of these complexes correlates with the enhancer activity. UV cross-linking analysis revealed that the A complex is a multi-protein complex and in addition to YY1, other proteins are required for formation of the protein complex. Cotransfection assays with a YY1 expression vector revealed that overexpression of YY1 resulted in an inhibitory effect on the repeated CATT(A/T) element, indicating that in addition to YY1, cofactors also are required for the activator function of the A complex. JF - Nucleic acids research AU - Ye, J AU - Young, H A AU - Ortaldo, J R AU - Ghosh, P AD - Laboratory of Experimental Immunology, DCT, NCI-FCRDC, MD 21702-1201. Y1 - 1994/12/25/ PY - 1994 DA - 1994 Dec 25 SP - 5672 EP - 5678 VL - 22 IS - 25 SN - 0305-1048, 0305-1048 KW - DNA-Binding Proteins KW - 0 KW - Erythroid-Specific DNA-Binding Factors KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - Transcription Factors KW - YY1 Transcription Factor KW - YY1 protein, human KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - Cell Line KW - Structure-Activity Relationship KW - Binding Sites KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77712872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Identification+of+a+DNA+binding+site+for+the+nuclear+factor+YY1+in+the+human+GM-CSF+core+promoter.&rft.au=Ye%2C+J%3BYoung%2C+H+A%3BOrtaldo%2C+J+R%3BGhosh%2C+P&rft.aulast=Ye&rft.aufirst=J&rft.date=1994-12-25&rft.volume=22&rft.issue=25&rft.spage=5672&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1994 Jan;14(1):128-37 [8264581] Mol Cell Biol. 1992 Jan;12(1):38-44 [1309593] Mol Cell Biol. 1994 Mar;14(3):2213-21 [8114751] J Biol Chem. 1994 Mar 4;269(9):6506-10 [8120001] Oncogene. 1994 Apr;9(4):1047-52 [8134108] Biochem Biophys Res Commun. 1994 Mar 15;199(2):1064-72 [8135780] Nucleic Acids Res. 1992 Jan 11;20(1):3-26 [1738600] Biotechniques. 1991 Dec;11(6):739-40, 742-3 [1809326] Mol Cell Biol. 1992 Sep;12(9):4209-14 [1508214] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9814-8 [1409704] J Biol Chem. 1993 Feb 25;268(6):4188-96 [8382696] Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1696-700 [8383323] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2466-70 [8460159] Mol Cell Biol. 1993 May;13(5):2787-801 [8474441] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6145-9 [8327494] Nature. 1993 Sep 30;365(6445):462-4 [8003102] J Exp Med. 1993 Nov 1;178(5):1483-96 [8228802] Mol Cell Biol. 1993 Dec;13(12):7399-407 [8246960] Cell. 1994 Mar 25;76(6):1115-21 [8137426] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Mol Cell Biol. 1988 May;8(5):1979-84 [2838738] Nucleic Acids Res. 1989 Dec 11;17(23):10130 [2557582] Mol Cell Biol. 1990 Feb;10(2):528-38 [2300053] Mol Cell Biol. 1990 Nov;10(11):6084-8 [2233734] Mol Cell Biol. 1991 Mar;11(3):1765-9 [1899910] Blood. 1991 Mar 15;77(6):1131-45 [2001448] Mol Cell Biol. 1991 May;11(5):2752-9 [1901946] Cell. 1991 Oct 18;67(2):377-88 [1655281] Nature. 1991 Oct 10;353(6344):563-6 [1922363] Mol Cell Biol. 1991 Dec;11(12):5894-901 [1944268] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9799-803 [1946404] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9804-8 [1946405] Nature. 1991 Nov 21;354(6350):241-5 [1720509] Science. 1993 Dec 17;262(5141):1889-92 [8266081] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fidelity of the human leading and lagging strand DNA replication apparatus with 8-oxodeoxyguanosine triphosphate. AN - 77709353; 7838719 AB - A product of oxidative metabolism, 8-oxodeoxyguanosine triphosphate (8-O-dGTP), readily pairs with adenine during DNA replication, ultimately causing A.T-->C.G transversions. This study utilized 8-O-dGTP as a probe to examine the fidelity of the leading and lagging strand replication apparatus in extracts of HeLa cells. Simian virus (SV) 40 T antigen-dependent DNA replication reactions were performed with two M13mp2 vectors with the SV40 origin located on opposite sides of the lacZ alpha sequence used to score replication errors. The presence of 8-O-dGTP at equimolar concentration with each of the 4 normal dNTPs resulted in a > 46-fold increase in error rate for A.T-->C.G transversion over that observed in the absence of 8-O-dGTP. A similar average error rate was observed on the (+) and (-) strands in both vectors, suggesting that the fidelity of replication by leading and lagging strand replication proteins is similar for the dA.8-O-dGMP mispair. Replication fidelity in the presence of 8-O-dGTP was reduced on both strands when an inhibitor of exonucleolytic proofreading (dGMP) was added to the reaction. These data suggest that the majority of dA.8-O-dGMP mispairs are proofread by both leading and lagging strand replication proteins. JF - Nucleic acids research AU - Minnick, D T AU - Pavlov, Y I AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/12/25/ PY - 1994 DA - 1994 Dec 25 SP - 5658 EP - 5664 VL - 22 IS - 25 SN - 0305-1048, 0305-1048 KW - Deoxyguanine Nucleotides KW - 0 KW - 8-oxodeoxyguanosine triphosphate KW - 139307-94-1 KW - Exonucleases KW - EC 3.1.- KW - Index Medicus KW - Oxidation-Reduction KW - Base Sequence KW - DNA Repair KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Mutagenesis KW - Exonucleases -- metabolism KW - Deoxyguanine Nucleotides -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77709353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=The+fidelity+of+the+human+leading+and+lagging+strand+DNA+replication+apparatus+with+8-oxodeoxyguanosine+triphosphate.&rft.au=Minnick%2C+D+T%3BPavlov%2C+Y+I%3BKunkel%2C+T+A&rft.aulast=Minnick&rft.aufirst=D&rft.date=1994-12-25&rft.volume=22&rft.issue=25&rft.spage=5658&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1982 Apr;28(4):767-79 [6178514] J Mol Biol. 1984 May 15;175(2):131-57 [6202875] Mol Cell Biol. 1985 Jun;5(6):1238-46 [2993858] Cell. 1988 Jun 17;53(6):837-40 [2838173] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7064-8 [3174620] J Biol Chem. 1990 Oct 25;265(30):18043-6 [1976634] J Mol Biol. 1990 Dec 5;216(3):475-9 [2258921] Biochim Biophys Acta. 1991 Jan 17;1088(1):11-24 [1846563] Biochemistry. 1991 Feb 5;30(5):1403-12 [1991121] Nature. 1991 Jan 31;349(6308):431-4 [1992344] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3465-9 [1901658] Biochemistry. 1991 Dec 24;30(51):11751-9 [1751492] J Biol Chem. 1992 Jan 5;267(1):166-72 [1730583] Nature. 1992 Jan 16;355(6357):273-5 [1309939] J Bacteriol. 1992 Oct;174(20):6321-5 [1328155] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11021-5 [1332067] Biochemistry. 1993 Apr 20;32(15):4083-9 [8385995] Cancer Res. 1993 Jul 15;53(14):3270-5 [8391921] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7744-8 [8356079] Trends Genet. 1993 Jul;9(7):246-9 [8379000] Biochemistry. 1993 Nov 2;32(43):11476-82 [8218213] J Biol Chem. 1993 Nov 5;268(31):23524-30 [8226881] Biochem Biophys Res Commun. 1993 Nov 15;196(3):1545-51 [8250910] J Biol Chem. 1994 Jan 21;269(3):1711-7 [8294419] J Biol Chem. 1994 Apr 8;269(14):10923-34 [8144677] Biochemistry. 1994 Apr 19;33(15):4695-701 [8161527] Nature. 1994 May 19;369(6477):207-12 [7910375] Annu Rev Genet. 1975;9:245-84 [55095] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acid changes alter the repair specificity of Drosophila Rrp1. Isolation of mutants deficient in repair of oxidative DNA damage. AN - 76906138; 7798276 AB - Drosophila Rrp1 has several tightly associated enzymatic activities, including double-strand DNA 3'-exonuclease, apurinic/apyrimidinic endonuclease, 3'-phosphatase, and 3'-phosphodiesterase. The carboxyl-terminal third of Rrp1, homologous to Escherichia coli exonuclease III, is sufficient to repair oxidative and alkylation-induced DNA damage in vivo. Using a screen for partial complementation of repair-deficient E. coli, we isolated three mutants of the nuclease domain of Rrp1: T462A, K463Q, and L484P, that protect against methyl methanesulfonate (MMS)-induced but not t-BuO2H-induced DNA damage. Thr-462 and Lys-463 are highly conserved residues found in a cluster of 5 conserved amino acids (LQETK), while Leu-484 is poorly conserved. Gln-460 Glu-461, Thr-462, and Lys-463 and Leu-484 were altered by site-directed mutagenesis using a plasmid including the entire Rrp1 gene and mutant proteins were purified. Mutants of the three residues Glu-461, Thr-462, and Lys-463 demonstrate 8-200-fold lower phosphodiesterase specific activity than wild-type Rrp1. E461A has a 30-fold reduction in AP endonuclease and is MMS-sensitive, but all other mutants have near-normal AP endonuclease and are MMS-resistant. Glu-461 appears to be essential for the nuclease function for Rrp1. Lys-463 and, to a lesser extent, Thr-462 influence the substrate specificity of the Rrp1 nuclease. JF - The Journal of biological chemistry AU - Gu, L AU - Huang, S M AU - Sander, M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/12/23/ PY - 1994 DA - 1994 Dec 23 SP - 32685 EP - 32692 VL - 269 IS - 51 SN - 0021-9258, 0021-9258 KW - Rrp1 KW - Amino Acids KW - 0 KW - DNA Primers KW - Drosophila Proteins KW - Nucleotidyltransferases KW - EC 2.7.7.- KW - Rrp1 protein, Drosophila KW - Index Medicus KW - Oxidation-Reduction KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - DNA Damage KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Mutation KW - Nucleotidyltransferases -- metabolism KW - Nucleotidyltransferases -- genetics KW - DNA Repair KW - Amino Acids -- genetics KW - Drosophila -- metabolism KW - Amino Acids -- metabolism KW - Drosophila -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76906138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Single+amino+acid+changes+alter+the+repair+specificity+of+Drosophila+Rrp1.+Isolation+of+mutants+deficient+in+repair+of+oxidative+DNA+damage.&rft.au=Gu%2C+L%3BHuang%2C+S+M%3BSander%2C+M&rft.aulast=Gu&rft.aufirst=L&rft.date=1994-12-23&rft.volume=269&rft.issue=51&rft.spage=32685&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 - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Rrp1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Growth and chemotherapeutic response of cells in a hollow-fiber in vitro solid tumor model. AN - 76878667; 7990159 AB - Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironmental heterogeneity that develops in these tumors as they grow. Heterogeneous tumor models are thus needed for drug screening. Our goal was to develop and test for drug evaluation a solid tumor model based on cell growth inside biocompatible hollow fibers. Building on the experience of Hollingshead and co-workers with a sparse-cell, hollow-fiber tumor model, we tested six human tumor cell lines for in vitro growth inside 450-microns internal-diameter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also examined using electron microscopy, and their doxorubicin sensitivity was assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay. Five of the human tumor cell lines tested grew to confluence, forming heterogeneous in vitro tumors with subpopulations of viable and necrotic cells. For SW620 hollow-fiber tumors, maximum viable cell populations in excess of 10(8) cells/mL were obtained after 8 days of growth. This viable cell density remained roughly constant for 3-4 days, permitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exposure than were tumor cells in monolayers: LC50 values (i.e., the drug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 microM and 0.16 microM were obtained for hollow-fiber tumors and monolayers, respectively. LC50 values decreased when drug exposure time was increased. Results from the colorimetric assay were in agreement with those from the clonogenic assay. The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose-response experiments with a relatively easy colorimetric assay demonstrate the potential of the hollow-fiber solid tumor model as a tool for experimental therapeutic research. Hollow-fiber solid tumors may prove useful for experimental drug evaluation. JF - Journal of the National Cancer Institute AU - Casciari, J J AU - Hollingshead, M G AU - Alley, M C AU - Mayo, J G AU - Malspeis, L AU - Miyauchi, S AU - Grever, M R AU - Weinstein, J N AD - Developmental Therapeutics Program, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/12/21/ PY - 1994 DA - 1994 Dec 21 SP - 1846 EP - 1852 VL - 86 IS - 24 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Biocompatible Materials KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Doxorubicin -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - Colorimetry KW - Antineoplastic Agents -- pharmacology KW - Tumor Cells, Cultured -- cytology KW - Tumor Cells, Cultured -- drug effects KW - Tumor Stem Cell Assay -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76878667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Growth+and+chemotherapeutic+response+of+cells+in+a+hollow-fiber+in+vitro+solid+tumor+model.&rft.au=Casciari%2C+J+J%3BHollingshead%2C+M+G%3BAlley%2C+M+C%3BMayo%2C+J+G%3BMalspeis%2C+L%3BMiyauchi%2C+S%3BGrever%2C+M+R%3BWeinstein%2C+J+N&rft.aulast=Casciari&rft.aufirst=J&rft.date=1994-12-21&rft.volume=86&rft.issue=24&rft.spage=1846&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential radon exposure and lung cancer among nonsmoking women. AN - 76877699; 7990157 AB - Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low. JF - Journal of the National Cancer Institute AU - Alavanja, M C AU - Brownson, R C AU - Lubin, J H AU - Berger, E AU - Chang, J AU - Boice, J D AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/12/21/ PY - 1994 DA - 1994 Dec 21 SP - 1829 EP - 1837 VL - 86 IS - 24 SN - 0027-8874, 0027-8874 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Registries KW - Aged, 80 and over KW - Missouri KW - Humans KW - Smoking Cessation KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Female KW - Air Pollution, Indoor -- adverse effects KW - Lung Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Adenocarcinoma -- etiology KW - Radon -- analysis KW - Radon -- adverse effects KW - Air Pollution, Radioactive -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76877699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Residential+radon+exposure+and+lung+cancer+among+nonsmoking+women.&rft.au=Alavanja%2C+M+C%3BBrownson%2C+R+C%3BLubin%2C+J+H%3BBerger%2C+E%3BChang%2C+J%3BBoice%2C+J+D&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1994-12-21&rft.volume=86&rft.issue=24&rft.spage=1829&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1994 Dec 21;86(24):1813-4 [7990151] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a cytoplasmic Ser-Thr-Leu motif that determines agonist-induced internalization of the AT1 angiotensin receptor. AN - 76881931; 7989302 AB - The type 1 angiotensin II (AT1) receptor undergoes rapid endocytosis and down-regulation after agonist binding. In studies on the structural determinants of agonist-induced endocytosis, serial deletions in the cytoplasmic tail of the rat AT1a receptor showed that the carboxyl-terminal 22 amino acids are not necessary for its internalization. However, internalization was markedly impaired by the removal of one additional amino acid (Leu337) and was reduced by 95% after removal of Ser335 and Thr336. Single alanine replacements of amino acids in this region showed that individual substitutions of Thr332, Ser335, Thr336, Leu337, and Ser338 caused moderate but significant impairment of the internalization rate. Replacement of both Ser335 and Thr336 with alanine residues further impaired the internalization rate, and triple alanine replacement of the Ser-Thr-Leu motif reduced internalization to almost the same extent as the corresponding tail deletion mutant. The Ser-Thr-Leu motif is highly conserved in mammalian AT1 receptors but is not present in the noninternalizing type 2 angiotensin II receptor. These data demonstrate that a serine/threonine-rich region including Leu337 in the cytoplasmic tail of the AT1 receptor is a major requirement for endocytosis of the hormone-receptor complex and support the concept that similar motifs in other G protein-coupled receptors are determinants of their agonist-induced internalization. JF - The Journal of biological chemistry AU - Hunyady, L AU - Bor, M AU - Balla, T AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12/16/ PY - 1994 DA - 1994 Dec 16 SP - 31378 EP - 31382 VL - 269 IS - 50 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Inositol Phosphates KW - Receptors, Angiotensin KW - Recombinant Proteins KW - Angiotensin II KW - 11128-99-7 KW - Index Medicus KW - Animals KW - Inositol Phosphates -- metabolism KW - Amino Acid Sequence KW - Angiotensin II -- pharmacology KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Rats KW - Endocytosis KW - Base Sequence KW - Down-Regulation KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Signal Transduction KW - DNA Primers -- chemistry KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76881931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+a+cytoplasmic+Ser-Thr-Leu+motif+that+determines+agonist-induced+internalization+of+the+AT1+angiotensin+receptor.&rft.au=Hunyady%2C+L%3BBor%2C+M%3BBalla%2C+T%3BCatt%2C+K+J&rft.aulast=Hunyady&rft.aufirst=L&rft.date=1994-12-16&rft.volume=269&rft.issue=50&rft.spage=31378&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 - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 5' enhancer of the mouse mammary tumor virus long terminal repeat contains a functional AP-2 element. AN - 76875225; 7989375 AB - The mouse mammary tumor virus (MMTV) retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV long terminal repeat (LTR) has been implicated in tissue-specific activation of these genes. In this study, we characterize an enhancer element (Ban2; -1075 to -978) at the 5' end of the MMTV LTR. We show that this enhancer is 5-fold more active in a murine mammary carcinoma cell line (34i) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity. DNA-binding proteins that interact with each of the four elements have been identified. One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2. The mp5/AP-2 DNA binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies. We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells, and requires an intact mp5-binding site. JF - The Journal of biological chemistry AU - Mellentin-Michelotti, J AU - John, S AU - Pennie, W D AU - Williams, T AU - Hager, G L AD - Laboratory of Molecular Virology, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12/16/ PY - 1994 DA - 1994 Dec 16 SP - 31983 EP - 31990 VL - 269 IS - 50 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Macromolecular Substances KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - Transcription Factor AP-2 KW - Transcription Factors KW - Index Medicus KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Mice KW - Gene Expression Regulation KW - Oligodeoxyribonucleotides -- metabolism KW - Nuclear Proteins -- metabolism KW - Binding Sites KW - Transcription Factors -- metabolism KW - Mammary Glands, Animal -- physiology KW - Enhancer Elements, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Mammary Tumor Virus, Mouse -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76875225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+5%27+enhancer+of+the+mouse+mammary+tumor+virus+long+terminal+repeat+contains+a+functional+AP-2+element.&rft.au=Mellentin-Michelotti%2C+J%3BJohn%2C+S%3BPennie%2C+W+D%3BWilliams%2C+T%3BHager%2C+G+L&rft.aulast=Mellentin-Michelotti&rft.aufirst=J&rft.date=1994-12-16&rft.volume=269&rft.issue=50&rft.spage=31983&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 - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic studies in alcohol research. AN - 77829846; 7726200 AB - The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful than those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. JF - American journal of medical genetics AU - Karp, R W AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 304 EP - 308 VL - 54 IS - 4 SN - 0148-7299, 0148-7299 KW - Index Medicus KW - United States KW - Animals KW - Humans KW - Chromosomes, Human KW - National Institutes of Health (U.S.) KW - Disease Models, Animal KW - Chromosome Mapping KW - Research Support as Topic KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77829846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Genetic+studies+in+alcohol+research.&rft.au=Karp%2C+R+W&rft.aulast=Karp&rft.aufirst=R&rft.date=1994-12-15&rft.volume=54&rft.issue=4&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Med Genet. 1994 Dec 15;54(4):293-4 [7726197] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human neuroscience at National Institute on Drug Abuse: implications for genetics research. AN - 77823417; 7726199 AB - It is becoming clear that there is a genetic component to drug abuse. Family studies, adoption studies, and critical twin studies have all pointed to some genetic vulnerability or risk factors for an individual to abuse psychoactive drugs depending on certain psychopathologies in the biological parents and/or parents' own drug use. The question for the next generation of research at the National Institute on Drug Abuse (NIDA) is to apply the rapidly developing technology in molecular genetics in an effort to determine the candidate genes contributing to the risk. JF - American journal of medical genetics AU - Gordon, H W AD - Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, Maryland, USA. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 300 EP - 303 VL - 54 IS - 4 SN - 0148-7299, 0148-7299 KW - Index Medicus KW - United States KW - Molecular Biology KW - Humans KW - Twin Studies as Topic KW - Family KW - Adoption KW - Genetics, Behavioral KW - National Institutes of Health (U.S.) KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77823417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Human+neuroscience+at+National+Institute+on+Drug+Abuse%3A+implications+for+genetics+research.&rft.au=Gordon%2C+H+W&rft.aulast=Gordon&rft.aufirst=H&rft.date=1994-12-15&rft.volume=54&rft.issue=4&rft.spage=300&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-19 N1 - Date created - 1995-05-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Med Genet. 1994 Dec 15;54(4):293-4 [7726197] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased risk of colorectal cancer among smokers: results of a 26-year follow-up of US veterans and a review. AN - 76877704; 7989109 AB - To clarify the relationship between tobacco use and risk of colorectal cancer, we evaluated a cohort of 248,046 American veterans followed prospectively for 26 years. In comparison with veterans who had never used tobacco, the risk of death was significantly increased for colon cancer and rectal cancer among current and former cigarette smokers and among pipe or cigar smokers, controlling for social class and occupational physical activity. Rectal-cancer risk was also significantly elevated among users of chewing tobacco or snuff. For both sites, risk increased significantly with pack-years, earlier age at first use, and number of cigarettes. These results reinforce 2 recent reports of the association of cigarette smoking and colorectal cancer in men and women. Inconsistencies in the findings of earlier epidemiologic studies appear to be due in large part to differences in length of follow-up or in choice of controls. Studies with at least 20 years of follow-up or population-based controls have tended to find elevated risk with tobacco smoking, while those with shorter follow-up or hospital controls have not. This, plus the strength and consistency of the association of smoking and colon polyps, suggest that smoking may primarily affect an early stage in the development of colon cancer. If this association is causal, tobacco use may be responsible for 16% of colon-cancer and 22% of rectal-cancer deaths among these veterans. JF - International journal of cancer AU - Heineman, E F AU - Zahm, S H AU - McLaughlin, J K AU - Vaught, J B AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20852. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 728 EP - 738 VL - 59 IS - 6 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Humans KW - Aged KW - Plants, Toxic KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Tobacco, Smokeless -- adverse effects KW - Follow-Up Studies KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Veterans KW - Rectal Neoplasms -- mortality KW - Colonic Neoplasms -- epidemiology KW - Colonic Neoplasms -- mortality KW - Smoking -- adverse effects KW - Rectal Neoplasms -- epidemiology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76877704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+risk+of+colorectal+cancer+among+smokers%3A+results+of+a+26-year+follow-up+of+US+veterans+and+a+review.&rft.au=Heineman%2C+E+F%3BZahm%2C+S+H%3BMcLaughlin%2C+J+K%3BVaught%2C+J+B&rft.aulast=Heineman&rft.aufirst=E&rft.date=1994-12-15&rft.volume=59&rft.issue=6&rft.spage=728&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 - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD44 is a cytotoxic triggering molecule in human peripheral blood NK cells. AN - 76876438; 7527443 AB - Previous studies have shown that target cells that bind to CD44 adhesion molecules on cloned cytotoxic T cells are lysed by the CTL. To determine whether CD44 is also a cytotoxic trigger molecule in human PBL, we tested a bispecific Ab consisting of anti-CD44 Fab cross-linked to a Fab against a target cell Ag, in cytotoxicity assays using PBL as effectors. We found that PBL mediated lysis in the presence of the anti-CD44 bispecific Ab provided that the effector cells were stimulated with either IL-2 or IL-12. Cell fractionation experiments showed that CD44-directed cytolysis was mediated exclusively by CD56+ low buoyant density cells, mainly by NK (CD16+) cells, but also to a lesser extent by CD56+ T cells. CD44-directed cytolysis appeared in these subsets 24 to 48 h after addition of IL-2 and paralleled the acquisition of Ab-independent (LAK) activity; in contrast, these cells mediated Ab-dependent cellular cytotoxicity and CD3 redirected lysis before stimulation with IL-2. Unstimulated CD56+ cells uniformly expressed high levels of CD44 that increased modestly after incubation with IL-2. No changes in isoform expression in the extracellular domain of CD44 could be detected upon activation with the use of isoform-specific mAbs. Thus, lymphokine stimulation caused CD44 to become a cytotoxic trigger in subsets of PBL that mediated other forms of cytotoxicity and expressed CD44 before activation, suggesting that activation of these cells was accompanied by a coupling of CD44 to their lytic machinery. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Sconocchia, G AU - Titus, J A AU - Segal, D M AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 5473 EP - 5481 VL - 153 IS - 12 SN - 0022-1767, 0022-1767 KW - Antibodies, Bispecific KW - 0 KW - Antigens, CD44 KW - Carrier Proteins KW - Interleukin-2 KW - Receptors, Cell Surface KW - Receptors, Lymphocyte Homing KW - Interleukin-12 KW - 187348-17-0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Antibodies, Bispecific -- immunology KW - Interleukin-12 -- physiology KW - Humans KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Flow Cytometry KW - Interleukin-2 -- physiology KW - Receptors, Cell Surface -- immunology KW - Receptors, Lymphocyte Homing -- immunology KW - Carrier Proteins -- immunology KW - Cytotoxicity, Immunologic -- immunology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76876438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Long-term+botulinum+toxin+treatment+of+focal+hand+dystonia.&rft.au=Karp%2C+B+I%3BCole%2C+R+A%3BCohen%2C+L+G%3BGrill%2C+S%3BLou%2C+J+S%3BHallett%2C+M&rft.aulast=Karp&rft.aufirst=B&rft.date=1994-01-01&rft.volume=44&rft.issue=1&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in murine keratinocyte differentiation induced by activated rasHa genes are mediated by protein kinase C-alpha. AN - 76876090; 7987836 AB - Primary mouse keratinocytes expressing the v-rasHa oncogene (v-rasHa keratinocytes) produce squamous papillomas when grafted onto nude mice and respond abnormally to signals for terminal differentiation both in vivo and in vitro. Since protein kinase C (PKC) activators and v-rasHa induce similar phenotypic changes in cultured keratinocytes, and cellular diacylglycerol levels are constitutively elevated in ras-transformed keratinocytes, we tested whether PKC is a downstream target for oncogenic ras in this cell type. Ca(2+)-dependent PKC activity was increased in lysates from cultured v-rasHa keratinocytes when compared to control cells; in contrast, Ca(2+)-independent activity decreased. Similar to PKC activators, v-rasHa blocked Ca(2+)-mediated expression of the early epidermal differentiation markers keratins K1 and K10 while inducing aberrant expression of K8. Pretreatment of v-rasHa keratinocytes with bryostatin to block PKC function restored Ca(2+)-mediated expression of K1 and K10 and blocked abnormal expression of K8, suggesting that these responses are mediated by the PKC pathway. Furthermore, expression of K1 is restored at bryostatin doses which specifically down-modulate PKC-alpha, the only Ca(2+)-dependent PKC isozyme detected in cultured keratinocytes. In contrast to the inhibition of K1 and K10, Ca(2+)-induced expression of the late epidermal differentiation markers loricrin, filaggrin, and keratinocyte transglutaminase was accelerated by v-rasHa, as previously reported in normal keratinocytes treated with PKC activators. Pretreatment of v-rasHa keratinocytes with bryostatin blocked expression of late markers in these cells, and this response was correlated with down-regulation of PKC-alpha. The results of this study suggest that oncogenic ras alters keratinocyte differentiation by altering the function of the PKC signaling pathway, and that PKC-alpha is the specific isozyme involved in down-modulating expression of keratins K1 and K10 and up-regulating expression of loricrin, filaggrin, and keratinocyte transglutaminase. JF - Cancer research AU - Dlugosz, A A AU - Cheng, C AU - Williams, E K AU - Dharia, A G AU - Denning, M F AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 6413 EP - 6420 VL - 54 IS - 24 SN - 0008-5472, 0008-5472 KW - c-rasHa KW - v-rasHa KW - Biomarkers KW - 0 KW - Bryostatins KW - Intermediate Filament Proteins KW - Isoenzymes KW - Lactones KW - Macrolides KW - Membrane Proteins KW - Protein Precursors KW - filaggrin KW - loricrin KW - bryostatin 1 KW - 37O2X55Y9E KW - Transglutaminases KW - EC 2.3.2.13 KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Protein Precursors -- metabolism KW - Dose-Response Relationship, Drug KW - Membrane Proteins -- metabolism KW - Cell Differentiation -- genetics KW - Mice KW - Mice, Inbred BALB C KW - Intermediate Filament Proteins -- metabolism KW - Lactones -- pharmacology KW - Transglutaminases -- metabolism KW - Down-Regulation KW - Cells, Cultured KW - Calcium -- physiology KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Isoenzymes -- physiology KW - Genes, ras -- physiology KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76876090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+murine+keratinocyte+differentiation+induced+by+activated+rasHa+genes+are+mediated+by+protein+kinase+C-alpha.&rft.au=Dlugosz%2C+A+A%3BCheng%2C+C%3BWilliams%2C+E+K%3BDharia%2C+A+G%3BDenning%2C+M+F%3BYuspa%2C+S+H&rft.aulast=Dlugosz&rft.aufirst=A&rft.date=1994-12-15&rft.volume=54&rft.issue=24&rft.spage=6413&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 - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-rasHa; v-rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. AN - 76859196; 7982185 AB - Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed. The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity. One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037). Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible. JF - Cancer AU - White, R L AU - Schwartzentruber, D J AU - Guleria, A AU - MacFarlane, M P AU - White, D E AU - Tucker, E AU - Rosenberg, S A AD - Surgery Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12/15/ PY - 1994 DA - 1994 Dec 15 SP - 3212 EP - 3222 VL - 74 IS - 12 SN - 0008-543X, 0008-543X KW - Interleukin-2 KW - 0 KW - Recombinant Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Arrhythmias, Cardiac -- chemically induced KW - Injections, Intravenous KW - Humans KW - Adult KW - Recombinant Proteins -- adverse effects KW - Aged KW - Middle Aged KW - Child KW - Cardiomyopathies -- chemically induced KW - Adolescent KW - Recombinant Proteins -- administration & dosage KW - Male KW - Female KW - Respiratory Insufficiency -- chemically induced KW - Kidney Neoplasms -- drug therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Melanoma -- secondary KW - Melanoma -- drug therapy KW - Cardiovascular Diseases -- chemically induced KW - Carcinoma, Renal Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76859196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cardiopulmonary+toxicity+of+treatment+with+high+dose+interleukin-2+in+199+consecutive+patients+with+metastatic+melanoma+or+renal+cell+carcinoma.&rft.au=White%2C+R+L%3BSchwartzentruber%2C+D+J%3BGuleria%2C+A%3BMacFarlane%2C+M+P%3BWhite%2C+D+E%3BTucker%2C+E%3BRosenberg%2C+S+A&rft.aulast=White&rft.aufirst=R&rft.date=1994-12-15&rft.volume=74&rft.issue=12&rft.spage=3212&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From the National Institutes of Health. AN - 76831918; 7966919 JF - JAMA AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism. Y1 - 1994/12/14/ PY - 1994 DA - 1994 Dec 14 SP - 1733 VL - 272 IS - 22 SN - 0098-7484, 0098-7484 KW - Neurotransmitter Agents KW - 0 KW - Naltrexone KW - 5S6W795CQM KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Animals KW - Humans KW - National Institutes of Health (U.S.) KW - Naltrexone -- therapeutic use KW - Brain Chemistry -- drug effects KW - Alcoholism -- physiopathology KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76831918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=From+the+National+Institutes+of+Health.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1994-12-14&rft.volume=272&rft.issue=22&rft.spage=1733&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of locally advanced cancer of the head and neck with 5'-iododeoxyuridine and hyperfractionated radiation therapy: measurement of cell labeling and thymidine replacement. AN - 76831890; 7966416 AB - The halogenated pyrimidines 5'-iododeoxyuridine (IdUrd) and 5'-bromodeoxyuridine (BrdUrd) are under active study as radiation sensitizers for a variety of malignancies. Head and neck neoplasms may also be suitable for halogenated pyrimidine-mediated sensitization; previous regimens using intra-arterial BrdUrd delivery, however, were poorly tolerated. A pilot study was undertaken with the use of intravenous IdUrd with hyperfractionated radiotherapy to assess tolerance. In addition, serial tumor biopsy specimens were obtained to determine the kinetics of IdUrd labeling and incorporation. Twelve patients with squamous cell carcinomas of the head and neck (one patient had stage II cancer, one had stage III, and 10 had stage IV) were treated with hyperfractionated radiation therapy at a dose of 1.2 or 1.5 Gy twice a day, to a total dose in the range of 70-76 Gy. IdUrd (1000 mg/m2 per day) was infused for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. A tumor biopsy specimen was obtained from 11 patients following initiation of treatment with IdUrd. Eight patients consented to serial biopsy to allow the study of IdUrd-labeling indices and thymidine replacement over time. Incorporation of IdUrd into tumor DNA was determined by high-performance liquid chromatography, and cell labeling was determined with the use of an anti-BrdUrd/IdUrd monoclonal antibody in conjunction with flow cytometry. Patients continue to be followed to assess local control. A plot of corrected IdUrd replacement as a function of infusion time suggests the possibility of a plateau after 5-7 days of infusion at 7.5%-8%. The average rate of replacement from days 1 to 5 was 1.3% per day and was determined by linear regression analysis. Acute toxic effects, especially mucositis, were severe enough to require delays in the radiation therapy. Eleven of 12 patients treated had complete clinical remissions. Seven of these patients remain clinically free of local disease at the time of death or most recent follow-up. The level of IdUrd incorporation and cell labeling should be adequate to produce sensitization. However, the treatment as prescribed in this study (two 14-day infusions of IdUrd during radical radiotherapy with only one planned split) was not completed in a single patient because of either dose-limiting hematologic toxicity or severe mucositis necessitating treatment break. Since this particular regimen is not tolerable, future protocols will have shorter exposures to IdUrd. Previous regimens using halogenated pyrimidine radiosensitizers have generally used protracted drug delivery schedules. In this study, a high level of IdUrd labeling was measured after 5-7 days of drug infusion. The halogenated pyrimidines deserve further study with the use of repetitive short courses to reduce toxicity and possibly improve efficacy. JF - Journal of the National Cancer Institute AU - Epstein, A H AU - Lebovics, R S AU - Goffman, T AU - Teague, D AU - Fuetsch, E S AU - Glatstein, E AU - Okunieff, P AU - Cook, J A AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, Md. Y1 - 1994/12/07/ PY - 1994 DA - 1994 Dec 07 SP - 1775 EP - 1780 VL - 86 IS - 23 SN - 0027-8874, 0027-8874 KW - Idoxuridine KW - LGP81V5245 KW - Index Medicus KW - Infusions, Intravenous KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Radiotherapy -- methods KW - Pilot Projects KW - Middle Aged KW - Flow Cytometry KW - Time Factors KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- pathology KW - Idoxuridine -- therapeutic use KW - Head and Neck Neoplasms -- drug therapy KW - Idoxuridine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76831890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+locally+advanced+cancer+of+the+head+and+neck+with+5%27-iododeoxyuridine+and+hyperfractionated+radiation+therapy%3A+measurement+of+cell+labeling+and+thymidine+replacement.&rft.au=Epstein%2C+A+H%3BLebovics%2C+R+S%3BGoffman%2C+T%3BTeague%2C+D%3BFuetsch%2C+E+S%3BGlatstein%2C+E%3BOkunieff%2C+P%3BCook%2C+J+A&rft.aulast=Epstein&rft.aufirst=A&rft.date=1994-12-07&rft.volume=86&rft.issue=23&rft.spage=1775&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 - 1994-12-16 N1 - Date created - 1994-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in the molecular structure of c-myc-activating recombinations in murine plasmacytomas and precursor cells. AN - 76892378; 7991585 AB - The translocation of c-myc on chromosome (chr.) 15 to an immunoglobulin heavy-chain switch region on chr. 12 is the critical oncogenic step in pristane-induced plasmacytoma (PCT) development in BALB/cAnPt mice. Applying a recently developed PCR method, we have been able to detect the most commonly occurring illegitimate recombinations between alpha-chain switch region (S alpha) and c-myc in preneoplastic B cells residing in mesenteric oil granuloma (OG) tissues 7-30 days postpristane. In this study, we compare the nucleotide sequences at the S alpha/c-myc breaksites on both the c-myc-activating chr. 12+ and the reciprocal chr. 15- from eight transplanted PCTs, seven primary PCTs, and five OGs that contained six B-cell clones. These junction sequences revealed a remarkable diversity of S alpha/c-myc recombinations. In nine cases--four PCTs and five B-cell clones--nearly precise reciprocal exchanges with a loss of only 3-35 bp in c-myc were found. Large deletions in c-myc that removed 369-878 bp were observed in seven PCTs but not in early B cells. Duplications of c-myc ranging from 103 to 229 bp were also restricted to PCTs and noticed in four cases. Clonally related but different reciprocal recombinations, 38 bp apart on chr. 12+ and 15 bp apart on chr. 15-, were isolated from two different specimens of the same OG tissue from a BALB/c mouse 30 days postpristane. A second OG from another 30-day mouse yielded four recombinational fragments--two clonally related chr. 12(+)-specific fragments and two chr. 15(-)-specific fragments--one of which carried a 143-bp insertion of a microsatellite at the breaksite. We suggest that the initial recombinational break-point regions between S alpha and c-myc in plasmacytoma precursor cells at the time of immunoglobulin heavy-chain switching are intrinsically labile and characterized by a persisting instability of c-myc, which can result in large secondary deletions of c-myc. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Müller, J R AU - Potter, M AU - Janz, S AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/12/06/ PY - 1994 DA - 1994 Dec 06 SP - 12066 EP - 12070 VL - 91 IS - 25 SN - 0027-8424, 0027-8424 KW - c-myc KW - Carcinogens KW - 0 KW - DNA Primers KW - Immunoglobulin Heavy Chains KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Terpenes -- toxicity KW - Polymerase Chain Reaction KW - Animals KW - Precancerous Conditions -- genetics KW - Base Sequence KW - Genes, Switch KW - Molecular Sequence Data KW - Mice KW - Mice, Inbred BALB C KW - B-Lymphocytes KW - Sequence Deletion KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Genes, myc KW - Recombination, Genetic KW - Immunoglobulin Heavy Chains -- genetics KW - Chromosome Mapping KW - Translocation, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76892378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+the+molecular+structure+of+c-myc-activating+recombinations+in+murine+plasmacytomas+and+precursor+cells.&rft.au=M%C3%BCller%2C+J+R%3BPotter%2C+M%3BJanz%2C+S&rft.aulast=M%C3%BCller&rft.aufirst=J&rft.date=1994-12-06&rft.volume=91&rft.issue=25&rft.spage=12066&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 - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - SuppNotes - Cited By: Cell. 1982 Dec;31(2 Pt 1):443-52 [6819085] Mol Cell Biol. 1994 Feb;14(2):1204-12 [8289801] J Exp Med. 1985 Mar 1;161(3):577-601 [2579186] Adv Cancer Res. 1986;47:189-234 [3096089] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1581-5 [2830623] Genomics. 1988 Apr;2(3):257-62 [3165083] J Immunol. 1989 Apr 15;142(8):2932-5 [2495330] Mol Cell Biol. 1989 May;9(5):1850-6 [2747637] J Biol Chem. 1990 Apr 25;265(12):6693-9 [2157707] Mol Cell Biol. 1990 May;10(5):1901-7 [2183011] Eur J Immunol. 1992 Jul;22(7):1827-34 [1623926] Science. 1992 Jul 10;257(5067):212-4 [1378649] Annu Rev Biochem. 1992;61:809-60 [1497324] Nature. 1992 Oct 8;359(6395):552-4 [1406975] Nature. 1992 Oct 8;359(6395):554-6 [1406976] Carcinogenesis. 1992 Oct;13(10):1681-97 [1423827] Mutat Res. 1993 Jan;293(2):173-86 [7678145] Nucleic Acids Res. 1993 Feb 11;21(3):365-72 [8441648] Curr Opin Genet Dev. 1993 Feb;3(1):44-9 [8453273] Cell Growth Differ. 1993 Feb;4(2):93-104 [8494788] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7361-5 [8346257] Oncogene. 1993 Sep;8(9):2547-53 [8361763] Cell. 1984 Apr;36(4):973-82 [6323031] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid humanization of the Fv of monoclonal antibody B3 by using framework exchange of the recombinant immunotoxin B3(Fv)-PE38. AN - 76884424; 7991583 AB - B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of carcinoma-specific antibody B3 is fused to a truncated form of Pseudomonas exotoxin (PE). The efficacy of monoclonal antibody B3 and B3 immunotoxins in cancer therapy and diagnosis may be limited by the human anti-mouse response. Here we describe the humanization of the Fv of B3(Fv)-PE38 by "framework exchange." The variable domains of the heavy (VH) and light (VL) chains were aligned with their best human homologs to identify framework residues that differ. Initially, 11 framework residues in VH and six in VL were changed by site-specific mutagenesis to human residues and introduced simultaneously into a preassembled single-chain Fv expression cassette. Six VH and five VL residues that differ were not changed because they were buried, in the interdomain interface, or previously found to result in decreased affinity when mutated. This basic design resulted in some 20-fold loss of activity. Changing VL residues at the interdomain interfacial position 100 and at the buried position 104 to the human sequence increased the activity 8-fold. Changing VH residue at position 82b from the human sequence back to that of the mouse restored the activity 2- to 3-fold to the full binding and cytotoxic activity of the mouse sequence. Humanized B3(Fv)-PE38 lost immunogenic epitopes recognized by sera from monkeys that had been immunized with B3(Fv)-PE38. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Benhar, I AU - Padlan, E A AU - Jung, S H AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/12/06/ PY - 1994 DA - 1994 Dec 06 SP - 12051 EP - 12055 VL - 91 IS - 25 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Models, Molecular KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Immunoglobulin Light Chains -- chemistry KW - Mice KW - Plasmids KW - Recombinant Proteins -- toxicity KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Immunoglobulin Heavy Chains -- chemistry KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Recombinant Proteins -- chemistry KW - Pseudomonas aeruginosa KW - Immunotoxins -- toxicity KW - Immunoglobulin Variable Region -- immunology KW - Immunoglobulin Variable Region -- biosynthesis KW - Immunoglobulin Variable Region -- chemistry KW - Exotoxins -- chemistry KW - Antibodies, Monoclonal -- chemistry KW - Antibodies, Monoclonal -- immunology KW - Immunotoxins -- chemistry KW - Antibodies, Monoclonal -- toxicity KW - Immunotoxins -- immunology KW - Exotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76884424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+phthalmustine%2C+a+new+anticancer+compound.+I.+Effect+on+Dalton%27s+ascitic+lymphoma+in+mice.&rft.au=Bhattacharya%2C+S%3BGanguly%2C+C%3BSanyal%2C+U%3BDas%2C+S&rft.aulast=Bhattacharya&rft.aufirst=S&rft.date=1994-01-01&rft.volume=41&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1971 Mar 10;246(5):1496-503 [5545092] Mol Immunol. 1991 Apr-May;28(4-5):489-98 [1905784] Nature. 1984 May 3-9;309(5963):73-6 [6325927] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Proc Natl Acad Sci U S A. 1986 Jan;83(2):226-30 [2417241] Nature. 1986 May 29-Jun 4;321(6069):522-5 [3713831] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] J Mol Biol. 1986 Aug 20;190(4):593-604 [3097327] Science. 1987 Nov 6;238(4828):791-3 [3118465] Nature. 1988 Mar 24;332(6162):323-7 [3127726] Cancer Res. 1991 Jul 15;51(14):3781-7 [1648444] Hum Antibodies Hybridomas. 1990;1(1):23-6 [2129418] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] Hum Antibodies Hybridomas. 1992 Jul;3(3):137-45 [1391663] J Mol Biol. 1992 Oct 5;227(3):799-817 [1404389] Anal Biochem. 1992 Sep;205(2):263-70 [1332541] Biotechnology (N Y). 1992 Nov;10(11):1455-60 [1369023] Cancer Res. 1993 Jun 15;53(12):2834-9 [8504427] Eur J Immunol. 1993 Jul;23(7):1456-61 [7916694] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7538-42 [8356052] J Mol Biol. 1994 Jan 7;235(1):53-60 [8289265] J Mol Biol. 1994 Jan 21;235(3):959-73 [7507176] Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):969-73 [8302875] J Biol Chem. 1994 May 6;269(18):13398-404 [8175770] Proteins. 1994 May;19(1):35-47 [8066084] Bioconjug Chem. 1994 Jul-Aug;5(4):321-6 [7948099] Science. 1988 Mar 25;239(4847):1534-6 [2451287] Proc Natl Acad Sci U S A. 1989 Dec;86(24):10029-33 [2513570] Immunogenetics. 1991;33(1):42-9 [1899853] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. AN - 76882371; 7991549 AB - Recent investigations have shown the presence of ras gene mutations and human papillomavirus (HPV) DNA in prostate carcinomas. In the present study, secondary adult human prostatic epithelial cells, upon transfection with a plasmid containing the entire HPV-18 genome, acquired an indefinite life-span in culture but did not undergo malignant conversion. Subsequent infection of these immortalized cells with the Kirsten murine sarcoma virus, which contains an activated Ki-ras oncogene, induced morphological transformation that led to the acquisition of neoplastic properties. These findings demonstrate the malignant transformation of adult human prostate epithelial cells in culture by a combination of viral oncogenes and the successive roles of HPV infection and Ki-ras activation in a multistep process responsible for prostate carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rhim, J S AU - Webber, M M AU - Bello, D AU - Lee, M S AU - Arnstein, P AU - Chen, L S AU - Jay, G AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12/06/ PY - 1994 DA - 1994 Dec 06 SP - 11874 EP - 11878 VL - 91 IS - 25 SN - 0027-8424, 0027-8424 KW - v-Ki-ras KW - DNA-Binding Proteins KW - 0 KW - E7 protein, Human papillomavirus type 18 KW - Oncogene Proteins, Viral KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression KW - Mice KW - Mice, Nude KW - Blotting, Western KW - Epithelial Cells KW - Transfection KW - Blotting, Southern KW - Cells, Cultured KW - Adult KW - Transplantation, Heterologous KW - Middle Aged KW - Epithelium -- pathology KW - Male KW - Genes, ras KW - Prostatic Neoplasms -- pathology KW - Proto-Oncogene Proteins p21(ras) -- biosynthesis KW - Proto-Oncogene Proteins p21(ras) -- analysis KW - Oncogene Proteins, Viral -- analysis KW - Prostate -- pathology KW - Papillomaviridae -- genetics KW - Genome, Viral KW - Oncogene Proteins, Viral -- biosynthesis KW - Prostate -- cytology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76882371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Natural+Toxins&rft.atitle=Is+the+A-ring+lactone+of+brevetoxin+PbTX-3+required+for+sodium+channel+orphan+receptor+binding+and+activity%3F&rft.au=Baden%2C+D+G%3BRein%2C+K+S%3BGawley%2C+R+E%3BJeglitsch%2C+G%3BAdams%2C+D+J&rft.aulast=Baden&rft.aufirst=D&rft.date=1994-01-01&rft.volume=2&rft.issue=4&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Natural+Toxins&rft.issn=10569014&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-Ki-ras N1 - SuppNotes - Cited By: Cell. 1983 Dec;35(2 Pt 1):457-65 [6197180] Cancer. 1992 May 1;69(9):2293-9 [1562975] Science. 1985 Mar 8;227(4691):1250-2 [2579430] Biochem Biophys Res Commun. 1985 Oct 30;132(2):548-54 [3904752] N Engl J Med. 1986 Jan 16;314(3):133-7 [2417118] Science. 1986 Apr 18;232(4748):385-8 [2421406] N Engl J Med. 1987 Oct 8;317(15):916-23 [3041217] J Virol. 1988 Jun;62(6):1917-24 [2452896] Cancer Res. 1988 Aug 15;48(16):4620-8 [2456144] Oncogene. 1989 Nov;4(11):1403-9 [2682464] Prostate. 1990;16(1):39-48 [1689482] Cancer Res. 1990 Nov 1;50(21):6830-2 [2208148] Eur J Cancer. 1990;26(7):786-9 [1699574] Cancer Res. 1992 Nov 1;52(21):5991-6 [1382850] CA Cancer J Clin. 1993 Jan-Feb;43(1):7-26 [8422609] Cancer. 1993 Feb 1;71(3 Suppl):880-6 [8428342] Cancer Metastasis Rev. 1993 Mar;12(1):1-2 [8448821] Prostate. 1993;22(2):171-80 [8384363] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5954-8 [8327466] Cancer Res. 1991 Mar 15;51(6):1632-7 [1998954] J Urol. 1991 Apr;145(4):850-3 [1848641] Virology. 1991 Sep;184(1):9-13 [1651607] Proc Natl Acad Sci U S A. 1984 Feb;81(4):1216-20 [6583704] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy. AN - 85262153; pmid-7699385 AB - An epidemic outbreak of peripheral neuropathy affected Cuba in 1992-93 resulting in 50,862 cases (national cumulative incidence rate (CIR) 461.4 per 100,000). Clinical forms included retrobulbar optic neuropathy, sensory and dysautonomic peripheral neuropathy, dorsolateral myeloneuropathy, sensorineural deafness, dysphonia and dysphagia, spastic paraparesis, and mixed forms. For epidemiological purposes, cases were classified as optic forms (CIR 242.39) or peripheral forms (CIR 219.25). Increased risk was found among smokers (odds ratio (OR) 4.9), those with history of missing meals (OR 4.7) resulting in lower intake of animal protein, fat, and foods that contain B-vitamins, combined drinking and smoking (OR 3.5), weight loss (OR 2.8), excessive sugar consumption (OR 2.7) and heavy drinking (OR 2.3). Optic neuropathy was characterized by decreased vision, bilateral and symmetric central or cecocentral scotomata, and loss of color vision due to selective lesion of the maculopapillary bundles. Peripheral neuropathy was a distal axonopathy lesion affecting predominantly large myelinated axons. Deafness produced selective high frequency (4-8 kHz) hearing loss. Myelopathy lesions combined dorsal column deficits and pyramidal involvement of lower limbs with spastic bladder. Clinical features were those of Strachan syndrome and beriberi. Intensive search for neurotoxic agents, in particular organophosphorus esters, chronic cyanide, and trichloroethylene intoxication, yielded negative results. Treatment of patients with B-group vitamins and folate produced rewarding results. Most patients improved significantly and less than 0.1% of them remained with sequelae; there were no fatal cases. Supplementation of multivitamins to the entire Cuban population resulted in curbing of the epidemic. Overt malnutrition was not present, but a deficit of micronutrients, in particular thiamine, cobalamine, folate and sulfur amino acids appears to have been a primary determinant of this epidemic. JF - Journal of the Neurological Sciences AU - Román G C AD - Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. PY - 1994 SP - 11 EP - 28 VL - 127 IS - 1 SN - 0022-510X, 0022-510X KW - Sensation Disorders KW - Cuba KW - Politics KW - Avitaminosis KW - Human KW - Food KW - Paraparesis, Tropical Spastic KW - Aged KW - Child KW - Deafness KW - Adult KW - Nutrition Disorders KW - Adolescent KW - Male KW - Vitamin B Complex KW - Trace Elements KW - Toxins KW - Folic Acid KW - Beriberi KW - Peripheral Nervous System Diseases KW - Case-Control Studies KW - Incidence KW - Middle Age KW - Optic Nerve Diseases KW - Female KW - Disease Outbreaks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85262153?accountid=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+the+Neurological+Sciences&rft.atitle=An+epidemic+in+Cuba+of+optic+neuropathy%2C+sensorineural+deafness%2C+peripheral+sensory+neuropathy+and+dorsolateral+myeloneuropathy.&rft.au=Rom%C3%A1n+G+C&rft.aulast=Rom%C3%A1n+G+C&rft.aufirst=&rft.date=1994-12-01&rft.volume=127&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Neurological+Sciences&rft.issn=0022510X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Technique for injection of botulinum toxin through the flexible nasolaryngoscope. AN - 85200487; pmid-7991260 AB - A new endoscopic method of injecting botulinum toxin into the thyroarytenoid muscles for treatment of adductor spasmodic dysphonia was evaluated. Twelve patients with adductor spasmodic dysphonia were given injections in the thyroarytenoid muscle under video visualization with a flexible catheter needle that was passed through the working channel of a flexible nasolaryngoscope. Six patients received unilateral injections, and six received bilateral injections. Preinjection and postinjection speech samples were compared by use of spectrographic analysis. Significant decreases in voice breaks and sentence duration were found after treatment with both unilateral and bilateral injections. Patient interviews and diaries documented the reported degree and duration of symptom reduction. All 12 patients reported that the injections were of significant benefit and that the endoscopic procedure was tolerable. We concluded that this is a safe and effective technique for injecting botulinium toxin into laryngeal muscles for treatment of spasmodic dysphonia. JF - Otolaryngology--Head and Neck Surgery AU - Rhew, K AU - Fiedler, D A AU - Ludlow, C L AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892. PY - 1994 SP - 787 EP - 794 VL - 111 IS - 6 SN - 0194-5998, 0194-5998 KW - Video Recording KW - Patient Satisfaction KW - Human KW - Injections, Intramuscular KW - Sound Spectrography KW - Lidocaine KW - Anesthetics, Local KW - Needles KW - Catheterization KW - Botulinum Toxins KW - Comparative Study KW - Adult KW - Middle Age KW - Laryngismus KW - Voice Disorders KW - Fiber Optics KW - Speech KW - Female KW - Male KW - Laryngeal Muscles KW - Laryngoscopes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85200487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=Technique+for+injection+of+botulinum+toxin+through+the+flexible+nasolaryngoscope.&rft.au=Rhew%2C+K%3BFiedler%2C+D+A%3BLudlow%2C+C+L&rft.aulast=Rhew&rft.aufirst=K&rft.date=1994-12-01&rft.volume=111&rft.issue=6&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Multisite clinical trials in alcoholism treatment research: organizational, methodological and management issues. AN - 77842643; 7722995 AB - Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues. JF - Journal of studies on alcohol. Supplement AU - Fuller, R K AU - Mattson, M E AU - Allen, J P AU - Randall, C L AU - Anton, R F AU - Babor, T F AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892-7003. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 30 EP - 37 VL - 12 SN - 0363-468X, 0363-468X KW - Index Medicus KW - Humans KW - Outcome and Process Assessment (Health Care) KW - Research KW - Clinical Protocols KW - Alcoholism -- rehabilitation KW - Multicenter Studies as Topic -- methods KW - Randomized Controlled Trials as Topic -- methods KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77842643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol.+Supplement&rft.atitle=Multisite+clinical+trials+in+alcoholism+treatment+research%3A+organizational%2C+methodological+and+management+issues.&rft.au=Fuller%2C+R+K%3BMattson%2C+M+E%3BAllen%2C+J+P%3BRandall%2C+C+L%3BAnton%2C+R+F%3BBabor%2C+T+F&rft.aulast=Fuller&rft.aufirst=R&rft.date=1994-12-01&rft.volume=12&rft.issue=&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol.+Supplement&rft.issn=0363468X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoresistance in the clinic: overview 1994. AN - 77838603; 7727860 AB - One of the most exciting areas in clinical oncology today is the translation of laboratory research in drug resistance into therapeutic tools to improve responses to antineoplastic drugs. Two areas of investigation are currently under study in both the laboratory and clinic: reversal of gluthathione-mediated resistance and of P-glycoprotein mediated resistance. Studies are directed toward determining the role of the resistance mechanism in cancer, and toward its reversal. Increased expression of gluthathione and related enzymes, such as the gluthathione S-transferases, has been shown in human tumor samples. Phase I clinical studies with buthionine sulfoxime (BSO) have shown that gluthathione can be depleted without undue normal tissue toxicity. Now, clinical studies are underway evaluating the ability of BSO to enhance the efficacy of chemotherapy. Expression of P-glycoprotein has been described in human tumors, with increased levels observed after natural product chemotherapy in some malignancies. Studies with P-glycoprotein antagonists have been conducted in leukemia, lymphoma, multiple myeloma and in a variety of advanced malignancies. These studies have employed "first generation" antagonists such as verapamil and cyclosporine which were toxic at concentrations needed to block P-glycoprotein. Currently, studies are underway with "second generation" antagonists such as the dex stereoisomer of verapamil and the cyclosporine analogue, PSC 833. These agents may help determine the role of P-glycoprotein in clinical drug resistance. Together, these studies are aimed toward improving chemotherapeutic sensitivity in human cancer. JF - Bulletin du cancer AU - Bates, S E AU - Regis, J I AU - Robey, R W AU - Zhan, Z AU - Scala, S AU - Meadows, B J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 55s EP - 61s VL - 81 Suppl 2 SN - 0007-4551, 0007-4551 KW - P-Glycoprotein KW - 0 KW - Dipyridamole KW - 64ALC7F90C KW - Cyclosporine KW - 83HN0GTJ6D KW - Verapamil KW - CJ0O37KU29 KW - Glutathione KW - GAN16C9B8O KW - Nifedipine KW - I9ZF7L6G2L KW - Index Medicus KW - Nifedipine -- therapeutic use KW - Humans KW - Glutathione -- metabolism KW - Cyclosporine -- therapeutic use KW - Dipyridamole -- therapeutic use KW - Verapamil -- therapeutic use KW - P-Glycoprotein -- antagonists & inhibitors KW - Neoplasms -- drug therapy KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77838603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemoresistance+in+the+clinic%3A+overview+1994.&rft.au=Bates%2C+S+E%3BRegis%2C+J+I%3BRobey%2C+R+W%3BZhan%2C+Z%3BScala%2C+S%3BMeadows%2C+B+J&rft.aulast=Bates&rft.aufirst=S&rft.date=1994-12-01&rft.volume=81+Suppl+2&rft.issue=&rft.spage=55s&rft.isbn=&rft.btitle=&rft.title=Bulletin+du+cancer&rft.issn=00074551&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-01 N1 - Date created - 1995-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenetics: detecting sensitive populations. AN - 77833983; 7737047 AB - Risk assessment models strive to predict risks to humans from toxic agents. Safety factors and assumptions are incorporated into these models to allow a margin of error. In the case of cancer, substantial evidence shows that the carcinogenic process is a multistage process driven by the interaction of exogenous carcinogenic exposures, genetic traits, and other endogenous factors. Current risk assessment models fail to consider genetic predispositions that make people more sensitive or resistant to exogenous exposures and endogenous processes. Several cytochrome P450 enzymes, responsible for metabolically activating carcinogens and medications, express wide interindividual variation whose genetic coding has now been identified as polymorphic and linked to cancer risk. For example, a restriction fragment-length polymorphism for cytochrome P4501A1, which metabolizes polycyclic aromatic hydrocarbons, and cytochrome P4502E1, which metabolizes N-nitrosamines and benzene, is linked to lung cancer risk. Cytochrome P4502D6, responsible for metabolizing many clinically important medications, also is linked to lung cancer risk. The frequency for each of these genetic polymorphisms vary among different ethnic and racial groups. In addition to inherited factors for the detection of sensitive populations, determining the biologically effective doses for carcinogenic exposures also should quantitatively and qualitatively enhance the risk assessment process. Levels of carcinogen-DNA adducts reflect the net effect of exposure, absorption, metabolic activation, detoxification, and DNA repair. These effects are genetically predetermined, inducibility notwithstanding. The combination of adduct and genotyping assays provide an assessment of risk that reflects recent exogenous exposure as well as one's lifetime ability to activate and detoxify carcinogens. JF - Environmental health perspectives AU - Shields, P G AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 81 EP - 87 VL - 102 Suppl 11 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Genetic Testing KW - Polymorphism, Restriction Fragment Length KW - Dose-Response Relationship, Drug KW - Cytochrome P-450 Enzyme System -- genetics KW - Risk Factors KW - Models, Genetic KW - Humans KW - Genetic Predisposition to Disease KW - Risk Assessment KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Pharmacogenetics -- methods KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77833983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pharmacogenetics%3A+detecting+sensitive+populations.&rft.au=Shields%2C+P+G&rft.aulast=Shields&rft.aufirst=P&rft.date=1994-12-01&rft.volume=102+Suppl+11&rft.issue=&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-08 N1 - Date created - 1995-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1988 Aug 1;48(15):4184-8 [3390812] J Clin Invest. 1988 Jul;82(1):145-53 [3392204] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5240-3 [2899325] Biochim Biophys Acta. 1988 Aug 3;948(1):37-66 [3293663] Cancer Res. 1988 Aug 15;48(16):4695-700 [3135117] Annu Rev Biochem. 1988;57:29-67 [3052275] Carcinogenesis. 1988 Dec;9(12):2309-13 [3191577] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9243-7 [3143115] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9788-91 [3200858] Carcinogenesis. 1989 Feb;10(2):251-7 [2912575] Cancer Res. 1989 Jul 1;49(13):3675-9 [2731181] Cancer Res. 1989 Aug 15;49(16):4446-51 [2743334] Cancer Res. 1989 Sep 1;49(17):4929-35 [2503247] Carcinogenesis. 1989 Sep;10(9):1563-6 [2670300] Carcinogenesis. 1989 Sep;10(9):1567-77 [2670301] Carcinogenesis. 1989 Nov;10(11):2149-53 [2805234] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7677-81 [2682618] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9697-701 [2602371] Carcinogenesis. 1990 Jan;11(1):33-6 [2295125] J Natl Cancer Inst. 1990 Feb 7;82(3):238-9 [1967321] Science. 1991 Mar 15;251(4999):1366-70 [1848370] Jpn J Cancer Res. 1991 Mar;82(3):254-6 [1673675] Carcinogenesis. 1991 Jun;12(6):949-55 [2044201] Science. 1991 Jul 5;253(5015):49-53 [1905840] Cancer Res. 1990 Mar 15;50(6):1857-62 [2407346] Curr Probl Cancer. 1990 Mar-Apr;14(2):73-114 [2407428] FEBS Lett. 1990 Apr 9;263(1):131-3 [1691986] J Natl Cancer Inst. 1990 Jun 6;82(11):927-33 [2111410] J Natl Cancer Inst. 1990 Aug 1;82(15):1264-72 [2374176] J Natl Cancer Inst. 1990 Aug 15;82(16):1333-9 [2380990] Int J Cancer. 1990 Aug 15;46(2):185-8 [2384269] Lancet. 1990 Sep 1;336(8714):529-32 [1975039] Carcinogenesis. 1990 Sep;11(9):1527-30 [1976046] Cancer Res. 1990 Oct 15;50(20):6580-4 [2208119] Science. 1990 Oct 5;250(4977):113-6 [2218501] Nature. 1990 Oct 25;347(6295):773-6 [1978251] Science. 1990 Nov 30;250(4985):1233-8 [1978757] Cell. 1991 Jan 25;64(2):235-48 [1988146] Carcinogenesis. 1991 Jan;12(1):25-8 [1988177] Mutat Res. 1991 Mar;247(1):113-27 [2002797] Cell. 1990 Jun 1;61(5):759-67 [2188735] Chem Biol Interact. 1990;75(2):131-40 [2114949] Carcinogenesis. 1990 Jul;11(7):1229-31 [2372881] Carcinogenesis. 1990 Jul;11(7):1241-3 [2372884] Carcinogenesis. 1991 Jul;12(7):1197-201 [2070484] Carcinogenesis. 1991 Jul;12(7):1301-5 [2070496] JAMA. 1991 Aug 7;266(5):681-7 [2072479] Science. 1991 Aug 9;253(5020):665-9 [1651563] Cancer Res. 1991 Sep 15;51(18 Suppl):5023s-5044s [1884379] Cancer Res. 1991 Oct 1;51(19):5177-80 [1655248] Chem Res Toxicol. 1989 Mar-Apr;2(2):104-8 [2519708] J Biochem. 1991 Sep;110(3):407-11 [1722803] J Biochem. 1991 Oct;110(4):559-65 [1778977] Pharmacogenetics. 1991 Oct;1(1):20-5 [1726950] Pharmacogenetics. 1991 Oct;1(1):26-32 [1844820] Ann Intern Med. 1974 Feb;80(2):221-48 [4811796] Cancer Res. 1980 Sep;40(9):3116-7 [7427930] Int J Cancer. 1981;27(4):417-25 [6268552] Cancer Res. 1982 Dec;42(12):5030-7 [6291746] Nature. 1983 Jun 9-15;303(5917):468-72 [6304528] Carcinogenesis. 1983 Dec;4(12):1565-8 [6652869] Cancer Res. 1984 Jun;44(6):2467-74 [6722789] Cancer Res. 1984 Jul;44(7):2855-7 [6722814] Nature. 1984 Nov 8-14;312(5990):169-70 [6504125] Nature. 1985 Jan 31-Feb 6;313(6001):369-74 [2578622] Carcinogenesis. 1985 Feb;6(2):199-201 [3971485] Carcinogenesis. 1985 Aug;6(8):1109-15 [3926334] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6672-6 [2413443] Cancer Res. 1985 Nov;45(11 Pt 2):5890-4 [4053059] Carcinogenesis. 1986 Jul;7(7):1115-20 [3719906] Cancer Res. 1986 Aug;46(8):4178-83 [3731085] Prog Exp Tumor Res. 1987;31:104-13 [3562855] Science. 1987 Apr 17;236(4799):286-90 [3563508] Arch Toxicol Suppl. 1987;10:172-9 [3107522] IARC Sci Publ. 1987;(84):534-7 [3679438] Int J Cancer. 1988 Feb 15;41(2):169-73 [3338869] Nature. 1988 Feb 4;331(6155):442-6 [3123997] Mutat Res. 1988 Mar;204(3):531-41 [3347220] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1759-62 [3162305] Cancer Res. 1988 Apr 15;48(8):2156-61 [3349485] Cancer Res. 1988 Apr 15;48(8):2288-91 [3127049] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2353-6 [2895475] Carcinogenesis. 1988 Jul;9(7):1265-9 [3133129] Mutat Res. 1988 Jul;194(1):23-37 [3386656] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A chronological review of empirical studies matching alcoholic clients to treatment. AN - 77825835; 7722993 AB - During the past 20 years researchers have become increasingly interested in exploring the benefits of differential assignment of alcoholics to treatments based on client-specific characteristics, rather than searching for a single "most effective" intervention for all clients. Thirty-one empirical studies on "client-treatment matching" are reviewed, particularly from the perspective of how research methodology in this area has evolved. In addition, general observations are provided on how research methodology on this topic can be further enhanced. Finally, several promising interactions between client characteristics and particular interventions are noted, based on empirical studies to date. JF - Journal of studies on alcohol. Supplement AU - Mattson, M E AU - Allen, J P AU - Longabaugh, R AU - Nickless, C J AU - Connors, G J AU - Kadden, R M AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892-7003. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 16 EP - 29 VL - 12 SN - 0363-468X, 0363-468X KW - Index Medicus KW - Multicenter Studies as Topic KW - Randomized Controlled Trials as Topic KW - Humans KW - Outcome and Process Assessment (Health Care) KW - Clinical Protocols KW - Alcoholism -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77825835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Microbiology&rft.atitle=The+homologous+operons+for+P1+and+P7+plasmid+partition+are+autoregulated+from+dissimilar+operator+sites&rft.au=Hayes%2C+F%3BRadnedge%2C+L%3BDavis%2C+MA%3BAustin%2C+S+J&rft.aulast=Hayes&rft.aufirst=F&rft.date=1994-01-01&rft.volume=11&rft.issue=2&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning, expression and characterization of the Fv fragments of the anti-carbohydrate mAbs B1 and B5 as single-chain immunotoxins. AN - 77810980; 7716163 AB - The mAbs B1 (IgG1 kappa) and B5 (IgM kappa) recognize carbohydrate epitopes on human carcinoma cells. The Fv regions of these antibodies were separately cloned from hybridoma RNA using reverse transcription and PCR with oligonucleotide primers designed according to the amino acid sequences of the N-termini. The Fv regions also provide sequences for translation initiation in Escherichia coli (Fr1 oligos) and sequences of the constant region of the heavy and light domains (CH1 or C-kappa oligos). Following the determination of the DNA sequence of the Fvs, primers were designed according to the 3' ends of the VH and VL domains. These also provided for a peptide linker at the C-terminus of the VH and a short connector at the C-terminus of the VL (Fr4 oligos). The VH and VL were then each PCR-amplified using their corresponding Fr1 and phosphorylated Fr4 oligos. The resulting PCR products were annealed as 'mutagenic primers' to a uracil-containing single-stranded template obtained from an expression plasmid encoding a single-chain immunotoxin in which the B3 single-chain Fv is fused to a truncated form of Pseudomonas exotoxin (PE). Thus, the B1 and B5 variable domains replaced their corresponding B3 domains in the expression plasmid by 'variable domain shuffling' without subcloning. The resulting B1(Fv)-PE38 and B5(Fv)-PE38 were expressed in E. coli and purified to near homogeneity. Both show specific cytotoxicities to human carcinoma cell lines, but B1(Fv)-PE38 is much more active, reflecting its higher affinity to the target cells. JF - Protein engineering AU - Benhar, I AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1509 EP - 1515 VL - 7 IS - 12 SN - 0269-2139, 0269-2139 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Carbohydrates KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Virulence Factors KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured -- immunology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Adenocarcinoma KW - Cloning, Molecular KW - Exotoxins -- pharmacology KW - Immunoglobulin Fragments -- genetics KW - Immunoglobulin Fragments -- isolation & purification KW - Immunoglobulin Variable Region -- immunology KW - Immunoglobulin Variable Region -- chemistry KW - Antibodies, Monoclonal -- chemistry KW - Antibodies, Monoclonal -- immunology KW - Immunoglobulin Fragments -- chemistry KW - Carbohydrates -- immunology KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77810980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Cloning%2C+expression+and+characterization+of+the+Fv+fragments+of+the+anti-carbohydrate+mAbs+B1+and+B5+as+single-chain+immunotoxins.&rft.au=Benhar%2C+I%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1994-12-01&rft.volume=7&rft.issue=12&rft.spage=1509&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-16 N1 - Date created - 1995-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality following radiation treatment for infertility of hormonal origin or amenorrhoea. AN - 77809657; 7721518 AB - Between 1920 and 1965, radiation treatment to the ovaries and/or pituitary gland was used for refractory hormonal infertility and amenorrhoea. The potential carcinogenic effects of hormonal infertility, as well as exposure to relatively low doses of ovarian and pituitary radiation can be studied among patients receiving these treatments. A cohort of 816 patients treated between 1925 and 1961 was identified from the medical records of a New York City radiologist. The mortality experience for 84% of these women was determined and radiation doses for individual patients were estimated. Doses were, on average, 87, 64, 54, and 29 cGy to the ovary, brain, colon, and active bone marrow, respectively. Compared with mortality rates in the US population, the risk of death was less than expected (standardized mortality ratio [SMR] = 0.87; 95% confidence interval [CI]: 0.75-1.00). Deaths due to circulatory and digestive diseases were significantly below expectation. Cancer mortality was about 10% higher than that expected based on New York City mortality rates. Based on a small number of cases, no increase was found for cancers of the ovary or brain, or leukaemia, sites for which direct radiation exposure occurred, but significant excesses of colon cancer and non-Hodgkin's lymphoma were observed. A deficit in mortality from female genital cancers was surprising, since nulliparity has been a consistently reported risk factor for cancers of the endometrium and ovary. Breast cancer mortality was close to expectation. Overall, this study provided little evidence that either infertility or its treatment with radiation increased the risk of total or cancer mortality. JF - International journal of epidemiology AU - Ron, E AU - Boice, J D AU - Hamburger, S AU - Stovall, M AD - Radiation Epidemiology Branch, National Cancer Institute, NIH, Bethesda, MD, USA. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1165 EP - 1173 VL - 23 IS - 6 SN - 0300-5771, 0300-5771 KW - Index Medicus KW - Radiation Dosage KW - New York City -- epidemiology KW - Neoplasms -- mortality KW - Humans KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Female KW - Risk Assessment KW - Mortality KW - Infertility, Female -- radiotherapy KW - Amenorrhea -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77809657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+following+radiation+treatment+for+infertility+of+hormonal+origin+or+amenorrhoea.&rft.au=Ron%2C+E%3BBoice%2C+J+D%3BHamburger%2C+S%3BStovall%2C+M&rft.aulast=Ron&rft.aufirst=E&rft.date=1994-12-01&rft.volume=23&rft.issue=6&rft.spage=1165&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 - 1995-05-22 N1 - Date created - 1995-05-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemical contaminants, pharmacokinetics, and the lactating mother. AN - 77803626; 7737048 AB - We review the commonly occurring persistent pesticides and industrial chemicals in breast milk. These chemicals are dichlorodiphenyl trichloroethane as dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane, heptachlor, polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated dibenzodioxins. We present a worked example of the kinds of pharmacokinetic assumptions and calculations necessary for setting regulatory limits of contaminants in the food supply, calculating dose of chemical contaminants to the nursed infant, converting risks from lifetime exposure in laboratory animals to risks for short-term exposure in humans, and estimating the excess cancer risk to the nursed infant. JF - Environmental health perspectives AU - Rogan, W J AU - Ragan, N B AD - Office of Clinical Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 89 EP - 95 VL - 102 Suppl 11 SN - 0091-6765, 0091-6765 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Animals KW - Maximum Allowable Concentration KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Body Burden KW - Neoplasms -- chemically induced KW - Food Contamination KW - Risk Assessment KW - Milk, Human -- chemistry KW - Breast Feeding KW - Hazardous Substances -- pharmacokinetics KW - Hazardous Substances -- analysis KW - Hazardous Substances -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77803626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+contaminants%2C+pharmacokinetics%2C+and+the+lactating+mother.&rft.au=Rogan%2C+W+J%3BRagan%2C+N+B&rft.aulast=Rogan&rft.aufirst=W&rft.date=1994-12-01&rft.volume=102+Suppl+11&rft.issue=&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-06-08 N1 - Date created - 1995-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Obstet Gynecol. 1970 Mar 15;106(6):939 [5414844] N Engl J Med. 1991 Oct 3;325(14):1036-8 [1886625] Regul Toxicol Pharmacol. 1991 Jun;13(3):228-40 [1947235] Pediatrics. 1991 Oct;88(4):737-44 [1896276] N Engl J Med. 1991 Oct 3;325(14):981-5 [1886634] Residue Rev. 1976;61:37-112 [778957] Am J Dis Child. 1976 Aug;130(8):837-9 [941882] Sci Total Environ. 1976 Sep;6(2):161-3 [989182] J Occup Med. 1977 Sep;19(9):619-22 [599394] Am J Epidemiol. 1981 Apr;113(4):413-22 [7211826] Bull Environ Contam Toxicol. 1981 Sep;27(3):406-11 [7296075] Bull Environ Contam Toxicol. 1981 Oct;27(4):506-11 [7306714] Science. 1982 Jul 9;217(4555):137-40 [7089547] Environ Res. 1982 Jun;28(1):106-12 [6179776] J Natl Cancer Inst. 1983 Jul;71(1):157-63 [6408294] Residue Rev. 1983;89:1-128 [6316441] J Assoc Off Anal Chem. 1984 Jan-Feb;67(1):122-9 [6321428] J Pediatr. 1984 Aug;105(2):315-20 [6431068] Am J Clin Nutr. 1984 Oct;40(4):808-19 [6486088] Environ Health Perspect. 1985 Feb;59:5-10 [3921364] Environ Health Perspect. 1985 Feb;59:53-8 [3921365] Annu Rev Pharmacol Toxicol. 1985;25:667-89 [3890712] Environ Health Perspect. 1985 May;60:215-21 [3928347] Child Dev. 1985 Aug;56(4):853-60 [3930167] Am J Public Health. 1986 Feb;76(2):172-7 [3080910] J Assoc Off Anal Chem. 1986 Jan-Feb;69(1):146-59 [3949687] Int J Cancer. 1986 Jul 15;38(1):109-16 [3087890] J Pediatr. 1986 Aug;109(2):335-41 [3090217] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] JAMA. 1988 Jan 15;259(3):374-7 [3336161] Arch Environ Contam Toxicol. 1988 Jan;17(1):65-71 [3337553] Science. 1988 Jul 15;241(4863):334-6 [3133768] J Pediatr. 1988 Dec;113(6):991-5 [3142988] Neurotoxicol Teratol. 1990 May-Jun;12(3):239-48 [2115098] J Ark Med Soc. 1992 Apr;88(11):553-7 [1644709] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications: the transition from research to practice. AN - 77800077; 7722994 AB - As validated and improved alcoholism treatment methods emerge from Project MATCH and other studies, a dedicated and systematic effort will be needed to incorporate them into ongoing programs, to monitor their success in real world settings and to make adjustments and refinements as needed. Accomplishing this involves responsibilities for both researchers and practitioners. A complex continuum of activities designed to move interventions from research to practice is common to all therapeutic areas, with a fundamental component being researcher-provider interactions. Challenges include "debunking" myths; realistic evaluations of the feasibility of making changes in the treatment system; effective communication between providers and researchers; and proactive guidance from leaders who set standards of practice. Findings from relevant studies in alcoholism research can be assimilated into the treatment system with as little delay as possible as linkages between researchers and providers are strengthened. These linkages will be further strengthened by research in organizational, management and delivery mechanisms conducted by emerging applied research areas such as health services. JF - Journal of studies on alcohol. Supplement AU - Mattson, M E AU - Donovan, D M AD - National Institute on Alcohol Abuse and Alcoholism, Division of Clinical and Prevention Research, Rockville, Maryland 20892-7003. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 163 EP - 166 VL - 12 SN - 0363-468X, 0363-468X KW - Index Medicus KW - Feasibility Studies KW - Humans KW - Outcome and Process Assessment (Health Care) KW - Research KW - Patient Selection KW - Clinical Protocols KW - Alcoholism -- rehabilitation KW - Multicenter Studies as Topic -- methods KW - Randomized Controlled Trials as Topic -- methods KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77800077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol.+Supplement&rft.atitle=Clinical+applications%3A+the+transition+from+research+to+practice.&rft.au=Mattson%2C+M+E%3BDonovan%2C+D+M&rft.aulast=Mattson&rft.aufirst=M&rft.date=1994-12-01&rft.volume=12&rft.issue=&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol.+Supplement&rft.issn=0363468X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of a locus for mouse lung tumor susceptibility to proximal chromosome 19. AN - 77799273; 7894154 AB - Previous studies have hypothesized that at least three genetic loci contribute to differences in pulmonary adenoma susceptibility between mouse strains A/J and C57BL/6J. One gene that may confer susceptibility to lung tumorigenesis is the Kras protooncogene. To identify other relevant loci involved in this polygenic trait, we determined tumor multiplicity in 56 randomly chosen N-ethyl-N-nitrosourea-treated (A/J x C57BL/6J) N1 x C57BL/6 backcross (AB6N2) progeny and correlated it with genotypes at 77 microsatellite markers spanning the genome. A correlation of lung tumor multiplicity phenotypes with genotypes of microsatellite markers on distal Chromosome (Chr) 6 in the Kras region (Pas1) was confirmed, and a new region on Chr 19 (designated Pas3) was identified that also contributes to susceptibility. Linkage analysis on Chr 19 with 270 AB6N2 mice localized the region flanked by D19Mit42 and D19Mit19 that is most closely associated with lung tumor susceptibility. The Pas3 locus may be an enhancer of the susceptibility locus on Chr 6. JF - Mammalian genome : official journal of the International Mammalian Genome Society AU - Devereux, T R AU - Wiseman, R W AU - Kaplan, N AU - Garren, S AU - Foley, J F AU - White, C M AU - Anna, C AU - Watson, M A AU - Patel, A AU - Jarchow, S AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 749 EP - 755 VL - 5 IS - 12 SN - 0938-8990, 0938-8990 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Genotype KW - Mice, Inbred Strains KW - Animals KW - Genetic Markers -- genetics KW - Mice, Inbred C57BL KW - Mice KW - Genetic Variation -- genetics KW - Genetic Predisposition to Disease KW - Male KW - Female KW - Lung Neoplasms -- genetics KW - Chromosome Mapping -- methods KW - Adenoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77799273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assignment+of+a+locus+for+mouse+lung+tumor+susceptibility+to+proximal+chromosome+19.&rft.au=Devereux%2C+T+R%3BWiseman%2C+R+W%3BKaplan%2C+N%3BGarren%2C+S%3BFoley%2C+J+F%3BWhite%2C+C+M%3BAnna%2C+C%3BWatson%2C+M+A%3BPatel%2C+A%3BJarchow%2C+S&rft.aulast=Devereux&rft.aufirst=T&rft.date=1994-12-01&rft.volume=5&rft.issue=12&rft.spage=749&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 - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of cytochrome P450 in developmental pharmacology. AN - 77793737; 7696283 AB - Numerous sources of human heterogeneity affect biotransformation of compounds. Cytochrome P450, the primary oxidative pathway of drug metabolism, is the dominant phase I oxidative system metabolizing, to some degree, most of the drugs used clinically in humans. The P450 pathway is a major site of drug-drug, drug-diet, and drug-disease/condition interactions. Functional variability in this system can have pronounced consequences in suboptimal therapeutic response or enhanced toxicity. Methods for cataloguing specific P450 enzymes are being developed and their identification will promote rational drug development, more efficient clinical trial evaluation, and improved therapeutic approaches to patients requiring special consideration. These methods will facilitate the study of the impact of pubertal development on function in this system. JF - The Journal of adolescent health : official publication of the Society for Adolescent Medicine AU - Rogers, A S AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7510. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 635 EP - 640 VL - 15 IS - 8 SN - 1054-139X, 1054-139X KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Drug Interactions KW - Humans KW - Infant, Newborn KW - Child KW - Pregnancy KW - Child, Preschool KW - Therapeutic Equivalency KW - Oxidation-Reduction KW - Genotype KW - Infant KW - Biotransformation KW - Adult KW - Adolescent KW - Female KW - Male KW - Sex KW - Puberty KW - Pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- physiology KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77793737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+adolescent+health+%3A+official+publication+of+the+Society+for+Adolescent+Medicine&rft.atitle=The+role+of+cytochrome+P450+in+developmental+pharmacology.&rft.au=Rogers%2C+A+S&rft.aulast=Rogers&rft.aufirst=A&rft.date=1994-12-01&rft.volume=15&rft.issue=8&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+adolescent+health+%3A+official+publication+of+the+Society+for+Adolescent+Medicine&rft.issn=1054139X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Silica radical-induced DNA damage and lipid peroxidation. AN - 77784360; 7705289 AB - In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (.OH), superoxide radical (O2.-) and singlet oxygen (1O2) were all detected. Superoxide dismutase (SOD) partially inhibited .OH yield, whereas catalase abolished .OH generation. H2O2 enhanced .OH generation while deferoxamine inhibited it, indicating that .OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O2.- and 1O2. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O2.- and 1O2. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Shi, X AU - Mao, Y AU - Daniel, L N AU - Saffiotti, U AU - Dalal, N S AU - Vallyathan, V AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 149 EP - 154 VL - 102 Suppl 10 SN - 0091-6765, 0091-6765 KW - Free Radicals KW - 0 KW - Linoleic Acids KW - Lipid Peroxides KW - Superoxides KW - 11062-77-4 KW - Silicon Dioxide KW - 7631-86-9 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Superoxides -- metabolism KW - Oxygen -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Linoleic Acids -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Oxygen -- chemistry KW - Silicon Dioxide -- pharmacology KW - DNA Damage KW - Lipid Peroxides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77784360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Silica+radical-induced+DNA+damage+and+lipid+peroxidation.&rft.au=Shi%2C+X%3BMao%2C+Y%3BDaniel%2C+L+N%3BSaffiotti%2C+U%3BDalal%2C+N+S%3BVallyathan%2C+V&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-12-01&rft.volume=102+Suppl+10&rft.issue=&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-10 N1 - Date created - 1995-05-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicology. 1979 May;13(1):51-72 [229587] Free Radic Biol Med. 1993 May;14(5):463-72 [8394268] Free Radic Biol Med. 1987;3(2):119-23 [3666515] Free Radic Biol Med. 1987;3(4):259-303 [2826304] J Toxicol Environ Health. 1988;25(2):237-45 [2845112] Am Rev Respir Dis. 1988 Nov;138(5):1213-9 [2849348] Biochem Biophys Res Commun. 1989 Mar 15;159(2):445-51 [2539111] J Toxicol Environ Health. 1989;27(4):435-54 [2547978] J Toxicol Environ Health. 1990;29(3):307-16 [2156083] Free Radic Res Commun. 1990;9(3-6):259-66 [2167264] Chem Pharm Bull (Tokyo). 1990 Nov;38(11):3072-5 [2085890] Toxicol Ind Health. 1990 Dec;6(6):571-98 [1965871] Biochemistry. 1991 Jun 25;30(25):6283-9 [2059635] Chem Res Toxicol. 1989 Jul-Aug;2(4):234-9 [2562423] J Biol Chem. 1986 May 5;261(13):5952-8 [3009436] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Divergent conformational requirements for angiotensin II receptor internalization and signaling. AN - 77783743; 7699988 JF - Kidney international AU - Hunyady, L AU - Tian, Y AU - Sandberg, K AU - Balla, T AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1496 EP - 1498 VL - 46 IS - 6 SN - 0085-2538, 0085-2538 KW - Receptors, Angiotensin KW - 0 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Endocytosis KW - Animals KW - Cytoplasm -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Signal Transduction KW - Cell Line KW - Protein Conformation KW - Muscle, Smooth -- metabolism KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- metabolism KW - Receptors, Angiotensin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77783743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Kidney+international&rft.atitle=Divergent+conformational+requirements+for+angiotensin+II+receptor+internalization+and+signaling.&rft.au=Hunyady%2C+L%3BTian%2C+Y%3BSandberg%2C+K%3BBalla%2C+T%3BCatt%2C+K+J&rft.aulast=Hunyady&rft.aufirst=L&rft.date=1994-12-01&rft.volume=46&rft.issue=6&rft.spage=1496&rft.isbn=&rft.btitle=&rft.title=Kidney+international&rft.issn=00852538&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Keratinocyte growth factor receptor ligands induce transforming growth factor alpha expression and activate the epidermal growth factor receptor signaling pathway in cultured epidermal keratinocytes. AN - 77774766; 7535082 AB - Epidermal growth factor receptor (EGFR) ligands are fundamental regulators of epithelial growth, differentiation, and neoplastic transformation. In addition to being potent mitogens for murine epidermal keratinocytes in vitro, transforming growth factor alpha (TGF alpha) and EGF elicit distinctive changes in keratin expression: Ca(2+)-mediated induction of the differentiation-specific keratins K1 and K10 is blocked, while simple epithelial keratins K8 and K18 are expressed aberrantly (C. Cheng et al., Cell Growth, & Differ., 4: 317-327, 1993). We have evaluated several additional growth factors to determine the specificity of this response for EGFR ligands. TGF alpha, keratinocyte growth factor (KGF), and acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF) or insulin-like growth factor type I, block Ca(2+)-mediated expression of K1 while inducing K8. Since KGF and aFGF (but not bFGF) are ligands for the KGF receptor (KGFR), we explored the possibility that the TGF alpha/EGFR pathway is an intermediary in signaling through the KGFR. TGF alpha mRNA was increased in cells treated with KGF, aFGF, or TGF alpha but not bFGF or insulin-like growth factor type I. Similar changes were detected at the protein level; TGF alpha in conditioned medium (CM) from control, KGF-, TGF alpha-, and aFGF-treated cultures was 54 (+/- 8, SEM), 365 (+/- 50), 146 (+/- 20), and 120 (+/- 50) pg/ml, respectively. KGF and TGF alpha also increased expression of cell-associated TGF alpha measured in keratinocyte lysates. KGF increased TGF alpha secretion and mRNA levels in human as well as mouse keratinocytes. CM from KGF-treated cultures stimulated cell growth when added to cultures of normal keratinocytes. Preincubation with neutralizing antibodies to both TGF alpha and KGF, but not KGF antibody alone, blocked cell growth in cultures treated with KGF CM, suggesting that the predominant keratinocyte mitogen in KGF CM is TGF alpha. In support of this hypothesis, treatment of keratinocytes for 5 min with either KGF CM or purified TGF alpha resulted in EGFR autophosphorylation. Furthermore, after approximately 24 h, KGF as well as TGF alpha induced EGFR down-regulation based on Western blot analysis and 125I-EGF binding. Induction of TGF alpha in KGF-treated keratinocytes, coupled to activation and down-modulation of the EGFR, suggests that TGF alpha may be a proximal effector of KGF action for at least certain aspects of epidermal growth and differentiation. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Dlugosz, A A AU - Cheng, C AU - Denning, M F AU - Dempsey, P J AU - Coffey, R J AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1283 EP - 1292 VL - 5 IS - 12 SN - 1044-9523, 1044-9523 KW - FGF7 protein, human KW - 0 KW - Fgf7 protein, mouse KW - Fibroblast Growth Factor 10 KW - Growth Substances KW - Ligands KW - RNA, Messenger KW - Receptors, Fibroblast Growth Factor KW - Receptors, Growth Factor KW - Transforming Growth Factor alpha KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Fibroblast Growth Factor 7 KW - 126469-10-1 KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, Fibroblast Growth Factor, Type 2 KW - keratinocyte growth factor receptor KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Fibroblast Growth Factor 2 -- pharmacology KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Blotting, Northern KW - Dose-Response Relationship, Drug KW - Humans KW - RNA, Messenger -- analysis KW - Mice KW - Calcium -- pharmacology KW - Epidermal Growth Factor -- pharmacology KW - Mice, Inbred BALB C KW - Insulin-Like Growth Factor I -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Animals, Newborn KW - Fibroblast Growth Factor 1 -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Epidermal Growth Factor -- metabolism KW - Gene Expression -- drug effects KW - Signal Transduction -- physiology KW - Skin -- metabolism KW - Receptors, Growth Factor -- physiology KW - Keratinocytes -- drug effects KW - Growth Substances -- pharmacology KW - Signal Transduction -- drug effects KW - Transforming Growth Factor alpha -- biosynthesis KW - Keratinocytes -- metabolism KW - Receptors, Growth Factor -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77774766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Keratinocyte+growth+factor+receptor+ligands+induce+transforming+growth+factor+alpha+expression+and+activate+the+epidermal+growth+factor+receptor+signaling+pathway+in+cultured+epidermal+keratinocytes.&rft.au=Dlugosz%2C+A+A%3BCheng%2C+C%3BDenning%2C+M+F%3BDempsey%2C+P+J%3BCoffey%2C+R+J%3BYuspa%2C+S+H&rft.aulast=Dlugosz&rft.aufirst=A&rft.date=1994-12-01&rft.volume=5&rft.issue=12&rft.spage=1283&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rash complicating carbamazepine treatment. AN - 77764068; 7884021 AB - Carbamazepine--widely used in the treatment of trigeminal neuralgia, seizure disorders, and more recently, manic-depressive illness--is generally safe and well tolerated. Although serious adverse reactions, such as hematologic toxicity, may occur rarely, we have found that carbamazepine-induced rash is common, occurring in 13 (12%) of 113 patients. We describe our experience with carbamazepine-induced rash, including clinical characteristics, demographic features, and associated laboratory findings. Integrating our findings with the literature, we also discuss incidence, possible mechanisms, and implications for treatment because these benign rashes can occasionally progress to more fulminant and life-threatening eruptions. JF - Journal of clinical psychopharmacology AU - Kramlinger, K G AU - Phillips, K A AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 408 EP - 413 VL - 14 IS - 6 SN - 0271-0749, 0271-0749 KW - Carbamazepine KW - 33CM23913M KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Carbamazepine -- adverse effects KW - Drug Eruptions -- etiology KW - Anxiety Disorders -- drug therapy KW - Depressive Disorder -- psychology KW - Anxiety Disorders -- psychology KW - Bipolar Disorder -- drug therapy KW - Carbamazepine -- administration & dosage KW - Depressive Disorder -- drug therapy KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77764068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Differential+activity+of+Rickettsia+rickettsii+ompA+and+ompB+promoter+regions+in+a+heterologous+reporter+gene+system&rft.au=Policastro%2C+P+F%3BHackstadt%2C+T&rft.aulast=Policastro&rft.aufirst=P&rft.date=1994-01-01&rft.volume=140&rft.issue=11&rft.spage=2941&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Psychopharmacol. 1996 Jun;16(3):263-4 [8784668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Curing lupus--views from the foothills. AN - 77740535; 7864683 JF - Annals of the rheumatic diseases AU - Klippel, J H AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 785 EP - 786 VL - 53 IS - 12 SN - 0003-4967, 0003-4967 KW - Adrenal Cortex Hormones KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Anemia, Aplastic -- chemically induced KW - Humans KW - Neoplasms -- chemically induced KW - Adrenal Cortex Hormones -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Lupus Erythematosus, Systemic -- drug therapy KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77740535?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+rheumatic+diseases&rft.atitle=Curing+lupus--views+from+the+foothills.&rft.au=Klippel%2C+J+H&rft.aulast=Klippel&rft.aufirst=J&rft.date=1994-12-01&rft.volume=53&rft.issue=12&rft.spage=785&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+rheumatic+diseases&rft.issn=00034967&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: JAMA. 1990 Apr 4;263(13):1812-5 [2313852] J Rheumatol. 1994 Nov;21(11):2068-70 [7532717] Nature. 1992 Mar 26;356(6367):314-7 [1372394] Lancet. 1992 Sep 26;340(8822):741-5 [1356175] Science. 1993 Feb 26;259(5099):1321-4 [7680493] J Clin Oncol. 1993 Jul;11(7):1306-10 [8315426] Lupus. 1991 Nov;1(1):31-5 [1845361] Ann Intern Med. 1993 Sep 1;119(5):366-9 [8338289] Lupus. 1993 Jun;2(3):151-6 [8103697] Science. 1993 Sep 24;261(5129):1727-30 [8378772] J Clin Invest. 1994 Mar;93(3):1029-34 [7510716] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2344-8 [7510888] Ann Intern Med. 1994 May 1;120(9):784-91 [7908507] Arthritis Rheum. 1994 Apr;37(4):551-8 [8147933] J Rheumatol. 1994 May;21(5):836-8 [8064722] Arch Dermatol. 1992 Jan;128(1):80-2 [1531405] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multistage models of carcinogenesis: an approximation for the size and number distribution of late-stage clones. AN - 77728681; 7846311 AB - Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two-stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth-death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth-death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic clones. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Sherman, C D AU - Portier, C J AU - Kopp-Schneider, A AD - Laboratory of Quantitative & Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1039 EP - 1048 VL - 14 IS - 6 SN - 0272-4332, 0272-4332 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Clone Cells KW - Animals KW - Carcinogens, Environmental -- adverse effects KW - Risk Assessment KW - Neoplasms, Experimental KW - Neoplasms -- chemically induced KW - Models, Statistical KW - Models, Biological KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77728681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+cholera+toxin+by+ADP-ribosylation+factors.&rft.au=Moss%2C+J%3BTsai%2C+S+C%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1994-01-01&rft.volume=235&rft.issue=&rft.spage=640&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 - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Malignant mesothelioma: attributable risk of asbestos exposure. AN - 77724733; 7849863 AB - To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive. JF - Occupational and environmental medicine AU - Spirtas, R AU - Heineman, E F AU - Bernstein, L AU - Beebe, G W AU - Keehn, R J AU - Stark, A AU - Harlow, B L AU - Benichou, J AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 804 EP - 811 VL - 51 IS - 12 SN - 1351-0711, 1351-0711 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Humans KW - Occupational Diseases -- etiology KW - Aged KW - Cause of Death KW - Occupational Diseases -- mortality KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Occupational Diseases -- pathology KW - Middle Aged KW - Female KW - Male KW - Industry KW - Peritoneal Neoplasms -- etiology KW - Pleural Neoplasms -- mortality KW - Mesothelioma -- etiology KW - Pleural Neoplasms -- pathology KW - Peritoneal Neoplasms -- pathology KW - Mesothelioma -- mortality KW - Mesothelioma -- pathology KW - Asbestos -- adverse effects KW - Pleural Neoplasms -- etiology KW - Peritoneal Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77724733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Malignant+mesothelioma%3A+attributable+risk+of+asbestos+exposure.&rft.au=Spirtas%2C+R%3BHeineman%2C+E+F%3BBernstein%2C+L%3BBeebe%2C+G+W%3BKeehn%2C+R+J%3BStark%2C+A%3BHarlow%2C+B+L%3BBenichou%2C+J&rft.aulast=Spirtas&rft.aufirst=R&rft.date=1994-12-01&rft.volume=51&rft.issue=12&rft.spage=804&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Ind Med. 1972 Oct;29(4):436-42 [4636663] Br Med J. 1965 Feb 6;1(5431):350-3 [14237901] Br J Ind Med. 1974 Apr;31(2):91-104 [4830768] Comput Biomed Res. 1975 Oct;8(5):423-46 [1181079] Int Arch Occup Environ Health. 1975 Nov 4;36(1):1-18 [1205629] Br J Ind Med. 1976 May;33(2):115-22 [1276091] Biometrics. 1976 Sep;32(3):599-606 [963173] J Air Pollut Control Assoc. 1977 Feb;27(2):121-6 [845325] Thorax. 1977 Aug;32(4):377-86 [929482] Arch Environ Health. 1978 Jan-Feb;33(1):15-9 [629592] Lancet. 1978 May 20;1(8073):1061-3 [77365] Ann N Y Acad Sci. 1979;330:423-32 [294193] Ann N Y Acad Sci. 1979;330:455-66 [294196] Ann N Y Acad Sci. 1979;330:761-4 [294219] Am J Med. 1980 Mar;68(3):356-62 [7361805] Cancer. 1980 Oct 1;46(7):1650-6 [7417959] Cancer Res. 1980 Nov;40(11):3875-9 [7471040] N Y State J Med. 1981 Apr;81(5):735-8 [6938842] Arch Pathol Lab Med. 1981 Jun;105(6):305-12 [6894526] Br J Cancer. 1982 Jan;45(1):124-35 [7059455] Cancer. 1982 Jun 1;49(11):2431-5 [7074556] Ann Intern Med. 1982 Jun;96(6 Pt 1):746-55 [7091938] Am J Ind Med. 1982;3(4):413-22 [7168449] J Occup Med. 1983 May;25(5):409-25 [6854431] Thorax. 1983 Oct;38(10):744-6 [6648853] Br J Ind Med. 1984 Feb;41(1):39-45 [6691935] Cancer. 1984 Feb 1;53(3):377-83 [6692252] Br J Ind Med. 1965 Oct;22(4):261-9 [5836565] Arch Environ Health. 1967 Apr;14(4):559-63 [6024480] Chest. 1971 Dec;60(6):564-70 [5126187] J Natl Cancer Inst. 1972 Mar;48(3):797-821 [5058974] Med J Aust. 1984 Jul 21;141(2):86-8 [6330509] Cancer. 1984 Sep 1;54(5):951-60 [6331632] Cancer. 1985 Feb 1;55(3):672-4 [3965116] Br J Cancer. 1985 May;51(5):699-705 [3994913] Br J Ind Med. 1985 Aug;42(8):563-4 [4016009] Am J Epidemiol. 1985 Nov;122(5):904-14 [4050778] Am J Epidemiol. 1986 Mar;123(3):481-9 [3946394] Am J Ind Med. 1986;9(4):323-32 [3706307] Am J Ind Med. 1986;9(5):397-407 [3717166] J Natl Cancer Inst. 1987 Jun;78(6):1053-60 [3473246] J Natl Cancer Inst. 1987 Jul;79(1):31-7 [3474447] Cancer. 1989 Apr 15;63(8):1544-7 [2924262] Med J Aust. 1989 Mar 6;150(5):242-3, 246 [2716620] Int J Epidemiol. 1989 Jun;18(2):320-9 [2767845] Pathol Res Pract. 1990 Feb;186(1):124-34 [1690413] Br J Ind Med. 1990 Nov;47(11):775-81 [2245188] Ann N Y Acad Sci. 1990;609:322-32; discussion 332-3 [2264654] Biometrics. 1990 Dec;46(4):991-1003 [2085643] Am J Ind Med. 1991;20(3):371-9 [1928113] J Clin Pathol. 1973 Nov;26(11):832-40 [4766195] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The importance of biological realism in dioxin risk assessment models. AN - 77708288; 7846331 AB - Mechanistic mathematical models of hepatocarcinogenesis in the female rat were constructed to investigate possible relationships among the Ah, estrogen, and EGF receptors in TCDD hepatocarcinogenicity. Each model generates dose-response curves for the expression of biomarker liver proteins CYP1A1, CYP1A2, and residual plasma membrane EGF receptor consequent to exposure to TCDD. The shapes of the response curves were strongly dependent on the assumed mechanisms of constitutive expression of these proteins. Assuming a constant level of the hepatic Ah receptor, a sigmoidal dose-response of hepatic CYP1A1 to total liver TCDD was computed. However, inclusion of induction of the Ah receptor by TCDD in a physiologically realistic dosimetric model produced a linear low-dose response of CYP1A1. This behavior was computed to arise from the net effect of sublinear response of CYP1A1 mRNA to the concentration of the Ah-TCDD complex and supralinear response of the protein concentration to the mRNA level, illustrating the importance of biological realism in dose-response modeling. The dosimetric model also computed effects of TCDD on the hepatic estradiol concentration and consequent effects on the binding capacity of the EGF receptor and suggests plausible mechanisms for tumor promotion by TCDD. Setting circulating estradiol levels in the model to values typical of the male rat indicated possible sources of the differences in the responses of the EGF receptor and in development of tumors in the two sexes. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Kohn, M C AU - Lucier, G W AU - Portier, C J AD - Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 993 EP - 1000 VL - 14 IS - 6 SN - 0272-4332, 0272-4332 KW - Biomarkers KW - 0 KW - DNA, Neoplasm KW - Dioxins KW - RNA, Messenger KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - RNA, Messenger -- analysis KW - Disease Models, Animal KW - Transcription, Genetic KW - DNA, Neoplasm -- analysis KW - Female KW - Risk Assessment KW - Liver Neoplasms -- enzymology KW - Biomarkers -- analysis KW - Liver Neoplasms -- chemically induced KW - Cytochrome P-450 Enzyme System -- metabolism KW - Dioxins -- toxicity KW - Models, Biological KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77708288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=The+importance+of+biological+realism+in+dioxin+risk+assessment+models.&rft.au=Kohn%2C+M+C%3BLucier%2C+G+W%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=1994-12-01&rft.volume=14&rft.issue=6&rft.spage=993&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salvage chemotherapy for epithelial ovarian carcinoma. AN - 77705322; 7835799 AB - Advanced epithelial ovarian cancer is a highly chemosensitive solid tumor with response rates of 70-80% to first-line chemotherapy, including a high proportion of complete responses. The majority of patients, however, eventually relapse and ultimately die of chemoresistant disease. Response rates to salvage agents are modest, and duration of response is relatively short. Important new agents have been identified in the salvage setting, however, and all patients with ovarian cancer recurring or persisting after front-line therapy should be encouraged to enroll in clinical trials. Phase II trials should include multiple adequately sized cohorts, for patients with platinum-sensitive disease and those with platinum-refractory disease. In addition, patients should be stratified by treatment-free interval. An effort should be made to report standard response endpoints, such as median duration of response, median time to progression, and median survival. Retreatment with a platinum-containing compound is appropriate in patients with platinum-sensitive disease. Trials of high-dose chemotherapy with hematologic support may be most appropriate for patients with minimal disease following first-line therapy, but are unlikely to benefit patients with platinum-resistant or bulky disease. Paclitaxel should figure prominently in consideration of salvage therapy for patients with platinum-resistant disease. Responses to other single agents or combination chemotherapy have been modest and generally of short duration. Efforts at hormonal therapy have been disappointing. Promising new agents include topoisomerase I inhibitors, such as topotecan, 9-aminocamptothecin, irinotecan (CPT-11), and pyrazoloacridine. Therapies focusing on novel molecular targets include antiangiogenesis agents, antimetastatic agents, and signal transduction inhibitors. Immunotherapy, including radioimmunotherapy, immunotoxins, and direct antitumor effects of monoclonal antibodies, may be useful. Greater understanding of the molecular pathology of ovarian cancer may help us develop more rational and effective treatment. JF - Gynecologic oncology AU - Christian, M C AU - Trimble, E L AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - S143 EP - S150 VL - 55 IS - 3 Pt 2 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents KW - 0 KW - Carboplatin KW - BG3F62OND5 KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Cisplatin -- therapeutic use KW - Humans KW - Salvage Therapy KW - Paclitaxel -- therapeutic use KW - Carboplatin -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Remission Induction KW - Antineoplastic Agents -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77705322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Salvage+chemotherapy+for+epithelial+ovarian+carcinoma.&rft.au=Christian%2C+M+C%3BTrimble%2C+E+L&rft.aulast=Christian&rft.aufirst=M&rft.date=1994-12-01&rft.volume=55&rft.issue=3+Pt+2&rft.spage=S143&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Options for primary chemotherapy of epithelial ovarian cancer: taxanes. AN - 77705274; 7835794 AB - The taxanes, a new class of anticancer agents, act by promoting the assembly of microtubules and stabilizing formed tubules. Two taxanes, paclitaxel and docetaxel, have clinical activity in epithelial ovarian carcinomas, including tumors with platinum resistance. Toxicities associated with the taxanes include hypersensitivity, leukopenia, neurotoxicity, and alopecia. Premedication with dexamethasone, diphenhydramine, and cimetidine decreases the incidence of severe anaphylactic reactions to less than 3%. In Phase II studies, response rates to paclitaxel in patients with previously treated ovarian cancer ranged from 20 to 48%. To date, only two Phase III study using paclitaxel in the treatment of ovarian cancer have mature data. In one trial in patients with suboptimally debulked stage III and IV ovarian cancer, conducted by the Gynecologic Oncology Group, patients receiving paclitaxel/cisplatin had a significantly greater clinical response rate and surgical response rate and a significantly smaller risk of progression than those of patients receiving cisplatin/cyclophosphamide. In a Phase III study of paclitaxel in previously treated patients at two different schedules (3- and 24-hr infusions), conducted by the Canadian-European Taxol Cooperative Group, patients on the 24-hr infusion experienced significantly more grade 4 neutropenia than those receiving the 3-hr infusion. The optimal dose, schedule, and combination for paclitaxel in the treatment of patients with ovarian cancer have not yet been defined. In Phase II studies of docetaxel in patients with previously treated ovarian cancer, response rates of 33-35% were noted. Peripheral edema was noted to be a clinically significant toxicity. JF - Gynecologic oncology AU - Trimble, E L AU - Arbuck, S G AU - McGuire, W P AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - S114 EP - S121 VL - 55 IS - 3 Pt 2 SN - 0090-8258, 0090-8258 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Bridged Bicyclo Compounds KW - Bridged-Ring Compounds KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - taxane KW - 1605-68-1 KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Humans KW - Paclitaxel -- analogs & derivatives KW - Paclitaxel -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Remission Induction KW - Cisplatin -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Bridged Bicyclo Compounds -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77705274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gynecologic+oncology&rft.atitle=Options+for+primary+chemotherapy+of+epithelial+ovarian+cancer%3A+taxanes.&rft.au=Trimble%2C+E+L%3BArbuck%2C+S+G%3BMcGuire%2C+W+P&rft.aulast=Trimble&rft.aufirst=E&rft.date=1994-12-01&rft.volume=55&rft.issue=3+Pt+2&rft.spage=S114&rft.isbn=&rft.btitle=&rft.title=Gynecologic+oncology&rft.issn=00908258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pentosan-induced thrombocytopenia: support for an immune complex mechanism. AN - 76932491; 7529541 AB - Pentosan polysulphate is a low molecular weight heparinoid that is used as an anticoagulant. Because the drug also has antineoplastic properties, it has been used experimentally at the National Institutes of Health to treat metastatic malignancies. We present the case of a patient who developed thrombocytopenia resembling Type II heparin-induced thrombocytopenia (HIT) during the course of pentosan therapy. The patient's plasma demonstrated platelet reactivity both by aggregometry and 14C-serotonin release in the presence of pentosan. Heparin and other polyanions could substitute for pentosan in aggregation studies. The aggregating activity co-purified with the patient's IgG and was inhibited by pre-incubation with monoclonal antibody (MoAb) to the platelet Fc receptor. To elucidate the relationship between the platelet, the polyanion and the antibody, we measured the binding of 3H-heparin to platelets in the presence of the patient's IgG and found that it was increased 6-fold over binding in the presence of control IgG. Heparin binding was not reduced by MoAb against the Fc receptor. Taken together, these data support a model in which polyanion-antibody complexes attach to the platelet surface by the polyanion and secondarily stimulate the platelet via their Fc termini. JF - British journal of haematology AU - Goad, K E AU - Horne, M K AU - Gralnick, H R AD - Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 803 EP - 808 VL - 88 IS - 4 SN - 0007-1048, 0007-1048 KW - Antigen-Antibody Complex KW - 0 KW - Immunoglobulin G KW - Receptors, Fc KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Receptors, Fc -- immunology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Adult KW - Heparin -- metabolism KW - Immunoglobulin G -- immunology KW - Blood Platelets -- metabolism KW - Antigen-Antibody Complex -- immunology KW - Thrombocytopenia -- immunology KW - Platelet Aggregation -- immunology KW - Thrombocytopenia -- chemically induced KW - Platelet Aggregation -- drug effects KW - Pentosan Sulfuric Polyester -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76932491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pentosan-induced+thrombocytopenia%3A+support+for+an+immune+complex+mechanism.&rft.au=Goad%2C+K+E%3BHorne%2C+M+K%3BGralnick%2C+H+R&rft.aulast=Goad&rft.aufirst=K&rft.date=1994-12-01&rft.volume=88&rft.issue=4&rft.spage=803&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 - 1995-02-14 N1 - Date created - 1995-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the toxicity of cinnamaldehyde when administered by microencapsulation in feed or by corn oil gavage. AN - 76925647; 7813982 AB - The toxicity of cinnamaldehyde (CNMA) was compared after administration by gavage and in dosed feed. Rats and mice of both sexes received CNMA by daily corn oil gavage (for 2 wk), or in microencapsulated form in feed (2 wk for rats, 3 wk for mice). Feed formulations contained 0-10% CNMA microcapsules, equivalent to approximate daily doses of 0-3000 mg CNMA/kg body weight for rats and 0-10,000 mg CNMA/kg body weight for mice. Concentrations were chosen to deliver CNMA doses approximately equal to doses in the gavage study. Gavage doses of 2620 mg/kg/day and above in mice and 940 mg/kg/day and above in rats produced nearly 100% mortality; there were no deaths in animals receiving microencapsulated CNMA. Rats and mice receiving CNMA in feed showed a dose-related decrease in body weight gain, which was accompanied in rats by hypoplastic changes in reproductive organs and accessory sex glands. CNMA administration by either route caused hyperplasia of the forestomach mucosa. These results demonstrate that microencapsulation in feed can present a useful alternative to gavage dosing for repeated-dose or prolonged-exposure studies, in that (1) the toxic effects of CNMA were similar after gavage dosing and after administration in microencapsulated form in feed, (2) ingestion of chemical in the feed more closely approximates human exposures, and (3) microencapsulation allows the delivery of higher net doses of chemical, while avoiding the acutely toxic effects of a bolus dose. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Hébert, C D AU - Yuan, J AU - Dieter, M P AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1107 EP - 1115 VL - 32 IS - 12 SN - 0278-6915, 0278-6915 KW - Antimutagenic Agents KW - 0 KW - Flavoring Agents KW - Acrolein KW - 7864XYD3JJ KW - Corn Oil KW - 8001-30-7 KW - cinnamic aldehyde KW - SR60A3XG0F KW - Index Medicus KW - Administration, Oral KW - Eating -- drug effects KW - Animals KW - Drug Compounding KW - Dose-Response Relationship, Drug KW - Kidney -- drug effects KW - Mice KW - Stomach -- drug effects KW - Rats KW - Genitalia -- drug effects KW - Stomach -- pathology KW - Rats, Inbred F344 KW - Animal Feed KW - Hyperplasia KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Spleen -- drug effects KW - Male KW - Female KW - Organ Size -- drug effects KW - Flavoring Agents -- toxicity KW - Antimutagenic Agents -- toxicity KW - Acrolein -- analogs & derivatives KW - Antimutagenic Agents -- administration & dosage KW - Flavoring Agents -- administration & dosage KW - Acrolein -- toxicity KW - Acrolein -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76925647?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+the+toxicity+of+cinnamaldehyde+when+administered+by+microencapsulation+in+feed+or+by+corn+oil+gavage.&rft.au=H%C3%A9bert%2C+C+D%3BYuan%2C+J%3BDieter%2C+M+P&rft.aulast=H%C3%A9bert&rft.aufirst=C&rft.date=1994-12-01&rft.volume=32&rft.issue=12&rft.spage=1107&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 - 1995-02-06 N1 - Date created - 1995-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping a mutator, mu2, which increases the frequency of terminal deletions in Drosophila melanogaster. AN - 76918761; 7808410 AB - A mutator, mu2, in Drosophila melanogaster has been identified recently that potentiates the recovery of terminal deficiencies. The deleted chromosomes behave as if they had been capped; that is, they are protected from degradation and from fusion with other chromosome fragments. The mutator maps near the telomere on the left arm of chromosome 3. Using the selectable marker Aprt, 150 deficiencies for region 62 of the cytological map have been recovered. These deficiencies identify the map position of mu2 as 62B11-C1. A yeast artificial chromosome spanning this region has been subcloned into lambda phage, and the positions of deficiency breakpoints on either side of the mu2 gene have been identified within the subclones. These positions limit the location of the left end of the gene to a 23 kb region. In the course of these experiments, three additional, presumptive mutant alleles were identified, suggesting that other mutator alleles remain undiscovered in many standard laboratory stocks. JF - Molecular & general genetics : MGG AU - Wang, M AU - Champion, L E AU - Biessmann, H AU - Mason, J M AD - Experimental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/12/01/ PY - 1994 DA - 1994 Dec 01 SP - 598 EP - 607 VL - 245 IS - 5 SN - 0026-8925, 0026-8925 KW - mu2 KW - Genetic Markers KW - 0 KW - Adenine Phosphoribosyltransferase KW - EC 2.4.2.7 KW - Index Medicus KW - Phenotype KW - Animals KW - Alleles KW - Adenine Phosphoribosyltransferase -- genetics KW - Chromosome Mapping -- veterinary KW - Male KW - Female KW - Chromosomes, Artificial, Yeast KW - Sequence Deletion KW - Drosophila melanogaster -- genetics KW - Telomere -- genetics KW - Mutation KW - Genes, Insect UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76918761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+%26+general+genetics+%3A+MGG&rft.atitle=Mapping+a+mutator%2C+mu2%2C+which+increases+the+frequency+of+terminal+deletions+in+Drosophila+melanogaster.&rft.au=Wang%2C+M%3BChampion%2C+L+E%3BBiessmann%2C+H%3BMason%2C+J+M&rft.aulast=Wang&rft.aufirst=M&rft.date=1994-12-01&rft.volume=245&rft.issue=5&rft.spage=598&rft.isbn=&rft.btitle=&rft.title=Molecular+%26+general+genetics+%3A+MGG&rft.issn=00268925&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mu2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitation of mitochondrial DNA in human lymphoblasts by a competitive polymerase chain reaction method: application to the study of inhibitors of mitochondrial DNA content. AN - 76914869; 7808425 AB - With increasing awareness of the mitochondrial toxicity associated with certain 2',3'-dideoxynucleosides used in anti-human immunodeficiency virus therapy, procedures for quantitative analyses of drug effects on mitochondrial DNA (mtDNA) have assumed enhanced importance. For this reason we have developed a method to measure the copy numbers of mtDNA in cultured MOLT-4 cells. First a hybrid competitive DNA template was synthesized by conventional polymerase chain reaction (PCR), using two custom-synthesized 40-mer composite primers incorporating mitochondrial displacement loop sequences linked by a non-mitochondrial cDNA template (a 76-base pair sequence from the tat/rev region of human immunodeficiency virus cDNA). For the competitive assay, increasing known copy numbers of the hybrid competitive template were added as an internal control to samples containing total cellular DNA. With this approach, two competitive PCR products were generated, 1) a mitochondrial displacement loop-derived fragment (182 base pairs) and 2) a competitive DNA template-derived fragment (156 base pairs). Absolute quantitation was achieved by radiometric comparison of the relative amounts of the two products. To test the versatility of this method, varying amounts of competitive template (6.6 x 10(4) to 6.6 x 10(9) copies) were used with a fixed quantity of total cellular DNA taken from cells cultured for 9 days in the presence or absence of selected pyrimidine and purine dideoxynucleosides. The results showed that the copy number of cellular mtDNA is 823 +/- 71 copies/cell in MOLT-4 cells. Little selective depletion of mtDNA, compared with total cellular DNA, was seen with the purine dideoxynucleosides examined; however, when the cells were exposed to the pyrimidine dideoxynucleoside 2',3'-dideoxycytidine (50 nM) for 9 days, mtDNA content was specifically depleted, although total cellular DNA decreased by only 10%. Thus, in addition to the presently used methods of assessing mitochondrial impairment, i.e., Southern blot analysis and electron microscopy, the competitive PCR method provides a third and convenient assay, with particular applicability to determination of mtDNA in very small numbers of cells. JF - Molecular pharmacology AU - Zhang, H AU - Cooney, D A AU - Sreenath, A AU - Zhan, Q AU - Agbaria, R AU - Stowe, E E AU - Fornace, A J AU - Johns, D G AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1063 EP - 1069 VL - 46 IS - 6 SN - 0026-895X, 0026-895X KW - DNA, Mitochondrial KW - 0 KW - 2'-fluoro-2',3'-dideoxyinosine KW - 134892-26-5 KW - Zalcitabine KW - 6L3XT8CB3I KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Cells, Cultured KW - Blotting, Southern KW - Humans KW - Molecular Sequence Data KW - Cell Division -- drug effects KW - Zalcitabine -- pharmacology KW - Didanosine -- pharmacology KW - Didanosine -- analogs & derivatives KW - Lymphocytes -- chemistry KW - Polymerase Chain Reaction -- methods KW - DNA, Mitochondrial -- analysis KW - DNA, Mitochondrial -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76914869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitation+of+mitochondrial+DNA+in+human+lymphoblasts+by+a+competitive+polymerase+chain+reaction+method%3A+application+to+the+study+of+inhibitors+of+mitochondrial+DNA+content.&rft.au=Zhang%2C+H%3BCooney%2C+D+A%3BSreenath%2C+A%3BZhan%2C+Q%3BAgbaria%2C+R%3BStowe%2C+E+E%3BFornace%2C+A+J%3BJohns%2C+D+G&rft.aulast=Zhang&rft.aufirst=H&rft.date=1994-12-01&rft.volume=46&rft.issue=6&rft.spage=1063&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 - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma. AN - 76900412; 8001221 AB - The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21. Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR). Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA. These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2-16 base pairs. In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour. The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event. JF - Carcinogenesis AU - Yeudall, W A AU - Crawford, R Y AU - Ensley, J F AU - Robbins, K C AD - Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2683 EP - 2686 VL - 15 IS - 12 SN - 0143-3334, 0143-3334 KW - CDK41 KW - MTS1 KW - MTS1/CDK41 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - DNA, Neoplasm KW - Neoplasm Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Exons KW - DNA Mutational Analysis KW - Humans KW - RNA, Neoplasm -- genetics KW - Chromosomes, Human, Pair 9 KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Neoplasm Metastasis KW - DNA, Neoplasm -- genetics KW - Sequence Deletion KW - Neoplasm Proteins -- biosynthesis KW - Genes, Tumor Suppressor KW - Carcinoma, Squamous Cell -- pathology KW - Carrier Proteins -- genetics KW - Neoplasm Proteins -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Mouth Neoplasms -- pathology KW - Mouth Neoplasms -- genetics KW - Carrier Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76900412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MTS1%2FCDK4I+is+altered+in+cell+lines+derived+from+primary+and+metastatic+oral+squamous+cell+carcinoma.&rft.au=Yeudall%2C+W+A%3BCrawford%2C+R+Y%3BEnsley%2C+J+F%3BRobbins%2C+K+C&rft.aulast=Yeudall&rft.aufirst=W&rft.date=1994-12-01&rft.volume=15&rft.issue=12&rft.spage=2683&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CDK41; MTS1; MTS1/CDK41 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human CYP2A6 activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): mutational specificity in the gpt gene of AS52 cells. AN - 76900367; 8001247 AB - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is a potential human carcinogen that is known to be metabolized to DNA-reactive intermediates by the cytochromes P450. We have examined the nature of NNK's DNA damaging effects in a mammalian cell system expressing a specific human cytochrome P450 (2A6) and containing a target gene for mutagenesis. Human CYP2A6, which is known to activate NNK to a mutagen, was lipofected via a retroviral vector into the Chinese hamster ovary AS52 cell line, which contains the bacterial gpt gene and can be mutated to 6-thioguanine resistance. AS52 cells expressed negligible CYP2A6-specific coumarin 7-hydroxylase activity (0.7 pmol/mg protein/min), while a CYP2A6 transfected clone (AS52-E8) expressed 30 pmol/mg protein/min. Both cell lines were equally sensitive to the cytotoxic and mutagenic effects of the direct-acting mutagen ethylmethanesulfonate; however, only the AS52-E8 cells exhibited a dose-dependent increase in cytotoxicity and mutant frequency upon treatment with NNK. At the highest NNK dose (1200 micrograms/ml), the mutant frequency in AS52-E8 cells was 14-fold (339 x 10(-6)) greater than the spontaneous frequency of 24 x 10(-6). Ninty-eight mutant clones were isolated following NNK treatment. Based on PCR analysis, 21 clones contained deletions/rearrangements and 77 were putative point mutants. Sequencing potential point mutants showed that 81% contained G:C to A:T transitions. Four of six G:C to A:T hotspots were at the second G of the GGT motif, which is the motif and major mutation found in codon 12 of Ki-ras from NNK-induced lung tumors in strain A mice. Since NNK may be metabolized via different pathways to pyridyloxobutylate or methylate DNA, the data suggest that methylation damage causes the major mutagenic events in AS52-E8 cells when NNK is activated by human CYP2A6. JF - Carcinogenesis AU - Tiano, H F AU - Wang, R L AU - Hosokawa, M AU - Crespi, C AU - Tindall, K R AU - Langenbach, R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, NIEHS, RTP, NC 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2859 EP - 2866 VL - 15 IS - 12 SN - 0143-3334, 0143-3334 KW - Ki-ras KW - dhfr KW - gpt KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Nitrosamines KW - Proteins KW - Recombinant Fusion Proteins KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2A6 protein, human KW - Cytochrome P-450 CYP2A6 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Pentosyltransferases KW - EC 2.4.2.- KW - Gpt protein, E coli KW - EC 2.4.2.22 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Bacterial Proteins -- genetics KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Genes, Reporter -- drug effects KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- metabolism KW - Genes, ras KW - Polymerase Chain Reaction KW - Mutagenicity Tests KW - Base Sequence KW - Biotransformation KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - CHO Cells KW - Cell Line KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Cricetinae KW - Nitrosamines -- toxicity KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Nitrosamines -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76900367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+CYP2A6+activation+of+4-%28methylnitrosamino%29-1-%283-pyridyl%29-1-butanone+%28NNK%29%3A+mutational+specificity+in+the+gpt+gene+of+AS52+cells.&rft.au=Tiano%2C+H+F%3BWang%2C+R+L%3BHosokawa%2C+M%3BCrespi%2C+C%3BTindall%2C+K+R%3BLangenbach%2C+R&rft.aulast=Tiano&rft.aufirst=H&rft.date=1994-12-01&rft.volume=15&rft.issue=12&rft.spage=2859&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Ki-ras; dhfr; gpt N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic analysis of malignant skin tumors induced in chemically treated TG-AC transgenic mice. AN - 76900082; 7999263 AB - TG.AC mice (which carry a v-Ha-ras transgene) rapidly develop papillomas in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Approximately 30% of the papillomas are associated with subsequent development of malignancies. Early-passage spindle-shaped tumor cells arising from explant cultures of TPA-induced tumors in TG.AC mice were tumorigenic when transplanted to syngeneic recipients. The v-Ha-ras transgene in the transplanted tumors was expressed at a high level. To identify possible genetic changes associated with the development of malignant tumors, explanted cells were cultured in vitro and assessed for karyotypic changes between the second and third passages by analyzing G-banded metaphase chromosomes. For comparison, skin malignancies were induced in nontransgenic FVB/N mice (parent strain) by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and TPA promotion, and their G-banded metaphase chromosomes were analyzed. Trisomy (in at least 50% of about 30 metaphases) of chromosome 15 (in five of 15 tumors) and chromosome 6 (four of 15 tumors) was observed in TG.AC mice, independent of chemical treatment or tumor type. Of six tumors from DMBA/TPA-treated FVB/N mice, three had trisomy 10 or 15 (or both), and two appeared normal. The absence of trisomy 7 is notable because c-Ha-ras maps to that chromosome. The absence of trisomy 7 in the six FVB/N DMBA/TPA-induced skin malignancies contrasts with DMBA/TPA-induced karyotypic effects in SENCAR mice. Expression of the v-Ha-ras transgene may have precluded the requirement for endogenous mutant ras and allelic imbalance involving chromosome 7 in TG.AC mice, but it could not have in FVB/N mice. These results suggest the possibility that the observed trisomies are consequential, rather than causal, events in the development of TG.AC or FVB/N skin malignancies. Molecular genetic analysis will be required to understand the changes associated with tumorigenesis in this transgenic line as well as in the parent mouse line. JF - Molecular carcinogenesis AU - French, J E AU - Libbus, B L AU - Hansen, L AU - Spalding, J AU - Tice, R R AU - Mahler, J AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 215 EP - 226 VL - 11 IS - 4 SN - 0899-1987, 0899-1987 KW - p53 KW - v-Ha-ras KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Benzene KW - J64922108F KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Neoplasm Transplantation KW - Karyotyping KW - Animals KW - Gene Expression KW - Mice KW - Papilloma -- genetics KW - Mice, Transgenic KW - Papilloma -- chemically induced KW - Male KW - Female KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Sarcoma, Experimental -- chemically induced KW - Skin Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Squamous Cell -- chemically induced KW - Sarcoma, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76900082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytogenetic+analysis+of+malignant+skin+tumors+induced+in+chemically+treated+TG-AC+transgenic+mice.&rft.au=French%2C+J+E%3BLibbus%2C+B+L%3BHansen%2C+L%3BSpalding%2C+J%3BTice%2C+R+R%3BMahler%2C+J%3BTennant%2C+R+W&rft.aulast=French&rft.aufirst=J&rft.date=1994-12-01&rft.volume=11&rft.issue=4&rft.spage=215&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 - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53; v-Ha-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemopreventive effects of the aromatase inhibitors vorozole (R-83842) and 4-hydroxyandrostenedione in the methylnitrosourea (MNU)-induced mammary tumor model in Sprague-Dawley rats. AN - 76898063; 8001234 AB - The chemopreventive activity of the aromatase inhibitors vorozole and 4-hydroxyandrostenedione were determined in the methylnitrosourea (MNU)-induced model of rat mammary tumorigenesis. Vorozole (5 and 2.5 mg/kg body wt) and 4-hydroxyandrostenedione (15 and 6 mg/rat) were administered daily (by gavage) to virgin female Sprague-Dawley rats starting at an age of 43 days. Seven days later animals were given a single dose of MNU. Following treatment with MNU, animals continued to be treated with vorozole and 4-hydroxyandrostenedione daily until the end of the experiment (100 days post MNU treatment). Vorozole at either dose proved to be a profound inhibitor of MNU-induced mammary tumors. Vorozole decreased tumor incidence from 100% to 10%, while simultaneously decreasing tumor multiplicity from 5 tumors per animal to 0.1 tumors per animal. This chemopreventive effect was accompanied by significant increases in body weight gain in the animals treated with vorozole when compared with control rats. In contrast, neither dose of 4-hydroxyandrostenedione had any effect on tumor incidence and only the higher dose slightly decreased tumor multiplicity. JF - Carcinogenesis AU - Lubet, R A AU - Steele, V E AU - Casebolt, T L AU - Eto, I AU - Kelloff, G J AU - Grubbs, C J AD - NCI-DCPC, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2775 EP - 2780 VL - 15 IS - 12 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Aromatase Inhibitors KW - Triazoles KW - Aminoglutethimide KW - 0O54ZQ14I9 KW - vorozole KW - 1E2S9YXV2A KW - Androstenedione KW - 409J2J96VR KW - Methylnitrosourea KW - 684-93-5 KW - formestane KW - PUB9T8T355 KW - Index Medicus KW - Rats KW - Drug Screening Assays, Antitumor KW - Animals KW - Aminoglutethimide -- pharmacology KW - Rats, Sprague-Dawley KW - Estrus -- drug effects KW - Female KW - Structure-Activity Relationship KW - Mammary Neoplasms, Experimental -- chemically induced KW - Androstenedione -- analogs & derivatives KW - Adenocarcinoma -- chemically induced KW - Anticarcinogenic Agents -- pharmacology KW - Androstenedione -- pharmacology KW - Triazoles -- pharmacology KW - Adenocarcinoma -- prevention & control KW - Mammary Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76898063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemopreventive+effects+of+the+aromatase+inhibitors+vorozole+%28R-83842%29+and+4-hydroxyandrostenedione+in+the+methylnitrosourea+%28MNU%29-induced+mammary+tumor+model+in+Sprague-Dawley+rats.&rft.au=Lubet%2C+R+A%3BSteele%2C+V+E%3BCasebolt%2C+T+L%3BEto%2C+I%3BKelloff%2C+G+J%3BGrubbs%2C+C+J&rft.aulast=Lubet&rft.aufirst=R&rft.date=1994-12-01&rft.volume=15&rft.issue=12&rft.spage=2775&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction: examination of clinical and preclinical pharmacologic data relating to abuse liability of l-deprenyl (selegiline). AN - 76896644; 7995013 JF - Clinical pharmacology and therapeutics AU - Goldberg, S R AU - Yasar, S AU - Bergman, J AU - Youdim, M B AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 721 EP - 724 VL - 56 IS - 6 Pt 2 SN - 0009-9236, 0009-9236 KW - Selegiline KW - 2K1V7GP655 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Selegiline -- adverse effects KW - Substance-Related Disorders -- etiology KW - Selegiline -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76896644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+pharmacology+and+therapeutics&rft.atitle=Introduction%3A+examination+of+clinical+and+preclinical+pharmacologic+data+relating+to+abuse+liability+of+l-deprenyl+%28selegiline%29.&rft.au=Goldberg%2C+S+R%3BYasar%2C+S%3BBergman%2C+J%3BYoudim%2C+M+B&rft.aulast=Goldberg&rft.aufirst=S&rft.date=1994-12-01&rft.volume=56&rft.issue=6+Pt+2&rft.spage=721&rft.isbn=&rft.btitle=&rft.title=Clinical+pharmacology+and+therapeutics&rft.issn=00099236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-18 N1 - Date created - 1995-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. AN - 76895981; 8001233 AB - The consistent deletion of 3p21 in lung cancer has led to intensive efforts to identify a lung tumor suppressor gene at this locus. We recently mapped the gene for the selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) to this location by in situ hybridization. We developed a polymerase chain reaction-based assay which demonstrated the existence of three GPX1 alleles characterized by the number of alanines in a polyalanine coding sequence in exon 1. These three alleles produced a heterozygote frequency of 70% in two separate populations: normal tissue DNA taken from Centre d'Etude du Polmorphisme Humain (CEPH) parents and normal tissue taken from cancer patients. In contrast, 10 heterozygote tumors were detected out of 64 lung cancer specimens. Linkage analysis of GPX1 to Genethon 3p markers in CEPH pedigrees demonstrated that GPX1 was located between the two microsatellite markers believed to flank the lung cancer deletion site. Nucleotide sequence analysis of GPX1 alleles did not reveal any mutations of this gene in lung tumors. However, sequence analysis did reveal that the three GPX1 alleles were characterized by three nucleotide substitutions in addition to the polyalanine polymorphism, including a substitution at codon 198 which results in either a proline or leucine at that position. Therefore, the different GPX1 alleles encode structurally different hGPx1 subunits. In addition, analysis of allele frequency suggests that the GPX1*ALA7 allele may occur less frequently in tumors with 3p21 deletions. JF - Carcinogenesis AU - Moscow, J A AU - Schmidt, L AU - Ingram, D T AU - Gnarra, J AU - Johnson, B AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2769 EP - 2773 VL - 15 IS - 12 SN - 0143-3334, 0143-3334 KW - GPX1 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Reference Values KW - Gene Frequency KW - Polymorphism, Genetic KW - Cytosol -- enzymology KW - DNA Mutational Analysis KW - Humans KW - Amino Acid Sequence KW - Genotype KW - Selenium -- physiology KW - Alleles KW - Base Sequence KW - Chromosomes, Human, Pair 3 KW - In Situ Hybridization KW - Genes KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Sequence Deletion KW - Lung Neoplasms -- enzymology KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Neoplasm Proteins -- genetics KW - Lung Neoplasms -- genetics KW - Carcinoma, Non-Small-Cell Lung -- enzymology KW - Glutathione Peroxidase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76895981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss+of+heterozygosity+of+the+human+cytosolic+glutathione+peroxidase+I+gene+in+lung+cancer.&rft.au=Moscow%2C+J+A%3BSchmidt%2C+L%3BIngram%2C+D+T%3BGnarra%2C+J%3BJohnson%2C+B%3BCowan%2C+K+H&rft.aulast=Moscow&rft.aufirst=J&rft.date=1994-12-01&rft.volume=15&rft.issue=12&rft.spage=2769&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - GPX1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adduct levels of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) in tissues of cynomolgus monkeys after single or multiple dosing. AN - 76895941; 8001231 AB - DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), a heterocyclic amine derived from cooked meat, were measured by the 32P-postlabeling method in tissues of cynomolgus monkeys given PhIP. Monkeys received either a single dose of PhIP (20 mg/kg orally) or nine daily doses of PhIP (20 mg/kg orally, days 1-5 and 8-11) and tissue samples were obtained 24 h after the last dose. Over 28 different tissues were examined for PhIP-DNA adducts. Adducts were detected in all tissues examined except the fat and bone marrow. After a single dose, adduct levels (mean value/10(7) nucleotides, n = 2 monkeys) were highest in the liver (2.1), followed by the lung (1.7), gall bladder (1.7) and pancreas (0.9). Low adduct levels were detected in the brain and aorta (0.06 and 0.02 respectively). Following multiple doses of PhIP, adduct levels (mean value/10(7) nucleotides +/- SE, n = 3 monkeys) were highest in the heart (5.7 +/- 2.0) followed by the liver (3.8 +/- 0.8), submandibular gland (2.7 +/- 1.8) and pancreas (2.2 +/- 0.5). Comparison of the adduct levels after a single dose with those found after multiple doses indicates that accumulation of PhIP-DNA adducts occurred in certain tissues. Adduct levels in liver, pancreas, kidney, small intestine and colon increased about 1.5- to 2.4-fold. PhIP-DNA adduct levels in submandibular gland and brain increased 4- to 5-fold. Adduct levels in heart increased 10-fold and levels in the aorta increased 31-fold. Adducts in white blood cell DNA increased with daily dosing for 9 days. No apparent changes in adduct levels were seen in the lung, stomach, bladder, muscle and spleen. The wide distribution of PhIP-DNA adducts and their presence in white blood cells suggests that there is transport of reactive metabolites from the liver to extrahepatic tissues. The relatively high adduct levels in the gall bladder in comparison with the liver suggests biliary excretion and possible reabsorption of reactive metabolites. The presence of DNA adducts in tissues implicates PhIP as a potential carcinogen in non-human primates. The possibility that PhIP-DNA adducts in tissues such as the heart and aorta may have toxicological consequences is discussed. JF - Carcinogenesis AU - Snyderwine, E G AU - Schut, H A AU - Sugimura, T AU - Nagao, M AU - Adamson, R H AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2757 EP - 2761 VL - 15 IS - 12 SN - 0143-3334, 0143-3334 KW - DNA Adducts KW - 0 KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Aorta -- metabolism KW - Administration, Oral KW - Animals KW - Meat -- toxicity KW - Macaca fascicularis KW - Dose-Response Relationship, Drug KW - Biotransformation KW - Liver -- metabolism KW - Tissue Distribution KW - Male KW - Female KW - Imidazoles -- pharmacokinetics KW - Imidazoles -- pharmacology KW - DNA Adducts -- analysis KW - DNA Damage KW - Imidazoles -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76895941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=DNA+adduct+levels+of+2-amino-1-methyl-6-phenylimidazo-%5B4%2C5-b%5Dpyridine+%28PhIP%29+in+tissues+of+cynomolgus+monkeys+after+single+or+multiple+dosing.&rft.au=Snyderwine%2C+E+G%3BSchut%2C+H+A%3BSugimura%2C+T%3BNagao%2C+M%3BAdamson%2C+R+H&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1994-12-01&rft.volume=15&rft.issue=12&rft.spage=2757&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-26 N1 - Date created - 1995-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A clinicopathologic report of the retinal lesions associated with didanosine. AN - 76889921; 7993216 AB - Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis, peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Whitcup, S M AU - Dastgheib, K AU - Nussenblatt, R B AU - Walton, R C AU - Pizzo, P A AU - Chan, C C AD - National Eye Institute, National Institutes of Health, Bethesda, Md. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1594 EP - 1598 VL - 112 IS - 12 SN - 0003-9950, 0003-9950 KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Hypertrophy KW - Humans KW - HIV Infections -- drug therapy KW - Choroid Diseases -- chemically induced KW - Choroid Diseases -- pathology KW - Female KW - Child, Preschool KW - Pigment Epithelium of Eye -- drug effects KW - Retinal Diseases -- chemically induced KW - Pigment Epithelium of Eye -- ultrastructure KW - Retinal Diseases -- pathology KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76889921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=A+clinicopathologic+report+of+the+retinal+lesions+associated+with+didanosine.&rft.au=Whitcup%2C+S+M%3BDastgheib%2C+K%3BNussenblatt%2C+R+B%3BWalton%2C+R+C%3BPizzo%2C+P+A%3BChan%2C+C+C&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1994-12-01&rft.volume=112&rft.issue=12&rft.spage=1594&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial. AN - 76885266; 7993207 AB - We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n = 16) vs 226 days in the immediate treatment group (n = 14) (P < .00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Martin, D F AU - Parks, D J AU - Mellow, S D AU - Ferris, F L AU - Walton, R C AU - Remaley, N A AU - Chew, E Y AU - Ashton, P AU - Davis, M D AU - Nussenblatt, R B AD - National Eye Institute, National Institutes of Health, Bethesda, Md. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1531 EP - 1539 VL - 112 IS - 12 SN - 0003-9950, 0003-9950 KW - Delayed-Action Preparations KW - 0 KW - Drug Implants KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Drug Implants -- adverse effects KW - Humans KW - Adult KW - Retinal Perforations KW - Disease Progression KW - Middle Aged KW - Follow-Up Studies KW - Bias (Epidemiology) KW - Male KW - Female KW - Cytomegalovirus Retinitis -- drug therapy KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Ganciclovir -- therapeutic use KW - Ganciclovir -- administration & dosage KW - AIDS-Related Opportunistic Infections -- mortality KW - Cytomegalovirus Retinitis -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76885266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Treatment+of+cytomegalovirus+retinitis+with+an+intraocular+sustained-release+ganciclovir+implant.+A+randomized+controlled+clinical+trial.&rft.au=Martin%2C+D+F%3BParks%2C+D+J%3BMellow%2C+S+D%3BFerris%2C+F+L%3BWalton%2C+R+C%3BRemaley%2C+N+A%3BChew%2C+E+Y%3BAshton%2C+P%3BDavis%2C+M+D%3BNussenblatt%2C+R+B&rft.aulast=Martin&rft.aufirst=D&rft.date=1994-12-01&rft.volume=112&rft.issue=12&rft.spage=1531&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Ophthalmol. 1995 Nov;113(11):1354-5 [7487584] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of human herpesvirus 6 and human papillomavirus 16 in cervical carcinoma. AN - 76882873; 7992853 AB - A subset of human papillomaviruses (HPVs) is associated with the majority of cervical cancers; however, cofactors appear to be required for carcinogenic progression of HPV-induced neoplasia. As human herpesvirus-6 (HHV-6) was recently shown to infect cervical epithelial cells in vitro and activate transcription of HPV-transforming genes, human cervical dysplasia and cancers were analyzed for the presence of HHV-6 by multiple methods, including polymerase chain reaction, slot blot, Southern blot, and in situ hybridization. HHV-6 DNA sequences were detected in 6 of 72 cases of squamous cervical carcinoma and cervical intraepithelial neoplasia. HPV-16 was found in four of the HHV-6-positive cases (two squamous cervical carcinomas and two cervical intraepithelial neoplasias). None of the 30 normal cervices and biopsies of patients with cervicitis was positive for HHV-6 DNA. These results are the first suggestion of an in vivo association between HHV-6 and some cervical neoplasia. JF - The American journal of pathology AU - Chen, M AU - Wang, H AU - Woodworth, C D AU - Lusso, P AU - Berneman, Z AU - Kingma, D AU - Delgado, G AU - DiPaolo, J A AD - Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1509 EP - 1516 VL - 145 IS - 6 SN - 0002-9440, 0002-9440 KW - DNA, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Cervix Uteri -- pathology KW - DNA, Viral -- analysis KW - Humans KW - Uterine Cervical Diseases -- virology KW - Uterine Cervical Diseases -- pathology KW - Cervix Uteri -- virology KW - Female KW - Herpesvirus 6, Human -- isolation & purification KW - Papillomaviridae -- isolation & purification KW - Cervical Intraepithelial Neoplasia -- virology KW - Carcinoma, Squamous Cell -- virology KW - Uterine Cervical Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76882873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Detection+of+human+herpesvirus+6+and+human+papillomavirus+16+in+cervical+carcinoma.&rft.au=Chen%2C+M%3BWang%2C+H%3BWoodworth%2C+C+D%3BLusso%2C+P%3BBerneman%2C+Z%3BKingma%2C+D%3BDelgado%2C+G%3BDiPaolo%2C+J+A&rft.aulast=Chen&rft.aufirst=M&rft.date=1994-12-01&rft.volume=145&rft.issue=6&rft.spage=1509&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 - 1995-01-06 N1 - Date created - 1995-01-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1986 Oct 31;234(4776):596-601 [2876520] J Natl Cancer Inst. 1962 Mar;28:605-27 [13863218] Proc Natl Acad Sci U S A. 1987 Feb;84(4):1070-4 [3029760] EMBO J. 1986 Dec 20;5(13):3461-6 [2881780] Methods Enzymol. 1987;151:539-51 [2448581] Leukemia. 1988 Mar;2(3):132-5 [3258048] J Exp Med. 1988 May 1;167(5):1659-70 [3259254] Lancet. 1988 May 7;1(8593):1058-9 [2896904] Lancet. 1988 May 14;1(8594):1065-7 [2896909] Leukemia. 1988 Aug;2(8):496-502 [3412023] Int J Cancer. 1988 Nov 15;42(5):787-91 [3053468] J Virol Methods. 1988 Sep;21(1-4):179-90 [3182953] J Virol Methods. 1988 Sep;21(1-4):199-208 [2846612] Nature. 1989 Jan 26;337(6205):370-3 [2463490] J Virol. 1989 Jul;63(7):3161-3 [2542623] Cancer Res. 1989 Jul 1;49(13):3598-601 [2567206] J Clin Pathol. 1989 Jun;42(6):592-600 [2544632] Hum Genet. 1990 Apr;84(5):383-6 [2323772] Lancet. 1990 Jun 30;335(8705):1598-9 [1972522] Lancet. 1990 Sep 8;336(8715):590-3 [1697399] Gynecol Oncol. 1990 Sep;38(3):377-82 [2227552] Lancet. 1990 Nov 17;336(8725):1255-6 [1978098] J Clin Microbiol. 1991 Feb;29(2):367-72 [1848868] Blood. 1991 May 15;77(10):2251-8 [1674220] Am J Pathol. 1991 Jun;138(6):1461-9 [1647139] J Virol. 1991 Aug;65(8):4534-8 [1649348] Virology. 1991 Sep;184(1):9-13 [1651607] Am J Obstet Gynecol. 1991 Aug;165(2):392-400 [1651648] Virology. 1991 Oct;184(2):545-52 [1653487] Lancet. 1993 Nov 13;342(8881):1242 [7901562] J Virol. 1994 Feb;68(2):1173-8 [8289346] Science. 1986 Oct 31;234(4776):601-3 [3020691] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma. AN - 76878654; 7989949 AB - To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Guleria, A S AU - Yang, J C AU - Topalian, S L AU - Weber, J S AU - Parkinson, D R AU - MacFarlane, M P AU - White, R L AU - Steinberg, S M AU - White, D E AU - Einhorn, J H AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2714 EP - 2722 VL - 12 IS - 12 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Adult KW - Skin Neoplasms -- pathology KW - Aged KW - Middle Aged KW - Child KW - Blood Urea Nitrogen KW - Adolescent KW - Creatinine -- blood KW - Male KW - Female KW - Kidney Neoplasms -- therapy KW - Kidney Neoplasms -- pathology KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Carcinoma, Renal Cell -- therapy KW - Kidney Diseases -- blood KW - Melanoma -- secondary KW - Carcinoma, Renal Cell -- secondary KW - Kidney Diseases -- etiology KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76878654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Renal+dysfunction+associated+with+the+administration+of+high-dose+interleukin-2+in+199+consecutive+patients+with+metastatic+melanoma+or+renal+carcinoma.&rft.au=Guleria%2C+A+S%3BYang%2C+J+C%3BTopalian%2C+S+L%3BWeber%2C+J+S%3BParkinson%2C+D+R%3BMacFarlane%2C+M+P%3BWhite%2C+R+L%3BSteinberg%2C+S+M%3BWhite%2C+D+E%3BEinhorn%2C+J+H&rft.aulast=Guleria&rft.aufirst=A&rft.date=1994-12-01&rft.volume=12&rft.issue=12&rft.spage=2714&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 - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A sporadic case of male-limited precocious puberty has the same constitutively activating point mutation in luteinizing hormone/choriogonadotropin receptor gene as familial cases. AN - 76874452; 7527413 AB - Familial male-limited precocious puberty (FMPP) is an autosomal dominant disorder characterized by marked elevation of serum testosterone despite low levels of gonadotropin. Recently, a single point mutation in the LH/hCG receptor (LH/CGR) gene was found in FMPP families that constitutively activates the LH/CGR, causing Leydig cell activation and precocious puberty. Among the Japanese population, only four sporadic cases of male-limited precocious puberty have been reported. In the current study, we examined one of the four reported Japanese patients with sporadic male-limited precocious puberty and found the same mutation as that in the FMPP families. Genomic DNA was isolated, and the polymerase chain reaction (PCR) was performed to amplify a fragment of LH/CGR DNA encoding amino acid residues that include transmembrane helixes 5 and 6. Sequencing of the PCR products revealed a heterozygous adenosine-guanine transition at nucleotide 1733 in codon 578. The mutation encodes an aspartic acid578-glycine substitution in transmembrane helix 6. The mutant LH/CGR, created by site-directed mutagenesis in vitro, exhibited constitutively higher cAMP levels in transfected COS-7 cells than the wild-type LH/CGR, as described previously; however, basal inositol phosphate levels were not increased by transfection with complementary DNA for the mutant receptor. The concentration and affinity of [125I]hCG-binding sites were similar in cells transfected with the mutant and wild-type LH/CGR complementary DNAs, indicating that the mutant did not alter the production of receptor or its ability to bind human LH/CG. The sporadic occurrence of this case was confirmed by further studies. The mutation creates a recognition site for the restriction endonuclease MspI. Restriction digestion was positive for the mutant not digested by MspI, indicating that the patient's mutant allele was not inherited from his parents. DNA analysis of the patient and the parents, using microsatellite repeat markers, was compatible with biological paternity and maternity. We conclude that the aspartic acid578-->glycine mutation in the LH/CGR has arisen in the Japanese population and is the cause of a sporadic case of male-limited precocious puberty. JF - The Journal of clinical endocrinology and metabolism AU - Yano, K AU - Hidaka, A AU - Saji, M AU - Polymeropoulos, M H AU - Okuno, A AU - Kohn, L D AU - Cutler, G B AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1818 EP - 1823 VL - 79 IS - 6 SN - 0021-972X, 0021-972X KW - Chorionic Gonadotropin KW - 0 KW - Inositol Phosphates KW - Receptors, LH KW - Aspartic Acid KW - 30KYC7MIAI KW - Luteinizing Hormone KW - 9002-67-9 KW - DNA KW - 9007-49-2 KW - Cyclic AMP KW - E0399OZS9N KW - Deoxyribonuclease HpaII KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Glycine KW - TE7660XO1C KW - Abridged Index Medicus KW - Index Medicus KW - Protein Structure, Secondary KW - Aspartic Acid -- genetics KW - Inositol Phosphates -- metabolism KW - Luteinizing Hormone -- pharmacology KW - Humans KW - Luteinizing Hormone -- metabolism KW - Child, Preschool KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - DNA -- isolation & purification KW - Base Sequence KW - Glycine -- genetics KW - Chorionic Gonadotropin -- pharmacology KW - Transfection KW - Chorionic Gonadotropin -- metabolism KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - DNA -- chemistry KW - Male KW - Japan KW - Receptors, LH -- chemistry KW - Receptors, LH -- genetics KW - Point Mutation KW - Receptors, LH -- metabolism KW - Puberty, Precocious -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76874452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+sporadic+case+of+male-limited+precocious+puberty+has+the+same+constitutively+activating+point+mutation+in+luteinizing+hormone%2Fchoriogonadotropin+receptor+gene+as+familial+cases.&rft.au=Yano%2C+K%3BHidaka%2C+A%3BSaji%2C+M%3BPolymeropoulos%2C+M+H%3BOkuno%2C+A%3BKohn%2C+L+D%3BCutler%2C+G+B&rft.aulast=Yano&rft.aufirst=K&rft.date=1994-12-01&rft.volume=79&rft.issue=6&rft.spage=1818&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 - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Receptor binding and signal transduction are dissociable functions requiring different sites on follicle-stimulating hormone. AN - 76873147; 7988456 AB - Separate sites for glycoprotein hormone receptor binding and signal transduction have yet to be elucidated. In general, certain peptide regions are thought to be critical for receptor binding, whereas the oligosacharides are thought to be important for signal transduction. Using site-directed mutagenesis of FSH, we made selective amino acid substitutions and oligosaccharide alterations to try and identify specific sites mediating receptor binding distinct from signal transduction and vice versa. We substituted Lys or Asp for beta Arg35 in the purported receptor binding loop between cysteine-32 and -51, and we substituted Gln for alpha Asn52, alpha Asn78, beta Asn7, or beta Asn24, the attachment sites for each of the oligosaccharide side-chains. We determined the binding and signal-transducing activity of wild-type and mutant human FSH at the human FSH receptor, as recent data suggest that glycoprotein hormone-receptor interactions are species specific. The binding activities of FSH with Lys or Asp substituted for beta Arg35 were reduced 71% and 98%, respectively, but their signal transduction, at equivalent levels of binding activity, was unaffected. The binding activity of FSH lacking the oligosaccharide at alpha Asn52 was enhanced 2- to 3-fold, but its signal-transducing activity, at equivalent levels of receptor binding, was decreased 72%. In contrast, the binding and signal-transducing activities of FSH lacking the alpha Asn78, or alpha Asn7, or beta Asn24 oligosaccharide were unaffected. Thus, a specific amino acid (beta Arg35) is important for high affinity binding, but is not involved in signal transduction, whereas a specific oligosaccharide (alpha Asn52) is important for signal transduction, but is not required for high affinity binding. Therefore, receptor binding and signal transduction are dissociable functions involving different sites on the FSH glycoprotein. JF - Endocrinology AU - Valove, F M AU - Finch, C AU - Anasti, J N AU - Froehlich, J AU - Flack, M R AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2657 EP - 2661 VL - 135 IS - 6 SN - 0013-7227, 0013-7227 KW - Oligosaccharides KW - 0 KW - Receptors, FSH KW - Recombinant Proteins KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Abridged Index Medicus KW - Index Medicus KW - Oligosaccharides -- metabolism KW - Mutagenesis, Site-Directed KW - Humans KW - Mutation KW - Follicle Stimulating Hormone -- metabolism KW - Follicle Stimulating Hormone -- genetics KW - Receptors, FSH -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76873147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Receptor+binding+and+signal+transduction+are+dissociable+functions+requiring+different+sites+on+follicle-stimulating+hormone.&rft.au=Valove%2C+F+M%3BFinch%2C+C%3BAnasti%2C+J+N%3BFroehlich%2C+J%3BFlack%2C+M+R&rft.aulast=Valove&rft.aufirst=F&rft.date=1994-12-01&rft.volume=135&rft.issue=6&rft.spage=2657&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-06 N1 - Date created - 1995-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selenocysteine tRNA and serine tRNA are aminoacylated by the same synthetase, but may manifest different identities with respect to the long extra arm. AN - 76871906; 7986071 AB - Selenocysteine (Sec) tRNA([Ser])Sec donates Sec to protein, but interestingly, this amino acid is synthesized on tRNA which is first aminoacylated with serine. Thus, the identity elements in tRNA([Ser])Sec for aminoacylation correspond to elements for seryl-tRNA synthetase recognition. As tRNA([Ser])Sec has low homology to the tRNA(Ser) isoacceptors, it would seem then that the identity elements in tRNA([Ser])Sec involve (1) very specific sequences, (2) conformational features, and/or (3) different points or domains for tRNA[Ser]Sec:synthetase and tRNASer:synthetase recognition. Initially, we confirmed that the same synthetase aminoacylates both tRNAs by showing that a mutant tRNA[Ser]Sec which has a blocked 3'-terminus is a competitive inhibitor of tRNASer aminoacylation with a partially purified and a highly purified seryl-tRNA synthetase preparation. The discriminator base (base G73) is essential for aminoacylation of tRNA([Ser])Sec and tRNA(Ser), while the long extra arm plays an important role which seems to be orientation- and length-specific in tRNA(Ser) and, in addition, may manifest sequence specificity in tRNA([Ser])Sec. This difference in the tRNA recognition specificity is discussed. The acceptor stem, DHU stem, and T phi C stem contribute to the recognition process, but to a lesser extent than the discriminator base and the long extra arm. JF - Archives of biochemistry and biophysics AU - Ohama, T AU - Yang, D C AU - Hatfield, D L AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 293 EP - 301 VL - 315 IS - 2 SN - 0003-9861, 0003-9861 KW - Anticodon KW - 0 KW - RNA, Transfer, Amino Acid-Specific KW - RNA, Transfer, Amino Acyl KW - tRNA, selenocysteine- KW - Serine-tRNA Ligase KW - EC 6.1.1.11 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - In Vitro Techniques KW - Molecular Sequence Data KW - Rabbits KW - Substrate Specificity KW - RNA, Transfer, Amino Acid-Specific -- metabolism KW - Transfer RNA Aminoacylation KW - Nucleic Acid Conformation KW - Structure-Activity Relationship KW - Cloning, Molecular KW - Serine-tRNA Ligase -- metabolism KW - RNA, Transfer, Amino Acyl -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76871906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selenocysteine+tRNA+and+serine+tRNA+are+aminoacylated+by+the+same+synthetase%2C+but+may+manifest+different+identities+with+respect+to+the+long+extra+arm.&rft.au=Ohama%2C+T%3BYang%2C+D+C%3BHatfield%2C+D+L&rft.aulast=Ohama&rft.aufirst=T&rft.date=1994-12-01&rft.volume=315&rft.issue=2&rft.spage=293&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 - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A placebo-controlled randomized double-blind study of adjuvant intrapleural BCG in patients with resected T1N0, T1N1, or T2N0 squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung. LCSG Protocol 771. AN - 76870267; 7988246 AB - This article reviews the design and findings of LCSG Protocol 771, a randomized double-blind comparison of postoperative adjuvant intrapleural bacillus Calmette-Guérin (BCG) against saline solution placebo control in 473 patients with resected T1N0, T1N1, or T2N0 non-small cell lung cancer. Patients were randomized from August 30, 1977, through October 20, 1980, and follow-up ended on January 1, 1990. There was no evidence of improved survival or time to recurrence among patients given BCG in contrast to earlier promising findings. A calculation suggests that false-positive results due to chance are not uncommon in small preliminary studies, indicating the need for larger confirmatory trials such as LCSG Protocol 771. Other contributions from this Protocol are also reviewed, including data on BCG toxicity, immunologic effects, patterns of recurrence, and identification of prognostic risk groups. JF - Chest AU - Gail, M H AD - Biostatistics Branch, National Cancer Institute, Bethesda, Md. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 287S EP - 292S VL - 106 IS - 6 Suppl SN - 0012-3692, 0012-3692 KW - BCG Vaccine KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Survival Rate KW - Double-Blind Method KW - Combined Modality Therapy KW - Risk Factors KW - Humans KW - Treatment Outcome KW - Prognosis KW - Follow-Up Studies KW - Neoplasm Recurrence, Local KW - Carcinoma, Squamous Cell -- surgery KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - BCG Vaccine -- therapeutic use KW - Carcinoma, Squamous Cell -- mortality KW - Adenocarcinoma -- mortality KW - Lung Neoplasms -- therapy KW - Lung Neoplasms -- mortality KW - Adenocarcinoma -- therapy KW - Lung Neoplasms -- surgery KW - Adenocarcinoma -- surgery KW - Carcinoma, Non-Small-Cell Lung -- therapy KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76870267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest&rft.atitle=A+placebo-controlled+randomized+double-blind+study+of+adjuvant+intrapleural+BCG+in+patients+with+resected+T1N0%2C+T1N1%2C+or+T2N0+squamous+cell+carcinoma%2C+adenocarcinoma%2C+or+large+cell+carcinoma+of+the+lung.+LCSG+Protocol+771.&rft.au=Gail%2C+M+H&rft.aulast=Gail&rft.aufirst=M&rft.date=1994-12-01&rft.volume=106&rft.issue=6+Suppl&rft.spage=287S&rft.isbn=&rft.btitle=&rft.title=Chest&rft.issn=00123692&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of tryptophan residues to conserved hydrophobic residues inhibits the processing of human KB cell folate receptor. AN - 76869774; 7986085 AB - We are interested in identifying the ligand binding site of the human folate receptor (hFR). Previous reports have suggested a role of tryptophan(W) residues in ligand binding. We used site-directed mutagenesis to change the conserved W residues in positions 86, 116, 142, 143, 156, 160, and 193 of the hFR to either leucine(L) or phenylalanine(F) to examine the role of these W residues in hFR function. Although all W to L changes except W86L produced unstable proteins, W to F changes were tolerated. Based on total folate binding and transport studies, Chinese hamster ovary (CHO) cells transfected with W86L, W116F, and W143F expressed high levels of functional hFR, equivalent to cells transfected with wt hFR. CHO cells transfected with W142F, W156F, W160F, and W193F expressed low or undetectable levels of functional hFR although mRNA was present. Of these four mutants, only W142F expressed easily detectable immunoprecipitable protein but it was not fully glycosylated. Since glycosylation may affect the ability of hFR to bind folate, we expressed W142F in Xenopus oocytes which glycosylate the mutant and wild type proteins to the same apparent extent. In oocytes, the stoichiometry of folate binding was identical between the fully processed mutant protein and the wild type hFR. These results indicate that in CHO cells three of the seven W mutations (W86L, W116F, and W143F) function normally, whereas four of the seven W mutations (W142F, W156F, W160F, and W193F) produce unstable or abnormally processed protein.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Archives of biochemistry and biophysics AU - Chung, K N AU - Paik, T H AU - Roberts, S AU - Kim, C H AU - Kirassova, M AU - Weinstein, J N AU - Trepel, J B AU - Elwood, P C AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 407 EP - 414 VL - 315 IS - 2 SN - 0003-9861, 0003-9861 KW - Carrier Proteins KW - 0 KW - Folate Receptors, GPI-Anchored KW - RNA, Messenger KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Tryptophan KW - 8DUH1N11BX KW - Index Medicus KW - Animals KW - Humans KW - Protein Processing, Post-Translational KW - Gene Expression KW - Amino Acid Sequence KW - Tryptophan -- chemistry KW - RNA, Messenger -- genetics KW - Molecular Weight KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Oocytes KW - Sequence Homology, Amino Acid KW - Cell Line KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76869774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-directed+mutagenesis+of+tryptophan+residues+to+conserved+hydrophobic+residues+inhibits+the+processing+of+human+KB+cell+folate+receptor.&rft.au=Chung%2C+K+N%3BPaik%2C+T+H%3BRoberts%2C+S%3BKim%2C+C+H%3BKirassova%2C+M%3BWeinstein%2C+J+N%3BTrepel%2C+J+B%3BElwood%2C+P+C&rft.aulast=Chung&rft.aufirst=K&rft.date=1994-12-01&rft.volume=315&rft.issue=2&rft.spage=407&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 - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An in vitro model of thyroid neoplasia: permanently transfected FRTL-5 cells with thyroglobulin promoter-cholera toxin A1 subunit minigene. AN - 76867282; 7985086 AB - Activating mutations of protein Gs alpha that stimulates adenylyl cyclase are present in a subset of thyroid adenomas. Cholera toxin A1 subunit (CT) mimics these mutations via adenosine diphosphate-ribosylation of Gs alpha. To test the role of activated Gs alpha in thyroid neoplasia we developed an in vitro model. With molecular genetic techniques a transgene (TG-CT) in which the thyroglobulin gene (TG) promoter directs expression of CT was made. This transgene was transfected into rat thyroid follicular cells (FRTL-5). Integration of TG-CT transgene and its expression were examined. Polymerase chain reaction of DNA from transfected FRTL-5 cells identified the TG-CT transgene in six cell lines. The TG-CT transfected clones exhibited up to a 65-fold (1.29 +/- 0.37 pmols cyclic adenosine monophosphate (cAMP)/micrograms DNA) increase in cAMP over nontransfected FRTL-5 cells (0.02 +/- 0.001 pmols cAMP/micrograms DNA). Insulin, a known stimulator of the TG promoter, further induced CT gene expression and led to a 209-fold (10.43 +/- 0.10 pmols cAMP/micrograms DNA) increase in cAMP over nontransfected cells (0.05 +/- 0.00 pmols cAMP/microgram DNA). By mimicking a known mutation associated with thyroid neoplasms, these permanently transfected FRTL-5 cell lines will serve as a model to examine the long-term potential neoplastic effects of activated Gs alpha on thyroid follicular cells. JF - Surgery AU - Saji, M AU - Levine, M A AU - Zeiger, M A AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1048 EP - 52; discussion 1052-3 VL - 116 IS - 6 SN - 0039-6060, 0039-6060 KW - Thyroglobulin KW - 9010-34-8 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Cyclic AMP -- biosynthesis KW - Animals KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Cell Line KW - Promoter Regions, Genetic KW - Thyroid Neoplasms -- genetics KW - Cholera Toxin -- genetics KW - Thyroid Neoplasms -- etiology KW - GTP-Binding Proteins -- physiology KW - GTP-Binding Proteins -- genetics KW - Thyroglobulin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76867282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgery&rft.atitle=An+in+vitro+model+of+thyroid+neoplasia%3A+permanently+transfected+FRTL-5+cells+with+thyroglobulin+promoter-cholera+toxin+A1+subunit+minigene.&rft.au=Saji%2C+M%3BLevine%2C+M+A%3BZeiger%2C+M+A&rft.aulast=Saji&rft.aufirst=M&rft.date=1994-12-01&rft.volume=116&rft.issue=6&rft.spage=1048&rft.isbn=&rft.btitle=&rft.title=Surgery&rft.issn=00396060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determinants of trimetrexate lethality in human colon cancer cells. AN - 76862211; 7981057 AB - We examined the cytotoxicity and biochemical effects of the lipophilic antifol trimetrexate (TMQ) in two human colon carcinoma cell lines, SNU-C4 and NCI-H630, with different inherent sensitivity to TMQ. While a 24 h exposure to 0.1 microM TMQ inhibited cell growth by 50-60% in both cell lines, it did not reduce clonogenic survival. A 24 h exposure to 1 and 10 microM TMQ produced 42% and 50% lethality in C4 cells, but did not affect H630 cells. Dihydrofolate reductase (DHFR) and thymidylate synthase were quantitatively and qualitatively similar in both lines. During drug exposure, DHFR catalytic activity was inhibited by > or = 85% in both cell lines; in addition, the reduction in apparent free DHFR binding capacity (< or = 20% of control), depletion of dTTP, ATP and GTP pools and inhibition of [6-3H]deoxyuridine incorporation into DNA were similar in C4 and H630 cells. TMQ produced a more striking alteration of the pH step alkaline elution profile of newly synthesised DNA in C4 cells compared with 630 cells, however, indicating greater interference with DNA chain elongation or more extensive DNA damage. When TMQ was removed after a 24 h exposure to 0.1 microM, recovery of DHFR catalytic activity and apparent free DHFR binding sites was evident over the next 24-48 h in both cell lines. With 1 and 10 microM, however, persistent inhibition of DHFR was evident in C4 cells, whereas DHFR recovered in H630 cells. These data suggest that, although DHFR inhibition during TMQ exposure produced growth inhibition, DHFR catalytic activity 48 h after drug removal was a more accurate predictor of lethality in these two cell lines. Several factors appeared to influence the duration of DHFR inhibition after drug removal, including initial TMQ concentration, declining cytosolic TMQ levels after drug removal, the ability to acutely increase total DHFR content and the extent of TMQ-mediated DNA damage. The greater sensitivity of C4 cells to TMQ-associated lethality may be attributed to the greater extent of TMQ-mediated DNA damage and more prolonged duration of DHFR inhibition after drug exposure. JF - British journal of cancer AU - Grem, J L AU - Voeller, D M AU - Geoffroy, F AU - Horak, E AU - Johnston, P G AU - Allegra, C J AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889-5105. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1075 EP - 1084 VL - 70 IS - 6 SN - 0007-0920, 0007-0920 KW - DNA, Neoplasm KW - 0 KW - Thymine Nucleotides KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Trimetrexate KW - UPN4ITI8T4 KW - Index Medicus KW - Thymine Nucleotides -- metabolism KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - In Vitro Techniques KW - Cell Division -- drug effects KW - Biological Transport KW - Thymidylate Synthase -- metabolism KW - Time Factors KW - Tetrahydrofolate Dehydrogenase -- metabolism KW - DNA, Neoplasm -- biosynthesis KW - Cell Cycle -- drug effects KW - Trimetrexate -- toxicity KW - Trimetrexate -- metabolism KW - Colorectal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76862211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Determinants+of+trimetrexate+lethality+in+human+colon+cancer+cells.&rft.au=Grem%2C+J+L%3BVoeller%2C+D+M%3BGeoffroy%2C+F%3BHorak%2C+E%3BJohnston%2C+P+G%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1994-12-01&rft.volume=70&rft.issue=6&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-03 N1 - Date created - 1995-01-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1982 Dec 25;257(24):15079-86 [7174686] Proc Natl Acad Sci U S A. 1987 Oct;84(20):7154-8 [3478688] Cancer Res. 1983 Nov;43(11):5286-92 [6225514] Biochem Pharmacol. 1984 May 15;33(10):1697-9 [6233981] J Biol Chem. 1984 Sep 10;259(17):10793-800 [6206061] Biochemistry. 1966 Nov;5(11):3546-8 [5972337] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Cell Biol. 1975 Jul;66(1):188-93 [49354] Proc Natl Acad Sci U S A. 1975 Sep;72(9):3683-6 [810804] Cancer Res. 1987 Dec 15;47(24 Pt 1):6710-8 [3479249] J Clin Oncol. 1987 Dec;5(12):2032-40 [2960788] Cancer Res. 1988 Apr 15;48(8):2149-55 [2450647] J Biol Chem. 1988 Jul 15;263(20):9840-7 [2838483] Cancer Res. 1988 Dec 15;48(24 Pt 1):6986-91 [2973370] Biochem Pharmacol. 1989 Jan 1;38(1):51-9 [2462882] J Clin Oncol. 1989 Jul;7(7):890-9 [2661735] J Biol Chem. 1989 Nov 5;264(31):18326-34 [2572592] Leuk Res. 1989;13(11):981-7 [2532692] Cancer Res. 1990 May 1;50(9):2658-66 [2328491] Cancer Res. 1990 Sep 15;50(18):5834-40 [1697502] Cancer Res. 1990 Nov 15;50(22):7279-84 [1699659] Cancer Res. 1991 Jun 1;51(11):2949-59 [1674447] J Biol Chem. 1993 Feb 25;268(6):4556-66 [8440739] Biochemistry. 1993 May 11;32(18):4756-60 [8490020] Nature. 1962 Jan 13;193:140-2 [13868435] Cancer Res. 1976 Jun;36(6):1991-7 [5189] Anal Biochem. 1976 May 7;72:248-54 [942051] Arch Biochem Biophys. 1977 Aug;182(2):646-56 [561567] Anal Biochem. 1978 Jul 1;87(2):460-5 [686366] Chromosoma. 1979;74(2):125-39 [41688] Proc Natl Acad Sci U S A. 1979 Nov;76(11):5924-8 [160558] J Biol Chem. 1981 Jun 10;256(11):5722-7 [7240168] Arch Biochem Biophys. 1981 Jun;209(1):127-36 [7283431] Mol Pharmacol. 1982 Mar;21(2):478-82 [7099148] Mol Cell Biol. 1981 Dec;1(12):1069-76 [7346712] Adv Enzyme Regul. 1984;22:15-26 [6475640] Adv Enzyme Regul. 1984;22:187-206 [6236675] Cancer Res. 1985 Jan;45(1):325-30 [3855284] Cancer Res. 1985 Jul;45(7):2967-72 [4005834] Biochem Pharmacol. 1985 Jul 1;34(13):2319-24 [3160352] Cancer Treat Rep. 1985 Jun;69(6):641-4 [3160459] J Biol Chem. 1985 Aug 15;260(17):9720-6 [2410416] J Clin Invest. 1985 Oct;76(4):1323-9 [2414316] Biochem Pharmacol. 1986 Apr 1;35(7):1143-7 [3964294] J Biol Chem. 1986 May 15;261(14):6478-85 [3700401] Cancer Lett. 1986 Jun;31(3):253-60 [2941142] Mol Pharmacol. 1986 Jul;30(1):69-76 [3724746] J Clin Invest. 1987 Mar;79(3):692-7 [3818945] Biochem Pharmacol. 1987 Mar 15;36(6):809-14 [3566784] Cancer Res. 1983 May;43(5):2155-8 [6831441] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 10A1 MuLV induces a murine leukemia that expresses hematopoietic stem cell markers by a mechanism that includes fli-1 integration. AN - 76856822; 7975258 AB - The 10A1 murine leukemia virus induces tumors that lack lineage-specific markers found on myeloid, T-cell, and B-cell lineages. Either erythroid or multipotent stem cells can have this phenotype; therefore we have used fluorescence-activated cell sorter analysis with either multipotent stem cell markers or markers found on lineage-restricted precursors to differentiate between these two possibilities. The results showed that tumors induced by 10A1 expressed multipotent stem cell markers as well as some lineage-restricted precursor markers. To further study the tumor phenotype, we analyzed total RNAs from 10A1-induced tumors by Northern blotting for c-kit, erythropoietin receptor, and T-cell gamma receptor mRNAs. Most of the tumors contained these mRNAs, which are characteristic of early hematopoietic cells. These results are consistent with the hypothesis that 10A1-induced tumor cells are early multipotent hematopoietic stem cells. Southern blot analysis revealed that 14 of 14 10A1-induced tumor cell DNAs examined contained MuLV integrations into the fli-1 gene. The results strongly suggested that promoter insertion into fli-1 is required for tumor formation. JF - Virology AU - Ott, D E AU - Keller, J AU - Rein, A AD - Laboratory of Molecular Virology and Carcinogenesis, PRI/DynCorp, Inc., NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 563 EP - 568 VL - 205 IS - 2 SN - 0042-6822, 0042-6822 KW - fli-1 KW - Antigens, Differentiation KW - 0 KW - DNA-Binding Proteins KW - Fli1 protein, mouse KW - Proto-Oncogene Protein c-fli-1 KW - Proto-Oncogene Proteins KW - Trans-Activators KW - Index Medicus KW - Animals KW - Base Sequence KW - Proto-Oncogenes -- genetics KW - Tumor Virus Infections -- genetics KW - Molecular Sequence Data KW - Mice KW - Flow Cytometry KW - Retroviridae Infections -- blood KW - Cell Separation KW - Retroviridae Infections -- genetics KW - Tumor Virus Infections -- blood KW - Leukemia Virus, Murine -- physiology KW - Leukemia Virus, Murine -- genetics KW - Hematopoietic Stem Cells -- pathology KW - Trans-Activators -- genetics KW - Hematopoietic Stem Cells -- chemistry KW - DNA-Binding Proteins -- genetics KW - Leukemia, Experimental -- blood KW - Antigens, Differentiation -- blood KW - Leukemia, Experimental -- virology KW - Virus Integration -- genetics KW - Leukemia, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76856822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=10A1+MuLV+induces+a+murine+leukemia+that+expresses+hematopoietic+stem+cell+markers+by+a+mechanism+that+includes+fli-1+integration.&rft.au=Ott%2C+D+E%3BKeller%2C+J%3BRein%2C+A&rft.aulast=Ott&rft.aufirst=D&rft.date=1994-12-01&rft.volume=205&rft.issue=2&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - fli-1 N1 - Genetic sequence - L31653; GENBANK; L31654 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia. AN - 76856819; 7975249 AB - Moloney murine leukemia virus (M-MuLV) induces promonocytic leukemias, called MML, in pristane-treated adult mice. These tumors invariably express fused gag-myb mRNA as a consequence of virus integration and activation of the c-myb locus. In the present study it was determined that while BALB/c and DBA/2N mice are highly susceptible, C57BL/6, C3H/He, STS/A, NFS, NIH/Swiss, SJL/J, and NZB mice are strongly resistant to tumor induction. Although C57BL/6 mice were resistant because they were unable to support early virus replication in hematopoietic tissue, NFS and C3H/He mice supported replication and were shown, using RT-PCR, to have cells in the bone marrow and spleen that expressed the aberrant, leukemia-related gag-myb mRNA. This provided evidence that early stages of leukemia were permitted to develop in these mice, but preneoplastic cells were unable to progress to the acute phase. Experiments in which MML was induced by M-MuLV plus pristane treatment in immunodeficient C3H/He nu/nu and sublethally irradiated C3H/He mice suggested that the immune response may play a role in eliminating preleukemic cells in immunocompetent C3H/He. Tumors from these mice had rearrangements at the c-myb locus and expressed gag-myb RNA. It was concluded that, at least in the case of C3H/He mice, resistance is not due to an inability of virus to activate c-myb or to a lack of other tumor promoting events. Rather, leukemia development appears to be restricted by an immune response, presumably T-cell mediated. Evidence is provided that non-H-2 MHC genes are required for resistance in both C57BL/6 and C3H/He mice and that resistance is dominant. This provides an animal model for the study of tumor progression as it relates to the immune response. JF - Virology AU - Nazarov, V AU - Hilbert, D AU - Wolff, L AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 479 EP - 485 VL - 205 IS - 2 SN - 0042-6822, 0042-6822 KW - c-myb KW - Carcinogens KW - 0 KW - H-2 Antigens KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Virus Replication KW - 3T3 Cells KW - Animals KW - Immunity, Innate -- immunology KW - Mice, Nude KW - Disease Susceptibility -- immunology KW - Mice KW - Immunity, Innate -- genetics KW - Proto-Oncogenes KW - Leukemia, Monocytic, Acute -- virology KW - Mice, Inbred Strains KW - H-2 Antigens -- genetics KW - Base Sequence KW - Whole-Body Irradiation KW - Molecular Sequence Data KW - Genetic Predisposition to Disease KW - Species Specificity KW - Female KW - Retroviridae Infections -- immunology KW - Moloney murine leukemia virus -- pathogenicity KW - Tumor Virus Infections -- physiopathology KW - Retroviridae Infections -- physiopathology KW - Leukemia, Experimental -- immunology KW - Tumor Virus Infections -- genetics KW - Tumor Virus Infections -- immunology KW - Leukemia, Experimental -- virology KW - Retroviridae Infections -- genetics KW - Leukemia, Experimental -- physiopathology KW - Leukemia, Experimental -- genetics KW - Moloney murine leukemia virus -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76856819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Susceptibility+and+resistance+to+Moloney+murine+leukemia+virus-induced+promonocytic+leukemia.&rft.au=Nazarov%2C+V%3BHilbert%2C+D%3BWolff%2C+L&rft.aulast=Nazarov&rft.aufirst=V&rft.date=1994-12-01&rft.volume=205&rft.issue=2&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myb N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An increase in p50/p65 NF-kB binding to the HIV-1 LTR is not sufficient to increase viral expression in the primary human astrocyte. AN - 76845416; 7975262 AB - Human astrocytes can be infected with HIV-1 both in vivo and in vitro. The amount of HIV-1 p24 structural protein production is low in comparison to that of the macrophage. Several weeks following infection or transfection, however, cocultivation with uninfected lymphocytes or stimulation with the cytokines TNF-alpha and IL 1-beta will increase viral production from this cell type. In the present study we demonstrate that phorbol 12-myristate 13-acetate (PMA) also increases HIV-1 p24 production from the primary human astrocyte. Using electrophoretic mobility shift assay (EMSA) in combination with supershift studies using specific antibodies, we demonstrate that PMA, like TNF-alpha, increases the p50/p65 form of NF-kB. Furthermore we demonstrate that the protein kinase inhibitor H7 inhibits PMA- and TNF-alpha-associated increases in HIV-1 expression at a time when it has little to no inhibitory effect on the associated increases in p50/p65 NF-kB. Thus, unless p50/p65 NF-kB or its binding is affected by H7 in a manner that cannot be resolved by EMSA, an increase in this form of NF-kB is not always sufficient to increase HIV-1 expression from the astrocyte. JF - Virology AU - Conant, K AU - Atwood, W J AU - Traub, R AU - Tornatore, C AU - Major, E O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 586 EP - 590 VL - 205 IS - 2 SN - 0042-6822, 0042-6822 KW - Isoquinolines KW - 0 KW - NF-kappa B KW - NF-kappa B p50 Subunit KW - Piperazines KW - Protein Kinase Inhibitors KW - Transcription Factor RelA KW - Tumor Necrosis Factor-alpha KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Fetus KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Piperazines -- pharmacology KW - HIV Long Terminal Repeat KW - Isoquinolines -- pharmacology KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Gene Expression Regulation, Viral -- physiology KW - Astrocytes -- virology KW - Gene Expression Regulation, Viral -- drug effects KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76845416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+increase+in+p50%2Fp65+NF-kB+binding+to+the+HIV-1+LTR+is+not+sufficient+to+increase+viral+expression+in+the+primary+human+astrocyte.&rft.au=Conant%2C+K%3BAtwood%2C+W+J%3BTraub%2C+R%3BTornatore%2C+C%3BMajor%2C+E+O&rft.aulast=Conant&rft.aufirst=K&rft.date=1994-12-01&rft.volume=205&rft.issue=2&rft.spage=586&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation by Raf and other oncogenes renders cells differentially sensitive to growth inhibition by a dominant negative c-jun mutant. AN - 76837770; 7970709 AB - In NIH3T3 cells expressing active Raf-1 protein serine/threonine kinase (PSK) c-jun expression is constitutive while c-fos expression is attenuated. This alteration prompted us to determine whether oncogene transformation would render cells differentially sensitive to growth inhibition by a dominant negative mutant of c-jun, TAM 67. Growth inhibition was observed in three types of assays: (1) transfection of TAM 67 into cells stably transformed by a variety of oncogenes, (2) cotransfection of TAM 67 with oncogene expression plasmids into NIH3T3 cells and (3) titration of oncogene-expressing retroviruses on cells stably expressing TAM 67. The results clearly demonstrate that Raf-1 dependent oncogenes, which include receptor protein tyrosine kinases (PTKs)-, intracellular PTKs- and Ras-derived genes share the Raf phenotype of constitutive c-jun expression, attenuated c-fos induction, and high sensitivity to growth suppression by TAM 67. Additionally, the intracellular PSK oncogene, mos and the nuclear oncogenes c-myc, c-fos, and SV40 T antigen were TAM 67-sensitive for transformation. This universal pattern of altered growth regulation in oncogene transformed fibroblast cell lines highlights the potential usefulness of c-jun based inhibitors for control of tumor cell growth. JF - Oncogene AU - Rapp, U R AU - Troppmair, J AU - Beck, T AU - Birrer, M J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 3493 EP - 3498 VL - 9 IS - 12 SN - 0950-9232, 0950-9232 KW - c-fos KW - c-jun KW - Retroviridae Proteins, Oncogenic KW - 0 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Oncogene Proteins v-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Rats KW - Animals KW - 3T3 Cells KW - Genes, Dominant KW - Mice KW - Cell Line KW - Oncogenes KW - Retroviridae Proteins, Oncogenic -- physiology KW - Mutation KW - Protein-Tyrosine Kinases -- physiology KW - Cell Transformation, Neoplastic -- genetics KW - Cell Division -- genetics KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76837770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transformation+by+Raf+and+other+oncogenes+renders+cells+differentially+sensitive+to+growth+inhibition+by+a+dominant+negative+c-jun+mutant.&rft.au=Rapp%2C+U+R%3BTroppmair%2C+J%3BBeck%2C+T%3BBirrer%2C+M+J&rft.aulast=Rapp&rft.aufirst=U&rft.date=1994-12-01&rft.volume=9&rft.issue=12&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 - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. AN - 76837427; 7970735 AB - DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis "proficient." JF - Oncogene AU - Zhan, Q AU - Fan, S AU - Bae, I AU - Guillouf, C AU - Liebermann, D A AU - O'Connor, P M AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 3743 EP - 3751 VL - 9 IS - 12 SN - 0950-9232, 0950-9232 KW - bax KW - bcl2 KW - gadd45 KW - p53 KW - BAX protein, human KW - 0 KW - Mutagens KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - bcl-2-Associated X Protein KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Neoplasms -- genetics KW - Gene Expression Regulation -- radiation effects KW - Apoptosis -- genetics KW - Genes, p53 KW - Mutagens -- toxicity KW - Gene Expression Regulation -- drug effects KW - Proto-Oncogene Proteins -- genetics KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76837427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+bax+by+genotoxic+stress+in+human+cells+correlates+with+normal+p53+status+and+apoptosis.&rft.au=Zhan%2C+Q%3BFan%2C+S%3BBae%2C+I%3BGuillouf%2C+C%3BLiebermann%2C+D+A%3BO%27Connor%2C+P+M%3BFornace%2C+A+J&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1994-12-01&rft.volume=9&rft.issue=12&rft.spage=3743&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - bax; bcl2; gadd45; p53 N1 - SuppNotes - Erratum In: Oncogene 1995 Mar 16;10(6):1259 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell antigen receptor signaling. AN - 76833497; 7526153 AB - T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T-cell receptor (TCR) signaling defects that are corrected by reexpression of wild-type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule containing the myristylation sequence of Src and the intracellular portion of CD45, previously shown to restore function in CD45- T cells, was mutagenized to determine if membrane-associated CD45 tyrosine phosphatase activity is required to restore TCR-mediated signaling in CD45- T cells. Abolition of enzymatic activity by substitution of a serine for a critical cysteine in the first catalytic domain resulted in failure of this molecule to restore TCR signaling. Another mutation, in which a single amino acid substitution destroyed the myristylation site, resulted in failure of the chimeric molecule to partition to the plasma membrane. Although expressed at high levels and enzymatically active, this form of intracellular CD45 also failed to restore normal signaling in CD45- T cells. These findings strongly suggest that CD45's function in TCR signaling requires its proximity to membrane-associated tyrosine phosphatase substrates. JF - Molecular and cellular biology AU - Niklinska, B B AU - Hou, D AU - June, C AU - Weissman, A M AU - Ashwell, J D AD - Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 8078 EP - 8084 VL - 14 IS - 12 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - Membrane Proteins KW - Myristates KW - Receptors, Antigen, T-Cell KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Antigens, CD45 KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatases KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Myristates -- metabolism KW - Protein Processing, Post-Translational KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cells, Cultured KW - In Vitro Techniques KW - Molecular Sequence Data KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Signal Transduction KW - DNA Primers -- chemistry KW - Membrane Proteins -- physiology KW - Protein Tyrosine Phosphatases -- metabolism KW - T-Lymphocytes -- physiology KW - Receptors, Antigen, T-Cell -- physiology KW - Antigens, CD45 -- metabolism KW - Antigens, CD45 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76833497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=CD45+tyrosine+phosphatase+activity+and+membrane+anchoring+are+required+for+T-cell+antigen+receptor+signaling.&rft.au=Niklinska%2C+B+B%3BHou%2C+D%3BJune%2C+C%3BWeissman%2C+A+M%3BAshwell%2C+J+D&rft.aulast=Niklinska&rft.aufirst=B&rft.date=1994-12-01&rft.volume=14&rft.issue=12&rft.spage=8078&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 - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Immunol. 1989;7:339-69 [2523715] Cell. 1989 Sep 22;58(6):1055-65 [2550143] J Immunol. 1990 Mar 1;144(5):1591-9 [1689750] Science. 1990 Mar 30;247(4950):1584-7 [2138816] Nature. 1990 Jul 5;346(6279):66-8 [2164155] EMBO J. 1990 Aug;9(8):2399-407 [1695146] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7085-9 [1976251] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722-6 [2217205] Eur J Immunol. 1990 Oct;20(10):2249-57 [1978709] Clin Res. 1990 Oct;38(3):517-28 [2177694] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2037-41 [1672451] Cell Growth Differ. 1991 Jan;2(1):59-65 [1848775] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453-6 [1828897] Cell. 1991 Sep 20;66(6):1133-44 [1717156] Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9166-70 [1717999] Eur J Immunol. 1992 Feb;22(2):365-71 [1531636] Nature. 1992 Mar 5;356(6364):68-71 [1311423] J Biol Chem. 1992 Apr 25;267(12):8035-41 [1314815] Science. 1992 Aug 7;257(5071):795-7 [1323144] Cell. 1992 Aug 21;70(4):585-93 [1505025] J Exp Med. 1992 Sep 1;176(3):835-44 [1380977] Cell. 1992 Sep 4;70(5):741-50 [1387588] Cell. 1992 Sep 4;70(5):751-63 [1516132] Immunol Rev. 1982;68:135-69 [6184304] Cell. 1984 Oct;38(3):779-89 [6386177] Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623-7 [2984663] Proc Natl Acad Sci U S A. 1985 Jul;82(14):4625-8 [2991884] J Virol. 1986 May;58(2):468-74 [3009860] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8 [2950524] Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831-5 [2440031] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8628-32 [2973067] EMBO J. 1992 Oct;11(10):3533-40 [1382975] J Biol Chem. 1993 Feb 25;268(6):4488-93 [8440731] J Biol Chem. 1993 Apr 5;268(10):6835-8 [8463207] Science. 1993 Apr 23;260(5107):541-4 [8475386] Science. 1993 Apr 23;260(5107):544-6 [8475387] Cell. 1993 May 7;73(3):541-54 [8490965] Cell. 1993 Jul 16;74(1):143-56 [8334701] Nature. 1993 Sep 30;365(6445):459-62 [8413590] Science. 1993 Nov 5;262(5135):902-5 [8235613] Cell. 1994 Feb 11;76(3):411-3 [8313462] J Biol Chem. 1994 May 6;269(18):13594-600 [8175795] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous propagation of RRE(-) and Rev(-)RRE(-) human immunodeficiency virus type 1 molecular clones containing a cis-acting element of simian retrovirus type 1 in human peripheral blood lymphocytes. AN - 76830678; 7966585 AB - Molecular clones of human immunodeficiency virus type 1 that contained either 37 point mutations in the Rev-responsive element (RRE) that did not affect the overlapping env reading frame or both a mutated RRE and two mutations that eliminated Rev were constructed. The mutations in the RRE were shown to remove both negative and Rev-inducible positive effects of the RRE on gene expression (G. Nasioulas, A. S. Zolotukhin, C. Tabernero, L. Solomin, C. P. Cunningham, G. N. Pavlakis, and B. K. Felber, J. Virol. 68:2986-2993, 1994). Upon insertion of a cis-acting element of simian retrovirus type 1 (SRV-1) into these clones, both RRE(-) and Rev(-)RRE(-) clones were expressed efficiently. The element of SRV-1 has properties similar to those of the recently identified element of Mason-Pfizer monkey virus (M. Bray, S. Prasad, J. W. Dubay, E. Hunter, K.-T. Jeang, D. Rekosh, and M.-L. Hammarskjold, Proc. Natl. Acad. Sci. USA 4:1256-1260, 1994). We demonstrated that virus preparations produced after transfections of these SRV-1 element-containing molecular clones in human cells were infectious after cell-free transmission, that they replicated about 5 to 10 times less efficiently than wild-type virus, and that they were propagated continuously for more than 7 months in human peripheral blood mononuclear cells. Growth characteristics and sequence analysis of these viruses after long-term culture demonstrated that no RRE(+)Rev(+) revertants developed. These data demonstrate that human immunodeficiency virus type 1 Rev and RRE can be replaced by heterologous regulatory systems, resulting in efficient virus production. The resulting Rev(-)RRE(-) virus can be prepared and propagated efficiently in tissue culture and can be used for further studies of the life cycle of the virus. The data also suggest that Rev acts exclusively through the RRE interaction and that it does not have any additional essential function in the life cycle of the virus. JF - Journal of virology AU - Zolotukhin, A S AU - Valentin, A AU - Pavlakis, G N AU - Felber, B K AD - Human Retrovirus Pathogenesis Group, National Cancer Institute--Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 7944 EP - 7952 VL - 68 IS - 12 SN - 0022-538X, 0022-538X KW - env KW - nef KW - rev KW - tat KW - vif KW - vpu KW - DNA Primers KW - 0 KW - DNA, Viral KW - Gene Products, rev KW - rev Gene Products, Human Immunodeficiency Virus KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Sequence Homology, Nucleic Acid KW - HeLa Cells KW - Open Reading Frames KW - Humans KW - Proviruses -- physiology KW - Chromosome Mapping KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Base Sequence KW - DNA, Viral -- chemistry KW - Transfection KW - Cells, Cultured KW - Kinetics KW - Proviruses -- genetics KW - Point Mutation KW - Molecular Sequence Data KW - Time Factors KW - DNA, Viral -- genetics KW - Cell Line KW - HIV-1 -- genetics KW - Gene Products, rev -- metabolism KW - Retroviruses, Simian -- genetics KW - Genes, env KW - HIV-1 -- physiology KW - Lymphocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76830678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Continuous+propagation+of+RRE%28-%29+and+Rev%28-%29RRE%28-%29+human+immunodeficiency+virus+type+1+molecular+clones+containing+a+cis-acting+element+of+simian+retrovirus+type+1+in+human+peripheral+blood+lymphocytes.&rft.au=Zolotukhin%2C+A+S%3BValentin%2C+A%3BPavlakis%2C+G+N%3BFelber%2C+B+K&rft.aulast=Zolotukhin&rft.aufirst=A&rft.date=1994-12-01&rft.volume=68&rft.issue=12&rft.spage=7944&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 - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - env; nef; rev; tat; vif; vpu N1 - Genetic sequence - S74214; GENBANK N1 - SuppNotes - Cited By: Genes Dev. 1989 Oct;3(10):1534-44 [2482226] Science. 1989 Dec 22;246(4937):1625-9 [2688093] Science. 1990 Feb 16;247(4944):845-8 [2406903] J Virol. 1990 Apr;64(4):1690-7 [2157051] J Virol. 1990 Jun;64(6):2505-18 [2186172] J Virol. 1990 Jun;64(6):2519-29 [2335812] Annu Rev Immunol. 1990;8:453-75 [2188670] J Clin Microbiol. 1990 Jul;28(7):1560-4 [2380380] Genes Dev. 1990 Jun;4(6):1014-22 [2116986] AIDS. 1990 Jun;4(6):499-509 [2201316] J Virol. 1990 Dec;64(12):5966-75 [2243382] Virology. 1973 Apr;52(2):456-67 [4705382] Nature. 1985 Jul 18-24;316(6025):262-5 [2410792] J Virol. 1986 Aug;59(2):284-91 [3016298] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Virology. 1987 Apr;157(2):317-29 [2435057] Nature. 1988 Oct 20;335(6192):738-40 [3262832] J Virol. 1989 Mar;63(3):1265-74 [2783738] J Virol. 1990 Dec;64(12):6010-7 [2243384] New Biol. 1989 Dec;1(3):318-28 [2562124] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):683-7 [1992459] J Virol. 1991 Mar;65(3):1053-6 [1995941] New Biol. 1990 Dec;2(12):1111-22 [2088501] Genes Dev. 1991 May;5(5):808-19 [1827422] Nucleic Acids Res. 1991 Apr 11;19(7):1577-83 [2027765] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5704-8 [1905815] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7145-9 [1871127] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7366-70 [1871141] Annu Rev Biochem. 1991;60:577-630 [1883204] Cell. 1991 Nov 1;67(3):529-36 [1934059] J Virol. 1992 Feb;66(2):1139-51 [1731093] Mol Cell Biol. 1992 Mar;12(3):1375-86 [1545819] New Biol. 1991 Dec;3(12):1220-32 [1725960] J Virol. 1992 Jun;66(6):3699-706 [1583728] J Virol. 1992 Dec;66(12):7176-82 [1433510] Science. 1992 Dec 18;258(5090):1938-41 [1470917] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4419-20 [8506281] J Virol. 1993 Jul;67(7):3997-4005 [8510213] AIDS. 1993;7 Suppl 1:S51-62 [8363803] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60 [8108397] J Virol. 1994 May;68(5):2986-93 [8151769] AIDS Res Hum Retroviruses. 1992 Mar;8(3):411-21 [1571200] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1989 May;63(5):1959-66 [2704072] Oncogene. 1989 Nov;4(11):1275-9 [2682457] Cell. 1990 Feb 23;60(4):685-93 [1689218] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus (VZV) open reading frame 10 protein, the homolog of the essential herpes simplex virus protein VP16, is dispensable for VZV replication in vitro. AN - 76830641; 7966575 AB - Varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein in the homolog of the herpes simplex virus type 1 (HSV-1) protein VP16. VZV ORF10 transactivates the VZV IE62 gene and is a tegument protein present in the virion. HSV-1 VP16, a potent transactivator of HSV-1 immediate-early genes and tegument protein, is essential for HSV-1 replication in vitro. To determine whether VZV ORF10 is required for viral replication in vitro, we constructed two VZV mutants which were unable to express ORF10. One mutant had a stop codon after the 61st codon of the ORF10 gene, and the other mutant was deleted for all but the last five codons of the gene. Both VZV mutants grew in cell culture to titers similar to that of the parental virus. To determine whether HSV-1 VP16 alters the growth of VZV, we constructed a VZV mutant in which VP16 was inserted in place of ORF10. Using immune electron microscopy, we found that HSV-1 VP16 was present in the tegument of the recombinant VZV virions. The VZV VP16 substitution mutant produced smaller plaques and grew to a lower titer than parental virus. Thus, VZV ORF10 is not required for growth of the virus in vitro, and substitution of HSV-1 VP16 for VZV ORF10 impairs the growth of VZV. JF - Journal of virology AU - Cohen, J I AU - Seidel, K AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 7850 EP - 7858 VL - 68 IS - 12 SN - 0022-538X, 0022-538X KW - Herpes Simplex Virus Protein Vmw65 KW - 0 KW - ORF 10 protein, varicella-zoster virus KW - Oligodeoxyribonucleotides KW - Trans-Activators KW - Index Medicus KW - Cosmids KW - Melanoma KW - Mutagenesis KW - Base Sequence KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - Cell-Free System KW - Sequence Deletion KW - Virus Replication KW - Herpesvirus 3, Human -- growth & development KW - Trans-Activators -- metabolism KW - Herpesvirus 3, Human -- genetics KW - Trans-Activators -- biosynthesis KW - Open Reading Frames KW - Herpesvirus 1, Human -- physiology KW - Herpes Simplex Virus Protein Vmw65 -- biosynthesis KW - Herpes Simplex Virus Protein Vmw65 -- metabolism KW - Herpesvirus 3, Human -- physiology KW - Herpesvirus 1, Human -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76830641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Varicella-zoster+virus+%28VZV%29+open+reading+frame+10+protein%2C+the+homolog+of+the+essential+herpes+simplex+virus+protein+VP16%2C+is+dispensable+for+VZV+replication+in+vitro.&rft.au=Cohen%2C+J+I%3BSeidel%2C+K&rft.aulast=Cohen&rft.aufirst=J&rft.date=1994-12-01&rft.volume=68&rft.issue=12&rft.spage=7850&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 - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1989 May;63(5):2260-9 [2539517] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9773-7 [2849116] J Gen Virol. 1990 Apr;71 ( Pt 4):897-906 [2157801] J Virol. 1991 Oct;65(10):5289-96 [1654442] J Virol. 1992 Jan;66(1):258-69 [1309245] J Virol. 1992 Jan;66(1):359-66 [1309252] J Virol. 1992 Jun;66(6):3899-903 [1316489] J Virol. 1992 Sep;66(9):5298-304 [1323696] J Virol. 1992 Dec;66(12):7303-8 [1366099] Hum Genet. 1992 Dec;90(4):450-6 [1483704] Virology. 1993 Mar;193(1):193-200 [7679857] J Neurosurg. 1967 Jan;26(1):Suppl:112-26 [4163660] Biken J. 1975 Mar;18(1):25-33 [167707] J Mol Biol. 1984 Nov 25;180(1):1-19 [6096556] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Proc Natl Acad Sci U S A. 1986 Dec;83(23):9094-8 [3024166] Virology. 1987 Feb;156(2):423-6 [3027986] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3896-900 [3035557] J Virol. 1993 May;67(5):2739-46 [8386275] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7376-80 [8394020] J Virol. 1994 Mar;68(3):1987-92 [8107260] Virology. 1994 Apr;200(1):297-300 [8128631] J Virol. 1994 Apr;68(4):2468-77 [8139031] J Virol. 1994 May;68(5):3317-23 [8151792] J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74 [2839594] Genes Dev. 1988 Jun;2(6):718-29 [2843425] Nature. 1988 Oct 6;335(6190):563-4 [3047590] J Gen Virol. 1988 Oct;69 ( Pt 10):2595-605 [2844968] Virology. 1989 Dec;173(2):700-9 [2556848] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bafilomycin A1 inhibits the action of tetanus toxin in spinal cord neurons in cell culture. AN - 76830566; 7964755 AB - Tetanus toxin (TeNT) is one of the clostridial neurotoxins that act intracellularly to block neurotransmitter release. However, neither the route of entry nor the mechanism by which these toxins gain access to the neuronal cytoplasm has been established definitively. In murine spinal cord cell cultures, release of the neurotransmitter glycine is particularly sensitive to blockade by TeNT. To test whether TeNT enters neurons through acidic endosomes or is routed through the Golgi apparatus, toxin action on potassium-evoked glycine release was assayed in cultures pretreated with bafilomycin A1 (baf A1) or brefeldin A (BFA). baf A1, which inhibits the vacuolar-type H(+)-ATPase responsible for endosome acidification, diminishes the staining of acidic compartments and interferes with the action of TeNT in a dose-dependent manner. TeNT blockade of evoked glycine release is inhibited by 50 and 90% in cultures pretreated with 50 and 100 nM baf A1, respectively, compared with cultures treated with the inhibitor alone. The effects of baf A1 are fully reversible. In contrast, BFA, which disrupts Golgi function, has no effect on TeNT action. These findings provide evidence that TeNT enters the neuronal cytoplasm through baf A1-sensitive acidic compartments and that TeNT is not trafficked through the Golgi apparatus before its translocation into the neuronal cytosol. JF - Journal of neurochemistry AU - Williamson, L C AU - Neale, E A AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2342 EP - 2345 VL - 63 IS - 6 SN - 0022-3042, 0022-3042 KW - Anti-Bacterial Agents KW - 0 KW - Dinitrobenzenes KW - Indicators and Reagents KW - Macrolides KW - Tetanus Toxin KW - bafilomycin A1 KW - 88899-55-2 KW - Monensin KW - 906O0YJ6ZP KW - 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine KW - 92585-03-0 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Cytosol -- metabolism KW - Animals KW - Synapses -- physiology KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Cells, Cultured KW - Hydrogen-Ion Concentration KW - Glycine -- secretion KW - Monensin -- pharmacology KW - Mice KW - Dinitrobenzenes -- metabolism KW - Endosomes -- metabolism KW - Golgi Apparatus -- metabolism KW - Tetanus Toxin -- antagonists & inhibitors KW - Neurons -- physiology KW - Anti-Bacterial Agents -- pharmacology KW - Spinal Cord -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76830566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Bafilomycin+A1+inhibits+the+action+of+tetanus+toxin+in+spinal+cord+neurons+in+cell+culture.&rft.au=Williamson%2C+L+C%3BNeale%2C+E+A&rft.aulast=Williamson&rft.aufirst=L&rft.date=1994-12-01&rft.volume=63&rft.issue=6&rft.spage=2342&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A putative nucleoside triphosphate-binding domain in the nonstructural protein of B19 parvovirus is required for cytotoxicity. AN - 76829657; 7966641 AB - Cytotoxicity secondary to B19 parvovirus infection is due to expression of the viral nonstructural protein. Nonstructural proteins of many parvoviruses contain a well-conserved nucleoside triphosphate (NTP)-binding motif, which has been shown to be essential for a variety of protein functions. We show here that cytotoxicity of the B19 parvovirus nonstructural protein was abolished by single mutations of amino acids within the NTP-binding domain, especially within the A motif, implicating NTP-binding in virus-induced cell death. JF - Journal of virology AU - Momoeda, M AU - Wong, S AU - Kawase, M AU - Young, N S AU - Kajigaya, S AD - Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 8443 EP - 8446 VL - 68 IS - 12 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - Viral Nonstructural Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Models, Structural KW - Conserved Sequence KW - Humans KW - Restriction Mapping KW - Point Mutation KW - Molecular Sequence Data KW - Parvovirus -- genetics KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Binding Sites KW - Parvovirus B19, Human -- genetics KW - Protein Structure, Secondary KW - Viral Nonstructural Proteins -- chemistry KW - Cell Death KW - Parvovirus B19, Human -- pathogenicity KW - Parvovirus B19, Human -- metabolism KW - Viral Nonstructural Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76829657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+putative+nucleoside+triphosphate-binding+domain+in+the+nonstructural+protein+of+B19+parvovirus+is+required+for+cytotoxicity.&rft.au=Momoeda%2C+M%3BWong%2C+S%3BKawase%2C+M%3BYoung%2C+N+S%3BKajigaya%2C+S&rft.aulast=Momoeda&rft.aufirst=M&rft.date=1994-12-01&rft.volume=68&rft.issue=12&rft.spage=8443&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 - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1974 Jul 19;250(463):194-9 [4368490] Br J Obstet Gynaecol. 1992 Jul;99(7):566-74 [1525097] Mol Cell Biol. 1983 Feb;3(2):220-8 [6300658] EMBO J. 1982;1(8):945-51 [6329717] Science. 1984 Dec 7;226(4679):1161-5 [6095448] J Virol. 1987 May;61(5):1448-56 [3033274] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4026-30 [3035562] Adv Virus Res. 1987;33:91-174 [3296697] Mol Cell Biol. 1987 Apr;7(4):1320-5 [3037312] Mol Cell Biol. 1987 Aug;7(8):2745-52 [3670292] J Virol. 1988 Aug;62(8):2884-9 [2969055] Gene. 1989 Apr 15;77(1):51-9 [2744487] Nucleic Acids Res. 1989 Nov 11;17(21):8413-40 [2555771] J Virol. 1990 Jan;64(1):387-96 [2293668] Virology. 1990 Feb;174(2):576-84 [2137660] J Virol. 1990 Apr;64(4):1764-70 [2157057] J Virol. 1990 Oct;64(10):4654-60 [2144594] Blood. 1992 Jan 1;79(1):18-24 [1728307] J Virol. 1992 Jul;66(7):4050-7 [1318396] J Virol. 1992 Aug;66(8):4686-92 [1385833] J Virol. 1992 Oct;66(10):5705-13 [1388209] J Virol. 1992 Oct;66(10):6058-69 [1326656] J Virol. 1993 Jan;67(1):562-6 [8416383] J Pathol. 1993 Feb;169(2):213-20 [8445486] Science. 1993 Oct 1;262(5130):114-7 [8211117] J Biol Chem. 1994 Feb 4;269(5):3283-9 [8106366] Adv Enzymol Relat Areas Mol Biol. 1978;47:45-148 [364941] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-4 and IL-13 induce Lsk, a Csk-like tyrosine kinase, in human monocytes. AN - 76827746; 7964512 AB - Lsk is a protein tyrosine kinase with homology to the COOH-terminal Src kinase (Csk). Unlike Csk that is ubiquitously expressed, Lsk has limited tissue distribution. Here we have examined the expression and regulation of Lsk and Csk in peripheral human monocytes. We have found that Lsk mRNA and protein were not expressed in resting monocytes but were induced by treatment with interleukin 4 (IL-4) or IL-13 but not by interferon gamma (IFN-gamma) or IL-2. In fact, IFN-gamma, but not IL-2, efficiently blocked Lsk induction by IL-4 or IL-13. In contrast, Csk was constitutively present in human monocytes and was upregulated by IFN-gamma but not by IL-4 or IL-13. These results suggest that despite their structural similarities, Lsk and Csk may play distinct regulatory roles in monocyte functions elicited by cytokines, with Lsk functioning specifically within the context of a Th2-type immune response. JF - The Journal of experimental medicine AU - Musso, T AU - Varesio, L AU - Zhang, X AU - Rowe, T K AU - Ferrara, P AU - Ortaldo, J R AU - O'Shea, J J AU - McVicar, D W AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/12/01/ PY - 1994 DA - 1994 Dec 01 SP - 2383 EP - 2388 VL - 180 IS - 6 SN - 0022-1007, 0022-1007 KW - Interleukin-13 KW - 0 KW - Interleukin-2 KW - RNA, Messenger KW - Recombinant Proteins KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - CSK tyrosine-protein kinase KW - EC 2.7.10.2 KW - MATK protein, human KW - Proto-Oncogene Proteins pp60(c-src) KW - src-Family Kinases KW - Index Medicus KW - Interleukin-2 -- pharmacology KW - Recombinant Proteins -- pharmacology KW - Blotting, Northern KW - Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Interferon-gamma -- pharmacology KW - Enzyme Induction KW - Sequence Homology, Amino Acid KW - RNA, Messenger -- biosynthesis KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Monocytes -- enzymology KW - Interleukin-4 -- pharmacology KW - Monocytes -- drug effects KW - Protein-Tyrosine Kinases -- isolation & purification KW - Protein-Tyrosine Kinases -- biosynthesis KW - Interleukin-13 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76827746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IL-4+and+IL-13+induce+Lsk%2C+a+Csk-like+tyrosine+kinase%2C+in+human+monocytes.&rft.au=Musso%2C+T%3BVaresio%2C+L%3BZhang%2C+X%3BRowe%2C+T+K%3BFerrara%2C+P%3BOrtaldo%2C+J+R%3BO%27Shea%2C+J+J%3BMcVicar%2C+D+W&rft.aulast=Musso&rft.aufirst=T&rft.date=1994-12-01&rft.volume=180&rft.issue=6&rft.spage=2383&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 - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1987 Jan 15-21;325(6101):262-5 [3100957] Oncogene. 1994 Jul;9(7):2037-44 [7516063] J Immunol. 1990 Aug 15;145(4):1137-43 [2143208] Cancer Cells. 1990 Oct;2(10):303-10 [1704247] Blood. 1991 May 1;77(9):1859-70 [2018830] Oncogene. 1991 Nov;6(11):2013-8 [1945408] Immunol Res. 1991;10(3-4):183-8 [1659603] J Biol Chem. 1991 Dec 25;266(36):24249-52 [1722201] J Immunol. 1992 Feb 1;148(3):795-800 [1730872] Gene. 1992 Jan 15;110(2):205-11 [1371489] Oncogene. 1992 Apr;7(4):703-10 [1373483] EMBO J. 1992 Aug;11(8):2919-24 [1639064] J Immunol. 1992 Nov 1;149(9):2961-8 [1383334] Nature. 1993 Mar 18;362(6417):248-50 [8096327] Cell. 1993 Jun 18;73(6):1051-4 [7685656] J Immunol. 1993 Sep 1;151(5):2725-32 [8360487] J Biol Chem. 1994 Jan 14;269(2):1068-74 [8288563] J Biol Chem. 1994 Feb 4;269(5):3897-902 [7508923] Oncogene. 1994 Apr;9(4):1155-61 [8134117] Immunol Today. 1994 Jan;15(1):19-26 [7907877] Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2597-601 [7511815] Oncogene. 1994 Jun;9(6):1625-31 [8183556] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4975-9 [8197166] J Exp Med. 1988 Nov 1;168(5):1801-10 [3141554] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of hemiparkinsonian syndrome in nonhuman primates by amnion implantation into caudate nucleus. AN - 76825924; 7965117 AB - Although recent animal and human experiments suggest that tissue implantation can ameliorate parkinsonism, there is controversy about what mechanism underlies recovery. Secretion of dopamine from the graft seems unlikely to be the sole restorative factor. Regenerative sprouting by the host brain may also underlie behavioral recovery. Fetal amnion and term amnion, which were shown to produce and secrete a factor that supports the outgrowth of neurite processes in vitro, were implanted in hemiparkinsonian monkeys. Fetal amnion implants induced sprouting of dopaminergic fibers from the host brain and behavioral improvement, despite failure of the grafts to survive. Animals implanted with term amnion also had some sprouted dopaminergic fibers and behavioral improvement, but these were limited and were similar to the recovery, in prior experiments using the same primate model of parkinsonism, of animals that received surgical cavitation only. Recovery after central nervous system grafting with fetal amnion, a fetal accessory tissue, does not require secretion of a deficient neurotransmitter(s) from the graft and occurs despite the failure of graft survival. Recovery after cerebral implantation of fetal tissues appears to depend more on the regenerative and recuperative processes of the host brain than on graft replacement of deficient neurotransmitters or development of functional synaptic connections between the graft and the host brain. JF - Journal of neurosurgery AU - Bankiewicz, K S AU - Palmatier, M AU - Plunkett, R J AU - Cummins, A AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 869 EP - 876 VL - 81 IS - 6 SN - 0022-3085, 0022-3085 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Dopamine beta-Hydroxylase KW - EC 1.14.17.1 KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Dopamine -- secretion KW - Animals KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- adverse effects KW - Apomorphine -- pharmacology KW - Cerebral Ventricles -- pathology KW - Motor Activity -- physiology KW - Nucleus Accumbens -- pathology KW - Tyrosine 3-Monooxygenase -- analysis KW - Putamen -- pathology KW - Dopamine beta-Hydroxylase -- analysis KW - Substantia Nigra -- pathology KW - Nerve Regeneration KW - Graft Survival KW - Nerve Fibers -- ultrastructure KW - Macaca mulatta KW - Motor Activity -- drug effects KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease, Secondary -- chemically induced KW - Caudate Nucleus -- surgery KW - Amnion -- transplantation KW - Parkinson Disease, Secondary -- surgery KW - Caudate Nucleus -- pathology KW - Fetal Tissue Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76825924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Reversal+of+hemiparkinsonian+syndrome+in+nonhuman+primates+by+amnion+implantation+into+caudate+nucleus.&rft.au=Bankiewicz%2C+K+S%3BPalmatier%2C+M%3BPlunkett%2C+R+J%3BCummins%2C+A%3BOldfield%2C+E+H&rft.aulast=Bankiewicz&rft.aufirst=K&rft.date=1994-12-01&rft.volume=81&rft.issue=6&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-15 N1 - Date created - 1994-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. AN - 76820434; 7964759 AB - Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to "therapeutic" concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme-selective decreases in the levels of PKC alpha and epsilon (but not delta or zeta) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or 3H-phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross-talk between neurotransmitter systems, the specific decreases in PKC alpha and epsilon may play a role in the antimanic effects of VPA. JF - Journal of neurochemistry AU - Chen, G AU - Manji, H K AU - Hawver, D B AU - Wright, C B AU - Potter, W Z AD - Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 2361 EP - 2364 VL - 63 IS - 6 SN - 0022-3042, 0022-3042 KW - Diglycerides KW - 0 KW - Isoenzymes KW - Phosphatidylserines KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Valproic Acid KW - 614OI1Z5WI KW - Protein Kinase C KW - EC 2.7.11.13 KW - diolein KW - Z3MP1W91CW KW - Index Medicus KW - Rats KW - Animals KW - Diglycerides -- pharmacology KW - Blotting, Western KW - Tumor Cells, Cultured KW - Cell Membrane -- enzymology KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Phosphatidylserines -- pharmacology KW - Kinetics KW - Cytosol -- enzymology KW - Glioma -- enzymology KW - Valproic Acid -- pharmacology KW - Protein Kinase C -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76820434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Chronic+sodium+valproate+selectively+decreases+protein+kinase+C+alpha+and+epsilon+in+vitro.&rft.au=Chen%2C+G%3BManji%2C+H+K%3BHawver%2C+D+B%3BWright%2C+C+B%3BPotter%2C+W+Z&rft.aulast=Chen&rft.aufirst=G&rft.date=1994-12-01&rft.volume=63&rft.issue=6&rft.spage=2361&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelotype analysis of mouse lung carcinomas reveals frequent allelic losses on chromosome 4 and an association between allelic imbalances on chromosome 6 and K-ras activation. AN - 76804090; 7954475 AB - We generated allelotypes of 38 methylene chloride-induced lung carcinomas from female C57BL/6J x C3H/6J F1 (hereafter called B6C3F1) mice. Two or more polymorphic markers per autosome, most of them microsatellites, were examined for loss of heterozygosity. Allelic losses throughout the genome were generally infrequent except for markers on chromosome 4, which were lost in approximately one-half of the carcinomas. Analysis of lung adenomas indicated that chromosome 4 loss was associated with malignant conversion. In addition, chromosome 4 loss were specific for lung carcinomas based on comparison to methylene chloride-induced liver tumors and additional studies of lung tumors from a variety of treatment protocols and different mouse strains. Preferential loss of the maternal chromosome 4 was observed in B6C3F1 carcinomas. Analyses of additional tumors induced in mice from two reciprocal crosses, A/J x C3H/HeJ F1 (hereafter called AC3F1) and C3H/HeJ x A/J F1 (hereafter called C3AF1), provided evidence for the inactivation of one allele of the putative chromosome 4 tumor suppressor gene by parental imprinting. Most B6C3F1 tumors lost all chromosome 4 markers examined, suggesting nondisjunction events. In contrast, several C3AF1 and AC3F1 tumors appeared to have interstitial deletions that defined the smallest region of overlap as a 9-cM interval between Ifa-2 and D4Nds2. The homologous region on human chromosome 9p21-22 is frequently lost in a variety of tumors including lung cancers. A candidate tumor suppressor gene, MTS1, is located in this region, which is homozygously deleted or mutated in cell lines derived from a variety of human tumors. Finally, an association between K-ras gene activation and allelic imbalances on chromosome 6 was observed for B6C3F1 lung tumors. JF - Cancer research AU - Hegi, M E AU - Devereux, T R AU - Dietrich, W F AU - Cochran, C J AU - Lander, E S AU - Foley, J F AU - Maronpot, R R AU - Anderson, M W AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1994/12/01/ PY - 1994 DA - 1994 Dec 01 SP - 6257 EP - 6264 VL - 54 IS - 23 SN - 0008-5472, 0008-5472 KW - K-ras KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - Animals KW - Mice KW - Mutation KW - Transcriptional Activation KW - Male KW - Female KW - Genes, ras KW - Gene Expression Regulation, Neoplastic KW - Chromosome Deletion KW - Alleles KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76804090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allelotype+analysis+of+mouse+lung+carcinomas+reveals+frequent+allelic+losses+on+chromosome+4+and+an+association+between+allelic+imbalances+on+chromosome+6+and+K-ras+activation.&rft.au=Hegi%2C+M+E%3BDevereux%2C+T+R%3BDietrich%2C+W+F%3BCochran%2C+C+J%3BLander%2C+E+S%3BFoley%2C+J+F%3BMaronpot%2C+R+R%3BAnderson%2C+M+W%3BWiseman%2C+R+W&rft.aulast=Hegi&rft.aufirst=M&rft.date=1994-12-01&rft.volume=54&rft.issue=23&rft.spage=6257&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 - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaginal epithelial DNA damage and expression of preneoplastic markers in mice during chronic dosing with tumorigenic levels of 3'-azido-2',3'-dideoxythymidine. AN - 76801172; 7954472 AB - 3'-Azido-2',3'-dideoxythymidine (AZT, Retrovir, zidovudine), a nucleoside analogue currently used in the therapy of acquired immunodeficiency syndrome, induces papillomas and carcinomas in vaginal epithelium of mice as a result of lifetime drug administration. In this study, female CD-1 mice were administered AZT at doses of 180, 360, and 720 micrograms/ml of drinking water for 28 days to determine whether AZT became incorporated into vaginal DNA and whether this was associated with preneoplastic changes within the target tissue. In addition, bone marrow, a target for AZT-induced cytotoxicity in mice and humans, was examined for chromosomal aberrations. A positive correlation was observed between dose level of AZT, proliferation of cells in the basal layer of vaginal epithelium, and incorporation of AZT into vaginal DNA. Incorporation of AZT into vaginal DNA was originally detected by radioimmunoassay and confirmed by immunohistochemistry. An aberrant pattern for alpha 6 integrin distribution, similar to the pattern described in skin papillomas with high risk for malignant conversion, also increased with dose in mice given AZT. Chromosomal aberrations in bone marrow increased more than 4-fold in AZT-exposed animals. The genotoxicity demonstrated by incorporation of AZT into vaginal DNA and proliferation of vaginal epithelium may play an essential part in the ability of AZT to induce abnormal differentiation in vaginal epithelium and vaginal tumorigenesis in mice. JF - Cancer research AU - Olivero, O A AU - Beland, F A AU - Fullerton, N F AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/12/01/ PY - 1994 DA - 1994 Dec 01 SP - 6235 EP - 6242 VL - 54 IS - 23 SN - 0008-5472, 0008-5472 KW - Integrin alpha6 KW - 0 KW - Integrins KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - DNA -- metabolism KW - Chromosome Aberrations KW - Cell Division -- drug effects KW - Mice KW - Epithelium -- pathology KW - Female KW - Epithelium -- drug effects KW - Vagina -- drug effects KW - Zidovudine -- toxicity KW - Zidovudine -- metabolism KW - DNA Damage KW - Vaginal Neoplasms -- chemically induced KW - Vagina -- pathology KW - Precancerous Conditions -- chemically induced KW - Integrins -- analysis KW - Vagina -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76801172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vaginal+epithelial+DNA+damage+and+expression+of+preneoplastic+markers+in+mice+during+chronic+dosing+with+tumorigenic+levels+of+3%27-azido-2%27%2C3%27-dideoxythymidine.&rft.au=Olivero%2C+O+A%3BBeland%2C+F+A%3BFullerton%2C+N+F%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=1994-12-01&rft.volume=54&rft.issue=23&rft.spage=6235&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 - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. AN - 76801102; 7954461 AB - Heterocyclic aromatic amines (HAAs) are formed when meat juices are pyrolyzed. In humans HAAs are activated in vivo by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) to mutagens or carcinogens. While activity of NAT2 is noninducible, exposure to cigarettes, polycyclic aromatic hydrocarbons, and cruciferous vegetables has been shown to induce CYP1A2 activity in humans. To date, it is unknown if pan-fried meat, which is consumed at high levels in the United States, is capable of inducing CYP1A2. In order to address this issue, we measured CYP1A2 and NAT2 activities in 66 healthy nonsmokers (33 males and 33 females) in a controlled metabolic feeding study. The study was designed to minimize the influence of known inducers of CYP1A2. Subjects consumed meat pan-fried at a low temperature (100 degrees C) for 7 days followed by 7 days of meat pan-fried at a high temperature (250 degrees C). The low temperature-cooked meat had undetectable levels of HAAs while the high temperature-cooked meat contained high amounts of HAAs [9.0 ng/g of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2.1 ng/g of 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 32.8 ng/g of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)]. In contrast, total polycyclic aromatic hydrocarbon content was similar in both meat samples (10.7 ng/g in low temperature-cooked meat and 10.1 ng/g in high temperature-cooked meat). At the end of each period, subjects were tested for CYP1A2 and NAT2 enzyme activity by caffeine metabolism phenotyping. NAT2 activity remained unchanged throughout the study while CYP1A2 activity increased in 47 of 65 (72%) of the subjects after consuming high temperature-cooked meat (P < 0.0002), suggesting induction by some compound(s) formed during high temperature cooking. If HAAs are shown to be human carcinogens in epidemiological studies, then meat cooked at high temperatures may pose an increased cancer risk because it contains both inducers of CYP1A2 and procarcinogens MeIQx, DiMeIQx, and PhIP known to be activated by this enzyme. JF - Cancer research AU - Sinha, R AU - Rothman, N AU - Brown, E D AU - Mark, S D AU - Hoover, R N AU - Caporaso, N E AU - Levander, O A AU - Knize, M G AU - Lang, N P AU - Kadlubar, F F AD - Environmental Epidemiology Branch/Epidemiology and Biostatistics Program, National Cancer Institute, NIH, Rockville, Maryland 20892. Y1 - 1994/12/01/ PY - 1994 DA - 1994 Dec 01 SP - 6154 EP - 6159 VL - 54 IS - 23 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Imidazoles KW - Polycyclic Compounds KW - Quinoxalines KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - 2-amino-3,7,8-trimethylimidazo(4,5-f)quinoxaline KW - 92180-79-5 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Meat KW - Enzyme Induction -- drug effects KW - Humans KW - Cooking KW - Male KW - Female KW - Hot Temperature KW - Imidazoles -- toxicity KW - Carcinogens -- metabolism KW - Quinoxalines -- toxicity KW - Polycyclic Compounds -- toxicity KW - Carcinogens -- toxicity KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Oxidoreductases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76801102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pan-fried+meat+containing+high+levels+of+heterocyclic+aromatic+amines+but+low+levels+of+polycyclic+aromatic+hydrocarbons+induces+cytochrome+P4501A2+activity+in+humans.&rft.au=Sinha%2C+R%3BRothman%2C+N%3BBrown%2C+E+D%3BMark%2C+S+D%3BHoover%2C+R+N%3BCaporaso%2C+N+E%3BLevander%2C+O+A%3BKnize%2C+M+G%3BLang%2C+N+P%3BKadlubar%2C+F+F&rft.aulast=Sinha&rft.aufirst=R&rft.date=1994-12-01&rft.volume=54&rft.issue=23&rft.spage=6154&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 - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plasma proteins as early biomarkers of exposure to carcinogenic aromatic amines. AN - 76739595; 7923441 AB - Two-dimensional gel electrophoresis (2DG) has been used to study the changes induced in dog plasma polypeptides by the known urinary bladder carcinogens, 4-aminobiphenyl (4-ABP) and 2-naphthylamine (2-NA). Treatment with 3-aminobiphenyl (3-ABP) and 1-naphthylamine (1-NA), both considered to be non-carcinogenic, were used as controls. The purpose of this study was: (1) to determine whether or not changes that occurred in the plasma protein patterns were specific to 4-ABP and/or other related carcinogenic arylamines; (2) to measure the time course in the changes of the major polypeptides during dosing and their resynthesis during a recovery period; and (3) to determine, by microsequencing, the biochemical identity of the affected proteins. The results indicate that only the most potent carcinogen, 4-ABP, had the effect of suppressing the expression of some proteins, while the other aromatic amines caused no discernible change in the 2DG patterns during a 12-week dosing period. The 4-ABP caused dramatic suppression of two sets of proteins. One set of three spots had an apparent molecular weight of 32.5 kDa, and a pI of 5.8-6.0. The major component in this group was identified as the beta-chain of haptoglobin. Expression of this protein decreased markedly during the first 2 weeks of treatment and recovered slowly after dosing stopped. Since haptoglobin functions to bind with free hemoglobin and facilitates its elimination from the blood stream, these results can be rationalized as a consequence of 4-ABP binding to hemoglobin in the erythrocyte, resulting in cell death and hemolysis. The 4-ABP modified hemoglobin then binds to haptoglobin and this tertiary complex is purged from the blood stream, resulting in the disappearance of free haptoglobin. A second set of spots (mol. wt., 65 kDa; pI, 6.5-6.6) disappeared much faster than the haptoglobin, and recovered more quickly. The major protein is about one-fifth the intensity of haptoglobin and appeared to be N-terminally blocked. Internal microsequencing of four fragments obtained from tryptic cleavage of the major spot of this group showed significant similarity to the serum albumin sequence of several species. This spot group is not the major serum albumin spot, however, since the latter is readily identified as the most abundant spot on the plasma map. During the course of this study, several other polypeptides in the 2DG map of dog plasma were identified and are presented here. JF - Chemico-biological interactions AU - Miller, M J AU - Parmelee, D C AU - Benjamin, T AU - Sechi, S AU - Dooley, K L AU - Kadlubar, F F AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255. Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 221 EP - 234 VL - 93 IS - 3 SN - 0009-2797, 0009-2797 KW - Amines KW - 0 KW - Aminobiphenyl Compounds KW - Apolipoprotein A-I KW - Biomarkers KW - Blood Proteins KW - Carcinogens KW - Haptoglobins KW - Serum Albumin KW - 4-biphenylamine KW - 16054949HJ KW - Fibrinogen KW - 9001-32-5 KW - 2-Naphthylamine KW - CKR7XL41N4 KW - Index Medicus KW - Serum Albumin -- metabolism KW - Animals KW - Computer Simulation KW - Humans KW - Amino Acid Sequence KW - Haptoglobins -- metabolism KW - Molecular Weight KW - Fibrinogen -- metabolism KW - Apolipoprotein A-I -- blood KW - Serum Albumin -- chemistry KW - Electrophoresis, Gel, Two-Dimensional KW - Molecular Sequence Data KW - Dogs KW - Female KW - Haptoglobins -- chemistry KW - 2-Naphthylamine -- toxicity KW - Aminobiphenyl Compounds -- toxicity KW - 2-Naphthylamine -- administration & dosage KW - Amines -- toxicity KW - Carcinogens -- toxicity KW - Blood Proteins -- chemistry KW - Blood Proteins -- metabolism KW - Aminobiphenyl Compounds -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76739595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Plasma+proteins+as+early+biomarkers+of+exposure+to+carcinogenic+aromatic+amines.&rft.au=Miller%2C+M+J%3BParmelee%2C+D+C%3BBenjamin%2C+T%3BSechi%2C+S%3BDooley%2C+K+L%3BKadlubar%2C+F+F&rft.aulast=Miller&rft.aufirst=M&rft.date=1994-12-01&rft.volume=93&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-07 N1 - Date created - 1994-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Effects of Domestic Violence on Children's Perceptions of Their Perpetrating and Nonperpetrating Parents AN - 61629775; 199504090 AB - Children's discrimination between parents as perpetrators/nonperpetrators of different forms of domestic violence was investigated among 110 Ss ages 8-12 living with their parents, recruited through the Dept of Family Services in Jerusalem & Tel Aviv, Israel. Per social worker interviews, 33 of the Ss had been physically abused by their parents within the last 6 months, 16 had witnessed spousal abuse, 30 had been both victims & witnesses, & 31 had experienced no known domestic abuse. Data obtained using the Family Relations Test indicated that Ss in the child abuse & abuse witness/victim groups had more negative perceptions of the abusive parent than did Ss in the comparison groups. Ss in the spousal abuse group perceived their violent fathers similarly to Ss in the comparison group, & had negative perceptions of abusive mothers. A significant main effect for Ss' sex was found, in that boys assigned both more positive & negative items to their father than girls. Further analyses showed that the experience of abuse shapes attitudes about the perpetrating, but not the nonperpetrating, parent. 6 Tables, 34 References. Adapted from the source document. JF - International Journal of Behavioral Development AU - Sternberg, Kathleen J AU - Lamb, Michael E AU - Greenbaum, Charles AU - Dawud, Samia AU - Cortes, Rosa Manela AU - Lorey, Fanny AD - Section Social & Emotional Development NICHD, 9190 Rockville Pike Bethesda MD 20814 Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 779 EP - 795 VL - 17 IS - 4 SN - 0165-0254, 0165-0254 KW - domestic violence, children's perceptions of perpetrating/nonperpetrating parent KW - interview/test data KW - Jerusalem/Tel Aviv, Israel KW - Tel Aviv, Israel KW - Perceptions KW - Jerusalem, Israel KW - Family Violence KW - Child Abuse KW - Children KW - Spouse Abuse KW - article KW - 6143: social welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61629775?accountid=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=International+Journal+of+Behavioral+Development&rft.atitle=The+Effects+of+Domestic+Violence+on+Children%27s+Perceptions+of+Their+Perpetrating+and+Nonperpetrating+Parents&rft.au=Sternberg%2C+Kathleen+J%3BLamb%2C+Michael+E%3BGreenbaum%2C+Charles%3BDawud%2C+Samia%3BCortes%2C+Rosa+Manela%3BLorey%2C+Fanny&rft.aulast=Sternberg&rft.aufirst=Kathleen&rft.date=1994-12-01&rft.volume=17&rft.issue=4&rft.spage=779&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Behavioral+Development&rft.issn=01650254&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Family Violence; Children; Perceptions; Jerusalem, Israel; Tel Aviv, Israel; Child Abuse; Spouse Abuse ER - TY - JOUR T1 - The Investigation of Child Sexual Abuse: An Interdisciplinary Consensus Statement AN - 61624298; 199502411 AB - Many Western industrialized nations have experienced large increases in reported cases of child sexual abuse over the past twenty years. It is often difficult to validate allegations of abuse, even though progress has been made in obtaining medical evidence. While child testimony can be useful, its value & limitations are often challenged in court. Accurate statements can be obtained from open-ended questioning & the use of props such as anatomically detailed dolls, provided the sessions are conducted by skilled interviewers as soon after the alleged event as is possible & are audio- or video-recorded to substantiate their legal validity. Repeated, highly leading & suggestive questions, & interviewing by parents, teachers, & friends may distort the events. More knowledge of the physical signs of abuse, developmental & cultural attitudes about sex, & repressed memories is necessary before they can be used reliably for diagnosis. J. MacDowell JF - Child Abuse and Neglect AU - Lamb, Michael E AD - Section Social & Emotional Development NICHD, 9190 Rockville Pike Bethesda MD 20814 Y1 - 1994/12// PY - 1994 DA - December 1994 SP - 1021 EP - 1028 VL - 18 IS - 12 SN - 0145-2134, 0145-2134 KW - reported child sexual abuse, legal substantiation KW - Evidence (Legal) KW - Courts KW - Industrial Societies KW - Law KW - Justice KW - Interdisciplinary Approach KW - Legal Cases KW - Legal System KW - Child Sexual Abuse KW - article KW - 6143: social welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61624298?accountid=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=Child+Abuse+and+Neglect&rft.atitle=The+Investigation+of+Child+Sexual+Abuse%3A+An+Interdisciplinary+Consensus+Statement&rft.au=Lamb%2C+Michael+E&rft.aulast=Lamb&rft.aufirst=Michael&rft.date=1994-12-01&rft.volume=18&rft.issue=12&rft.spage=1021&rft.isbn=&rft.btitle=&rft.title=Child+Abuse+and+Neglect&rft.issn=01452134&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Child Sexual Abuse; Interdisciplinary Approach; Industrial Societies; Courts; Law; Evidence (Legal); Legal System; Justice; Legal Cases ER - TY - JOUR T1 - Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals. AN - 36327158; 201002-31-0247239 (CE); 11701580 (EN) AB - The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides. Images Figure 3. A Figure 3. B JF - Environmental Health Perspectives AU - Saffiotti, U AU - Daniel, L N AU - Mao, Y AU - Shi, X AU - Williams, A O AU - Kaighn, M E AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041. PY - 1994 SP - 159 EP - 163 PB - U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES VL - 102 SN - 0091-6765, 0091-6765 KW - Civil Engineering (CE); Environmental Engineering (EN) KW - Silicon dioxide KW - Crystal structure KW - Deoxyribonucleic acid KW - Radicals KW - Binding KW - Carcinogens KW - Mice KW - Hamsters KW - Article KW - EE 10:General Environmental Engineering (EN) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/36327158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvironmentalengabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Mechanisms+of+carcinogenesis+by+crystalline+silica+in+relation+to+oxygen+radicals.&rft.au=Saffiotti%2C+U%3BDaniel%2C+L+N%3BMao%2C+Y%3BShi%2C+X%3BWilliams%2C+A+O%3BKaighn%2C+M+E&rft.aulast=Saffiotti&rft.aufirst=U&rft.date=1994-12-01&rft.volume=102&rft.issue=&rft.spage=159&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 - 2010-02-01 N1 - Last updated - 2011-11-14 ER - TY - JOUR T1 - Detection of oxygen-derived radicals in biological systems using electron spin resonance. AN - 21260024; 11703513 AB - Oxygen-centered radicals, particularly the hydroxyl and superoxide radicals, have been postulated in many biochemical reactions and have been implicated in many adverse reactions in vivo. This article begins with a review of spin-trapping detection of oxygen-centered radicals in vitro and concludes with a presentation of our approach to the detection of the hydroxyl radicals in models of acute iron and copper poisoning. JF - Environmental Health Perspectives AU - Mason, R P AU - Hanna, P M AU - Burkitt, M J AU - Kadiiska, M B AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/12// PY - 1994 DA - Dec 1994 SP - 33 EP - 36 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 102 IS - Suppl 10 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Biochemistry KW - Reviews KW - Poisoning KW - Copper KW - Iron KW - Side effects KW - Hydroxyl radicals KW - ENA 07:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21260024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Detection+of+oxygen-derived+radicals+in+biological+systems+using+electron+spin+resonance.&rft.au=Mason%2C+R+P%3BHanna%2C+P+M%3BBurkitt%2C+M+J%3BKadiiska%2C+M+B&rft.aulast=Mason&rft.aufirst=R&rft.date=1994-12-01&rft.volume=102&rft.issue=Suppl+10&rft.spage=33&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 - Biochemistry; Reviews; Poisoning; Copper; Iron; Side effects; Hydroxyl radicals ER - TY - JOUR T1 - Clinical advisory: Carotid endarterectomy for patients with asymptomatic internal carotid artery stenosis AN - 197737054 JF - Stroke AU - National Institute of Neurological Disorders and Stroke AU - National Institutes of Health AU - Department of Health and Human Services AD - National Institute of Neurological Disorders and Stroke ; National Institutes of Health ; Department of Health and Human Services Y1 - 1994/12// PY - 1994 DA - Dec 1994 SP - 2523 CY - Hagerstown PB - American Heart Association, Inc. VL - 25 IS - 12 SN - 00392499 KW - Medical Sciences--Cardiovascular Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/197737054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Clinical+advisory%3A+Carotid+endarterectomy+for+patients+with+asymptomatic+internal+carotid+artery+stenosis&rft.au=National+Institute+of+Neurological+Disorders+and+Stroke%3BNational+Institutes+of+Health%3BDepartment+of+Health+and+Human+Services&rft.aulast=National+Institute+of+Neurological+Disorders+and+Stroke&rft.aufirst=&rft.date=1994-12-01&rft.volume=25&rft.issue=12&rft.spage=2523&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=00392499&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Heart Association, Inc. Dec 1994 N1 - Last updated - 2014-05-16 N1 - CODEN - SJCCA7 ER - TY - JOUR T1 - Glucocorticoid receptor (GR)-mediated effects on cocaine kindling in rats. AN - 76945616; 7825898 JF - Annals of the New York Academy of Sciences AU - Kling, M A AU - Pluznik, D AU - Glowa, J R AU - Gold, P W AU - Smith, M A AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/11/30/ PY - 1994 DA - 1994 Nov 30 SP - 400 EP - 402 VL - 746 SN - 0077-8923, 0077-8923 KW - Receptors, Glucocorticoid KW - 0 KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Drug Synergism KW - Male KW - Receptors, Glucocorticoid -- drug effects KW - Kindling, Neurologic -- drug effects KW - Dexamethasone -- pharmacology KW - Kindling, Neurologic -- physiology KW - Cocaine -- pharmacology KW - Receptors, Glucocorticoid -- physiology KW - Mifepristone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76945616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoid+receptor+%28GR%29-mediated+effects+on+cocaine+kindling+in+rats.&rft.au=Kling%2C+M+A%3BPluznik%2C+D%3BGlowa%2C+J+R%3BGold%2C+P+W%3BSmith%2C+M+A&rft.aulast=Kling&rft.aufirst=M&rft.date=1994-11-30&rft.volume=746&rft.issue=&rft.spage=400&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 - 1995-02-16 N1 - Date created - 1995-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 8-Hydroxy-2'-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals. AN - 76895285; 7999014 AB - The 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and DNA damage by sulfur trioxide anion radicals (SO3.-) were investigated using ESR spin trapping, HPLC, and electrophoretic assays. Sulfite (SO3(2-) autoxidation generated both hydroxyl (.OH) and SO3.- radicals. Oxidation of SO3(2-) by chromium (VI) generated only SO3.- with much enhanced yield. Incubation of 2'-deoxyguanosine (dG) with SO3(2-) generated 8-OHdG albeit at low yield. Chromium (VI) enhanced the yield four-fold. Electrophoretic assays showed that SO3.- radicals generated by chromium (VI) oxidation of SO3(2-) caused DNA double strand breaks. The results demonstrate that SO3.- radicals are capable of causing dG hydroxylation and DNA double strand breaks. JF - Biochemical and biophysical research communications AU - Shi, X AU - Mao, Y AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/11/30/ PY - 1994 DA - 1994 Nov 30 SP - 141 EP - 147 VL - 205 IS - 1 SN - 0006-291X, 0006-291X KW - Anions KW - 0 KW - Free Radical Scavengers KW - Free Radicals KW - Mutagens KW - Sulfur Oxides KW - Chromium KW - 0R0008Q3JB KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - DNA KW - 9007-49-2 KW - Deoxyguanosine KW - G9481N71RO KW - sulfur trioxide KW - HH2O7V4LYD KW - Index Medicus KW - Oxidation-Reduction KW - Electron Spin Resonance Spectroscopy KW - Drug Synergism KW - Chromium -- toxicity KW - DNA -- drug effects KW - Deoxyguanosine -- biosynthesis KW - DNA Damage KW - Mutagens -- toxicity KW - Sulfur Oxides -- toxicity KW - Sulfur Oxides -- chemistry KW - Mutagens -- chemistry KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76895285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=8-Hydroxy-2%27-deoxyguanosine+formation+and+DNA+damage+induced+by+sulfur+trioxide+anion+radicals.&rft.au=Shi%2C+X%3BMao%2C+Y&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-11-30&rft.volume=205&rft.issue=1&rft.spage=141&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 - 1995-01-17 N1 - Date created - 1995-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity and metabolism of 4-methoxy-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine in HCT 116 colon cancer cells. AN - 76907421; 7528507 AB - We examined the cytotoxicity, biochemical effects and metabolism of 4-methoxy-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP), a synthetic nucleoside inhibitor of phosphoribosylpyrophosphate synthetase, in HCT 116 human colorectal cancer cells. A 4-hr exposure to 1 and 10 microM MRPP inhibited cell growth over a 72-hr period by 76 and 89%, and inhibited clonogenic capacity by 36 and 65%, respectively. MRPP was avidly metabolized to the 5'-monophosphate derivative (MRPP-MP), and MRPP-MP formation increased with increasing MRPP exposure (microM.hr). MRPP-MP was stable, and the intracellular half-life was in excess of 48 hr. A 4-hr exposure to 10 microM MRPP resulted in significant decreases in ATP, UTP, GTP, CTP, dATP, dTTP, and PRPP pools. Near maximal ribonucleotide triphosphate depletion was achieved with > or = 24 microM.hr MRPP, and growth inhibition as a function of MRPP microM.hr closely reflected the biochemical effects. Ribonucleotide triphosphate pools remained depleted for up to 48 hr after drug removal, apparently as a consequence of the prolonged retention of MRPP-MP. MRPP (10 microM) inhibited the salvage of [3H]guanine, [3H]adenine and [3H]guanosine, and concurrent exposure to MRPP and either 100 microM adenine, hypoxanthine, or guanine did not reverse ATP or GTP depletion. Concurrent exposure to 10 microM MRPP and either 10 microM adenosine, uridine or thymidine was accompanied by repletion of ATP, UTP, and dTTP pools, respectively, but depletion of other nucleotide pools was not corrected. In contrast, 10 microM guanosine did not correct GTP depletion in the presence of MRPP. The combination of 10 microM each of thymidine, uridine, adenosine and guanosine during and following a 24-hr exposure to MRPP provided partial protection against 0.1 or 1 microM MRPP, but did not affect the cytotoxicity associated with 10 microM MRPP. MRPP is a novel antimetabolite that inhibits both de novo and salvage pathways for purine synthesis and de novo pyrimidine synthesis. JF - Biochemical pharmacology AU - Grem, J L AU - Daychild, P AU - Drake, J AU - Geoffroy, F AU - Trepel, J B AU - Pirnia, F AU - Allegra, C J AD - NCI-Navy Medical Oncology Branch, Bethesda, MD 20889-5105. Y1 - 1994/11/29/ PY - 1994 DA - 1994 Nov 29 SP - 2117 EP - 2126 VL - 48 IS - 11 SN - 0006-2952, 0006-2952 KW - Antimetabolites KW - 0 KW - Nucleosides KW - Pyrimidine Nucleosides KW - 4-methoxy-8-(ribofuranosylamino)pyrimido(5,4-d)pyrimidine KW - 118515-48-3 KW - RNA KW - 63231-63-0 KW - Cytidine Triphosphate KW - 65-47-4 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - DNA KW - 9007-49-2 KW - Uridine Triphosphate KW - UT0S826Z60 KW - Index Medicus KW - DNA -- isolation & purification KW - Phosphorylation KW - Cytidine Triphosphate -- metabolism KW - Nucleosides -- pharmacology KW - Hydrogen-Ion Concentration KW - Humans KW - Adenosine Triphosphate -- metabolism KW - DNA -- biosynthesis KW - Uridine Triphosphate -- metabolism KW - Cell Line KW - RNA -- biosynthesis KW - Pyrimidine Nucleosides -- metabolism KW - Antimetabolites -- toxicity KW - Antimetabolites -- metabolism KW - Pyrimidine Nucleosides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76907421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Cytotoxicity+and+metabolism+of+4-methoxy-8-%28beta-D-ribofuranosylamino%29pyrimido%5B5%2C4-d%5Dpyrimidine+in+HCT+116+colon+cancer+cells.&rft.au=Grem%2C+J+L%3BDaychild%2C+P%3BDrake%2C+J%3BGeoffroy%2C+F%3BTrepel%2C+J+B%3BPirnia%2C+F%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1994-11-29&rft.volume=48&rft.issue=11&rft.spage=2117&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-23 N1 - Date created - 1995-01-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Primer extension by various polymerases using oligonucleotide templates containing stereoisomeric benzo[a]pyrene-deoxyadenosine adducts. AN - 76793857; 7524675 AB - Four isomeric benzo[a]pyrene-deoxyadenosine adducts, corresponding to the products of trans opening of the epoxide ring in the four configurationally isomeric benzo[a]pyrene dihydrodiol epoxides by the amino group of deoxyadenosine, were separately introduced into each of two 16-mer sequence contexts. The sequences were from the supF gene, and the site of the adducted adenine was known, for some hydrocarbon dihydrodiol epoxides, to be a hotspot for mutation in Context I and a coldspot for mutation in Context II. Using primers complementary to the 3' ends of these oligonucleotides, the abilities of several polymerases to replicate these templates in vitro were investigated. Each adduct proved to be an effective block to primer extension such that only with high concentrations of exo- Klenow fragment was any bypass of adducts seen. DNA polymerase alpha and HIV-1 reverse transcriptase were blocked 3' to the adduct when the configuration at C10 of the hdyrocarbon was S, and some introduction of thymine opposite the adenine adduct was seen with the R configuration. Incorporation of a nucleotide opposite the adduct occurred more readily with Sequenase and the Klenow fragment, and the mutagenic introduction of adenine was apparent in most cases. This corresponded to the A-->T transversions frequently seen in mutation studies with hydrocarbon dihydrodiol epoxides that react extensively with adenine in DNA. Overall, it was clear that sequence context, adduct stereochemistry, and the choice of polymerase all influenced the polymerization reaction. With these in vitro systems, no major differences correlating with the differing tumorigenicities of the isomeric dihydrodiol epoxides or with the hotspot or coldspot nature of the sequences were detected. JF - Biochemistry AU - Christner, D F AU - Lakshman, M K AU - Sayer, J M AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/11/29/ PY - 1994 DA - 1994 Nov 29 SP - 14297 EP - 14305 VL - 33 IS - 47 SN - 0006-2960, 0006-2960 KW - supF KW - Deoxyadenosines KW - 0 KW - Oligodeoxyribonucleotides KW - Benzo(a)pyrene KW - 3417WMA06D KW - DNA Polymerase I KW - EC 2.7.7.- KW - DNA Polymerase II KW - bacteriophage T7 induced DNA polymerase KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Stereoisomerism KW - Base Sequence KW - Humans KW - DNA Polymerase II -- metabolism KW - Molecular Sequence Data KW - HIV-1 -- enzymology KW - Templates, Genetic KW - RNA-Directed DNA Polymerase -- metabolism KW - DNA Polymerase I -- metabolism KW - Structure-Activity Relationship KW - Oligodeoxyribonucleotides -- chemistry KW - Benzo(a)pyrene -- chemistry KW - Deoxyadenosines -- chemistry KW - Oligodeoxyribonucleotides -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76793857?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Primer+extension+by+various+polymerases+using+oligonucleotide+templates+containing+stereoisomeric+benzo%5Ba%5Dpyrene-deoxyadenosine+adducts.&rft.au=Christner%2C+D+F%3BLakshman%2C+M+K%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Christner&rft.aufirst=D&rft.date=1994-11-29&rft.volume=33&rft.issue=47&rft.spage=14297&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-28 N1 - Date created - 1994-12-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Utilization of selenocysteyl-tRNA[Ser]Sec and seryl-tRNA[Ser]Sec in protein synthesis. AN - 76817248; 7961966 AB - The UGA selenocysteine (Sec) codon in glutathione peroxidase mRNA and in selenoprotein P and the UGA stop codon in rabbit beta-globin mRNA were employed to study the utilization of Sec-tRNA[Ser]Sec and Ser-tRNA[Ser]Sec in protein synthesis. In vitro Ser-tRNA[Ser]Sec served as a suppressor of the UGA Sec codon as well as the UGA stop codon, while Sec-tRNA[Ser]Sec did not. However, in vivo Sec-tRNA[Ser]Sec did donate Sec to glutathione peroxidase in Xenopus oocytes microinjected with glutathione peroxidase mRNA and Sec-tRNA. A ribosome binding assay was devised to investigate the interaction of aminoacyl-tRNA, rabbit reticulocyte ribosomes, and eukaryotic elongation factor 1 (eEF-1) in response to the appropriate trinucleoside diphosphate template. Ser-tRNA[Ser]Sec bound weakly to ribosomes in the presence of eEF-1 and UGA as compared to Phe-tRNA, Ser-tRNAIGA, and Met-tRNAm which bound more efficiently in the presence of eEF-1 and the appropriate template. No increase in the binding of Sec-tRNA[Ser]Sec was observed under the same conditions as Ser-tRNA[Ser]Sec. The ribosome binding studies substantiated the finding that Ser-tRNA[Ser]Sec serves as a suppressor of UGA codons in protein synthesis, but Sec-tRNA[Ser]Sec does not. In addition, these studies provide strong evidence that a specific elongation factor is required in mammalian cells for insertion of Sec into protein from Sec-tRNA[Ser]Sec. JF - The Journal of biological chemistry AU - Jung, J E AU - Karoor, V AU - Sandbaken, M G AU - Lee, B J AU - Ohama, T AU - Gesteland, R F AU - Atkins, J F AU - Mullenbach, G T AU - Hill, K E AU - Wahba, A J AD - Laboratory of Experimental Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/25/ PY - 1994 DA - 1994 Nov 25 SP - 29739 EP - 29745 VL - 269 IS - 47 SN - 0021-9258, 0021-9258 KW - Codon KW - 0 KW - RNA, Transfer, Amino Acyl KW - selenocysteinyl-tRNA KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Index Medicus KW - Ribosomes -- metabolism KW - Animals KW - Glutathione Peroxidase -- metabolism KW - Rabbits KW - Acylation KW - Mutation KW - Protein Biosynthesis KW - RNA, Transfer, Amino Acyl -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76817248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Utilization+of+selenocysteyl-tRNA%5BSer%5DSec+and+seryl-tRNA%5BSer%5DSec+in+protein+synthesis.&rft.au=Jung%2C+J+E%3BKaroor%2C+V%3BSandbaken%2C+M+G%3BLee%2C+B+J%3BOhama%2C+T%3BGesteland%2C+R+F%3BAtkins%2C+J+F%3BMullenbach%2C+G+T%3BHill%2C+K+E%3BWahba%2C+A+J&rft.aulast=Jung&rft.aufirst=J&rft.date=1994-11-25&rft.volume=269&rft.issue=47&rft.spage=29739&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 - 1994-12-28 N1 - Date created - 1994-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of rat brain phospholipase D by ADP-ribosylation factors 1,5, and 6: separation of ADP-ribosylation factor-dependent and oleate-dependent enzymes. AN - 76843663; 7972129 AB - Two major forms of phospholipase D (PLD) activity, solubilized from rat brain membranes with Triton X-100, were separated by HPLC on a heparin-5PW column with buffer containing octyl glucoside. One form was completely dependent on sodium oleate for activity. The other, which was dramatically activated by the addition of ADP-ribosylation factor (ARF) 1 and guanine 5' [gamma-thio]triphosphate, required the presence of phosphatidylinositol 4,5-bisphosphate in the phosphatidylcholine substrate for demonstration of activity, as described by others. Oleate-dependent activity was unaffected by guanine 5' [gamma-thio]triphosphate, or phosphatidylinositol 4,5-bisphosphate. Both sodium oleate-and ARF-dependent activities catalyzed transphosphatidylation, thus identifying them as PLDs. ARF-dependent PLD was activated by recombinant ARF5 (class II) and ARF6 (class III), as well as ARF1 (class I). Myristoylated recombinant ARFs were more effective than their nonmyristoylated counterparts. ARFs were originally identified as activators of cholera toxin ADP-ribosyltransferase activity. The effects of recombinant ARF proteins from the three classes on cholera toxin activity (assayed under conditions identical to those used to assay PLD activity) did not, however, correlate with those on PLD, consistent with the notion that different aspects of ARF structure are involved in the two functions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Massenburg, D AU - Han, J S AU - Liyanage, M AU - Patton, W A AU - Rhee, S G AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11/22/ PY - 1994 DA - 1994 Nov 22 SP - 11718 EP - 11722 VL - 91 IS - 24 SN - 0027-8424, 0027-8424 KW - Oleic Acids KW - 0 KW - Oleic Acid KW - 2UMI9U37CP KW - Cholera Toxin KW - 9012-63-9 KW - Phospholipase D KW - EC 3.1.4.4 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Arf5 protein, mouse KW - Arf5 protein, rat KW - Index Medicus KW - Rats KW - Animals KW - Cell Membrane -- enzymology KW - Enzyme Activation KW - In Vitro Techniques KW - Mice KW - Cholera Toxin -- metabolism KW - Phospholipase D -- metabolism KW - Brain -- enzymology KW - Oleic Acids -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Phospholipase D -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76843663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+rat+brain+phospholipase+D+by+ADP-ribosylation+factors+1%2C5%2C+and+6%3A+separation+of+ADP-ribosylation+factor-dependent+and+oleate-dependent+enzymes.&rft.au=Massenburg%2C+D%3BHan%2C+J+S%3BLiyanage%2C+M%3BPatton%2C+W+A%3BRhee%2C+S+G%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Massenburg&rft.aufirst=D&rft.date=1994-11-22&rft.volume=91&rft.issue=24&rft.spage=11718&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 - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1991 May 7;1064(2):242-50 [2036440] J Biol Chem. 1990 Oct 15;265(29):17512-9 [2211645] Nature. 1992 Jan 30;355(6359):409-15 [1734280] J Biol Chem. 1992 Jun 5;267(16):11131-6 [1597450] J Biol Chem. 1992 Aug 25;267(24):16859-65 [1512228] J Biol Chem. 1992 Sep 5;267(25):17766-72 [1517219] J Biol Chem. 1993 Jan 15;268(2):930-7 [8419372] J Biol Chem. 1993 Apr 5;268(10):7064-8 [8463239] J Biol Chem. 1993 May 25;268(15):10820-5 [8496147] Eur J Biochem. 1993 Jul 15;215(2):389-96 [8344305] Biochem J. 1993 Aug 1;293 ( Pt 3):649-55 [8352731] Cell Signal. 1993 Jul;5(4):367-79 [8373721] Cell. 1993 Dec 17;75(6):1045-8 [8261507] Cell. 1993 Dec 17;75(6):1137-44 [8261513] Science. 1994 Jan 28;263(5146):523-6 [8290961] J Biol Chem. 1994 Apr 1;269(13):9743-5 [8144566] J Biol Chem. 1994 Jun 3;269(22):15583-7 [8195204] Biochem Biophys Res Commun. 1973 Jul 17;53(2):391-8 [4736814] Arch Biochem Biophys. 1974 Oct;164(2):420-8 [4460875] Adv Lipid Res. 1978;16:267-326 [362867] Biochem Biophys Res Commun. 1980 Sep 30;96(2):742-7 [7426012] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] J Neurochem. 1985 Nov;45(5):1578-84 [4045465] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5540-4 [3475691] J Biol Chem. 1987 Nov 5;262(31):15309-15 [3117799] FEBS Lett. 1987 Dec 10;225(1-2):201-4 [3319693] J Biol Chem. 1988 Sep 5;263(25):12472-7 [3165977] Biochem Biophys Res Commun. 1988 Aug 30;155(1):249-55 [3046613] Biochim Biophys Acta. 1988 Oct 14;962(3):282-96 [2844277] J Biol Chem. 1989 Jun 5;264(16):9412-9 [2722841] Biochem Biophys Res Commun. 1989 Aug 30;163(1):657-64 [2505772] J Biol Chem. 1989 Oct 15;264(29):17069-77 [2793844] J Biol Chem. 1990 Jan 5;265(1):1-4 [2104616] Biochemistry. 1990 Jan 30;29(4):855-61 [2111167] J Biol Chem. 1991 Aug 15;266(23):14877-80 [1869526] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpression of human cyclin D1 reduces the transforming growth factor beta (TGF-beta) type II receptor and growth inhibition by TGF-beta 1 in an immortalized human esophageal epithelial cell line. AN - 76838568; 7972105 AB - Cyclin D1 has been implicated in G1 cell cycle progression and is frequently amplified, overtranscribed, and oversynthesized in human tumors, including esophageal carcinomas. To further address the role of cyclin D1 in cell cycle control and tumorigenesis, we have stably transfected the human cyclin D1 in the nontumorigenic esophageal epithelial cell line HET-1A. These transfected cells, which express increased amounts of cyclin D1, have enhanced colony-forming efficiency and saturation density and are resistant to growth inhibition by TGF-beta 1 compared with the parental cell line or a control vector cell clone. The clones which express increased amounts of cyclin D1 exhibited a decrease in the amount of TGF-beta type II receptor, indicating a plausible mechanism for their diminished response to TGF-beta 1. Therefore, deregulated expression of the cyclin D1 gene can modulate the negative growth factor pathway of TGF-beta 1 and may disturb the control of epithelial cell proliferation in esophageal carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Okamoto, A AU - Jiang, W AU - Kim, S J AU - Spillare, E A AU - Stoner, G D AU - Weinstein, I B AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11/22/ PY - 1994 DA - 1994 Nov 22 SP - 11576 EP - 11580 VL - 91 IS - 24 SN - 0027-8424, 0027-8424 KW - Cyclins KW - 0 KW - Oncogene Proteins KW - Proliferating Cell Nuclear Antigen KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Cyclin D1 KW - 136601-57-5 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDK4 protein, human KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Protein-Serine-Threonine Kinases -- metabolism KW - Epithelial Cells KW - Humans KW - In Vitro Techniques KW - Esophagus -- cytology KW - Gene Expression KW - RNA, Messenger -- genetics KW - Cell Cycle KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Cell Line KW - Transforming Growth Factor beta -- pharmacology KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Cyclins -- metabolism KW - Oncogene Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76838568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+cyclin+D1+reduces+the+transforming+growth+factor+beta+%28TGF-beta%29+type+II+receptor+and+growth+inhibition+by+TGF-beta+1+in+an+immortalized+human+esophageal+epithelial+cell+line.&rft.au=Okamoto%2C+A%3BJiang%2C+W%3BKim%2C+S+J%3BSpillare%2C+E+A%3BStoner%2C+G+D%3BWeinstein%2C+I+B%3BHarris%2C+C+C&rft.aulast=Okamoto&rft.aufirst=A&rft.date=1994-11-22&rft.volume=91&rft.issue=24&rft.spage=11576&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 - 1994-12-27 N1 - Date created - 1994-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Growth Factors. 1993;8(1):1-9 [8448037] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Genes Dev. 1993 May;7(5):812-21 [8491378] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5359-63 [8389483] Genes Dev. 1993 Aug;7(8):1559-71 [8339933] Genes Dev. 1993 Aug;7(8):1572-83 [8101826] Cell. 1993 Sep 24;74(6):1009-20 [8402878] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9026-30 [8415648] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10315-9 [7694291] Biochem Biophys Res Commun. 1993 Oct 29;196(2):1010-6 [8240318] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Oncogene. 1993 Dec;8(12):3447-57 [8247550] Nature. 1993 Dec 16;366(6456):701-4 [8259214] Nature. 1993 Dec 16;366(6456):704-7 [8259215] Science. 1994 Jan 7;263(5143):87-9 [8272871] Genes Dev. 1994 Jan;8(1):9-22 [8288131] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):709-13 [8290586] Oncogene. 1994 Jan;9(1):323-6 [8302597] Mol Cell Biol. 1994 Mar;14(3):1669-79 [8114703] Nature. 1994 Apr 21;368(6473):753-6 [8152487] Science. 1994 Apr 15;264(5157):436-40 [8153634] Cell. 1994 Jul 15;78(1):59-66 [8033212] Cell. 1994 Jul 15;78(1):67-74 [8033213] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11045-9 [7972006] J Biol Chem. 1989 Feb 5;264(4):2272-8 [2536702] Environ Health Perspect. 1989 Mar;80:209-20 [2538323] Science. 1989 Nov 3;246(4930):603-8 [2683075] Cell. 1990 Jul 13;62(1):175-85 [2163767] J Biol Chem. 1990 Oct 25;265(30):18518-24 [2170414] Cancer Res. 1990 Dec 1;50(23):7581-6 [1701348] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9958-61 [2263646] Cancer Res. 1991 Jan 1;51(1):365-71 [1703038] Nature. 1991 Apr 11;350(6318):512-5 [1826542] Cell. 1991 May 17;65(4):691-9 [1827756] Cell. 1991 May 17;65(4):701-13 [1827757] Oncogene. 1992 Feb;7(2):355-61 [1532244] Cancer Surv. 1992;12:81-103 [1638549] Science. 1993 Apr 23;260(5107):536-9 [8475385] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search. AN - 76831971; 7966317 AB - Using an iterative approach to sequence database search that combines scanning with individual amino acid sequences and with alignment blocks, we show that bacterial haloacid dehalogenases (HADs) belong to a large superfamily of hydrolases with diverse substrate specificity. The superfamily also includes epoxide hydrolases, different types of phosphatases, and numerous uncharacterized proteins from eubacteria, eukaryotes, and Archaea. Nine putative proteins of the HAD superfamily with functions unknown, in addition to two known enzymes, were found in Escherichia coli alone, making it one of the largest groups of enzymes and indicating that a variety of hydrolytic enzyme activities remain to be described. Many of the proteins with known enzymatic activities in the HAD superfamily are involved in detoxification of xenobiotics or metabolic by-products. All the proteins in the superfamily contain three conserved sequence motifs. Along with the conservation of the predicted secondary structure, motifs I, II, and III include a conserved aspartic acid residue, a lysine, and a nucleophile, namely aspartic acid or serine, respectively. A specific role in the catalysis of the hydrolysis of carbon-halogen and other bonds is assigned to each of these residues. JF - Journal of molecular biology AU - Koonin, E V AU - Tatusov, R L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894. Y1 - 1994/11/18/ PY - 1994 DA - 1994 Nov 18 SP - 125 EP - 132 VL - 244 IS - 1 SN - 0022-2836, 0022-2836 KW - Carboxylic Acids KW - 0 KW - Hydrocarbons, Halogenated KW - Xenobiotics KW - Hydrolases KW - EC 3.- KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - 2-haloacid dehalogenase KW - EC 3.8.1.2 KW - Index Medicus KW - Biological Evolution KW - Xenobiotics -- metabolism KW - Computers KW - Hydrocarbons, Halogenated -- metabolism KW - Amino Acid Sequence KW - Carboxylic Acids -- metabolism KW - Models, Biological KW - Binding Sites KW - Epoxide Hydrolases -- genetics KW - Conserved Sequence KW - Molecular Sequence Data KW - Databases, Factual KW - Biodegradation, Environmental KW - Models, Chemical KW - Substrate Specificity KW - Statistics as Topic KW - Sequence Homology, Amino Acid KW - Bacteria -- enzymology KW - Multigene Family KW - Hydrolases -- genetics KW - Sequence Alignment -- methods KW - Hydrolases -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76831971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Computer+analysis+of+bacterial+haloacid+dehalogenases+defines+a+large+superfamily+of+hydrolases+with+diverse+specificity.+Application+of+an+iterative+approach+to+database+search.&rft.au=Koonin%2C+E+V%3BTatusov%2C+R+L&rft.aulast=Koonin&rft.aufirst=E&rft.date=1994-11-18&rft.volume=244&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - UNKNOWN; GENBANK; SWISSPROT; PIR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saintopin, a dual inhibitor of DNA topoisomerases I and II, as a probe for drug-enzyme interactions. AN - 76821388; 7961822 AB - Stabilization of the topoisomerase-cleavable complexes is the common initial event leading to the cytotoxicity of topoisomerase I and II (top1 and top2) inhibitors. Using saintopin (STP), a poison of both topoisomerases, we studied top1- and top2-cleavable complexes (Yamashita, Y., Kawada, S.-Z., Fujii, N., and Nakano, H. (1991) Biochemistry 30, 5838-5845). top1 and top2 sites induced in the presence of STP showed the same preferences for the base located 3' to the topoisomerase-induced DNA break (position +1): preference for G and not C. A camptothecin-resistant top1 with a mutation (Asn722-->Ser) next to the catalytic tyrosine (Tyr723) was cross-resistant to STP, suggesting that both STP and camptothecin interact with the protein near the catalytic tyrosine. These results are consistent with a dual interaction of the drug with the enzyme and the DNA and provide further evidence for the "drug-stacking" model. This model proposes that topoisomerase inhibitors bind, possibly through hydrogen bonding and/or stacking, with one of the bases flanking the DNA termini (guanine at position +1 in the case of STP) and within the enzyme catalytic pocket, most likely by stacking with the catalytic tyrosine. JF - The Journal of biological chemistry AU - Leteurtre, F AU - Fujimori, A AU - Tanizawa, A AU - Chhabra, A AU - Mazumder, A AU - Kohlhagen, G AU - Nakano, H AU - Pommier, Y AD - Division of Cancer Treatment, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/18/ PY - 1994 DA - 1994 Nov 18 SP - 28702 EP - 28707 VL - 269 IS - 46 SN - 0021-9258, 0021-9258 KW - Benz(a)Anthracenes KW - 0 KW - DNA Primers KW - Molecular Probes KW - Topoisomerase I Inhibitors KW - Topoisomerase II Inhibitors KW - saintopin KW - 131190-63-1 KW - Tyrosine KW - 42HK56048U KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Base Sequence KW - Humans KW - DNA Topoisomerases, Type II -- metabolism KW - Molecular Sequence Data KW - Tyrosine -- metabolism KW - Hydrolysis KW - Benz(a)Anthracenes -- pharmacology KW - Benz(a)Anthracenes -- metabolism KW - DNA Topoisomerases, Type I -- metabolism KW - Catalysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76821388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Saintopin%2C+a+dual+inhibitor+of+DNA+topoisomerases+I+and+II%2C+as+a+probe+for+drug-enzyme+interactions.&rft.au=Leteurtre%2C+F%3BFujimori%2C+A%3BTanizawa%2C+A%3BChhabra%2C+A%3BMazumder%2C+A%3BKohlhagen%2C+G%3BNakano%2C+H%3BPommier%2C+Y&rft.aulast=Leteurtre&rft.aufirst=F&rft.date=1994-11-18&rft.volume=269&rft.issue=46&rft.spage=28702&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 - 1994-12-19 N1 - Date created - 1994-12-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X00364; GENBANK; K01908; V00501 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ferrous-citrate complex and nigral degeneration: evidence for free-radical formation and lipid peroxidation. AN - 77721677; 7832447 AB - Increased nigral iron content in the parkinsonian brain is now well documented and is implicated in the pathogenesis of this movement disorder. Free iron in the pigmented DA-containing neurons catalyze DA autoxidation and Fenton reaction to produce cytotoxic .OH, initiating lipid peroxidation and consequent cell damage. The present results clearly demonstrate that a regional increase in the levels of the "labile iron pool" can result in the degeneration of dopaminergic nigral neurons as reflected by a significant inhibition in the expression of tyrosine hydroxylase mRNA and DA depletion. Iron-complex-induced damage of dopaminergic neurons in the substantia nigra, might have resulted from a sequence of cytotoxic events including the .OH generation and lipid peroxidation as demonstrated in this study. This free-radical-induced oxidative nigral injury may be a reliable free-radical model for studying parkinsonism and may be relevant to idiopathic Parkinson's disease. This apparent nigral injury stimulated by Fe(2+)-citrate is more severe than that produced by ferric iron and its citrate complex. Moreover, these data indicate that Fe(2+)-citrate is as potent as MPP+ in causing oxidative injury to the substantia nigral neurons. However, the nigral toxicity of MPTP and its congeners are not progressive, while Fe(2+)-citrate complex may produce a progressive degeneration of the nigrostriatal neurons which is similar to the progression of ideopathic Parkinson's disease. Thus, this unique Fe(2+)-citrate complex animal model could be used for studying neuroprotective treatments for retarding or halting the progressive nigrostriatal degeneration caused by free radicals in the iron-rich basal ganglia. JF - Annals of the New York Academy of Sciences AU - Mohanakumar, K P AU - de Bartolomeis, A AU - Wu, R M AU - Yeh, K J AU - Sternberger, L M AU - Peng, S Y AU - Murphy, D L AU - Chiueh, C C AD - Laboratory of Clinical Sciences, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1264. Y1 - 1994/11/17/ PY - 1994 DA - 1994 Nov 17 SP - 392 EP - 399 VL - 738 SN - 0077-8923, 0077-8923 KW - Ferrous Compounds KW - 0 KW - Free Radicals KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Hydroxyl Radical KW - 3352-57-6 KW - monoferrous acid citrate KW - 33KM3X4QQW KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Kinetics KW - Dopamine -- metabolism KW - Free Radicals -- metabolism KW - Male KW - Substantia Nigra -- metabolism KW - Neurons -- metabolism KW - Substantia Nigra -- pathology KW - Hydroxyl Radical -- metabolism KW - Ferrous Compounds -- pharmacology KW - Neurons -- drug effects KW - Corpus Striatum -- metabolism KW - Lipid Peroxidation -- drug effects KW - Substantia Nigra -- drug effects KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77721677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ferrous-citrate+complex+and+nigral+degeneration%3A+evidence+for+free-radical+formation+and+lipid+peroxidation.&rft.au=Mohanakumar%2C+K+P%3Bde+Bartolomeis%2C+A%3BWu%2C+R+M%3BYeh%2C+K+J%3BSternberger%2C+L+M%3BPeng%2C+S+Y%3BMurphy%2C+D+L%3BChiueh%2C+C+C&rft.aulast=Mohanakumar&rft.aufirst=K&rft.date=1994-11-17&rft.volume=738&rft.issue=&rft.spage=392&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobiology of NO. and .OH: basic research and clinical relevance. AN - 77719710; 7832438 JF - Annals of the New York Academy of Sciences AU - Chiueh, C C AD - Unit on Neurotoxicology and Neuroprotection, National Institute of Mental Health, NIH Clinical Center, Bethesda, Maryland 20892-1264. Y1 - 1994/11/17/ PY - 1994 DA - 1994 Nov 17 SP - 279 EP - 281 VL - 738 SN - 0077-8923, 0077-8923 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Reactive Oxygen Species KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydroxyl Radical KW - 3352-57-6 KW - Index Medicus KW - Animals KW - Free Radical Scavengers -- therapeutic use KW - Antioxidants -- pharmacology KW - Humans KW - Brain -- pathology KW - Brain -- drug effects KW - Antioxidants -- therapeutic use KW - Brain -- metabolism KW - Free Radical Scavengers -- pharmacology KW - Reactive Oxygen Species -- metabolism KW - Hydroxyl Radical -- metabolism KW - Brain Diseases -- pathology KW - Nitric Oxide -- physiology KW - Brain Diseases -- prevention & control KW - Models, Neurological KW - Brain Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77719710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neurobiology+of+NO.+and+.OH%3A+basic+research+and+clinical+relevance.&rft.au=Chiueh%2C+C+C&rft.aulast=Chiueh&rft.aufirst=C&rft.date=1994-11-17&rft.volume=738&rft.issue=&rft.spage=279&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline). AN - 77719545; 7832430 AB - The current research has demonstrated that MPP+ can induce lipid peroxidation in the nigrostriatal system of rat in vivo. Antioxidant agent U-78517F and .OH scavenger DMSO may protect against MPP+ toxicity through the inhibition of .OH radical-mediated oxidative injury in the substantia nigra. These findings indicate that the cytotoxic hydroxyl radical generated from dopamine oxidation in the iron-rich basal ganglia may contribute to the mechanism underlying the selective A9 melanized nigral degeneration in MPTP-Parkinsonism and possibly in idiopathic Parkinson's disease. In addition, the present studies also clearly demonstrate that deprenyl can substantially protect dopaminergic neurons against MPP+ toxicity in the substantia nigra zona compacta in vivo. The neuroprotective effect provided by deprenyl may not be the consequence of its inhibition of MAO-B activity or prevention of the uptake of MPP+ by dopaminergic neurons. A unique antioxidant property of deprenyl by suppressing .OH formation and associated oxidative injury induced by MPP+ may contribute to the apparent neuroprotective action. In perspective, this putative antioxidant effect of deprenyl may provide another mechanism to its overt neuroprotective effects against oxygen radical-mediated oxidative injury in some neurotoxic chemicals, such as 6-OHDA and DSP-4, and probably in Alzheimer's disease and senescent changes. Finally, based on the present data, a possible neuroprotective therapeutic window of deprenyl in the treatment of early Parkinson's disease has been proposed. It is suggested that deprenyl should be introduced as early as possible in de novo Parkinsonian patients to achieve its full neuroprotective effect on nigral degeneration. Moreover, a combination of early detection of individuals at risk of developing Parkinson's disease and early intervention of deprenyl and/or other centrally active antioxidants to these patients may provide a new preventive therapeutic strategy in the future, in addition to the current conventional levodopa treatment of Parkinson's disease. JF - Annals of the New York Academy of Sciences AU - Wu, R M AU - Mohanakumar, K P AU - Murphy, D L AU - Chiueh, C C AD - Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health Clinical Center 10/3D-41, Bethesda, Maryland 20892. Y1 - 1994/11/17/ PY - 1994 DA - 1994 Nov 17 SP - 214 EP - 221 VL - 738 SN - 0077-8923, 0077-8923 KW - Antioxidants KW - 0 KW - Free Radicals KW - Selegiline KW - 2K1V7GP655 KW - Hydroxyl Radical KW - 3352-57-6 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Lipid Peroxidation -- drug effects KW - Alzheimer Disease -- metabolism KW - Monoamine Oxidase -- metabolism KW - Free Radicals -- metabolism KW - Neurons -- metabolism KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Hydroxyl Radical -- metabolism KW - Corpus Striatum -- metabolism KW - Neurons -- drug effects KW - Parkinson Disease -- metabolism KW - Substantia Nigra -- drug effects KW - Parkinson Disease -- drug therapy KW - Neurons -- pathology KW - Substantia Nigra -- metabolism KW - Selegiline -- pharmacology KW - Antioxidants -- metabolism KW - Substantia Nigra -- pathology KW - Corpus Striatum -- drug effects KW - 1-Methyl-4-phenylpyridinium -- antagonists & inhibitors KW - Corpus Striatum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77719545?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antioxidant+mechanism+and+protection+of+nigral+neurons+against+MPP%2B+toxicity+by+deprenyl+%28selegiline%29.&rft.au=Wu%2C+R+M%3BMohanakumar%2C+K+P%3BMurphy%2C+D+L%3BChiueh%2C+C+C&rft.aulast=Wu&rft.aufirst=R&rft.date=1994-11-17&rft.volume=738&rft.issue=&rft.spage=214&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia. AN - 77711680; 7832434 AB - The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS) JF - Annals of the New York Academy of Sciences AU - Chiueh, C C AU - Wu, R M AU - Mohanakumar, K P AU - Sternberger, L M AU - Krishna, G AU - Obata, T AU - Murphy, D L AD - Unit on Neurotoxicology and Neuroprotection, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/17/ PY - 1994 DA - 1994 Nov 17 SP - 25 EP - 36 VL - 738 SN - 0077-8923, 0077-8923 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Free Radicals KW - Melanins KW - Salicylates KW - Selegiline KW - 2K1V7GP655 KW - Hydroxyl Radical KW - 3352-57-6 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Melanins -- biosynthesis KW - Nerve Degeneration -- drug effects KW - Animals KW - Selegiline -- pharmacology KW - Antioxidants -- pharmacology KW - Selegiline -- therapeutic use KW - Humans KW - Free Radicals -- metabolism KW - Hydroxyl Radical -- metabolism KW - Corpus Striatum -- metabolism KW - Parkinson Disease -- metabolism KW - Dopamine -- metabolism KW - Substantia Nigra -- drug effects KW - Parkinson Disease -- drug therapy KW - Basal Ganglia -- pathology KW - Substantia Nigra -- metabolism KW - Substantia Nigra -- pathology KW - MPTP Poisoning KW - Corpus Striatum -- drug effects KW - Hydroxyl Radical -- analysis KW - Basal Ganglia -- drug effects KW - Basal Ganglia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77711680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=In+vivo+generation+of+hydroxyl+radicals+and+MPTP-induced+dopaminergic+toxicity+in+the+basal+ganglia.&rft.au=Chiueh%2C+C+C%3BWu%2C+R+M%3BMohanakumar%2C+K+P%3BSternberger%2C+L+M%3BKrishna%2C+G%3BObata%2C+T%3BMurphy%2C+D+L&rft.aulast=Chiueh&rft.aufirst=C&rft.date=1994-11-17&rft.volume=738&rft.issue=&rft.spage=25&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide protects against the cytotoxic effects of reactive oxygen species. AN - 77700998; 7832437 JF - Annals of the New York Academy of Sciences AU - Wink, D A AU - Hanbauer, I AU - Laval, F AU - Cook, J A AU - Krishna, M C AU - Mitchell, J B AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/11/17/ PY - 1994 DA - 1994 Nov 17 SP - 265 EP - 278 VL - 738 SN - 0077-8923, 0077-8923 KW - Reactive Oxygen Species KW - 0 KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - Hydrogen Peroxide KW - BBX060AN9V KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Cricetulus KW - Dopamine -- metabolism KW - Mesencephalon -- cytology KW - Rats KW - Hydrogen Peroxide -- toxicity KW - Liver Neoplasms, Experimental KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Lung KW - Nitroprusside -- pharmacology KW - Cell Line KW - Female KW - Cricetinae KW - Nitric Oxide -- toxicity KW - Cell Survival -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Nitric Oxide -- pharmacology KW - Reactive Oxygen Species -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77700998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide+protects+against+the+cytotoxic+effects+of+reactive+oxygen+species.&rft.au=Wink%2C+D+A%3BHanbauer%2C+I%3BLaval%2C+F%3BCook%2C+J+A%3BKrishna%2C+M+C%3BMitchell%2C+J+B&rft.aulast=Wink&rft.aufirst=D&rft.date=1994-11-17&rft.volume=738&rft.issue=&rft.spage=265&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 - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of SO3.- and OH radicals in SO3(2-) reactions with inorganic environmental pollutants and its implications to SO3(2-) toxicity. AN - 76901244; 7798899 AB - Electron spin resonance (ESR) spin trapping and high performance liquid chromatography (HPLC) with electron chemical detection were utilized to investigate the generation of free radicals in reactions of sulfite (SO3(2-)) with inorganic environmental pollutants. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Incubation of SO3(2-) with nitrite (NO2-) generated sulfur trioxide anion radical (SO3.-), whose yield approached saturation levels in approximately four minutes. Fe2+ promoted SO3.- formation. Molecular oxygen was required for radical generation. This was demonstrated by experiments carried out in an argon environment as well as by oxygen consumption measurements. Transition metal ions, CrO4(2-), VO2+, Fe3+, Mn2+, Ni2+, and Fe2+ enhanced SO3.- generation from SO3(2-) either through direct SO3(2-) oxidation by metal ions or by metal ions-catalyzed SO3(2-) oxidation by molecular oxygen. Incubation of SO3(2-) with H2O2 generated both SO3.- and .OH radicals as verified by spin trapping competition measurements using ethanol and formate as .OH radical scavengers. HPLC measurements showed that .OH radicals generated by reaction of SO3(2-) with H2O2 caused 2'-deoxyguanine hydroxylation to generate 8-hydroxy-2'-deoxyguanine, a DNA damage marker. The implications of SO3.- and .OH radical formation in relation to SO3(2-) toxicity are discussed. JF - Journal of inorganic biochemistry AU - Shi, X AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 155 EP - 165 VL - 56 IS - 3 SN - 0162-0134, 0162-0134 KW - Cyclic N-Oxides KW - 0 KW - Environmental Pollutants KW - Free Radicals KW - Spin Labels KW - Sulfur Dioxide KW - 0UZA3422Q4 KW - Hydroxyl Radical KW - 3352-57-6 KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Kinetics KW - Electron Spin Resonance Spectroscopy KW - Electrochemistry KW - Chromatography, High Pressure Liquid KW - Deoxyguanosine -- analogs & derivatives KW - Sulfur Dioxide -- toxicity KW - Environmental Pollutants -- toxicity KW - DNA Damage KW - Sulfur Dioxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76901244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=Generation+of+SO3.-+and+OH+radicals+in+SO3%282-%29+reactions+with+inorganic+environmental+pollutants+and+its+implications+to+SO3%282-%29+toxicity.&rft.au=Shi%2C+X&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-11-15&rft.volume=56&rft.issue=3&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-25 N1 - Date created - 1995-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A P-loop related motif (GxxGxxK) highly conserved in sulfotransferases is required for binding the activated sulfate donor. AN - 76858240; 7980593 AB - A nucleotide binding motif termed the P-loop has been described for ATP- and GTP-binding proteins. The primary structure typically consists of a glycine-rich region followed by a conserved lysine. A related structure (GxxGxxK) noted in sulfotransferases has been suggested to be important for the binding of the cofactor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), the universal sulfate donor for this class of enzymes. Using molecular techniques, point mutations that substituted alanines for the putative critical residues were introduced into the cDNA for estrogen sulfotransferase. The altered construct, although fully expressed by Chinese hamster ovary-K1 cells, demonstrated negligible enzymatic activity and failed to photoaffinity label with [35S]PAPS. In contrast, a construct in which three other amino acids in the region of the P-loop motif were similarly mutated retained activity and was photoaffinity labeled with [35S]PAPS. These data strongly support the notion that the P-loop motif found in all cloned sulfotransferases constitutes, at least in part, the PAPS binding site for these enzymes. JF - Biochemical and biophysical research communications AU - Komatsu, K AU - Driscoll, W J AU - Koh, Y C AU - Strott, C A AD - Section on Steroid Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 1178 EP - 1185 VL - 204 IS - 3 SN - 0006-291X, 0006-291X KW - Affinity Labels KW - 0 KW - Recombinant Proteins KW - Sulfur Radioisotopes KW - Phosphoadenosine Phosphosulfate KW - 482-67-7 KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Protein Structure, Secondary KW - Guinea Pigs KW - Humans KW - Mice KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Rats KW - Mutagenesis, Site-Directed KW - Cattle KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Point Mutation KW - Molecular Sequence Data KW - CHO Cells KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Phosphoadenosine Phosphosulfate -- metabolism KW - Cricetinae KW - Sulfotransferases -- genetics KW - Sulfotransferases -- metabolism KW - Conserved Sequence KW - Sulfotransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76858240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+P-loop+related+motif+%28GxxGxxK%29+highly+conserved+in+sulfotransferases+is+required+for+binding+the+activated+sulfate+donor.&rft.au=Komatsu%2C+K%3BDriscoll%2C+W+J%3BKoh%2C+Y+C%3BStrott%2C+C+A&rft.aulast=Komatsu&rft.aufirst=K&rft.date=1994-11-15&rft.volume=204&rft.issue=3&rft.spage=1178&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 - 1994-12-22 N1 - Date created - 1994-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the X gene promoter of woodchuck hepatitis virus. AN - 76844279; 7975227 AB - During the course of woodchuck hepatitis virus (WHV) replication three virus-specific mRNA transcripts that encode four essential proteins are produced. The transcripts are 3.6, 2.3, and 0.7 kb in size. The 3.6-kb transcript serves as the replicative intermediate as well as the template for translation of the nucleocapsid and polymerase proteins. The 2.3-kb mRNA serves as the template for translation of the virus envelope proteins. Both the 3.6- and 2.3-kb transcripts are polyadenylated and are readily found in the cytoplasm of infected hepatocytes. However, the 0.7-kb transcript, specific for the X gene, accumulates in the nucleus of infected cells and is polyadenylated poorly in hepatocytes. Thus, while it is likely that the 0.7-kb transcript is the template for translation of the X protein, it is possible that it also has a function at the RNA level to regulate virus replication or gene expression. In order to characterize the WHV X promoter we cloned the region of the WHV8 genome encompassing the viral enhancer through the amino terminus of the X gene into the vector pSV0CAT. We transfected Huh-7 and WLC-3 cells with the WHV X promoter construct, along with a plasmid encoding human growth hormone to control for transfection efficiency, and assayed for the presence of chloramphenicol acetyl transferase activity. We found that the WHV X promoter was about one-half as active as the well-studied simian virus 40 early or Rous sarcoma virus promoters. Next, we made a series of 5' and 3' deletion mutants and mapped the WHV X promoter to a 21-nucleotide domain (1482-GGGGAAGCTGACGTCCTTTCC-1502) which is approximately 100 bp downstream of the corresponding promoter in hepatitis B virus. Further analysis, using oligonucleotide-directed mutagenesis, demonstrated that the essential nucleotides comprising the WHV X promoter are located in a 10-nucleotide domain near the initiation codon of the X gene. Mutation of either nucleotide T at position 1490 or G at position 1491 within this domain was sufficient to reduce the level of promoter activity by 100-fold. Thus, we have defined the important nucleotides within the promoter of the WHV X transcript which is a first step in understanding the role of this transcript in WHV replication and gene expression. JF - Virology AU - Sugata, F AU - Chen, H S AU - Kaneko, S AU - Purcell, R H AU - Miller, R H AD - Hepatitis Virus Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 314 EP - 320 VL - 205 IS - 1 SN - 0042-6822, 0042-6822 KW - Oligodeoxyribonucleotides KW - 0 KW - Trans-Activators KW - Viral Proteins KW - protein X, Woodchuck hepatitis B virus KW - 147829-08-1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Middle Aged KW - Male KW - Sequence Deletion KW - Viral Proteins -- genetics KW - Hepatitis B Virus, Woodchuck -- genetics KW - Promoter Regions, Genetic KW - Trans-Activators -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76844279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+the+X+gene+promoter+of+woodchuck+hepatitis+virus.&rft.au=Sugata%2C+F%3BChen%2C+H+S%3BKaneko%2C+S%3BPurcell%2C+R+H%3BMiller%2C+R+H&rft.aulast=Sugata&rft.aufirst=F&rft.date=1994-11-15&rft.volume=205&rft.issue=1&rft.spage=314&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-06 N1 - Date created - 1994-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against SR 4233 (Tirapazamine) aerobic cytotoxicity by the metal chelators desferrioxamine and tiron. AN - 76823412; 7960991 AB - Metal chelating agents and antioxidants were evaluated as potential protectors against aerobic SR 4233 cytotoxicity in Chinese hamster V79 cells. The differential protection of aerobic and hypoxic cells by two metal chelators, desferrioxamine and Tiron, is discussed in the context of their potential use in the on-going clinical trials with SR 4233. Cytotoxicity was evaluated using clonogenic assay. SR 4233 exposure was done in glass flasks as a function of time either alone or in the presence of the following agents: superoxide dismutase, catalase, 5,5-dimethyl-1-pyrroline, Trolox, ICRF-187, desferrioxamine, Tiron (1,2-dihydroxybenzene-3,5-disulfonate), and ascorbic acid. Experiments done under hypoxic conditions were carried out in specially designed glass flasks that were gassed with humidified nitrogen/carbon dioxide mixture and with a side-arm reservoir from which SR 4233 was added to cell media after hypoxia was obtained. Electron paramagnetic resonance studies were also performed. Electron paramagnetic resonance and spectrophotometry experiments suggest that under aerobic conditions SR 4233 undergoes futile redox cycling to produce superoxide. Treatment of cells during aerobic exposure to SR 4233 with the enzymes superoxide dismutase and catalase, the spin trapping agent DMPO, the water-soluble vitamin E analog Trolox, and the metal chelator ICRF-187 provided little or no protection against aerobic SR 4233 cytotoxicity. However, two other metal chelators, desferrioxamine and Tiron, afforded significant protection against aerobic SR 4233 cytotoxicity (protection factors at 50% survival were 3.8 and 3.1, respectively), while exhibiting minimal protection to hypoxic cells treated with SR 4233. One potential mechanism of aerobic cytotoxicity is redox cycling of SR 4233 with molecular oxygen resulting in several potentially toxic oxidative species that overburden the intrinsic intracellular detoxification systems such as superoxide dismutase, catalase, and glutathione peroxidase. This study identifies two metal chelating agents, desferrioxamine and Tiron, that were able to protect against aerobic but not hypoxic SR 4233 cytotoxicity. JF - International journal of radiation oncology, biology, physics AU - Herscher, L L AU - Krishna, M C AU - Cook, J A AU - Coleman, C N AU - Biaglow, J E AU - Tuttle, S W AU - Gonzalez, F J AU - Mitchell, J B AD - Radiation Biology Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 879 EP - 885 VL - 30 IS - 4 SN - 0360-3016, 0360-3016 KW - Antioxidants KW - 0 KW - Chelating Agents KW - Triazines KW - tirapazamine KW - 1UD32YR59G KW - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt KW - 4X87R5T106 KW - NADP KW - 53-59-8 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - Deferoxamine KW - J06Y7MXW4D KW - Index Medicus KW - Animals KW - Drug Interactions KW - Cricetulus KW - Enzyme Activation KW - NADPH-Ferrihemoprotein Reductase -- metabolism KW - NADP -- metabolism KW - Cell Hypoxia -- physiology KW - Oxidation-Reduction KW - Chelating Agents -- pharmacology KW - Antioxidants -- pharmacology KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Electron Spin Resonance Spectroscopy KW - Aerobiosis KW - Cricetinae KW - Triazines -- toxicity KW - Deferoxamine -- pharmacology KW - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76823412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Protection+against+SR+4233+%28Tirapazamine%29+aerobic+cytotoxicity+by+the+metal+chelators+desferrioxamine+and+tiron.&rft.au=Herscher%2C+L+L%3BKrishna%2C+M+C%3BCook%2C+J+A%3BColeman%2C+C+N%3BBiaglow%2C+J+E%3BTuttle%2C+S+W%3BGonzalez%2C+F+J%3BMitchell%2C+J+B&rft.aulast=Herscher&rft.aufirst=L&rft.date=1994-11-15&rft.volume=30&rft.issue=4&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-15 N1 - Date created - 1994-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of analgesics and risk of renal cell cancer. AN - 76809012; 7960214 AB - Although heavy or long-term use of analgesics has been related to risk of renal cell cancer in several studies, evidence for such an association remains inconclusive. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with lifetime consumption among those who reported during in-person interviews regular (at least 2 or more times per week for 1 month or longer) use of analgesics. Odds ratios (OR) were computed using logistic regression analyses. No excess risk was associated with regular use of aspirin, acetaminophen, phenacetin or combinations of these agents, nor did risks rise with increasing cumulative intake of these analgesics. A non-significant increased risk (OR = 2.1, 95% CI = 0.6-6.9) was observed among women who used only acetaminophen-containing analgesics, but little excess was seen in men. Earlier studies reported a link to phenacetin-containing analgesics, but no one reported exclusive use of phenacetin-containing drugs in our study. The findings suggest that use of analgesics is not likely to play a major role in renal cell cancer development and that for cases diagnosed in the late 1980s or later, after the earlier withdrawal of phenacetin-containing drugs from the market, a hazard from this analgesic no longer exists. JF - International journal of cancer AU - Chow, W H AU - McLaughlin, J K AU - Linet, M S AU - Niwa, S AU - Mandel, J S AD - Biostatistics Branch, National Cancer Institute, Bethesda, MD. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 467 EP - 470 VL - 59 IS - 4 SN - 0020-7136, 0020-7136 KW - Drug Combinations KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Phenacetin KW - ER0CTH01H9 KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Odds Ratio KW - Logistic Models KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Risk Assessment KW - Population Surveillance KW - Phenacetin -- adverse effects KW - Carcinoma, Renal Cell -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Aspirin -- adverse effects KW - Acetaminophen -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76809012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+analgesics+and+risk+of+renal+cell+cancer.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BLinet%2C+M+S%3BNiwa%2C+S%3BMandel%2C+J+S&rft.aulast=Chow&rft.aufirst=W&rft.date=1994-11-15&rft.volume=59&rft.issue=4&rft.spage=467&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 - 1994-12-08 N1 - Date created - 1994-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. AN - 76800061; 7954409 AB - The present study assessed the role of the p53 tumor suppressor gene in cell cycle arrest and apoptosis following treatment of Burkitt's lymphoma and lymphoblastoid cell lines with gamma-rays, etoposide, nitrogen mustard, and cisplatin. Cell cycle arrest was measured by flow cytometry; p53 and p21Waf1/Cip1 protein levels were measured by Western blotting; cell survival was measured in 72-96-h growth inhibition assays and by trypan blue staining, and apoptotic DNA fragmentation was assessed by either agarose gel electrophoresis or a modified filter elution method. We found that gamma-rays and etoposide induced a strong G1 arrest in the wild-type p53 lines while nitrogen mustard and cisplatin induced relatively little G1 arrest. All agents failed to induce G1 arrest in cells containing mutant p53 genes. The degree of G1 arrest observed with these agents correlated with the rate of p53 and p21Waf1/Cip1 protein accumulation: gamma-rays and etoposide induced rapid accumulation of both p53 and p21Waf1/Cip1; nitrogen mustard and cisplatin induced slow accumulation of p53 and no major accumulation of the p21Waf1/Cip1 protein. Despite differences in G1 arrest and kinetics of p53 or p21Waf1/Cip1 protein accumulation, all agents tended to decrease survival to a greater extent in the wild-type p53 lines compared to the mutant p53 lines. Cell death in the wild-type p53 lines was associated with intracellular DNA degradation into oligonucleosomal sized DNA fragments, indicative of apoptosis. We also observed an inverse sensitivity relationship between nitrogen mustard/cisplatin and etoposide in the mutant p53 lines and this was found to correlate with topoisomerase II mRNA levels in the cells. Our results suggest that p53 gene status is an important determinant of both radio- and chemosensitivity in lymphoid cell lines and that p53 mutations are often associated with decreased sensitivity to DNA damaging agents. JF - Cancer research AU - Fan, S AU - el-Deiry, W S AU - Bae, I AU - Freeman, J AU - Jondle, D AU - Bhatia, K AU - Fornace, A J AU - Magrath, I AU - Kohn, K W AU - O'Connor, P M AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 5824 EP - 5830 VL - 54 IS - 22 SN - 0008-5472, 0008-5472 KW - p53 KW - CDKN1A protein, human KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Mechlorethamine KW - 50D9XSG0VR KW - Etoposide KW - 6PLQ3CP4P3 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Cisplatin KW - Q20Q21Q62J KW - Nocodazole KW - SH1WY3R615 KW - Index Medicus KW - Drug Resistance -- genetics KW - Tumor Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Flow Cytometry KW - DNA Topoisomerases, Type II -- analysis KW - Lymphocytes KW - Nocodazole -- pharmacology KW - Radiation Tolerance -- genetics KW - Etoposide -- pharmacology KW - G1 Phase -- genetics KW - Gamma Rays KW - Genes, p53 -- physiology KW - Burkitt Lymphoma -- genetics KW - G1 Phase -- radiation effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Apoptosis -- genetics KW - Mutation -- physiology KW - Genes, p53 -- genetics KW - Cisplatin -- pharmacology KW - Mutation -- genetics KW - Cyclins -- metabolism KW - G1 Phase -- drug effects KW - Mechlorethamine -- pharmacology KW - Burkitt Lymphoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76800061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=p53+gene+mutations+are+associated+with+decreased+sensitivity+of+human+lymphoma+cells+to+DNA+damaging+agents.&rft.au=Fan%2C+S%3Bel-Deiry%2C+W+S%3BBae%2C+I%3BFreeman%2C+J%3BJondle%2C+D%3BBhatia%2C+K%3BFornace%2C+A+J%3BMagrath%2C+I%3BKohn%2C+K+W%3BO%27Connor%2C+P+M&rft.aulast=Fan&rft.aufirst=S&rft.date=1994-11-15&rft.volume=54&rft.issue=22&rft.spage=5824&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 - 1994-12-02 N1 - Date created - 1994-12-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute arterial thrombosis in a patient with breast cancer after chemotherapy with 5-fluorouracil, doxorubicin, leucovorin, cyclophosphamide, and interleukin-3. AN - 76795332; 7954241 AB - Interleukin-3 (IL-3) is an experimental agent used to ameliorate neutropenia in patients receiving chemotherapy. Arterial thrombotic episodes after use of IL-3 have not been reported previously. The case of a patient with Stage III adenocarcinoma of the breast who developed hypotension and acute cerebellar artery and superior mesenteric artery thrombosis after receiving chemotherapy and treatment with IL-3 is reported. To the authors' knowledge, this is the first patient with arterial thrombosis reported after treatment with IL-3. Interleukin-3 may be associated with increased propensity for thrombosis. JF - Cancer AU - Theodossiou, C AU - Kroog, G AU - Ettinghausen, S AU - Tolcher, A AU - Cowan, K AU - O'Shaughnessy, J AD - Warren Grant Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/15/ PY - 1994 DA - 1994 Nov 15 SP - 2808 EP - 2810 VL - 74 IS - 10 SN - 0008-543X, 0008-543X KW - Interleukin-3 KW - 0 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Acute Disease KW - Mesenteric Artery, Superior KW - Cerebellum -- blood supply KW - Leucovorin -- administration & dosage KW - Humans KW - Middle Aged KW - Doxorubicin -- administration & dosage KW - Intracranial Embolism and Thrombosis -- chemically induced KW - Female KW - Thrombosis -- chemically induced KW - Breast Neoplasms -- drug therapy KW - Myeloproliferative Disorders -- prevention & control KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Myeloproliferative Disorders -- chemically induced KW - Interleukin-3 -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76795332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+arterial+thrombosis+in+a+patient+with+breast+cancer+after+chemotherapy+with+5-fluorouracil%2C+doxorubicin%2C+leucovorin%2C+cyclophosphamide%2C+and+interleukin-3.&rft.au=Theodossiou%2C+C%3BKroog%2C+G%3BEttinghausen%2C+S%3BTolcher%2C+A%3BCowan%2C+K%3BO%27Shaughnessy%2C+J&rft.aulast=Theodossiou&rft.aufirst=C&rft.date=1994-11-15&rft.volume=74&rft.issue=10&rft.spage=2808&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-06 N1 - Date created - 1994-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of gene-specific repair of alkylation damage in cells depleted of poly(ADP-ribose) polymerase. AN - 76868185; 7984410 AB - The role of the enzyme poly(adenosine diphosphate-ribose) polymerase (PADPRP) in DNA repair at the level of the gene was investigated with human HeLa cells in which PADPRP antisense transcripts are inducible with dexamethasone. After such induction, the cellular content of PADPRP is reduced by 90%. DNA damage and its repair was studied in the essential dihydrofolate reductase (DHFR) gene after exposure of the cells to either ultraviolet (UV) irradiation or the alkylating agent nitrogen mustard. The expression of the antisense construct had no effect on gene-specific repair of UV-induced pyrimidine dimers. In contrast, induced antisense cells were deficient in the gene-specific repair of nitrogen mustard-induced lesions. Dexamethasone itself did not inhibit gene-specific repair in control cells. Thus, PADPRP appears to participate in the gene-specific repair of alkylation damage, but not in the repair of UV-induced pyrimidine dimers. Clonal survival assays revealed that cells depleted of PADPRP showed an increased susceptibility to nitrogen mustard, supporting the notion that repair of essential genes is critical for cellular survival. JF - Nucleic acids research AU - Stevnsner, T AU - Ding, R AU - Smulson, M AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994/11/11/ PY - 1994 DA - 1994 Nov 11 SP - 4620 EP - 4624 VL - 22 IS - 22 SN - 0305-1048, 0305-1048 KW - Pyrimidine Dimers KW - 0 KW - RNA, Antisense KW - Mechlorethamine KW - 50D9XSG0VR KW - Dexamethasone KW - 7S5I7G3JQL KW - DNA KW - 9007-49-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Gene Expression -- drug effects KW - Ultraviolet Rays KW - HeLa Cells KW - Pyrimidine Dimers -- metabolism KW - Dexamethasone -- pharmacology KW - Humans KW - Alkylation KW - DNA -- drug effects KW - Mechlorethamine -- toxicity KW - Cell Survival -- drug effects KW - DNA -- genetics KW - Mechlorethamine -- pharmacology KW - DNA -- radiation effects KW - Tetrahydrofolate Dehydrogenase -- genetics KW - DNA Repair -- physiology KW - DNA Damage KW - Poly(ADP-ribose) Polymerases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76868185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Inhibition+of+gene-specific+repair+of+alkylation+damage+in+cells+depleted+of+poly%28ADP-ribose%29+polymerase.&rft.au=Stevnsner%2C+T%3BDing%2C+R%3BSmulson%2C+M%3BBohr%2C+V+A&rft.aulast=Stevnsner&rft.aufirst=T&rft.date=1994-11-11&rft.volume=22&rft.issue=22&rft.spage=4620&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-03 N1 - Date created - 1995-01-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1990 Aug 15;265(23):13906-13 [2380193] Biochem Cell Biol. 1988 Jun;66(6):626-35 [3139015] J Biol Chem. 1991 Apr 15;266(11):7101-7 [2016318] Mutat Res. 1991 Sep;255(2):155-62 [1656249] Carcinogenesis. 1991 Nov;12(11):1983-92 [1934282] Nature. 1992 Mar 26;356(6367):356-8 [1549180] J Biol Chem. 1992 Jun 25;267(18):12804-12 [1618781] J Biol Chem. 1992 Sep 15;267(26):18858-65 [1326536] J Cell Sci. 1992 Aug;102 ( Pt 4):663-70 [1429884] J Biol Chem. 1993 Jan 25;268(3):1650-7 [8420940] J Biol Chem. 1993 Feb 5;268(4):2649-54 [8428941] J Biol Chem. 1993 Mar 15;268(8):5480-7 [7680646] Toxicol Lett. 1993 Apr;67(1-3):129-50 [8451755] EMBO J. 1993 May;12(5):2109-17 [8491199] Carcinogenesis. 1993 Aug;14(8):1591-6 [8353843] Nature. 1979 Dec 13;282(5740):740-1 [229416] Biochemistry. 1980 Jan 22;19(2):289-93 [7352988] Nature. 1980 Feb 7;283(5747):593-6 [6243744] J Biol Chem. 1980 Nov 10;255(21):10502-8 [6253477] Biochemistry. 1982 Aug 17;21(17):4007-13 [7126529] Science. 1984 Feb 10;223(4636):589-91 [6420886] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3830-3 [3459159] Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82 [3466163] Cancer Res. 1987 Dec 15;47(24 Pt 1):6426-36 [3315187] Mol Cell Biochem. 1993 May 26;122(2):171-93 [8232248] Cell. 1994 Apr 8;77(1):9-12 [8156601] Biochemistry. 1994 May 24;33(20):6186-91 [8193132] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3723-7 [2836856] Cancer Res. 1991 Feb 1;51(3):775-9 [1899045] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Essential RNA binding and packaging domains of the Gag-Pol fusion protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae. AN - 76818291; 7961783 AB - The crucial process in the assembly of the L-A double-stranded RNA virus is the recognition of its (+) single-stranded RNA by the Gag-Pol protein. The Pol region of this protein has RNA binding activity and is necessary for RNA packaging. Here we show that there are actually two in vitro RNA-binding domains of Pol (residues 172-190 and 770-819), and both are necessary for viral propagation, (but not for particle assembly). Furthermore, the N-terminal RNA-binding domain is necessary for in vivo packaging of viral (+) single-stranded RNA. We precisely define the extent of the Pol packaging domain (residues 67-213), which includes the N-terminal RNA-binding domain. This suggests that the N-terminal RNA-binding domain is responsible for binding the genomic RNA in the process of packaging and that additional surrounding residues are responsible for the specificity of binding. JF - The Journal of biological chemistry AU - Ribas, J C AU - Fujimura, T AU - Wickner, R B AD - Section on Genetics of Simple Eukaryotes, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/11/ PY - 1994 DA - 1994 Nov 11 SP - 28420 EP - 28428 VL - 269 IS - 45 SN - 0021-9258, 0021-9258 KW - gag KW - pol KW - Fusion Proteins, gag-pol KW - 0 KW - RNA, Double-Stranded KW - RNA, Viral KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Open Reading Frames KW - Transcription, Genetic KW - Amino Acid Sequence KW - Nucleic Acid Conformation KW - Binding Sites KW - Frameshift Mutation KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Mutagenesis, Insertional KW - Fusion Proteins, gag-pol -- metabolism KW - RNA, Double-Stranded -- chemistry KW - RNA-Binding Proteins -- metabolism KW - RNA, Viral -- biosynthesis KW - Saccharomyces cerevisiae -- virology KW - RNA-Binding Proteins -- chemistry KW - Fusion Proteins, gag-pol -- chemistry KW - RNA, Double-Stranded -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Fusion Proteins, gag-pol -- biosynthesis KW - RNA Viruses -- metabolism KW - RNA, Viral -- chemistry KW - RNA, Double-Stranded -- biosynthesis KW - RNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76818291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Essential+RNA+binding+and+packaging+domains+of+the+Gag-Pol+fusion+protein+of+the+L-A+double-stranded+RNA+virus+of+Saccharomyces+cerevisiae.&rft.au=Ribas%2C+J+C%3BFujimura%2C+T%3BWickner%2C+R+B&rft.aulast=Ribas&rft.aufirst=J&rft.date=1994-11-11&rft.volume=269&rft.issue=45&rft.spage=28420&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 - 1994-12-16 N1 - Date created - 1994-12-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag; pol N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations and altered expression of p16INK4 in human cancer. AN - 76841755; 7972006 AB - Cell cycle arrest at the G1 checkpoint allows completion of critical macromolecular events prior to S phase. Regulators of the G1 checkpoint include an inhibitor of cyclin-dependent kinase, p16INK4; two tumor-suppressor proteins, p53 and RB (the product of the retinoblastoma-susceptibility gene); and cyclin D1. Neither p16INK4 nor the RB protein was detected in 28 of 29 tumor cell lines from human lung, esophagus, liver, colon, and pancreas. The presence of p16INK4 protein is inversely correlated with detectable RB or cyclin D1 proteins and is not correlated with p53 mutations. Homozygous deletions of p16INK4 were detected in several cell lines, but intragenic mutations of this gene were unusual in either cell lines or primary tumors. Transfection of the p16INK4 cDNA expression vector into carcinoma cells inhibits their colony-forming efficiency and the p16INK4 expressing cells are selected against with continued passage in vitro. These results are consistent with the hypothesis that p16INK4 is a tumor-suppressor protein and that genetic and epigenetic abnormalities in genes controlling the G1 checkpoint can lead to both escape from senescence and cancer formation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Okamoto, A AU - Demetrick, D J AU - Spillare, E A AU - Hagiwara, K AU - Hussain, S P AU - Bennett, W P AU - Forrester, K AU - Gerwin, B AU - Serrano, M AU - Beach, D H AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11/08/ PY - 1994 DA - 1994 Nov 08 SP - 11045 EP - 11049 VL - 91 IS - 23 SN - 0027-8424, 0027-8424 KW - INK4 KW - Carrier Proteins KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclins KW - DNA Primers KW - DNA, Neoplasm KW - Oncogene Proteins KW - Cyclin D1 KW - 136601-57-5 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Humans KW - In Situ Hybridization, Fluorescence KW - Oncogene Proteins -- genetics KW - Chromosomes, Human, Pair 9 KW - Polymorphism, Single-Stranded Conformational KW - Cloning, Molecular KW - Gene Deletion KW - Base Sequence KW - Genes KW - Genes, Retinoblastoma KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Cyclins -- genetics KW - DNA Primers -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Cell Cycle KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76841755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+and+altered+expression+of+p16INK4+in+human+cancer.&rft.au=Okamoto%2C+A%3BDemetrick%2C+D+J%3BSpillare%2C+E+A%3BHagiwara%2C+K%3BHussain%2C+S+P%3BBennett%2C+W+P%3BForrester%2C+K%3BGerwin%2C+B%3BSerrano%2C+M%3BBeach%2C+D+H&rft.aulast=Okamoto&rft.aufirst=A&rft.date=1994-11-08&rft.volume=91&rft.issue=23&rft.spage=11045&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 - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - INK4 N1 - Genetic sequence - S74231; GENBANK; S74232 N1 - SuppNotes - Cited By: Science. 1989 Nov 3;246(4930):603-8 [2683075] Cell. 1993 Jun 18;73(6):1059-65 [8513492] Carcinogenesis. 1990 Apr;11(4):673-81 [2323006] Science. 1990 Aug 10;249(4969):666-9 [2166342] Science. 1990 Aug 24;249(4971):912-5 [2144057] Cancer Res. 1991 Mar 15;51(6):1684-8 [1998958] Science. 1991 Jul 5;253(5015):49-53 [1905840] Science. 1991 Nov 22;254(5035):1138-46 [1659741] Cell. 1992 Jul 24;70(2):337-50 [1638634] Cancer Res. 1993 Aug 15;53(16):3674-6 [8339274] Genes Dev. 1993 Aug;7(8):1559-71 [8339933] Am J Hum Genet. 1993 Sep;53(3):752-9 [8352280] Mol Cell Biol. 1993 Oct;13(10):6314-25 [8413230] N Engl J Med. 1993 Oct 28;329(18):1318-27 [8413413] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9571-5 [8415743] Cancer Res. 1993 Nov 1;53(21):5093-5 [8221642] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Oncogene. 1993 Dec;8(12):3447-57 [8247550] Cell. 1993 Dec 3;75(5):839-41 [8252620] Hum Mutat. 1993;2(5):338-46 [8257985] Nature. 1993 Dec 16;366(6456):704-7 [8259215] Cancer Res. 1994 Jan 15;54(2):531-8 [8275491] Genes Dev. 1994 Jan;8(1):9-22 [8288131] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):709-13 [8290586] Oncogene. 1994 Jan;9(1):323-6 [8302597] Cell. 1992 Jul 24;70(2):351-64 [1638635] Science. 1992 Oct 16;258(5081):424-9 [1411535] Cell. 1992 Oct 30;71(3):505-14 [1358458] Cell. 1992 Nov 13;71(4):543-6 [1423612] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10557-61 [1438246] Mol Cell Biol. 1993 Jan;13(1):367-72 [8380224] Mol Cell Biol. 1993 Mar;13(3):1610-8 [8441401] Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):1985-6 [8134335] Cancer Res. 1994 Mar 15;54(6):1422-4 [8137242] Cell. 1994 Mar 25;76(6):1013-23 [8137420] Nature. 1994 Apr 21;368(6473):753-6 [8152487] Science. 1994 Apr 15;264(5157):436-40 [8153634] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2945-9 [8159685] Cancer Res. 1994 Jul 1;54(13):3396-7 [8012957] Science. 1994 Jul 15;265(5170):415-7 [8023167] Exp Cell Res. 1994 Mar;211(1):90-8 [8125163] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Cancer Res. 1993 May 15;53(10 Suppl):2410-5 [7683574] Cell. 1993 May 7;73(3):487-97 [8343202] Cell. 1993 May 7;73(3):499-511 [8490963] Nat Genet. 1993 May;4(1):42-6 [8099841] N Engl J Med. 1990 Jan 11;322(2):77-82 [2294436] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid gene-specific repair of cisplatin lesions at the human DUG/DHFR locus comprising the divergent upstream gene and dihydrofolate reductase gene during early G1 phase of the cell cycle assayed by using the exonucleolytic activity of T4 DNA polymerase. AN - 76841671; 7971995 AB - A novel assay to detect strand-specific DNA repair after cellular exposure to cisplatin at IC50 levels, is used to measure rapid repair in the divergent upstream gene (DUG), a human MutS homolog, and in the bidirectional promoter for dihydrofolate reductase gene (DHFR) and the contiguous upstream DUG. Single-stranded DNA capable of hybridizing to gene-specific probes is generated enzymatically by the 3'-5' exonuclease activity of T4 DNA polymerase. The presence of cisplatin lesions inhibit the exonucleolytic activity of T4 DNA polymerase and block the formation of single-stranded DNA. This decreases the amount of complementary sequence produced when assayed by gene-specific probe hybridization. With the progression of repair, increasing quantities of single-stranded DNA become available for probe hybridization. This assay was applied to human A2780 ovarian carcinoma cells treated with cisplatin at the beginning of G1 phase. A dose-response experiment showed that the assay was applicable down to cisplatin concentrations of 2.5 microM. To assay for strand-specific gene repair, the synchronized cells were treated with cisplatin and then allowed time to repair in drug-free medium. Extensive removal of cisplatin lesions after 2 hr of cellular repair during early G1 phase in the DUG and the DUG/DHFR promoter was measured, with no evidence of repair in the unexpressed delta-globin gene. The extent of preferential DNA repair was much more distinct than has been observed previously at high-drug dosage in asynchronous cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rampino, N J AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994/11/08/ PY - 1994 DA - 1994 Nov 08 SP - 10977 EP - 10981 VL - 91 IS - 23 SN - 0027-8424, 0027-8424 KW - DHFR KW - DUG KW - MSH3 KW - mutS KW - Viral Proteins KW - 0 KW - gene 43 protein, Enterobacteria phage T4 KW - Globins KW - 9004-22-2 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - DNA Damage KW - Cells, Cultured KW - Kinetics KW - Humans KW - Restriction Mapping KW - In Vitro Techniques KW - Globins -- genetics KW - Cell Cycle KW - Promoter Regions, Genetic KW - DNA Repair KW - Cisplatin -- toxicity KW - Tetrahydrofolate Dehydrogenase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76841671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rapid+gene-specific+repair+of+cisplatin+lesions+at+the+human+DUG%2FDHFR+locus+comprising+the+divergent+upstream+gene+and+dihydrofolate+reductase+gene+during+early+G1+phase+of+the+cell+cycle+assayed+by+using+the+exonucleolytic+activity+of+T4+DNA+polymerase.&rft.au=Rampino%2C+N+J%3BBohr%2C+V+A&rft.aulast=Rampino&rft.aufirst=N&rft.date=1994-11-08&rft.volume=91&rft.issue=23&rft.spage=10977&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 - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DHFR; DUG; MSH3; mutS N1 - SuppNotes - Cited By: Carcinogenesis. 1989 Sep;10(9):1681-4 [2766459] J Biol Chem. 1989 Jun 15;264(17):10057-64 [2722860] Biochem Biophys Res Commun. 1991 Sep 30;179(3):1344-51 [1930179] Carcinogenesis. 1991 Nov;12(11):1983-92 [1934282] Nucleic Acids Res. 1991 Nov 25;19(22):6209-14 [1956780] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2307-11 [1372440] Annu Rev Genet. 1991;25:229-53 [1812808] Nucleic Acids Res. 1992 Jul 11;20(13):3485-94 [1630919] Mol Cell Biol. 1992 Sep;12(9):3689-98 [1380646] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10772-6 [1438274] J Biol Chem. 1993 Feb 5;268(4):2649-54 [8428941] Mol Gen Genet. 1993 May;239(1-2):97-108 [8510668] J Biol Chem. 1993 Jul 25;268(21):15674-80 [8340392] Biochem J. 1993 Jul 15;293 ( Pt 2):451-3 [8343124] J Biol Chem. 1993 Sep 25;268(27):20116-25 [8376370] Cell. 1994 Jan 14;76(1):1-4 [8287470] J Biol Chem. 1994 Jan 14;269(2):787-90 [8288625] Cell. 1994 Apr 8;77(1):9-12 [8156601] J Clin Invest. 1991 Mar;87(3):772-7 [1999494] J Biol Chem. 1972 May 25;247(10):3139-46 [4554914] Ann Intern Med. 1984 May;100(5):704-13 [6370067] J Mol Biol. 1984 Jun 25;176(2):169-87 [6235374] Biochemistry. 1985 Jan 29;24(3):707-13 [4039603] Nucleic Acids Res. 1985 May 10;13(9):3285-304 [2987881] Nucleic Acids Res. 1985 Oct 25;13(20):7207-21 [4059056] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3830-3 [3459159] Biochemistry. 1986 Jul 1;25(13):3912-5 [3741840] Biochemistry. 1987 Jun 16;26(12):3307-14 [3651386] Erratum In: Proc Natl Acad Sci U S A 1995 May 23;92(11):5249 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of protein kinase C in inducing Alzheimer's A68 protein expression in the culture of human neuroblastoma cells. AN - 77798346; 7898780 AB - By using the monoclonal antibody Alz50, we studied the role of protein kinase C (PKC) in inducing A68 protein expression in a human neuronal cell line. Both phorbol 12-myristate 13-acetate and H7 strongly induced A68 protein, while HA1004 and calphoslin C had no effect. The results suggest that the inhibitor and activator of PKC induce A68 protein expression by different mechanisms. JF - Neuroscience letters AU - Zhang, L AD - Lab. of Clinical Science, NIMH/NIH, Baltimore, MD 21224. Y1 - 1994/11/07/ PY - 1994 DA - 1994 Nov 07 SP - 95 EP - 97 VL - 181 IS - 1-2 SN - 0304-3940, 0304-3940 KW - Antibodies, Monoclonal KW - 0 KW - Isoquinolines KW - MAPT protein, human KW - Nerve Tissue Proteins KW - Piperazines KW - Sulfonamides KW - tau Proteins KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - N-(2-guanidinoethyl)-5-isoquinolinesulfonamide KW - 91742-10-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Isoquinolines -- pharmacology KW - Immunoblotting KW - Tumor Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Piperazines -- pharmacology KW - Immunochemistry KW - Protein Kinase C -- antagonists & inhibitors KW - Nerve Tissue Proteins -- metabolism KW - Protein Kinase C -- physiology KW - Neuroblastoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77798346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=The+role+of+protein+kinase+C+in+inducing+Alzheimer%27s+A68+protein+expression+in+the+culture+of+human+neuroblastoma+cells.&rft.au=Zhang%2C+L&rft.aulast=Zhang&rft.aufirst=L&rft.date=1994-11-07&rft.volume=181&rft.issue=1-2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. AN - 76840331; 7973634 AB - Hydroxyurea, a drug widely used in therapy of several human diseases, inhibits deoxynucleotide synthesis--and, consequently, DNA synthesis--by blocking the cellular enzyme ribonucleotide reductase. Hydroxyurea inhibits human immunodeficiency virus-type 1 (HIV-1) DNA synthesis in activated peripheral blood lymphocytes by decreasing the amount of intracellular deoxynucleotides, thus suggesting that this drug has an antiviral effect. Hydroxyurea has now been shown to block HIV-1 replication in acutely infected primary human lymphocytes (quiescent and activated) and macrophages, as well as in blood cells infected in vivo obtained from individuals with acquired immunodeficiency syndrome (AIDS). The antiviral effect was achieved at nontoxic doses of hydroxyurea, lower than those currently used in human therapy. Combination of hydroxyurea with the nucleoside analog didanosine (2',3'-dideoxyinosine, or ddl) generated a synergistic inhibitory effect without increasing toxicity. In some instances, inhibition of HIV-1 by hydroxyurea was irreversible, even several weeks after suspension of drug treatment. The indirect inhibition of HIV-1 by hydroxyurea is not expected to generate high rates of escape mutants. Hydroxyurea therefore appears to be a possible candidate for AIDS therapy. JF - Science (New York, N.Y.) AU - Lori, F AU - Malykh, A AU - Cara, A AU - Sun, D AU - Weinstein, J N AU - Lisziewicz, J AU - Gallo, R C AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255. Y1 - 1994/11/04/ PY - 1994 DA - 1994 Nov 04 SP - 801 EP - 805 VL - 266 IS - 5186 SN - 0036-8075, 0036-8075 KW - DNA, Viral KW - 0 KW - HIV Core Protein p24 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Acquired Immunodeficiency Syndrome -- virology KW - Dose-Response Relationship, Drug KW - Humans KW - Zidovudine -- pharmacology KW - Macrophage Activation KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - HIV Core Protein p24 -- analysis KW - DNA Replication -- drug effects KW - Lymphocyte Activation KW - DNA, Viral -- biosynthesis KW - Cell Survival -- drug effects KW - DNA, Viral -- analysis KW - Acquired Immunodeficiency Syndrome -- immunology KW - Drug Synergism KW - Didanosine -- pharmacology KW - Leukocytes, Mononuclear -- virology KW - Virus Replication -- drug effects KW - Macrophages -- virology KW - Hydroxyurea -- pharmacology KW - HIV-1 -- physiology KW - Macrophages -- drug effects KW - Leukocytes, Mononuclear -- drug effects KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76840331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Hydroxyurea+as+an+inhibitor+of+human+immunodeficiency+virus-type+1+replication.&rft.au=Lori%2C+F%3BMalykh%2C+A%3BCara%2C+A%3BSun%2C+D%3BWeinstein%2C+J+N%3BLisziewicz%2C+J%3BGallo%2C+R+C&rft.aulast=Lori&rft.aufirst=F&rft.date=1994-11-04&rft.volume=266&rft.issue=5186&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Ser77]transforming growth factor-beta 1. Selective biological activity and receptor binding in mink lung epithelial cells. AN - 76825880; 7961688 AB - Transforming growth factor-beta 1 (TGF-beta 1) is a homodimeric protein stabilized by a single disulfide bridge between Cys77 on the respective monomers and two paired complementary hydrophobic interfaces between the two subunits. A TGF-beta 1 mutant with Cys77 replaced by serine has been expressed in stably transfected Chinese hamster ovary cells and purified to homogeneity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirms that the sole interchain disulfide bond in TGF-beta 1 has been eliminated. It is 20% as potent as native TGF-beta 1 in the induction of plasminogen activator inhibitor-1 promoter expression in mink lung epithelial cells (Mv1Lu), although it is less than 1% as potent as native TGF-beta 1 in inhibition of growth in the same cell line. The mutant acts as a full agonist in both bioassays. [Ser77]TGF-beta 1 binds to soluble type II receptors and competes with native TGF-beta 1 in sandwich-enzyme-linked immunosorbent assays; however, in Mv1Lu cells, the mutant shows preferential cross-linking to type I rather than type II receptors. [Ser77]TGF-beta 1 is a useful tool for understanding the different ligand-receptor complexes and numerous biological activities of this multifunctional cytokine. JF - The Journal of biological chemistry AU - Amatayakul-Chantler, S AU - Qian, S W AU - Gakenheimer, K AU - Böttinger, E P AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/04/ PY - 1994 DA - 1994 Nov 04 SP - 27687 EP - 27691 VL - 269 IS - 44 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Recombinant Proteins KW - Transforming Growth Factor beta KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Mink KW - Models, Molecular KW - Biological Assay KW - Mice KW - Serine -- chemistry KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Disulfides -- chemistry KW - In Vitro Techniques KW - CHO Cells KW - Cell Line KW - Protein Conformation KW - Cricetinae KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Transforming Growth Factor beta -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76825880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BSer77%5Dtransforming+growth+factor-beta+1.+Selective+biological+activity+and+receptor+binding+in+mink+lung+epithelial+cells.&rft.au=Amatayakul-Chantler%2C+S%3BQian%2C+S+W%3BGakenheimer%2C+K%3BB%C3%B6ttinger%2C+E+P%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Amatayakul-Chantler&rft.aufirst=S&rft.date=1994-11-04&rft.volume=269&rft.issue=44&rft.spage=27687&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 - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thioredoxin-dependent peroxide reductase from yeast. AN - 76822397; 7961686 AB - A 25-kDa antioxidant enzyme that provides protection against oxidation systems capable of generating reactive oxygen and sulfur species has previously been identified. The nature of the oxidant eliminated by, and the physiological source of reducing equivalents for, this enzyme, however, were not known. The 25-kDa enzyme is now shown to be a peroxidase that reduces H2O2 and alkyl hydroperoxides with the use of hydrogens provided by thioredoxin, thioredoxin reductase, and NADPH. This protein is the first peroxidase to be identified that uses thioredoxin as the immediate hydrogen donor and is thus named thioredoxin peroxidase (TPx). TPx exists as a dimer of identical 25-kDa subunits that contain 2 cysteine residues, Cys47 and Cys170. Cys47-SH appears to be the site of oxidation by peroxides, and the oxidized Cys47 probably reacts with Cys170-SH of the other subunit to form an intermolecular disulfide. Mutant TPx proteins lacking either Cys47 or Cys170, therefore, do not exhibit thioredoxin-coupled peroxidase activity. The TPx disulfide is specifically reduced by thioredoxin, but can also be reduced (less effectively) by a small molecular size thiol. The Saccharomyces cerevisiae thioredoxin reductase gene was also cloned and sequenced, and the deduced amino sequence was shown to be 51% identical with that of the Escherichia coli enzyme. JF - The Journal of biological chemistry AU - Chae, H Z AU - Chung, S J AU - Rhee, S G AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/04/ PY - 1994 DA - 1994 Nov 04 SP - 27670 EP - 27678 VL - 269 IS - 44 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Fungal Proteins KW - Neoplasm Proteins KW - Proteins KW - Thioredoxins KW - 52500-60-4 KW - NADP KW - 53-59-8 KW - Peroxidases KW - EC 1.11.1.- KW - Peroxiredoxins KW - EC 1.11.1.15 KW - Thioredoxin-Disulfide Reductase KW - EC 1.8.1.9 KW - Cysteine KW - K848JZ4886 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - NADP -- metabolism KW - Amino Acid Sequence KW - Molecular Weight KW - Structure-Activity Relationship KW - Cloning, Molecular KW - Dithiothreitol -- chemistry KW - Mutagenesis, Site-Directed KW - Oxidation-Reduction KW - Base Sequence KW - Cysteine -- chemistry KW - Molecular Sequence Data KW - Antioxidants -- chemistry KW - Ascorbic Acid -- chemistry KW - Protein Conformation KW - Fungal Proteins -- metabolism KW - Genes, Fungal KW - Thioredoxin-Disulfide Reductase -- genetics KW - Thioredoxins -- metabolism KW - Saccharomyces cerevisiae -- enzymology KW - Proteins -- metabolism KW - Peroxidases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76822397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thioredoxin-dependent+peroxide+reductase+from+yeast.&rft.au=Chae%2C+H+Z%3BChung%2C+S+J%3BRhee%2C+S+G&rft.aulast=Chae&rft.aufirst=H&rft.date=1994-11-04&rft.volume=269&rft.issue=44&rft.spage=27670&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 - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U10274; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rescue and activation of a binding-deficient insulin receptor. Evidence for intermolecular transphosphorylation. AN - 76816768; 7525562 AB - Binding of insulin to the alpha subunit of the insulin receptor (IR) leads to autophosphorylation of the beta subunit. The reaction proceeds as intramolecular transphosphorylation between alpha beta half-receptors of the heterotetrameric receptor dimer (alpha 2 beta 2). Since IRs are mobile in the plane of the plasma membrane, it is also possible that transphosphorylation may occur between adjacent holoreceptors (alpha 2 beta 2) by an intermolecular reaction. To address this question, we cotransfected NIH-3T3 cells with two IR cDNA constructs: a truncated but functionally normal IR lacking the C-terminal 43 amino acids (delta 43) and a full-length Leu323 mutant receptor that is expressed on the cell surface but that does not bind insulin. A clonal cell line was selected from cells cotransfected with a 1/5 ratio of delta 43 cDNA/Leu323 cDNA. The two homodimers (Leu323 and delta 43) were expressed without detectable formation of hybrid receptors. By using specific antibodies, we demonstrate that in cells coexpressing both homodimers, the Leu323 mutant receptor was phosphorylated in vivo by the delta 43 IR in an insulin-dependent manner. However, when the Leu323 mutant receptor was expressed alone, no phosphorylation was detected. In addition, we demonstrate the association of the phosphorylated Leu323 mutant receptor with insulin receptor substrate-1 and with phosphatidylinositol 3-kinase. These findings indicate that insulin binding is not required for phosphorylation of the Leu323 mutant receptor, that the phosphorylation of the Leu323 mutant receptor occurs by an intermolecular transphosphorylation mechanism, and, finally, that the Leu323 mutant receptor, once phosphorylated, can associate with insulin receptor substrate-1 and phosphatidylinositol 3-kinase. JF - The Journal of biological chemistry AU - Taouis, M AU - Levy-Toledano, R AU - Roach, P AU - Taylor, S I AU - Gorden, P AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/04/ PY - 1994 DA - 1994 Nov 04 SP - 27762 EP - 27766 VL - 269 IS - 44 SN - 0021-9258, 0021-9258 KW - Insulin KW - 0 KW - Insulin Receptor Substrate Proteins KW - Irs1 protein, mouse KW - Phosphoproteins KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Enzyme Activation KW - Insulin -- pharmacology KW - Mice KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Transfection KW - In Vitro Techniques KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Insulin Resistance KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Phosphoproteins -- metabolism KW - Receptor, Insulin -- chemistry KW - Receptor, Insulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76816768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rescue+and+activation+of+a+binding-deficient+insulin+receptor.+Evidence+for+intermolecular+transphosphorylation.&rft.au=Taouis%2C+M%3BLevy-Toledano%2C+R%3BRoach%2C+P%3BTaylor%2C+S+I%3BGorden%2C+P&rft.aulast=Taouis&rft.aufirst=M&rft.date=1994-11-04&rft.volume=269&rft.issue=44&rft.spage=27762&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 - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociation of phorbol esters leads to immediate redistribution to the cytosol of protein kinases C alpha and C delta in mouse keratinocytes. AN - 76813145; 7961621 AB - We have measured the dissociation rate of phorbol 12-myristate 13-acetate (PMA), a potent tumor promoter, phorbol 12,13-dibutyrate (PDBu), a weak tumor promoter, and 12-deoxyphorbol 13-phenylacetate (dPP), an antitumor promoter, from intact mouse keratinocytes. PDBu and dPP showed a very rapid release from the cells (t1/2 = 1 min), whereas PMA showed a slower release (t1/2 = 9 min). Western blot analysis of the amounts of protein kinase C alpha (PKC alpha) and PKC delta in the soluble fraction and the Triton X-100-soluble particulate fraction revealed that translocation of both isozymes from the soluble to the particulate fraction was reversible when the phorbol esters were washed off. Washes of 5-15 min resulted in complete redistribution of the PKC isozymes when the cells were previously treated with 1 microM dPP or 1 microM PDBu for 5 min. In the case of treatment with 100 or 10 nM PMA, the redistribution required a longer time; nevertheless, the PKC isozymes returned to the soluble fraction within 60 min. Longer initial treatments with PMA, dPP, and PDBu (up to 60 min) translocated PKC in a very similar, completely reversible fashion. We conclude that in this cell line phorbol esters do not induce the conversion of PKC isozymes to an integral membrane state. JF - The Journal of biological chemistry AU - Szallasi, Z AU - Smith, C B AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/04/ PY - 1994 DA - 1994 Nov 04 SP - 27159 EP - 27162 VL - 269 IS - 44 SN - 0021-9258, 0021-9258 KW - Caenorhabditis elegans Proteins KW - 0 KW - Carrier Proteins KW - Isoenzymes KW - Phorbol Esters KW - Receptors, Drug KW - phorbol ester binding protein KW - phorbol ester receptor KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Cytosol -- enzymology KW - Cell Compartmentation KW - In Vitro Techniques KW - Mice KW - Protein Kinase C -- metabolism KW - Receptors, Drug -- metabolism KW - Phorbol Esters -- metabolism KW - Keratinocytes -- enzymology KW - Keratinocytes -- ultrastructure KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76813145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dissociation+of+phorbol+esters+leads+to+immediate+redistribution+to+the+cytosol+of+protein+kinases+C+alpha+and+C+delta+in+mouse+keratinocytes.&rft.au=Szallasi%2C+Z%3BSmith%2C+C+B%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1994-11-04&rft.volume=269&rft.issue=44&rft.spage=27159&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 - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of multiple myeloma by occupation and industry among men and women: a 24-state death certificate study. AN - 85266143; pmid-7861265 AB - This cancer surveillance investigation uses death certificates from 24 states for the period 1984-1989 to identify multiple myeloma and occupation associations and to stimulate hypotheses. A case-control study of multiple myeloma was created from 3,159,417 certificates in which 12,148 male and female cases were frequency matched by age, race, and gender with five controls per case. We screened 231 industries and 509 occupations. Women demonstrated significant excess risk among managers and administrators, post-secondary teachers, elementary teachers, social workers, other sales workers, waitresses, and hospital maids. Men showed significant risks among computer system scientists, veterinarians, elementary teachers, authors, engineering technicians, general office supervisors, insurance adjusters, barbers, electronic repairers, supervisors of extracting industries, production supervisors, photoengravers, and grader/dozer operators. Men and women elementary school teachers demonstrated the most consistent, statistically significant increased risk of multiple myeloma. JF - Journal of Occupational Medicine : Official Publication of the Industrial Medical Association AU - Figgs, L W AU - Dosemeci, M AU - Blair, A AD - Occupational Studies Section, National Cancer Institute, Bethesda, Maryland 20892-7364. PY - 1994 SP - 1210 EP - 1221 VL - 36 IS - 11 SN - 0096-1736, 0096-1736 KW - United States KW - Odds Ratio KW - Faculty KW - Women's Health KW - Human KW - Aged KW - Multiple Myeloma KW - Population Surveillance KW - Women, Working KW - Adult KW - Death Certificates KW - Case-Control Studies KW - Middle Age KW - Occupational Diseases KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85266143?accountid=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+Occupational+Medicine+%3A+Official+Publication+of+the+Industrial+Medical+Association&rft.atitle=Risk+of+multiple+myeloma+by+occupation+and+industry+among+men+and+women%3A+a+24-state+death+certificate+study.&rft.au=Figgs%2C+L+W%3BDosemeci%2C+M%3BBlair%2C+A&rft.aulast=Figgs&rft.aufirst=L&rft.date=1994-11-01&rft.volume=36&rft.issue=11&rft.spage=1210&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+Medicine+%3A+Official+Publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Expression and mutagenesis of recombinant cholera toxin A subunit. AN - 77839248; 7723660 AB - ADP-ribosylating protein exotoxins from Vibrio cholerae (CT) and Escherichia coli (LT-I) share two short regions of sequence similarity with Bordetella pertussis toxin (PT). Previous studies have indicated that substitution of arginine for lysine 7 within the first region of CT drastically decreases ADP ribosyltransferase activity. We have more closely defined the role of other amino acids in this region by generating modified proteins in which arginine 7 was replaced with lysine (R7K), aspartate 9 was replaced with arginine (D9R), glycine was substituted for proline 12 (P12G), amino acids 6 to 13 were deleted (delta 613) or the C-terminal KDEL sequence was changed to NEDL. The modified proteins R7K, D9R and delta 613 exhibited undetectable ADP ribosyltransferase activity. Comparison of the tryptic digest of R7K with native CT suggested that changes in protein conformation may be responsible for the loss of ADP-ribosylation activity. JF - Microbial pathogenesis AU - Vadheim, K L AU - Singh, Y AU - Keith, J M AD - Laboratory of Microbial Ecology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 339 EP - 346 VL - 17 IS - 5 SN - 0882-4010, 0882-4010 KW - Recombinant Proteins KW - 0 KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - Base Sequence KW - Recombinant Proteins -- biosynthesis KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Adenosine Diphosphate Ribose -- metabolism KW - Structure-Activity Relationship KW - Cholera Toxin -- biosynthesis KW - Cholera Toxin -- genetics KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77839248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbial+pathogenesis&rft.atitle=Expression+and+mutagenesis+of+recombinant+cholera+toxin+A+subunit.&rft.au=Vadheim%2C+K+L%3BSingh%2C+Y%3BKeith%2C+J+M&rft.aulast=Vadheim&rft.aufirst=K&rft.date=1994-11-01&rft.volume=17&rft.issue=5&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=Microbial+pathogenesis&rft.issn=08824010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-23 N1 - Date created - 1995-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An EPR study of free radicals formed by antipsoriatic and tumor-promoting 9-anthrones in nonpolar solvents. AN - 77792931; 7696546 AB - Certain 9-anthrone derivatives are useful in treating psoriasis and are also known to be tumor promoters in mouse skin. Their therapeutic use is accompanied by side effects of severe skin inflammation, irritation, and staining. The precise biochemical mechanisms of therapeutic action, tumor promotion, and side effects are presently uncertain, although the corresponding 9-anthron-10-yl radicals have been proposed as important intermediates. In order to gain insight into the possible role of anthrone-derived radicals in mediating the biological effects of these compounds, in the present study free radicals from a number of anthrone derivatives were generated by thermolysis in nonpolar solvents. Hyperfine splitting constants (hfsc) of the radicals were determined by electron paramagnetic resonance (EPR) spectroscopy. The experimentally determined hfsc's were also compared with spin densities obtained by molecular calculations (MOPAC 6.0). The experimental and theoretical data were found to be consistent in all cases. The formation of 9-anthron-10-yl radicals appears to be a general phenomenon among 9-anthrones regardless of therapeutic or tumor-promoting effectiveness, although there is a trend toward easier radical formation for the more active compounds. JF - Chemical research in toxicology AU - Motten, A G AU - Sik, R H AU - Chignell, C F AU - Hayden, P J AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 877 EP - 881 VL - 7 IS - 6 SN - 0893-228X, 0893-228X KW - Anthracenes KW - 0 KW - Anti-Inflammatory Agents KW - Carcinogens KW - Free Radicals KW - Solvents KW - chrysarobin KW - 6307EF51M1 KW - Index Medicus KW - Anti-Inflammatory Agents -- chemistry KW - Electron Spin Resonance Spectroscopy KW - Psoriasis -- drug therapy KW - Free Radicals -- chemistry KW - Administration, Topical KW - Structure-Activity Relationship KW - Anthracenes -- chemistry KW - Carcinogens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77792931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=An+EPR+study+of+free+radicals+formed+by+antipsoriatic+and+tumor-promoting+9-anthrones+in+nonpolar+solvents.&rft.au=Motten%2C+A+G%3BSik%2C+R+H%3BChignell%2C+C+F%3BHayden%2C+P+J&rft.aulast=Motten&rft.aufirst=A&rft.date=1994-11-01&rft.volume=7&rft.issue=6&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-01 N1 - Date created - 1995-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inflammation and hyperalgesia in rats neonatally treated with capsaicin: effects on two classes of nociceptive neurons in the superficial dorsal horn. AN - 77788915; 7892027 AB - To address the mechanisms of hyperalgesia and dorsal horn plasticity following peripheral tissue inflammation, the effects of adjuvant-induced inflammation of the rat hindpaw on behavioral nociception and nociceptive neuronal activity in the superficial dorsal horn were examined in neonatally capsaicin-treated rats 6-8 weeks of age. Capsaicin treatment resulted in an 82% loss of unmyelinated fibers in L5 dorsal roots, a dramatic reduction of substance P-like immunoreactivity in the spinal cord, and a significant decrease in the percentage of dorsal horn nociceptive neurons that responded to C-fiber stimulation and noxious heating of the skin. The thermal nociceptive threshold was significantly increased in capsaicin-treated rats, but behavioral hyperalgesia to thermal stimuli still developed in response to inflammation. Following inflammation, there was a significant decrease in mechanical threshold and an increase in response duration to mechanical stimuli in both vehicle- and capsaicin-treated rats, suggesting that a state of mechanical hyperalgesia was also induced. The capsaicin treatment appears to have differential effects on nociceptive specific (NS) and wide-dynamic-range (WDR) neurons in inflamed rats. Expansion of the receptive fields of nociceptive neurons, a measure of the effect of inflammation-induced CNS plasticity, was less extensive for NS than for WDR neurons in capsaicin-treated rats. Compared to vehicle-treated rats, a smaller population of NS neurons, but a similar percentage of WDR neurons, had background activity in inflamed capsaicin-treated rats. C-fiber strength electrical stimulation of the sciatic nerve produced expansion of the receptive fields in a greater portion of NS neurons (53%, P < 0.05) in capsaicin- than in vehicle-treated rats (32%). There was no difference in stimulation-induced expansion of the receptive fields for WDR neurons between vehicle- or capsaicin-treated rats. An N-methyl-D-aspartate receptor antagonist, MK-801, attenuated the behavioral hyperalgesia and reduced the receptive field size of dorsal horn neurons in inflamed capsaicin- and vehicle-treated rats. The data suggest that while capsaicin-sensitive primary afferents may be involved in neuronal plasticity induced by peripheral tissue inflammation, changes in the capsaicin-insensitive WDR and NS populations are sufficient to produce thermal and mechanical hyperalgesia after the loss of capsaicin-sensitive primary afferents. JF - Pain AU - Ren, K AU - Williams, G M AU - Ruda, M A AU - Dubner, R AD - Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 287 EP - 300 VL - 59 IS - 2 SN - 0304-3959, 0304-3959 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Freund's Adjuvant KW - 9007-81-2 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Nerve Fibers -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Nerve Fibers -- ultrastructure KW - Neurons, Afferent -- drug effects KW - Behavior, Animal -- physiology KW - Microscopy, Electron KW - Physical Stimulation KW - Electric Stimulation KW - Immunohistochemistry KW - Neurons, Afferent -- physiology KW - Female KW - Dizocilpine Maleate -- pharmacology KW - Hyperalgesia -- psychology KW - Hyperalgesia -- pathology KW - Nociceptors -- physiology KW - Inflammation -- chemically induced KW - Spinal Cord -- pathology KW - Spinal Cord -- physiology KW - Hyperalgesia -- chemically induced KW - Animals, Newborn -- physiology KW - Inflammation -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77788915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=Inflammation+and+hyperalgesia+in+rats+neonatally+treated+with+capsaicin%3A+effects+on+two+classes+of+nociceptive+neurons+in+the+superficial+dorsal+horn.&rft.au=Ren%2C+K%3BWilliams%2C+G+M%3BRuda%2C+M+A%3BDubner%2C+R&rft.aulast=Ren&rft.aufirst=K&rft.date=1994-11-01&rft.volume=59&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-14 N1 - Date created - 1995-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice. AN - 77785610; 7889889 AB - Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Dieter, M P AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 93 EP - 97 VL - 102 Suppl 7 SN - 0091-6765, 0091-6765 KW - Boric Acids KW - 0 KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Testis -- drug effects KW - Neoplasms, Experimental -- chemically induced KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Mice KW - Long-Term Care KW - Atrophy KW - Spermatogenesis -- drug effects KW - Male KW - Female KW - Hematopoiesis, Extramedullary -- drug effects KW - Boric Acids -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77785610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicity+and+carcinogenicity+studies+of+boric+acid+in+male+and+female+B6C3F1+mice.&rft.au=Dieter%2C+M+P&rft.aulast=Dieter&rft.aufirst=M&rft.date=1994-11-01&rft.volume=102+Suppl+7&rft.issue=&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Pediatr. 1953 Dec;43(6):631-43 [13109660] Bulletin NY Med Coll. 1953;16:92-101 [13160723] AMA Am J Dis Child. 1954 Jul;88(1):72-80 [13170814] Dermatologica. 1971;143(4):227-34 [5157956] Toxicol Appl Pharmacol. 1972 Nov;23(3):351-64 [4673567] Obstet Gynecol. 1974 Jun;43(6):893-5 [4597792] Environ Health Perspect. 1976 Feb;13:69-75 [1269509] Environ Mutagen. 1983;5 Suppl 1:1-142 [6365529] Environ Health Perspect. 1984 Dec;58:385-92 [6525993] Toxicology. 1959 May;1(3):267-76 [13659534] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo free radical generation by chromium(VI): an electron spin resonance spin-trapping investigation. AN - 77775915; 7696535 AB - Although studies in chemical and biological systems have demonstrated that free radical formation is mediated by Cr(VI), no ESR evidence for the generation of free radicals in vivo has been reported. We have employed an ESR spin-trapping technique to detect an adduct of the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) in the bile of animals given an intragastric dose of potassium dichromate. In this study, we provide evidence for in vivo radical generation resulting from Cr(VI)-poisoned rats. Upon the administration of Cr(VI) and 4-POBN, the ESR spectrum of the radical adducts present in the bile exhibited hyperfine coupling constants aN = 15.71 G and a beta H = 2.90 G. We suggest that the radical responsible for this 4-POBN adduct is carbon-centered and derived from endogenous lipids. The radical adducts detected in the bile from Cr(VI)-treated rats are proposed to be formed and trapped in the liver and excreted into bile. This is the first report of electron spin resonance evidence for the in vivo generation of free radicals by Cr(VI). JF - Chemical research in toxicology AU - Kadiiska, M B AU - Xiang, Q H AU - Mason, R P AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 800 EP - 805 VL - 7 IS - 6 SN - 0893-228X, 0893-228X KW - Free Radicals KW - 0 KW - Nitrogen Oxides KW - Pyridines KW - alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Potassium Dichromate KW - T4423S18FM KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Alanine Transaminase -- blood KW - Nitrogen Oxides -- pharmacology KW - Electron Spin Resonance Spectroscopy KW - L-Lactate Dehydrogenase -- blood KW - Liver -- metabolism KW - Bile -- metabolism KW - Free Radicals -- metabolism KW - Male KW - Potassium Dichromate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77775915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=In+vivo+free+radical+generation+by+chromium%28VI%29%3A+an+electron+spin+resonance+spin-trapping+investigation.&rft.au=Kadiiska%2C+M+B%3BXiang%2C+Q+H%3BMason%2C+R+P&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=1994-11-01&rft.volume=7&rft.issue=6&rft.spage=800&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-01 N1 - Date created - 1995-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene transfer into hematopoietic progenitor and stem cells: progress and problems. AN - 77770966; 7881358 AB - Gene transfer to hematopoietic cells for the purpose of "gene therapy" is a new and rapidly developing field with clinical trials in progress. A fundamental goal of research in this field is the incorporation of exogenous genes into the chromosomes of the most primitive hematopoietic progenitor cells--stem cells. Recombinantly engineered retroviral vectors are the best characterized and are currently the only vector type in clinical trials directed at the hematopoietic system. High efficiency gene transfer and expression in murine stem cells and their progeny is now routine, but in larger animal models such as dogs or primates and preliminary clinical trials, gene transfer has been less successful. Problems such as retroviral efficiency, gene expression, insertional mutagenesis and helper virus contamination are being addressed. A promising new vector, the adeno-associated virus (AAV), has shown promise and may allow production of high titer, stable, recombinant virions without helper contamination and with potentially better safety parameters. However, the technology for AAV gene transfer is currently underdeveloped, and issues related to the reproducible production of vectors must be addressed. Other non-viral vector systems are being explored, but little data are available on applications to hematopoietic cells. Better preclinical models are needed to study gene targeting and expression in human cells. An overview of recombinant retroviral and adeno-associated viral vector production, preclinical data and preliminary clinical data will be given, and problems needing to be addressed at all stages of development before broad clinical utility can be achieved will be discussed. JF - Stem cells (Dayton, Ohio) AU - Dunbar, C E AU - Emmons, R V AD - Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 563 EP - 576 VL - 12 IS - 6 SN - 1066-5099, 1066-5099 KW - Index Medicus KW - Animals KW - Genetic Engineering KW - Humans KW - Genetic Vectors KW - Safety KW - Dependovirus -- genetics KW - Retroviridae -- genetics KW - Models, Biological KW - Clinical Protocols KW - Hematopoietic Stem Cell Transplantation -- trends KW - Genetic Therapy -- adverse effects KW - Genetic Therapy -- trends KW - Gene Transfer Techniques KW - Hematopoietic Stem Cells KW - Genetic Therapy -- methods KW - Hematopoietic Stem Cell Transplantation -- methods KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77770966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=Gene+transfer+into+hematopoietic+progenitor+and+stem+cells%3A+progress+and+problems.&rft.au=Dunbar%2C+C+E%3BEmmons%2C+R+V&rft.aulast=Dunbar&rft.aufirst=C&rft.date=1994-11-01&rft.volume=12&rft.issue=6&rft.spage=563&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-10 N1 - Date created - 1995-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies. AN - 77769911; 7889890 AB - High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation (IS) that may progress to atrophy. In vivo and in vitro studies addressed possible mechanisms. In vivo, boron tissue disposition was examined, since no detailed data existed, and relevant boron concentrations for in vitro studies needed to be set. Since BA induces riboflavinuria and also affects calcium/phosphorus homeostasis, and testis zinc appears essential for normal testis function, we examined BA effects on flavin status and testis levels of phosphorus (P), calcium (Ca) and zinc (Zn). Data showed that the testicular toxicity and central nervous system (CNS) hormonal effect were not due to selective boron accumulation in testis or brain/hypothalamus, with testis boron concentrations at approximately 1 to 2 mM; that riboflavin deficiency is not involved, due to both the absence of overt signs of deficiency and effects on tissue flavin content during BA exposure; and that changes in testis P, Ca and Zn levels did not precede atrophy, and are therefore unlikely to be mechanistically relevant. In vitro studies addressed the hallmarks of the BA testicular toxicity: the mild hormone effect, the initial IS, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic adenosine monophosphate (cAMP) produces IS, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we examined in vitro BA effects on both Sertoli cell cAMP accumulation and PA activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Ku, W W AU - Chapin, R E AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 99 EP - 105 VL - 102 Suppl 7 SN - 0091-6765, 0091-6765 KW - Boric Acids KW - 0 KW - Trace Elements KW - Testosterone KW - 3XMK78S47O KW - Cyclic AMP KW - E0399OZS9N KW - Boron KW - N9E3X5056Q KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Testosterone -- metabolism KW - Spermatogenesis -- drug effects KW - Tissue Distribution KW - Boron -- metabolism KW - Trace Elements -- metabolism KW - DNA Replication -- drug effects KW - Rats KW - Cells, Cultured KW - Cyclic AMP -- metabolism KW - Atrophy KW - Male KW - Testis -- drug effects KW - Boric Acids -- toxicity KW - Testis -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77769911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+the+testicular+toxicity+of+boric+acid+in+rats%3A+in+vivo+and+in+vitro+studies.&rft.au=Ku%2C+W+W%3BChapin%2C+R+E&rft.aulast=Ku&rft.aufirst=W&rft.date=1994-11-01&rft.volume=102+Suppl+7&rft.issue=&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Cell Res. 1973 Jul;80(1):120-6 [4783737] Eur J Biochem. 1977 Nov 1;80(2):551-6 [200428] Mol Cell Endocrinol. 1977 Dec;9(2):227-36 [202528] Curr Top Dev Biol. 1978;12:11-36 [352625] Tissue Cell. 1980;12(2):309-22 [6251577] Toxicology. 1980;15(3):197-202 [7466832] Bull Environ Contam Toxicol. 1980 Nov;25(5):782-9 [7470654] J Reprod Fertil. 1981 Jul;62(2):399-405 [7252921] Am J Vet Res. 1981 Mar;42(3):474-7 [7271012] J Pharm Sci. 1972 Jul;61(7):1081-5 [5044806] Hoppe Seylers Z Physiol Chem. 1968 Aug;349(8):989-94 [4878428] J Cell Biol. 1962 Jul;14:1-18 [14475361] Environ Health Perspect. 1994 Nov;102 Suppl 7:87-91 [7889888] Environ Health Perspect. 1994 Nov;102 Suppl 7:113-7 [7889870] Reprod Toxicol. 1993 Jul-Aug;7(4):321-31 [7691281] Reprod Toxicol. 1993 Jul-Aug;7(4):305-19 [8400621] Mol Endocrinol. 1991 Dec;5(12):1789-98 [1791830] Toxicol Appl Pharmacol. 1991 Oct;111(1):145-51 [1949031] Toxicol Appl Pharmacol. 1991 Feb;107(2):325-35 [1994514] Biol Reprod. 1981 Aug;25(1):143-6 [7197172] Biol Trace Elem Res. 1990 Jan;24(1):1-11 [1702655] J Toxicol Environ Health. 1990 Oct;31(2):133-46 [2213925] Biochemistry. 1990 Jan 30;29(4):1063-8 [1692734] Toxicol Appl Pharmacol. 1989 Oct;101(1):124-34 [2552614] Toxicol Appl Pharmacol. 1989 Feb;97(2):377-85 [2538009] Toxicol Appl Pharmacol. 1988 Sep 30;95(3):484-9 [2847363] Toxicol Appl Pharmacol. 1988 Mar 15;92(3):467-79 [3353991] J Endocrinol. 1988 Jan;116(1):7-9 [3276808] FASEB J. 1987 Nov;1(5):394-7 [3678698] Biol Reprod. 1987 Apr;36(3):769-83 [3496123] Biochem Biophys Res Commun. 1987 Jan 15;142(1):147-54 [3101684] Toxicology. 1986 Dec 15;42(2-3):121-30 [3798463] Tissue Cell. 1981;13(2):369-80 [6458924] Life Sci. 1983 Apr 25;32(17):1997-2005 [6300595] Proc Natl Acad Sci U S A. 1983 Jun;80(11):3377-81 [6407012] Am J Ind Med. 1985;7(1):31-43 [3970022] Biol Reprod. 1986 Jun;34(5):895-904 [3730484] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The developmental toxicity of boric acid in mice, rats, and rabbits. AN - 77769599; 7889869 AB - Boric acid (BA) is a naturally occurring agent used in manufacturing processes and numerous consumer products. Because of the potential for both industrial and consumer exposure to boron-containing compounds, and the lack of developmental toxicity data, the National Toxicology Program evaluated the potential for boric acid to cause developmental toxicity in pregnant Swiss (CD-1) mice, Sprague-Dawley rats (n = 26-28/group), and New Zealand rabbits (n = 18-23/group). BA was provided in the feed to mice and rats at 0, 0.1, 0.2, or 0.4% throughout gestation to attain steady-state exposure as early as possible during development. Average doses (mg/kg/day) were 248, 452, or 1003 for mice, and 78, 163, or 330 in rats. A separate group of rats received 0.8% BA in the feed, or 539 mg/kg/day only on gestation days (gd) 6 to 15. Rabbits were given BA (0, 62.5, 125, or 250 mg/kg) by gavage administration on gd 6 to 19. Maternal body weight, food and/or water consumption and signs of toxicity were monitored at regular intervals. At termination, gd 17 (mice), 20 (rats), or 30 (rabbits), the uterus was examined to determine the number of resorptions, dead, or live fetuses. Fetuses were weighed and live fetuses were examined for external, visceral, and skeletal defects. Mouse dams exhibited mild renal lesions (> or = 248 mg/kg/day BA), increased water intake and relative kidney weight (1003 mg/kg/day BA), and decreased weight gain during treatment.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Heindel, J J AU - Price, C J AU - Schwetz, B A AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 107 EP - 112 VL - 102 Suppl 7 SN - 0091-6765, 0091-6765 KW - Boric Acids KW - 0 KW - Teratogens KW - boric acid KW - R57ZHV85D4 KW - Index Medicus KW - Rats KW - Abnormalities, Drug-Induced -- pathology KW - Litter Size -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Rabbits KW - Mice KW - Uterus -- pathology KW - Female KW - Pregnancy KW - Boric Acids -- toxicity KW - Pregnancy, Animal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77769599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+developmental+toxicity+of+boric+acid+in+mice%2C+rats%2C+and+rabbits.&rft.au=Heindel%2C+J+J%3BPrice%2C+C+J%3BSchwetz%2C+B+A&rft.aulast=Heindel&rft.aufirst=J&rft.date=1994-11-01&rft.volume=102+Suppl+7&rft.issue=&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1972 Nov;23(3):351-64 [4673567] Toxicol Appl Pharmacol. 1978 Aug;45(2):577-90 [705788] Teratog Carcinog Mutagen. 1984;4(2):181-8 [6145223] Pediatr Clin North Am. 1986 Apr;33(2):363-7 [2870462] J Reprod Fertil. 1964 Jun;7:401-3 [14180733] Toxicol Appl Pharmacol. 1991 Feb;107(2):325-35 [1994514] Fundam Appl Toxicol. 1992 Feb;18(2):266-77 [1601227] Environ Health Perspect. 1994 Nov;102 Suppl 7:133-7 [7889874] Teratology. 1990 Mar;41(3):311-7 [2326755] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subnanomolar concentration of VIP induces the nuclear translocation of protein kinase C in neonatal rat cortical astrocytes. AN - 77764294; 7884816 AB - At subnanomolar concentrations, vasoactive intestinal peptide (VIP) can act as an astroglial mitogen and as a secretagogue for neurotrophic substances released from glia (Brenneman et al.: J Neurosci Res 25:386-394, 1990). Here we report that treatment with subnanomolar (0.1 nM) VIP, that does not produce an increase in intracellular cAMP levels, induced the translocation of protein kinase C (PKC) from the cytoplasm to the nucleus in neonatal cortical astrocytes, as revealed by immunohistochemistry, Western blot analysis, and measurements of the enzyme activity. Western blot analysis of subcellular fractions, using PKC isotype-specific antisera, showed PKC alpha as well as the two novel PKC isotypes, delta and zeta immunoreactivities, whereas PKC beta or gamma immunoreactivities were not detected. PKC alpha was associated predominantly with the cytosolic compartment, while PKC delta was found in the plasma membrane and in nuclear fractions. In contrast, PKC zeta was distributed ubiquitously within the major subcellular fractions. Treatment of the cells with 0.1 nM VIP caused a marked increase in nuclear PKC alpha and, to a lesser extent, PKC delta and PKC zeta immunoreactivities. Western blot analysis showed that a low (1 nM) concentration of phorbol, 12-myristate, 13 acetate also caused the subcellular redistribution of PKC immunoreactivities from the cytoplasm to the nuclear fraction, similar to VIP treatment. Exposure of astrocytes to high concentrations (1 microM) of phorbol, 12-myristate, 13 acetate resulted in the down-regulation of PKC alpha and PKC delta, while distribution of PKC zeta immunoreactivities were only slightly altered.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of neuroscience research AU - Oláh, Z AU - Lehel, C AU - Anderson, W B AU - Brenneman, D E AU - van Agoston, D AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 355 EP - 363 VL - 39 IS - 4 SN - 0360-4012, 0360-4012 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Animals, Newborn KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Dose-Response Relationship, Drug KW - Cell Fractionation -- methods KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Immunohistochemistry KW - Vasoactive Intestinal Peptide -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- analysis KW - Astrocytes -- cytology KW - Cerebral Cortex -- metabolism KW - Cell Nucleus -- metabolism KW - Astrocytes -- drug effects KW - Cell Nucleus -- drug effects KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77764294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Subnanomolar+concentration+of+VIP+induces+the+nuclear+translocation+of+protein+kinase+C+in+neonatal+rat+cortical+astrocytes.&rft.au=Ol%C3%A1h%2C+Z%3BLehel%2C+C%3BAnderson%2C+W+B%3BBrenneman%2C+D+E%3Bvan+Agoston%2C+D&rft.aulast=Ol%C3%A1h&rft.aufirst=Z&rft.date=1994-11-01&rft.volume=39&rft.issue=4&rft.spage=355&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-10 N1 - Date created - 1995-04-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cystic fibrosis-related diabetes is associated with HLA DQB1 alleles encoding Asp-57- molecules. AN - 77763181; 7883862 AB - The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed for DQA1 and DQB1 alleles. HLA DQB1*0201 (Asp57-) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57+ molecules was lower in diabetics relative to both the cystic fibrosis-only controls (P = 0.025) and the general population (P = 0.008). The presence of at least one protective DQA1-DQB1 heterodimer (i.e., Arg52- and Asp57+, respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulin-dependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis. JF - Journal of clinical immunology AU - Carrington, M AU - Krueger, L J AU - Holsclaw, D S AU - Iannuzzi, M C AU - Dean, M AU - Mann, D AD - Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 353 EP - 358 VL - 14 IS - 6 SN - 0271-9142, 0271-9142 KW - HLA-DQ Antigens KW - 0 KW - HLA-DQ alpha-Chains KW - HLA-DQ beta-Chains KW - HLA-DQA1 antigen KW - HLA-DQB1 antigen KW - Index Medicus KW - Base Sequence KW - Alleles KW - Humans KW - Adult KW - Molecular Sequence Data KW - Mutation -- genetics KW - Middle Aged KW - Child KW - Adolescent KW - Male KW - Female KW - Diabetes Mellitus, Type 1 -- etiology KW - Cystic Fibrosis -- genetics KW - HLA-DQ Antigens -- genetics KW - Diabetes Mellitus, Type 1 -- genetics KW - Cystic Fibrosis -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77763181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Cystic+fibrosis-related+diabetes+is+associated+with+HLA+DQB1+alleles+encoding+Asp-57-+molecules.&rft.au=Carrington%2C+M%3BKrueger%2C+L+J%3BHolsclaw%2C+D+S%3BIannuzzi%2C+M+C%3BDean%2C+M%3BMann%2C+D&rft.aulast=Carrington&rft.aufirst=M&rft.date=1994-11-01&rft.volume=14&rft.issue=6&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+immunology&rft.issn=02719142&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-12 N1 - Date created - 1995-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus. AN - 77759523; 7532717 AB - To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE). An open label phase I study of CD5 Plus. A dose of 0.1 mg/kg was administered intravenously on 5 consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response one to 2 months later. Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis; no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T cell count was 69% at 2 weeks, 32% at one month, and 34% at 6 months following initial treatment. A comparable decrease in all subpopulations of mature T cells was noted, using a variety of surface markers, including CD4 and CD8. The mean percentage of T cells expressing the activation markers HLA-DR and interleukin 2R (IL-2R) was high before treatment, and remained so. There was a transient decrease in CD5+ B cells, but no persistent depletion of total B cell numbers. There was no consistent change in natural killer cell populations. Anti-CD5 ricin A chain immunoconjugate is well tolerated in patients with SLE, causes modest T cell depletion which may persist for months, and may have some clinical efficacy in lupus nephritis. JF - The Journal of rheumatology AU - Stafford, F J AU - Fleisher, T A AU - Lee, G AU - Brown, M AU - Strand, V AU - Austin, H A AU - Balow, J E AU - Klippel, J H AD - Arthritis and Rheumatism Branch (ARB), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 2068 EP - 2070 VL - 21 IS - 11 SN - 0315-162X, 0315-162X KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, CD5 KW - Immunoconjugates KW - Immunotoxins KW - zolimomab aritox KW - 141483-72-9 KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Injections, Intravenous KW - Humans KW - Pilot Projects KW - B-Lymphocytes KW - Lymphocyte Count KW - Flow Cytometry KW - Follow-Up Studies KW - Antigens, CD -- immunology KW - Female KW - Male KW - T-Lymphocyte Subsets KW - Platelet Count KW - Lupus Nephritis -- therapy KW - Ricin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Immunoconjugates -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77759523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=A+pilot+study+of+anti-CD5+ricin+A+chain+immunoconjugate+in+systemic+lupus+erythematosus.&rft.au=Stafford%2C+F+J%3BFleisher%2C+T+A%3BLee%2C+G%3BBrown%2C+M%3BStrand%2C+V%3BAustin%2C+H+A%3BBalow%2C+J+E%3BKlippel%2C+J+H&rft.aulast=Stafford&rft.aufirst=F&rft.date=1994-11-01&rft.volume=21&rft.issue=11&rft.spage=2068&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality from gastric cardia and lower esophagus cancer and occupation. AN - 77755530; 7861266 AB - The incidence of adenocarcinoma of the gastric cardia and esophagus is increasing steadily in the United States. Little is known about the etiology of these cancers. We used occupation and industry information on the death certificates from 24 states (1984 to 1989) to conduct a case-control analysis of gastric cardia and gastric cardia/lower esophagus cancer. Risks were also calculated for other gastric cancers combined. Controls were deaths from other causes except cancer and gastrointestinal disorders. Increased risks of gastric cardia and cardia/lower esophagus among white women were found for administrative jobs (cardia odds ratio (OR) = 3.9; 95% confidence interval (CI), 1.5-9.8) and health professionals (cardia OR = 1.8; 95% CI, 0.6-5.3). Occupations associated with a lower socioeconomic status showed no significant excess risks. A similar pattern in risks was seen for men. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Ward, M H AU - Dosemeci, M AU - Cocco, P AD - Occupational Studies Section, National Cancer Institute, Rockville, Maryland. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1222 EP - 1227 VL - 36 IS - 11 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Odds Ratio KW - Women's Health KW - Humans KW - Aged KW - Women, Working KW - Aged, 80 and over KW - Adult KW - Death Certificates KW - Cardia KW - Case-Control Studies KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Male KW - Stomach Neoplasms -- mortality KW - Occupational Diseases -- mortality KW - Esophageal Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77755530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Mortality+from+gastric+cardia+and+lower+esophagus+cancer+and+occupation.&rft.au=Ward%2C+M+H%3BDosemeci%2C+M%3BCocco%2C+P&rft.aulast=Ward&rft.aufirst=M&rft.date=1994-11-01&rft.volume=36&rft.issue=11&rft.spage=1222&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and hematopoietic and lymphoproliferative malignancies among women: a linked registry study. AN - 77755466; 7861262 AB - Using a nationwide linked registry, we evaluated the incidence of several hematopoietic and lymphoproliferative (HLP) malignancies among Swedish women from 1961 to 1979 by industry and occupation. The risks of one or more types of HLP cancers (including the leukemias, non-Hodgkin's lymphoma, multiple myeloma, and mycosis fungoides) were significantly increased among women working in the agriculture and textile industries, housekeepers, and post office employees. Limitations of these linked-registry data include lack of detailed information on specific exposures and duration of employment, and the relatively small sizes of specific occupational cohorts. Nevertheless, as the proportion of women entering the workforce continues to increase, this data resource may provide additional clues to occupational determinants of HLP and other malignancies. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Linet, M S AU - McLaughlin, J K AU - Malker, H S AU - Chow, W H AU - Weiner, J A AU - Stone, B J AU - Ericsson, J L AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892-7368. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1187 EP - 1198 VL - 36 IS - 11 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Women, Working KW - Women's Health KW - Leukemia, Lymphoid -- epidemiology KW - Humans KW - Sweden -- epidemiology KW - Incidence KW - Textile Industry KW - Female KW - Registries KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Mycosis Fungoides -- epidemiology KW - Leukemia -- epidemiology KW - Multiple Myeloma -- epidemiology KW - Skin Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77755466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Occupation+and+hematopoietic+and+lymphoproliferative+malignancies+among+women%3A+a+linked+registry+study.&rft.au=Linet%2C+M+S%3BMcLaughlin%2C+J+K%3BMalker%2C+H+S%3BChow%2C+W+H%3BWeiner%2C+J+A%3BStone%2C+B+J%3BEricsson%2C+J+L%3BFraumeni%2C+J+F&rft.aulast=Linet&rft.aufirst=M&rft.date=1994-11-01&rft.volume=36&rft.issue=11&rft.spage=1187&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational cancer mortality among women employed in the telephone industry. AN - 77752102; 7861264 AB - We conducted a mortality odds ratio (MOR) analysis among women employed in the telephone industry, using death certificates from 24 reporting states for 1984 through 1989. Usual occupation and industry from the death certificates were coded using the 1980 Bureau of the Census occupational and industrial classification system. There were 2444 cancer deaths among women in the telephone industry (code 441). Among younger (age < 49) white women, significant excess risks were observed from cancers of the rectum (MOR = 3.3; 95% confidence interval [CI] = 1.2 to 8.7), connective tissue (MOR = 4.4; 95% CI = 2.2 to 8.8), breast (MOR = 1.6; 95% CI = 1.3 to 2.1), corpus uteri (MOR = 3.3; 95% CI = 1.5 to 7.5), ovary (MOR = 2.1; 95% CI = 1.3 to 3.5), and brain (MOR = 2.1; 95% CI = 1.2 to 3.7). Cancer of the connective tissue showed an almost sixfold risk (MOR = 5.5; 95% CI = 2.0 to 14.8) for the age group of 30 to 39 years. Excess risks of cancer of the connective tissue were observed among engineers and technicians, office workers, telephone operators, and mechanics and repairers (MOR = 8.5, 4.9, 1.7, and 4.4, respectively), suggesting a possible relationship with modern technological exposures in the telephone industry. Risks for cancers of the breast, corpus uteri, ovary, and brain were also elevated among these jobs. We did not have information on other risk factors for these cancer sites; therefore, socioeconomic status or lifestyle may explain these observed associations, particularly for the cancers of the reproductive system.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Dosemeci, M AU - Blair, A AD - National Cancer Institute, National Institutes of Health, Occupational Studies Section, Bethesda, MD 20892-7364. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1204 EP - 1209 VL - 36 IS - 11 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Life Style KW - Odds Ratio KW - Women, Working KW - Telephone KW - Women's Health KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Neoplasms -- mortality KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77752102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Occupational+cancer+mortality+among+women+employed+in+the+telephone+industry.&rft.au=Dosemeci%2C+M%3BBlair%2C+A&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1994-11-01&rft.volume=36&rft.issue=11&rft.spage=1204&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of alcohol abuse and alcoholism in adolescents: a case for developing animal models. AN - 77751070; 7857239 AB - This paper reviews the ontogeny of neurotransmitter systems and neuropharmacological challenge within transmitter systems and discusses the actions of alcohol on such systems during the juvenile through adolescent periods. To place the animal research within the context of human development, an attempt is made to first examine some fundamental principles of developmental research as they relate to the adolescent period. Evidence presented from animal studies indicates that unique neurochemical and behavioral changes are occurring during postnatal development, including adolescence, that could mediate the response to alcohol. The limited number of studies on the neurochemical and behavioral response to alcohol during adolescence has employed rats and has been restricted by the relatively brief adolescent period in that species. While one alternative is to use primates, it is suggested that innovative behavioral paradigms be developed for adolescent animals in other species to study behaviors such as alcohol self-administration or alcohol stimulus discrimination. It is also suggested that existing behavioral models that are more easily adapted to younger age ranges (e.g., conditioned place preference, conditioned taste aversion, thermal response to ethanol) be extended to make ontogenetic comparisons through adolescence and adulthood. This may further our understanding of alcohol's immediate consequences during each maturational stage and, more important, the contribution of early alcohol exposure to excessive drinking and abnormal cognitive and social functioning during subsequent stages of development. JF - Behavioral and neural biology AU - Witt, E D AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 168 EP - 177 VL - 62 IS - 3 SN - 0163-1047, 0163-1047 KW - Neurotransmitter Agents KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Age Factors KW - Fetal Alcohol Spectrum Disorders -- physiopathology KW - Avoidance Learning -- physiology KW - Taste -- physiology KW - Risk Factors KW - Humans KW - Adolescent KW - Species Specificity KW - Brain -- physiopathology KW - Neurotransmitter Agents -- physiology KW - Disease Models, Animal KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77751070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+neural+biology&rft.atitle=Mechanisms+of+alcohol+abuse+and+alcoholism+in+adolescents%3A+a+case+for+developing+animal+models.&rft.au=Witt%2C+E+D&rft.aulast=Witt&rft.aufirst=E&rft.date=1994-11-01&rft.volume=62&rft.issue=3&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Behavioral+and+neural+biology&rft.issn=01631047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-13 N1 - Date created - 1995-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in mRNA levels of D2 receptors and neuropeptides in striatonigral and striatopallidal neurons of rats with neuroleptic-induced dyskinesias. AN - 77749906; 7531873 AB - Chronic neuroleptic treatment in rat produces vacuous chewing movements (VCMs), analogous to TD in humans. We hypothesized that these hyperkinetic movements were due to alterations in striatonigral and striatopallidal GABAergic spiny II neurons. Rats were treated for 36 weeks with haloperidol decanoate and withdrawn for 28 weeks. Striatonigral and striatopallidal neurons were assessed using in situ hybridization histochemistry for mRNA levels of D1 and D2 dopamine receptors, preproenkephalin (ENK), prodynorphin (DYN), protachykinin (substance P), and glutamate decarboxylase (GAD67) in the dorsolateral and ventromedial striatum as well as the nucleus accumbens. Rats that did not develop VCMs (-VCM) had increased D2 receptor and DYN mRNA, and reduced substance P mRNA in the dorsolateral striatum. Rats with persistent VCMs (+VCM) had increased D2 receptor, ENK, and DYN mRNA in both striatal regions, and increased ENK and DYN mRNA in the nucleus accumbens, compared with controls. Relative to -VCM rats, however, +VCM rats only had increased ENK mRNA in the nucleus accumbens. Considering the overall pattern of mRNA changes, the data suggest that alterations in both the D1-mediated striatonigral and the D2-mediated striatopallidal pathways play a role in the expression of the VCM syndrome. To the extent that gene expression parallels changes in neuronal activity, this implies that the VCM syndrome is associated with increased activity in both pathways. JF - Synapse (New York, N.Y.) AU - Egan, M F AU - Hurd, Y AU - Hyde, T M AU - Weinberger, D R AU - Wyatt, R J AU - Kleinman, J E AD - Neuropsychiatry Branch, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, Washington, DC 20032. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 178 EP - 189 VL - 18 IS - 3 SN - 0887-4476, 0887-4476 KW - Enkephalins KW - 0 KW - RNA, Messenger KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Substance P KW - 33507-63-0 KW - Dynorphins KW - 74913-18-1 KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Rats KW - Glutamate Decarboxylase -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - Male KW - Haloperidol -- adverse effects KW - Dyskinesia, Drug-Induced -- metabolism KW - Dynorphins -- drug effects KW - RNA, Messenger -- drug effects KW - Substance P -- metabolism KW - Enkephalins -- drug effects KW - Receptors, Dopamine D1 -- drug effects KW - Basal Ganglia Diseases -- metabolism KW - Dyskinesia, Drug-Induced -- physiopathology KW - Receptors, Dopamine D1 -- metabolism KW - Receptors, Dopamine D2 -- metabolism KW - RNA, Messenger -- metabolism KW - Receptors, Dopamine D2 -- drug effects KW - Enkephalins -- metabolism KW - Basal Ganglia Diseases -- physiopathology KW - Dynorphins -- metabolism KW - Substance P -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77749906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Alterations+in+mRNA+levels+of+D2+receptors+and+neuropeptides+in+striatonigral+and+striatopallidal+neurons+of+rats+with+neuroleptic-induced+dyskinesias.&rft.au=Egan%2C+M+F%3BHurd%2C+Y%3BHyde%2C+T+M%3BWeinberger%2C+D+R%3BWyatt%2C+R+J%3BKleinman%2C+J+E&rft.aulast=Egan&rft.aufirst=M&rft.date=1994-11-01&rft.volume=18&rft.issue=3&rft.spage=178&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer and noncancer risk to women in agriculture and pest control: the Agricultural Health Study. AN - 77745519; 7532217 AB - The Agricultural Health Study is a collaborative effort involving the National Cancer Institute, the US Environmental Protection Agency, and the National Institute of Environmental Health Sciences. A goal of this investigation is to establish a large cohort of men and women that can be followed prospectively for 10 years or more to evaluate the role of agricultural exposures in the development of cancer, neurologic disease, reproductive difficulties, childhood developmental problems, and other chronic diseases. The study also will provide an opportunity to assess the role that diet, cooking methods, and other lifestyle factors have on the cause of cancer and other diseases. The cohort will be composed of approximately 112,000 adult study subjects, including 42,000 women, making this one of the largest cohorts of women ever assembled for an epidemiologic investigation of environmental and occupational exposures. Children of farm families also will be enrolled. The study will be conducted in Iowa and North Carolina. Enrollment will begin in December 1993 and continue for 3 years. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Alavanja, M C AU - Akland, G AU - Baird, D AU - Blair, A AU - Bond, A AU - Dosemeci, M AU - Kamel, F AU - Lewis, R AU - Lubin, J AU - Lynch, C AD - National Cancer Institute, Rockville, MD 20852. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1247 EP - 1250 VL - 36 IS - 11 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Women's Health KW - Humans KW - Child KW - North Carolina -- epidemiology KW - Women, Working KW - Prospective Studies KW - Nervous System Diseases -- epidemiology KW - Agricultural Workers' Diseases -- epidemiology KW - Adult KW - Case-Control Studies KW - Reproduction KW - Chronic Disease KW - Developmental Disabilities -- epidemiology KW - Female KW - Iowa -- epidemiology KW - Male KW - Neoplasms -- epidemiology KW - Pest Control -- statistics & numerical data KW - Agriculture -- statistics & numerical data KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77745519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Cancer+and+noncancer+risk+to+women+in+agriculture+and+pest+control%3A+the+Agricultural+Health+Study.&rft.au=Alavanja%2C+M+C%3BAkland%2C+G%3BBaird%2C+D%3BBlair%2C+A%3BBond%2C+A%3BDosemeci%2C+M%3BKamel%2C+F%3BLewis%2C+R%3BLubin%2C+J%3BLynch%2C+C&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1994-11-01&rft.volume=36&rft.issue=11&rft.spage=1247&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-17 N1 - Date created - 1995-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Major histocompatibility complex class II haplotypes and linkage disequilibrium values observed in the CEPH families. AN - 77744670; 7868379 JF - Human immunology AU - Carrington, M AU - Stephens, J C AU - Klitz, W AU - Begovich, A B AU - Erlich, H A AU - Mann, D AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 234 EP - 240 VL - 41 IS - 3 SN - 0198-8859, 0198-8859 KW - Antigen Peptide Transporter-1 KW - 0 KW - Antigen Peptide Transporter-2 KW - HLA-D Antigens KW - HLA-DP Antigens KW - HLA-DQ Antigens KW - HLA-DR Antigens KW - TAP1 protein, human KW - TAP2 protein, human KW - 145892-13-3 KW - Index Medicus KW - France KW - Humans KW - HLA-DR Antigens -- genetics KW - HLA-DQ Antigens -- genetics KW - HLA-DP Antigens -- genetics KW - Haplotypes -- genetics KW - HLA-D Antigens -- genetics KW - ATP-Binding Cassette Transporters -- genetics KW - Linkage Disequilibrium -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77744670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Major+histocompatibility+complex+class+II+haplotypes+and+linkage+disequilibrium+values+observed+in+the+CEPH+families.&rft.au=Carrington%2C+M%3BStephens%2C+J+C%3BKlitz%2C+W%3BBegovich%2C+A+B%3BErlich%2C+H+A%3BMann%2C+D&rft.aulast=Carrington&rft.aufirst=M&rft.date=1994-11-01&rft.volume=41&rft.issue=3&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Human+immunology&rft.issn=01988859&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-28 N1 - Date created - 1995-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of disulfiram administration on glutamate uptake by synaptosomes in the rat brain. AN - 77736941; 7867694 AB - Although disulfiram used as a pharmacological agent in the treatment of alcoholism is reported to act on both peripheral and central nervous systems with several adverse effects, the neurotoxic property of the drug has not been properly elucidated. We observed that the chronic administration of the drug to rats significantly inhibited synaptosomal (Na+,K+)-ATPase and basal Mg(2+)-ATPase activities. Further, the uptake of gamma-aminobutyric acid and L-glutamate which rely on the energy provided by this system was depleted following chronic drug administration. Similar findings were observed when the isolated synaptosomes were treated with the drug in an in vitro system. Further, treatment of synaptosomes with ouabain, a known inhibitor of (Na+, K+)-ATPase resulted in significant depletion of 3H-GABA and L-[3H]glutamate uptake into synaptosomes indicating the importance of the enzyme in the uptake mechanism. However, diethyldithiocarbamate, a major metabolite of disulfiram did not elicit any change in either the enzyme activity or the uptake of these neurotransmitters. On the basis of these evidences, we suggest that the chronic disulfiram administration attenuated the neurotransmitter uptake mechanism and resulted in higher extracellular concentration of glutamate that could lead to glutamate-induced neurotoxicity. JF - European journal of pharmacology AU - Mamatha, R K AU - Nagendra, S N AD - Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 89 EP - 94 VL - 292 IS - 1 SN - 0014-2999, 0014-2999 KW - Neurotransmitter Uptake Inhibitors KW - 0 KW - Glutamic Acid KW - 3KX376GY7L KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Ditiocarb KW - 99Z2744345 KW - Ca(2+) Mg(2+)-ATPase KW - EC 3.6.1.- KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Disulfiram KW - TR3MLJ1UAI KW - Index Medicus KW - Rats KW - Sodium-Potassium-Exchanging ATPase -- antagonists & inhibitors KW - Animals KW - Rats, Sprague-Dawley KW - Drug Administration Schedule KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Kinetics KW - Ca(2+) Mg(2+)-ATPase -- antagonists & inhibitors KW - gamma-Aminobutyric Acid -- physiology KW - Male KW - Ca(2+) Mg(2+)-ATPase -- metabolism KW - Brain -- enzymology KW - Synaptosomes -- drug effects KW - Synaptosomes -- enzymology KW - Brain -- drug effects KW - Neurotransmitter Uptake Inhibitors -- toxicity KW - Glutamic Acid -- physiology KW - Brain -- physiology KW - Disulfiram -- toxicity KW - Synaptosomes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77736941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+disulfiram+administration+on+glutamate+uptake+by+synaptosomes+in+the+rat+brain.&rft.au=Mamatha%2C+R+K%3BNagendra%2C+S+N&rft.aulast=Mamatha&rft.aufirst=R&rft.date=1994-11-01&rft.volume=292&rft.issue=1&rft.spage=89&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 - 1995-03-30 N1 - Date created - 1995-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of streptonigrin cytotoxicity by nitroxide SOD mimics. AN - 77725846; 7835744 AB - Nitroxides are cell-permeable, stable radicals that react readily with paramagnetic species such as transition metals or short-lived free radicals, though not generally with diamagnetic molecules. Nitroxides can undergo one-electron selective redox reactions and thereby potentially modify the activity of cytotoxic drugs. Streptonigrin (SN) toxicity requires bioreduction to yield the semiquinone radical, and the toxicity is reportedly mediated by transition metals and oxygen-derived reactive species via redox-cycling of the semiquinone intermediate. The present study shows that (1) nitroxides protected isolated DNA and also aerated or hypoxic bacterial cells from SN toxicity; (2) H2O2 potentiated the hypoxic cytotoxicity of the drug but inhibited the damage to aerated cells; (3) pretreatment of cells with H2O2 conferred some protection, but not when the drug alone was preexposed to H2O2; and (4) desferrioxamine and 2,2-dipyridyl, though neither diethylenetriamino pentaacetate, exogenous catalase, or superoxide dismutase, decreased SN-induced cell killing. The mechanisms by which nitroxides protect from SN toxicity involve both a selective radical-radical reaction with SN semiquinone and the reoxidation of reduced cellular transition metal ions. On the other hand, H2O2 appears to exert two opposing effects: (1) facilitation of cell killing by the Fenton reaction and (2) lowering the cellular level of reducing equivalents, thus inhibiting the bioreductive activation of SN. JF - Free radical biology & medicine AU - Krishna, M C AU - Halevy, R F AU - Zhang, R AU - Gutierrez, P L AU - Samuni, A AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 379 EP - 388 VL - 17 IS - 5 SN - 0891-5849, 0891-5849 KW - Cyclic N-Oxides KW - 0 KW - Free Radicals KW - Spin Labels KW - Superoxides KW - 11062-77-4 KW - tempamine KW - 14691-88-4 KW - Streptonigrin KW - 261Q3JB310 KW - Hydroxyl Radical KW - 3352-57-6 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Hydrogen Peroxide -- toxicity KW - Superoxides -- analysis KW - Kinetics KW - Electron Spin Resonance Spectroscopy KW - Hydroxyl Radical -- analysis KW - Aerobiosis KW - Anaerobiosis KW - DNA Damage KW - Escherichia coli -- drug effects KW - Cyclic N-Oxides -- pharmacology KW - Streptonigrin -- toxicity KW - Escherichia coli -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77725846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Modulation+of+streptonigrin+cytotoxicity+by+nitroxide+SOD+mimics.&rft.au=Krishna%2C+M+C%3BHalevy%2C+R+F%3BZhang%2C+R%3BGutierrez%2C+P+L%3BSamuni%2C+A&rft.aulast=Krishna&rft.aufirst=M&rft.date=1994-11-01&rft.volume=17&rft.issue=5&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-24 N1 - Date created - 1995-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Organic brain syndromes and opioid administration for cancer pain. AN - 77725721; 7531737 AB - To clarify the range of potential etiologies that may contribute to organic brain syndrome in patients receiving systemic opioids for cancer pain, we describe 15 patients who presented this complication. In 11 cases, concomitant conditions were found that could contribute to the onset of organic brain syndrome. These data illustrate that multiple causes often play a role in the development of mental status changes in advanced cancer. Opioids are seldom the only causal factor implicated. JF - Journal of pain and symptom management AU - Caraceni, A AU - Martini, C AU - De Conno, F AU - Ventafridda, V AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 527 EP - 533 VL - 9 IS - 8 SN - 0885-3924, 0885-3924 KW - Narcotics KW - 0 KW - Index Medicus KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Female KW - Substance-Related Disorders -- etiology KW - Narcotics -- therapeutic use KW - Narcotics -- adverse effects KW - Neoplasms -- therapy KW - Palliative Care -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77725721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pain+and+symptom+management&rft.atitle=Organic+brain+syndromes+and+opioid+administration+for+cancer+pain.&rft.au=Caraceni%2C+A%3BMartini%2C+C%3BDe+Conno%2C+F%3BVentafridda%2C+V&rft.aulast=Caraceni&rft.aufirst=A&rft.date=1994-11-01&rft.volume=9&rft.issue=8&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Journal+of+pain+and+symptom+management&rft.issn=08853924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shoe-leather epidemiology--the footpads of mice and rats: animal tests in assessment of occupational risks. AN - 77708073; 7838166 JF - The Mount Sinai journal of medicine, New York AU - Rall, D P AD - National Institute of Environmental Health Sciences, Washington, D.C. 20015. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 504 EP - 508 VL - 61 IS - 6 SN - 0027-2507, 0027-2507 KW - Index Medicus KW - United States KW - Rats KW - Animals KW - Humans KW - Predictive Value of Tests KW - Mice KW - Male KW - Female KW - Risk Assessment KW - Occupational Exposure -- prevention & control KW - Foot KW - Carcinogenicity Tests KW - Rodentia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77708073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Mount+Sinai+journal+of+medicine%2C+New+York&rft.atitle=Shoe-leather+epidemiology--the+footpads+of+mice+and+rats%3A+animal+tests+in+assessment+of+occupational+risks.&rft.au=Rall%2C+D+P&rft.aulast=Rall&rft.aufirst=D&rft.date=1994-11-01&rft.volume=61&rft.issue=6&rft.spage=504&rft.isbn=&rft.btitle=&rft.title=The+Mount+Sinai+journal+of+medicine%2C+New+York&rft.issn=00272507&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption, alcohol abuse and alcohol dependence. The United States as an example. AN - 77708064; 7841843 AB - This paper presents national estimates of alcohol consumption and DSM-IV alcohol abuse and dependence in the United States. Fifty-two percent of the adults surveyed were classified as current drinkers and nearly 9.0% met criteria for DSM-IV alcohol abuse or dependence. Greater percentages of males and whites were classified as current drinkers and as alcohol abusers or dependent, compared with females and non-whites, respectively. There is a need for future epidemiological research to collect better data on drinking patterns as an aid to interpreting socio-demographic differentials and to estimate more precisely the association between alcohol consumption and abuse and dependence in multivariate statistical environments. The critical need to examine the unprecedented reversal of the abuse-to-dependence ratio resulting from the application of the DSM-IV classification is emphasized. The role of future longitudinal alcohol epidemiological research in elucidating the initiation and maintenance of consumption patterns and alcohol use disorders is stressed. JF - Addiction (Abingdon, England) AU - Grant, B F AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1357 EP - 1365 VL - 89 IS - 11 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Cross-Sectional Studies KW - Psychiatric Status Rating Scales KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- classification KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77708064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alcohol+consumption%2C+alcohol+abuse+and+alcohol+dependence.+The+United+States+as+an+example.&rft.au=Grant%2C+B+F&rft.aulast=Grant&rft.aufirst=B&rft.date=1994-11-01&rft.volume=89&rft.issue=11&rft.spage=1357&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 - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Addiction. 1995 Jun;90(6):848 [7633305] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice. AN - 77109360; 7625882 AB - Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days to a significant increase in A1-adenosine, nicotinic and muscarinic receptors, and a significant decrease of beta 1-adrenoceptors in cerebral cortical membranes. Plasma levels of caffeine in the chronically treated mice range from 0.70 to 5.7 micrograms/ml. The changes in receptors reverse after withdrawal of caffeine within 7 days. An increase in nitrendipine binding sites, associated with L-type calcium channels, also occurs within 4 days and has reversed in 7 days after withdrawal. There is no change in the levels of striatal nicotinic receptors of D2-dopamine receptors, nor of [3H]cocaine binding to dopamine uptake sites. Levels of opioid receptors are either increased (delta) or unaltered (mu, kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase by forskolin, dopamine and NECA are not significantly affected after chronic caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine-elicited increases in locomotor activity and partly reverses the cocaine-elicited increases. The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice. NECA reverses the stimulation of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is more effective in the chronic caffeine mice. The behavioral depressant effects of the muscarinic agonist, oxotremorine, are not markedly altered after chronic caffeine ingestion. JF - Archives internationales de pharmacodynamie et de therapie AU - Shi, D AU - Nikodijević, O AU - Jacobson, K A AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1994 SP - 261 EP - 287 VL - 328 IS - 3 SN - 0003-9780, 0003-9780 KW - Calcium Channels KW - 0 KW - Receptors, Adrenergic, beta-1 KW - Receptors, Cholinergic KW - Receptors, Dopamine D2 KW - Receptors, Muscarinic KW - Receptors, Nicotinic KW - Receptors, Opioid KW - Receptors, Purinergic P1 KW - Adenosine-5'-(N-ethylcarboxamide) KW - 35920-39-9 KW - Caffeine KW - 3G6A5W338E KW - Nicotine KW - 6M3C89ZY6R KW - Nitrendipine KW - 9B627AW319 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Adenosine KW - K72T3FS567 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Drug Interactions KW - Nicotine -- toxicity KW - Dose-Response Relationship, Drug KW - Adenosine -- analogs & derivatives KW - Adenylyl Cyclases -- metabolism KW - Mice KW - Radioligand Assay KW - Corpus Striatum -- enzymology KW - Receptors, Dopamine D2 -- metabolism KW - Acetylcholine -- metabolism KW - Adenosine -- pharmacology KW - Receptors, Nicotinic -- metabolism KW - Calcium Channels -- drug effects KW - In Vitro Techniques KW - Binding, Competitive KW - Receptors, Nicotinic -- drug effects KW - Receptors, Muscarinic -- drug effects KW - Receptors, Dopamine D2 -- drug effects KW - Corpus Striatum -- drug effects KW - Nitrendipine -- metabolism KW - Male KW - Receptors, Muscarinic -- metabolism KW - Caffeine -- blood KW - Receptors, Adrenergic, beta-1 -- metabolism KW - Caffeine -- administration & dosage KW - Receptors, Purinergic P1 -- drug effects KW - Receptors, Opioid -- metabolism KW - Receptors, Cholinergic -- drug effects KW - Receptors, Opioid -- drug effects KW - Caffeine -- pharmacology KW - Motor Activity -- drug effects KW - Receptors, Purinergic P1 -- metabolism KW - Receptors, Cholinergic -- metabolism KW - Receptors, Adrenergic, beta-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77109360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internationales+de+pharmacodynamie+et+de+therapie&rft.atitle=Effects+of+chronic+caffeine+on+adenosine%2C+dopamine+and+acetylcholine+systems+in+mice.&rft.au=Shi%2C+D%3BNikodijevi%C4%87%2C+O%3BJacobson%2C+K+A%3BDaly%2C+J+W&rft.aulast=Shi&rft.aufirst=D&rft.date=1994-11-01&rft.volume=328&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Archives+internationales+de+pharmacodynamie+et+de+therapie&rft.issn=00039780&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-31 N1 - Date created - 1995-08-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1994 Jul 4;650(1):153-6 [7953667] Cell Mol Neurobiol. 1993 Jun;13(3):247-61 [8242688] Proc Natl Acad Sci U S A. 1980 Sep;77(9):5547-51 [6254090] Anal Biochem. 1974 Apr;58(2):541-8 [4827395] J Pharmacol Exp Ther. 1993 Sep;266(3):1268-76 [8371136] Pharmacol Biochem Behav. 1993 Jan;44(1):199-216 [7679219] Neurosci Lett. 1982 Jul 20;31(1):47-52 [6289200] Proc Natl Acad Sci U S A. 1981 May;78(5):3260-4 [6265942] J Pharmacol Exp Ther. 1983 Oct;227(1):167-73 [6194284] Brain Res. 1984 Feb 27;294(1):186-9 [6697237] Neurosci Lett. 1984 Jun 15;47(2):91-8 [6205333] Acta Physiol Scand. 1984 Sep;122(1):55-9 [6095597] J Clin Invest. 1986 Jan;77(1):222-7 [3003150] J Clin Invest. 1988 Jul;82(1):242-7 [3392208] J Neurochem. 1983 Jul;41(1):172-8 [6864217] Clin Chem. 1988 Nov;34(11):2345-8 [3180432] Brain Res Bull. 1988 Sep;21(3):479-82 [3214753] J Neural Transm Gen Sect. 1989;78(1):9-15 [2547026] Mol Pharmacol. 1989 Aug;36(2):265-72 [2549383] Pharmacol Biochem Behav. 1990 Feb;35(2):477-9 [2320659] Mol Pharmacol. 1990 May;37(5):694-703 [2160061] Mol Pharmacol. 1991 Feb;39(2):222-32 [1847495] Mol Pharmacol. 1992 Feb;41(2):352-9 [1311411] Brain Res Brain Res Rev. 1992 May-Aug;17(2):139-70 [1356551] Brain Res. 1992 Oct 23;594(1):124-30 [1467931] Neuroscience. 1992 Dec;51(3):501-12 [1488111] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer (United States). AN - 76945531; 7827235 AB - This study examines the relationship between menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer, focusing on whether associations differ according to whether the tumors are in situ or invasive. Data are from a prospective study conducted 1980-89 on 49,017 selected participants in the Breast Cancer Detection Demonstration Project, a five-year screening program conducted between 1973 and 1980 in the United States. Overall, the rate ratio for estrogen-only use compared with no-hormone use was 1.0, and that for the estrogen-progestin combination was 1.2 (95 percent confidence interval [CI] = 1.0-1.6). However, the associations differed according to whether the tumors were in situ or invasive. The rate ratios of in situ breast cancer associated with use of estrogens alone and the combination regimen were 1.4 (CI = 1.0-2.0) and 2.3 (CI = 1.3-3.9), respectively. Duration of estrogen-only use also was associated with risk of in situ tumors, with users for 10 or more years at twice the risk of nonusers (P-value for trend test = 0.02). Duration of use was not associated with risk of invasive cancer. Our results are consistent with the hypothesis that hormone replacement therapy is related to earlier-stage breast cancer; however, the possibility that the results reflect increased breast cancer surveillance among those taking hormones cannot be ruled out. JF - Cancer causes & control : CCC AU - Schairer, C AU - Byrne, C AU - Keyl, P M AU - Brinton, L A AU - Sturgeon, S R AU - Hoover, R N AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 491 EP - 500 VL - 5 IS - 6 SN - 0957-5243, 0957-5243 KW - Estrogens KW - 0 KW - Progestins KW - Index Medicus KW - Prospective Studies KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Menopause KW - Female KW - Estrogen Replacement Therapy -- adverse effects KW - Breast Neoplasms -- pathology KW - Progestins -- adverse effects KW - Progestins -- administration & dosage KW - Breast Neoplasms -- chemically induced KW - Estrogens -- adverse effects KW - Estrogens -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76945531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Menopausal+estrogen+and+estrogen-progestin+replacement+therapy+and+risk+of+breast+cancer+%28United+States%29.&rft.au=Schairer%2C+C%3BByrne%2C+C%3BKeyl%2C+P+M%3BBrinton%2C+L+A%3BSturgeon%2C+S+R%3BHoover%2C+R+N&rft.aulast=Schairer&rft.aufirst=C&rft.date=1994-11-01&rft.volume=5&rft.issue=6&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safe disposal of diisopropyl fluorophosphate (DFP). AN - 76931553; 7818266 AB - Diisopropyl fluorophosphate (DFP), a volatile highly toxic enzyme inhibitor, in buffer (pH 3, pH 5, pH 7, pH 9, pH 11, Hank's, Dulbecco's, PBS, TBE, and HEPES) or water (10 mM), in DMF solution (200 mM), and bulk quantities can be degraded by adding 1M NaOH. The DFP was completely degraded, as determined by enzymatic assay, and the final reaction mixtures were not mutagenic. JF - Applied biochemistry and biotechnology AU - Lunn, G AU - Sansone, E B AD - Program Resources, Inc./Dyn Corp, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 165 EP - 172 VL - 49 IS - 2 SN - 0273-2289, 0273-2289 KW - Buffers KW - 0 KW - Solvents KW - Isoflurophate KW - 12UHW9R67N KW - benzoyltyrosine ethyl ester KW - 3483-82-7 KW - Tyrosine KW - 42HK56048U KW - Sodium Hydroxide KW - 55X04QC32I KW - Chymotrypsin KW - EC 3.4.21.1 KW - Index Medicus KW - Mutagenicity Tests KW - Solvents -- chemistry KW - Chymotrypsin -- chemistry KW - Spectrophotometry, Ultraviolet KW - Salmonella typhimurium -- drug effects KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Salmonella typhimurium -- genetics KW - Hydrolysis KW - Waste Disposal, Fluid -- standards KW - Isoflurophate -- chemistry KW - Sodium Hydroxide -- chemistry KW - Isoflurophate -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76931553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+biochemistry+and+biotechnology&rft.atitle=Safe+disposal+of+diisopropyl+fluorophosphate+%28DFP%29.&rft.au=Lunn%2C+G%3BSansone%2C+E+B&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-11-01&rft.volume=49&rft.issue=2&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Applied+biochemistry+and+biotechnology&rft.issn=02732289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-06 N1 - Date created - 1995-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accumulation and persistence of individual polychlorinated biphenyl congeners in liver, blood, and adipose tissue of rats following dietary exposure to Aroclor 1254. AN - 76923691; 7811109 AB - Female F344/NCr rats were exposed continuously to Aroclor 1254 (1, 3.3, 10, 33, or 100 ppm in the diet) for 7, 28, or 84 days in order to assess the accumulation of polychlorinated biphenyls (PCBs) in liver, blood, and adipose tissue. The persistence of the individual PCB congeners which are detected in liver was examined in the three tissues of additional groups of rats exposed for 7 days followed by 21 days on control diet, or for 28 days followed by 56 days on control diet. Limited accumulation of PCB congeners with low chlorine substitution (tri- and tetrachlorobiphenyls) in the liver and blood, and preferential retention of highly substituted PCB congeners (penta- and hexachlorobiphenyls) were observed in rats continuously exposed to Aroclor. In these rats, time- and dose-dependent increases in the relative levels of two congeners which cause profound phenobarbital-type induction [2,2',3,4,4',5'-hexachlorobiphenyl (BZ# 138) and 2,2',4,4',5,5'-hexachlorobiphenyl (BZ# 153)] were detected in the liver and adipose tissue. Rats receiving control diet following Aroclor treatment displayed a time- and dose-dependent decrease in the relative levels in blood, adipose and hepatic tissue of 2,3,3',4,4'-pentachlorobiphenyl (BZ# 105) and 2,3',4,4',5-pentachlorobiphenyl (BZ# 118), two of the major congeners showing both TCDD- and phenobarbital-type induction. These rats also displayed increases in the relative adipose levels of another relatively potent mixed-type inducer, 2,3,3',4,4',5-hexachlorobiphenyl (BZ# 156), and increases in adipose and hepatic levels of the pure phenobarbital-type inducer, 2,2',4,4',5-pentachlorobiphenyl (BZ# 99). JF - Archives of environmental contamination and toxicology AU - Nims, R W AU - Fox, S D AU - Issaq, H J AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 513 EP - 520 VL - 27 IS - 4 SN - 0090-4341, 0090-4341 KW - Aroclors KW - 0 KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Phenobarbital -- pharmacology KW - Diet KW - Female KW - Adipose Tissue -- metabolism KW - Polychlorinated Biphenyls -- metabolism KW - Liver -- metabolism KW - Aroclors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76923691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+environmental+contamination+and+toxicology&rft.atitle=Accumulation+and+persistence+of+individual+polychlorinated+biphenyl+congeners+in+liver%2C+blood%2C+and+adipose+tissue+of+rats+following+dietary+exposure+to+Aroclor+1254.&rft.au=Nims%2C+R+W%3BFox%2C+S+D%3BIssaq%2C+H+J%3BLubet%2C+R+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1994-11-01&rft.volume=27&rft.issue=4&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+contamination+and+toxicology&rft.issn=00904341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Social and legal factors related to drug abuse in the United States and Japan. AN - 76905746; 7800780 AB - This article is an overview of social and legal differences in the United States and in Japan that are related to patterns of current drug abuse epidemics in these countries. These two nations have drug abuse problems with different histories and take different approaches currently to handling illicit drug marketing and use. Histories of opiate and cocaine abuse in the United States and of stimulant and inhalant abuse in Japan are discussed. The United States has experienced three heroin epidemics in the last three decades; cocaine addiction began to merit national concern by the end of the 1980s. In Japan, the first methamphetamine epidemic began after World War II; it was controlled in the 1950s. The current inhalant epidemic began in the late 1960s and was followed by the second methamphetamine epidemic that began in 1970; both are continuing to the present. The criminal justice system is always given first consideration when assessing societal measures employed to reduce drug use. Legal penalties for illicit drug offenses reflect the societal differences of these two nations with respect to the seriousness of particular types of crimes. Characteristics of the health care system of a nation may also influence patterns of drug abuse, particularly where functions of criminal justice and health care systems overlap. Health care systems in the United States and in Japan are based on different treatment philosophies and patients' expectations; these differences are discussed along with explanations of their potential influence on the epidemiology of drug abuse. JF - Public health reports (Washington, D.C. : 1974) AU - Greberman, S B AU - Wada, K AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224. PY - 1994 SP - 731 EP - 737 VL - 109 IS - 6 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - Japan -- epidemiology KW - Cultural Characteristics KW - Delivery of Health Care -- organization & administration KW - Humans KW - Cross-Cultural Comparison KW - Incidence KW - United States -- epidemiology KW - Prevalence KW - Attitude to Health -- ethnology KW - Drug and Narcotic Control -- legislation & jurisprudence KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76905746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Social+and+legal+factors+related+to+drug+abuse+in+the+United+States+and+Japan.&rft.au=Greberman%2C+S+B%3BWada%2C+K&rft.aulast=Greberman&rft.aufirst=S&rft.date=1994-11-01&rft.volume=109&rft.issue=6&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Addiction. 1993 Jan;88(1):89-100 [8448518] Med J Malaysia. 1974 Dec;29(2):136-44 [4282402] Bull Narc. 1976 Jan-Mar;28(1):55-65 [1046373] Public Health Rep. 1978 Mar-Apr;93(2):153-60 [635090] Br J Addict. 1981 Mar;76(1):85-90 [6937211] Bull Narc. 1989;41(1-2):83-93 [2765722] Public Health Rep. 1983 Jan-Feb;98(1):85-90 [6828642] Drug Alcohol Depend. 1983 Feb;11(1):55-6 [6851857] Public Health Rep. 1984 May-Jun;99(3):319-23 [6429733] Am J Drug Alcohol Abuse. 1984;10(3):317-46 [6397066] Bull Narc. 1986 Jan-Jun;38(1-2):41-53 [3535959] Int J Addict. 1988 Jan;23(1):1-17 [3360531] Bull Pan Am Health Organ. 1990;24(1):53-62 [2331559] Med Care. 1989 Jan;27(1):85-94 [2911221] Med Care. 1992 Nov;30(11):989-1003 [1434962] Drug Alcohol Depend. 1990 Nov;26(3):217-25 [2265589] J Psychoactive Drugs. 1981 Jan-Mar;13(1):35-8 [7024493] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH. AN - 76902676; 7798895 AB - Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX). Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Thus, the spin trapping measurements provided no evidence for hydroxyl (.OH) radical generation in peroxynitrite decomposition at physiological pH. Thiols (glutathione, cysteine, and penicillamine) and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The one-electron oxidation of thiols by peroxynitrite may be one of the important mechanisms for peroxynitrite-induced toxicity and ascorbate may provide a detoxification pathway. JF - Journal of inorganic biochemistry AU - Shi, X AU - Rojanasakul, Y AU - Gannett, P AU - Liu, K AU - Mao, Y AU - Daniel, L N AU - Ahmed, N AU - Saffiotti, U AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 77 EP - 86 VL - 56 IS - 2 SN - 0162-0134, 0162-0134 KW - 5,5-dimethylpyrrolidin-2-one-1-oxide KW - 0 KW - Cyclic N-Oxides KW - Free Radicals KW - Nitrates KW - Spin Labels KW - Sulfhydryl Compounds KW - peroxynitric acid KW - 26404-66-0 KW - semidehydroascorbic acid KW - 6730-29-6 KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dehydroascorbic Acid KW - Y2Z3ZTP9UM KW - Index Medicus KW - Hydrogen-Ion Concentration KW - Electron Spin Resonance Spectroscopy KW - Models, Biological KW - Sulfhydryl Compounds -- chemistry KW - Dehydroascorbic Acid -- analogs & derivatives KW - Ascorbic Acid -- chemistry KW - Nitrates -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76902676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+inorganic+biochemistry&rft.atitle=Generation+of+thiyl+and+ascorbyl+radicals+in+the+reaction+of+peroxynitrite+with+thiols+and+ascorbate+at+physiological+pH.&rft.au=Shi%2C+X%3BRojanasakul%2C+Y%3BGannett%2C+P%3BLiu%2C+K%3BMao%2C+Y%3BDaniel%2C+L+N%3BAhmed%2C+N%3BSaffiotti%2C+U&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-11-01&rft.volume=56&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Journal+of+inorganic+biochemistry&rft.issn=01620134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-20 N1 - Date created - 1995-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement by 2'-deoxycoformycin of the 5'-phosphorylation and anti-human immunodeficiency virus activity of 2',3'-dideoxyadenosine and 2'-beta-fluoro-2',3'-dideoxyadenosine. AN - 76836460; 7969062 AB - The anti-human immunodeficiency virus agents 2',3'-dideoxyadenosine (ddAdo) and 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo) are rapidly converted, both in vitro and in vivo, to the corresponding inosine analogs by the widely distributed enzyme adenosine deaminase (EC 3.5.4.4). We have determined the effects of the potent adenosine deaminase inhibitor 2'-deoxycoformycin (2'-dCF) on ddAdo and 2'-beta-F-ddAdo metabolism in MOLT-4 cells and on ddAdo antiviral activity in the ATH8 test system. At levels as low as 5 nM in the incubation medium, 2'-dCF effectively blocks the extracellular deamination of both agents, thus permitting their rapid cellular uptake as the unchanged parent compounds, rather than as the less lipid-soluble 2',3'-dideoxyinosine or 2'-beta-fluoro-2',3'-dideoxyinosine. The result is a significant increase in intracellular levels of the pharmacologically active forms 2',3'-dideoxyadenosine-5'-triphosphate and 2'-beta-fluoro-2',3'-dideoxyadenosine-5'-triphosphate. The effect becomes maximal over the range of 50-250 nM 2'-dCF and declines to control levels when extracellular 2'-dCF levels exceed 1 microM. This decrease in ddAdo and 2'-beta-F-ddAdo phosphorylation with higher levels of the inhibitor appears to result from intracellular penetration of 2'-dCF and consequent inhibition of intracellular deamination, a critical step in the activation of both agents through the 5'-nucleotidase pathway. In anti-human immunodeficiency virus assays, a 2.2-fold increase in ddAdo antiviral potency was seen at 2'-dCF levels of 20 and 50 nM. JF - Molecular pharmacology AU - Ahluwalia, G S AU - Cooney, D A AU - Shirasaka, T AU - Mitsuya, H AU - Driscoll, J S AU - Johns, D G AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1002 EP - 1008 VL - 46 IS - 5 SN - 0026-895X, 0026-895X KW - Adenosine Deaminase Inhibitors KW - 0 KW - Pentostatin KW - 395575MZO7 KW - lodenosine KW - 3WB2LGT4R1 KW - Ribavirin KW - 49717AWG6K KW - Dideoxyadenosine KW - 4Q86AH641A KW - IMP Dehydrogenase KW - EC 1.1.1.205 KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Ribavirin -- pharmacology KW - Drug Synergism KW - Didanosine -- pharmacokinetics KW - Cell Line KW - Phosphorylation -- drug effects KW - IMP Dehydrogenase -- antagonists & inhibitors KW - HIV -- drug effects KW - Dideoxyadenosine -- metabolism KW - Dideoxyadenosine -- pharmacology KW - Dideoxyadenosine -- pharmacokinetics KW - Dideoxyadenosine -- analogs & derivatives KW - Pentostatin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76836460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhancement+by+2%27-deoxycoformycin+of+the+5%27-phosphorylation+and+anti-human+immunodeficiency+virus+activity+of+2%27%2C3%27-dideoxyadenosine+and+2%27-beta-fluoro-2%27%2C3%27-dideoxyadenosine.&rft.au=Ahluwalia%2C+G+S%3BCooney%2C+D+A%3BShirasaka%2C+T%3BMitsuya%2C+H%3BDriscoll%2C+J+S%3BJohns%2C+D+G&rft.aulast=Ahluwalia&rft.aufirst=G&rft.date=1994-11-01&rft.volume=46&rft.issue=5&rft.spage=1002&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 - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bryostatin 1 protects protein kinase C-delta from down-regulation in mouse keratinocytes in parallel with its inhibition of phorbol ester-induced differentiation. AN - 76832008; 7969070 AB - Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-epsilon to the Triton X-100-soluble fraction with an approximately 2-order of magnitude higher potency, compared with translocation of PKC-alpha and PKC-delta. The kinetics of translocation were fastest for PKC-epsilon, slower for PKC-alpha, and slowest for PKC-delta. At 5-20 min bryostatin 1 showed potency similar to that of PMA for translocating PKC-alpha, higher potency for translocating PKC-delta, and lower potency for translocating PKC-epsilon. At a later time (6 hr), bryostatin 1 was 1-2 orders magnitude more potent than PMA for causing loss of PKC-alpha, -delta, and -epsilon from the soluble fraction. Bryostatin 1 was 40-fold more potent than PMA for down-regulating PKC-alpha and showed a biphasic dose-response curve for down-regulating PKC-delta. Bryostatin 1 at 0.1-1 nM down-regulated PKC-delta to a similar extent as did PMA. Bryostatin 1 at 100 nM to 1 microM, on the other hand, failed to induce down-regulation, and these high (100 nM to 1 microM) doses of bryostatin 1 showed noncompetitive inhibition of PKC-delta down-regulation by 1 microM PMA after coapplication. This protected portion of PKC-delta retained kinase activity. The dose-response curve for bryostatin 1 protection of PKC-delta from down-regulation by PMA correlated with bryostatin 1 inhibition of the effects of PMA on cornified envelope formation (a marker of differentiation) and epidermal growth factor binding. Although PKC-epsilon was readily translocated by both PMA and bryostatin 1, the PKC-epsilon originally associated with the particulate fraction showed no down-regulation by either of these agents. We hypothesize that differential regulation of PKC isozymes by PMA and bryostatin 1 may contribute to the different patterns of biological responses that they induce. JF - Molecular pharmacology AU - Szallasi, Z AU - Denning, M F AU - Smith, C B AU - Dlugosz, A A AU - Yuspa, S H AU - Pettit, G R AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 840 EP - 850 VL - 46 IS - 5 SN - 0026-895X, 0026-895X KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Isoenzymes KW - Lactones KW - Macrolides KW - Protein Synthesis Inhibitors KW - bryostatin 1 KW - 37O2X55Y9E KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Prkce protein, mouse KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Protein Kinase C-delta KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - Biological Transport -- drug effects KW - Protein Synthesis Inhibitors -- pharmacology KW - Cells, Cultured KW - Molecular Sequence Data KW - Cell Differentiation -- drug effects KW - Down-Regulation -- drug effects KW - Protein Kinase C -- drug effects KW - Keratinocytes -- enzymology KW - Keratinocytes -- drug effects KW - Keratinocytes -- cytology KW - Isoenzymes -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Tetradecanoylphorbol Acetate -- antagonists & inhibitors KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76832008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bryostatin+1+protects+protein+kinase+C-delta+from+down-regulation+in+mouse+keratinocytes+in+parallel+with+its+inhibition+of+phorbol+ester-induced+differentiation.&rft.au=Szallasi%2C+Z%3BDenning%2C+M+F%3BSmith%2C+C+B%3BDlugosz%2C+A+A%3BYuspa%2C+S+H%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1994-11-01&rft.volume=46&rft.issue=5&rft.spage=840&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 - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice. AN - 76829958; 7525844 AB - Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS. JF - The Journal of experimental medicine AU - Browning, P J AU - Roberts, D D AU - Zabrenetzky, V AU - Bryant, J AU - Kaplan, M AU - Washington, R H AU - Panet, A AU - Gallo, R C AU - Vogel, T AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 1949 EP - 1954 VL - 180 IS - 5 SN - 0022-1007, 0022-1007 KW - Apolipoprotein E3 KW - 0 KW - Apolipoproteins E KW - Recombinant Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Cell Movement -- drug effects KW - Cell Division -- drug effects KW - Mice, Nude KW - Mice KW - Neovascularization, Pathologic -- prevention & control KW - Mice, Inbred BALB C KW - HIV-1 KW - DNA -- biosynthesis KW - Recombinant Proteins -- therapeutic use KW - Male KW - Sarcoma, Kaposi -- drug therapy KW - Apolipoproteins E -- therapeutic use KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Sarcoma, Kaposi -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76829958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apolipoprotein+E+%28ApoE%29%2C+a+novel+heparin-binding+protein+inhibits+the+development+of+Kaposi%27s+sarcoma-like+lesions+in+BALB%2Fc+nu%2Fnu+mice.&rft.au=Browning%2C+P+J%3BRoberts%2C+D+D%3BZabrenetzky%2C+V%3BBryant%2C+J%3BKaplan%2C+M%3BWashington%2C+R+H%3BPanet%2C+A%3BGallo%2C+R+C%3BVogel%2C+T&rft.aulast=Browning&rft.aufirst=P&rft.date=1994-11-01&rft.volume=180&rft.issue=5&rft.spage=1949&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 - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1992 Jun 5;267(16):10931-4 [1375931] JAMA. 1992 Apr 1;267(13):1798-805 [1347573] J Virol. 1993 Jan;67(1):277-87 [8416373] J Cell Physiol. 1993 Jan;154(1):1-6 [8419396] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):823-7 [8430092] J Clin Endocrinol Metab. 1992 May;74(5):1045-52 [1373735] Nature. 1993 Apr 29;362(6423):801-9 [8479518] J Immunol. 1993 Jun 1;150(11):5195-201 [8098726] J Clin Endocrinol Metab. 1993 Jun;76(6):1423-7 [8501146] Science. 1993 Aug 13;261(5123):921-3 [8346443] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8098-102 [8367470] J Cell Biochem. 1993 Sep;53(1):74-84 [8227183] Science. 1983 Jul 15;221(4607):281-3 [6190230] Science. 1984 May 4;224(4648):500-3 [6200936] Ann Intern Med. 1984 May;100(5):671-6 [6712031] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8696-700 [3909150] Science. 1988 Apr 29;240(4852):622-30 [3283935] JAMA. 1988 Oct 7;260(13):1917-21 [3418853] Science. 1988 Oct 21;242(4877):426-30 [3262925] Science. 1988 Oct 21;242(4877):430-3 [2459779] Science. 1989 Jan 13;243(4888):223-6 [2643161] Mol Cell Biol. 1989 Jul;9(7):2847-53 [2779549] Infect Immun. 1989 Nov;57(11):3619-28 [2572558] Cancer Res. 1989 Dec 1;49(23):6727-30 [2479471] Int J Dermatol. 1989 Nov;28(9):571-3 [2684881] J Gen Virol. 1989 Nov;70 ( Pt 11):3079-84 [2555438] J Cell Biol. 1990 Aug;111(2):765-72 [1696271] Proc Natl Acad Sci U S A. 1990 Sep;87(17):6624-8 [1697685] Am J Med. 1991 Feb;90(2):154-62 [1996584] Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2648-52 [2011576] Am J Med. 1991 Apr;90(4):427-33 [1707230] Int J Radiat Biol. 1991 Jul-Aug;60(1-2):79-83 [1713945] J Clin Invest. 1992 Feb;89(2):706-11 [1737858] Science. 1992 Mar 13;255(5050):1430-2 [1542792] Science. 1992 Mar 13;255(5050):1432-4 [1542793] Science. 1992 Mar 13;255(5050):1437-40 [1371891] J Immunol. 1992 Dec 1;149(11):3727-34 [1431144] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Scintigraphic detection of melanoma metastases with a radiolabeled benzamide ([iodine-123]-(S)-IBZM). AN - 76828162; 7965150 AB - Iodine-123-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ([123I]-(S)-IBZM) is a radiolabeled benzamide usually employed to study neuropsychiatric disorders, such as schizophrenia and Parkinson's disease. The ectodermic origin of melanocytes and the presence of melanin in the substantia nigra are the theoretic basis of the experimental use of this class of tracers for melanoma imaging. Eleven patients with proven metastatic melanoma entered the study. Whole-body and planar scintigrams were performed 2, 4 and 24 hr after intravenous injection of a mean tracer activity of 205 MBq. The dosimetric evaluation was performed by the Medical Internal Radiation Dose Committee method. The [123I]-(S)-IBZM scans allowed the detection of all six cutaneous lesions, five of six superficial pathologic lymph nodes, four of five pulmonary and one of two hepatic metastases. The maximum tumor-to-background ratio was 2.6 in planar images. The hepatobiliary excretion of the tracer may limit detection of intra-abdominal lesions. Dosimetry is similar to data for nononcologic patients. Although it is unclear if the mechanism of radiopharmaceutical uptake in melanoma is due to binding to membrane receptors or due to interactions with intracellular structures, radiolabeled benzamide is a promising tracer to detect melanoma. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Maffioli, L AU - Mascheroni, L AU - Mongioj, V AU - Gasparini, M AU - Baldini, M T AU - Seregni, E AU - Castellani, M R AU - Cascinelli, N AU - Buraggi, G L AD - Nuclear Medicine Department, National Cancer Institute, Milan, Italy. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1741 EP - 1747 VL - 35 IS - 11 SN - 0161-5505, 0161-5505 KW - Benzamides KW - 0 KW - Contrast Media KW - Dopamine Antagonists KW - Iodine Radioisotopes KW - Pyrrolidines KW - 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide KW - 84226-06-2 KW - Index Medicus KW - Radiation Dosage KW - Tomography, Emission-Computed, Single-Photon KW - Lymphatic Metastasis KW - Humans KW - Lung Neoplasms -- secondary KW - Liver Neoplasms -- diagnostic imaging KW - Aged KW - Liver Neoplasms -- secondary KW - Lung Neoplasms -- diagnostic imaging KW - Evaluation Studies as Topic KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Male KW - Female KW - Melanoma -- diagnostic imaging KW - Melanoma -- secondary KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- diagnostic imaging KW - Skin Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76828162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Scintigraphic+detection+of+melanoma+metastases+with+a+radiolabeled+benzamide+%28%5Biodine-123%5D-%28S%29-IBZM%29.&rft.au=Maffioli%2C+L%3BMascheroni%2C+L%3BMongioj%2C+V%3BGasparini%2C+M%3BBaldini%2C+M+T%3BSeregni%2C+E%3BCastellani%2C+M+R%3BCascinelli%2C+N%3BBuraggi%2C+G+L&rft.aulast=Maffioli&rft.aufirst=L&rft.date=1994-11-01&rft.volume=35&rft.issue=11&rft.spage=1741&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium and prostate cancer. AN - 76825509; 7966437 AB - Prostatic cancer is a common and frequently lethal malignant disease. In the United States and other countries the incidence and mortality rate of prostate cancer continue to rise. Cancer of the prostate has an extremely complex etiology and appears dependent on a variety of factors, making linkage to a single factor very difficult to detect. Cadmium is a metallic toxin of great environmental and occupational concern. Cadmium exposure has been associated with human prostatic cancer in some, but not all, epidemiologic studies. Some studies indicate that tissue levels of cadmium in the human prostate correlate with malignant disease. Any association between cadmium and prostatic cancer has been controversial, in large part because of a previous lack of relevant animal models. However, several chronic studies in rats revealing a correlation between cadmium exposure and prostatic tumors have been published over the last several years. These include a study of oral cadmium exposure, a route extremely relevant to human exposure. Several of these chronic studies indicate a hormonal dependence of cadmium-induced prostate cancer. Other supportive work continues to accumulate, such as studies showing in vitro malignant transformation of prostatic epithelial cells with cadmium exposure. In addition, there are indications that the primary biologic tolerance system for cadmium (i.e., the metallothionein gene) may be only poorly active in the specific lobes of the rat prostate in which cadmium induces tumors. The induction in rats of prostate cancer by cadmium treatment clearly supports, but does not definitively establish, a possible role for cadmium as an etiological agent in human prostate cancer. Further research, however, will be required to establish the precise role of cadmium in this important human malignancy. JF - Journal of toxicology and environmental health AU - Waalkes, M P AU - Rehm, S AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 251 EP - 269 VL - 43 IS - 3 SN - 0098-4108, 0098-4108 KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Rats KW - Occupational Exposure KW - Prostate -- drug effects KW - Animals KW - Prostate -- chemistry KW - Humans KW - Environmental Exposure KW - Cell Transformation, Neoplastic -- chemically induced KW - Disease Models, Animal KW - Prostate -- pathology KW - Male KW - Prostatic Neoplasms -- chemistry KW - Cadmium -- adverse effects KW - Prostatic Neoplasms -- epidemiology KW - Cadmium -- analysis KW - Prostatic Neoplasms -- chemically induced KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76825509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Cadmium+and+prostate+cancer.&rft.au=Waalkes%2C+M+P%3BRehm%2C+S&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1994-11-01&rft.volume=43&rft.issue=3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region. AN - 76820592; 7962071 AB - The 40-S subunit of eukaryotic ribosomes binds to the capped 5'-end of mRNA and scans for the first AUG in a favorable sequence context to initiate translation. Most eukaryotic mRNAs therefore have a short 5'-untranslated region (5'-UTR) and no AUGs upstream of the translational start site; features that seem to assure efficient translation. However, approximately 5-10% of all eukaryotic mRNAs, particularly those encoding for regulatory proteins, have complex leader sequences that seem to compromise translational initiation. The retinoic-acid-receptor-beta 2 (RAR beta 2) mRNA is such a transcript with a long (461 nucleotides) 5'-UTR that contains five, partially overlapping, upstream open reading frames (uORFs) that precede the major ORF. We have begun to investigate the function of this complex 5'-UTR in transgenic mice, by introducing mutations in the start/stop codons of the uORFs in RAR beta 2-lacZ reporter constructs. When we compared the expression patterns of mutant and wild-type constructs we found that these mutations affected expression of the downstream RAR beta 2-ORF, resulting in an altered regulation of RAR beta 2-lacZ expression in heart and brain. Other tissues were unaffected. RNA analysis of adult tissues demonstrated that the uORFs act at the level of translation; adult brains and hearts of transgenic mice carrying a construct with either the wild-type or a mutant UTR, had the same levels of mRNA, but only the mutant produced protein. Our study outlines an unexpected role for uORFs: control of tissue-specific and developmentally regulated gene expression. JF - The Journal of cell biology AU - Zimmer, A AU - Zimmer, A M AU - Reynolds, K AD - Unit on Developmental Biology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1111 EP - 1119 VL - 127 IS - 4 SN - 0021-9525, 0021-9525 KW - Codon KW - 0 KW - Oligodeoxyribonucleotides KW - Protein Sorting Signals KW - RNA Caps KW - RNA, Messenger KW - Receptors, Retinoic Acid KW - Recombinant Fusion Proteins KW - retinoic acid receptor beta KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Embryo, Mammalian -- physiology KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Ribosomes -- metabolism KW - Sequence Homology, Nucleic Acid KW - Humans KW - RNA Caps -- metabolism KW - Transcription, Genetic KW - Mice, Transgenic KW - Myocardium -- metabolism KW - Mutagenesis, Site-Directed KW - Embryonic and Fetal Development KW - Molecular Sequence Data KW - beta-Galactosidase -- biosynthesis KW - Sequence Homology, Amino Acid KW - Protein Sorting Signals -- metabolism KW - Peptide Chain Initiation, Translational KW - Mice KW - Amino Acid Sequence KW - Organ Specificity KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Restriction Mapping KW - Receptors, Retinoic Acid -- genetics KW - Receptors, Retinoic Acid -- biosynthesis KW - Open Reading Frames KW - Gene Expression KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76820592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tissue+specific+expression+of+the+retinoic+acid+receptor-beta+2%3A+regulation+by+short+open+reading+frames+in+the+5%27-noncoding+region.&rft.au=Zimmer%2C+A%3BZimmer%2C+A+M%3BReynolds%2C+K&rft.aulast=Zimmer&rft.aufirst=A&rft.date=1994-11-01&rft.volume=127&rft.issue=4&rft.spage=1111&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 - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Microbiol Rev. 1992 Jun;56(2):291-315 [1620067] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2718-22 [1313565] Science. 1992 Sep 18;257(5077):1685-9 [1382315] EMBO J. 1992 Nov;11(11):4153-8 [1396596] Biochem Biophys Res Commun. 1992 Oct 30;188(2):695-702 [1332705] Pharmacol Ther. 1992;54(3):307-17 [1465480] Int J Dev Biol. 1992 Dec;36(4):465-76 [1338286] Development. 1992 Dec;116(4):977-83 [1338313] Ann N Y Acad Sci. 1993 Mar 15;678:22-36 [8494265] Cell. 1993 Jul 16;74(1):9-14 [7687524] EMBO J. 1993 Sep;12(9):3365-72 [8253064] Cell. 1977 May;11(1):187-200 [559547] Biochem Biophys Res Commun. 1977 Jul 11;77(1):124-31 [196596] Nature. 1984 Sep 6-11;311(5981):79-81 [6088993] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2315-9 [3857582] Cell. 1986 Apr 25;45(2):201-7 [3516411] Nature. 1987 Dec 17-23;330(6149):667-70 [2825037] Mol Cell Biol. 1988 Jan;8(1):284-92 [3275870] Nature. 1988 Mar 10;332(6160):117-8 [2894611] Nature. 1988 Mar 10;332(6160):171-3 [3347254] Science. 1988 May 13;240(4854):889-95 [3283939] EMBO J. 1988 Jul;7(7):2097-105 [3046931] J Biol Chem. 1989 Feb 15;264(5):2773-7 [2914929] J Cell Biol. 1989 Feb;108(2):229-41 [2645293] Genes Dev. 1989 Aug;3(8):1217-25 [2676723] Nature. 1990 Jun 7;345(6275):544-7 [2348862] EMBO J. 1991 Jan;10(1):71-81 [1846599] J Biol Chem. 1991 Jun 5;266(16):10446-51 [2037592] Mol Cell Biol. 1991 Sep;11(9):4306-13 [1875922] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7729-33 [1679235] Annu Rev Biochem. 1991;60:717-55 [1883206] New Biol. 1991 May;3(5):511-24 [1883814] J Cell Biol. 1991 Nov;115(4):887-903 [1955461] Mech Dev. 1991 Dec;36(1-2):15-29 [1664231] Cell. 1992 Feb 7;68(3):585-96 [1739968] Development. 1991 Nov;113(3):723-34 [1668276] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Steroid potentiation and inhibition of N-methyl-D-aspartate receptor-mediated intracellular Ca++ responses: structure-activity studies. AN - 76818387; 7965782 AB - Pregnenolone sulfate and 15 related steroids were investigated for their effects on N-methyl-D-aspartate (NMDA)-induced elevations in intracellular Ca++ ([Ca++]i) in cultured rat hippocampal neurons by microspectrofluorimetry with the Ca(++)-sensitive indicator fura-2. Several pregn-5-ene steroids markedly potentiated NMDA-mediated [Ca++]i responses. Pregnenolone sulfate and its 21-acetoxy derivative and pregnenolone hemisuccinate were the most active. At a concentration of 50 microM, each produced approximately 300% potentiation of 5 microM NMDA responses. In addition, several steroids were identified that inhibited NMDA-induced elevations in [Ca++]i, the most potent of which was 3 alpha-hydroxy-5 beta-pregnan-20-one sulfate (IC50, 37 microM). Concentration-response curves for NMDA in the presence of active steroids revealed noncompetitive interaction(s) of these steroids with the NMDA receptor. Although the mechanism(s) responsible for either steroid-induced augmentation or inhibition of NMDA-receptor responses is unknown, these data suggest the presence of one or more steroid recognition sites with a high degree of structural specificity associated with NMDA receptors. These results further raise the possibility that pregn-5-ene 3-sulfates and pregnane 3-sulfates could be endogenous modulators of NMDA receptor-mediated synaptic events. JF - The Journal of pharmacology and experimental therapeutics AU - Irwin, R P AU - Lin, S Z AU - Rogawski, M A AU - Purdy, R H AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 677 EP - 682 VL - 271 IS - 2 SN - 0022-3565, 0022-3565 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - pregnenolone sulfate KW - 04Y4D91RG0 KW - N-Methylaspartate KW - 6384-92-5 KW - Pregnenolone KW - 73R90F7MQ8 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - N-Methylaspartate -- pharmacology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Hippocampus -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors KW - Drug Synergism KW - Structure-Activity Relationship KW - Hippocampus -- drug effects KW - Calcium -- metabolism KW - Pregnenolone -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76818387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Steroid+potentiation+and+inhibition+of+N-methyl-D-aspartate+receptor-mediated+intracellular+Ca%2B%2B+responses%3A+structure-activity+studies.&rft.au=Irwin%2C+R+P%3BLin%2C+S+Z%3BRogawski%2C+M+A%3BPurdy%2C+R+H%3BPaul%2C+S+M&rft.aulast=Irwin&rft.aufirst=R&rft.date=1994-11-01&rft.volume=271&rft.issue=2&rft.spage=677&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Staurosporine inhibits invasion of erythrocytes by malarial merozoites. AN - 76816887; 7957765 AB - Staurosporine, a protein kinase inhibitor, inhibits the invasion of rhesus by Plasmodium knowlesi merozoites with an IC50 of 250 nM. The drug exerts its effects primarily on the merozoite, with little or no effect on the erythrocyte. Okadaic acid, an inhibitor of protein phosphatases, can partially abrogate the inhibitory effects of staurosporine. Staurosporine arrests invasion at a step which is ultrastructurally similar to the arrest caused by cytochalasins B and D: the merozoite attaches, apically reorients, and forms a junction with the erythrocyte, but it does not internalize. These results suggest that protein phosphorylation within the merozoite plays an important role in the internalization step of invasion. JF - Experimental parasitology AU - Ward, G E AU - Fujioka, H AU - Aikawa, M AU - Miller, L H AD - Laboratory of Malaria Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 480 EP - 487 VL - 79 IS - 3 SN - 0014-4894, 0014-4894 KW - Alkaloids KW - 0 KW - Ethers, Cyclic KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Animals KW - Phosphorylation KW - Microscopy, Electron KW - Macaca mulatta KW - Ethers, Cyclic -- pharmacology KW - Signal Transduction KW - Erythrocytes -- ultrastructure KW - Erythrocytes -- parasitology KW - Erythrocytes -- drug effects KW - Protein Kinase C -- antagonists & inhibitors KW - Plasmodium knowlesi -- physiology KW - Plasmodium knowlesi -- ultrastructure KW - Plasmodium knowlesi -- drug effects KW - Alkaloids -- pharmacology KW - Alkaloids -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76816887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+parasitology&rft.atitle=Staurosporine+inhibits+invasion+of+erythrocytes+by+malarial+merozoites.&rft.au=Ward%2C+G+E%3BFujioka%2C+H%3BAikawa%2C+M%3BMiller%2C+L+H&rft.aulast=Ward&rft.aufirst=G&rft.date=1994-11-01&rft.volume=79&rft.issue=3&rft.spage=480&rft.isbn=&rft.btitle=&rft.title=Experimental+parasitology&rft.issn=00144894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of recombinant soluble CD4 Pseudomonas exotoxin, a novel immunotoxin, for treatment of persons infected with human immunodeficiency virus. AN - 76815032; 7963711 AB - Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 micrograms/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 micrograms/kg. The major toxicity was a transient dose-dependent elevation in hepatic aminotransferases peaking 48 h after infusion. Anti-Pseudomonas exotoxin antibody developed in 58% of recipients, and sera from 13 of 17 showed neutralizing activity against sCD4-PE40. No consistent changes in immunologic or virologic markers were observed. Weekly infusions of < or = 10 micrograms/kg of sCD4-PE40 are generally well tolerated, but additional studies correlating optimal dosing and frequency of administration with efficacy will be needed to define the role of this novel agent in the management of HIV-1-infected patients. JF - The Journal of infectious diseases AU - Davey, R T AU - Boenning, C M AU - Herpin, B R AU - Batts, D H AU - Metcalf, J A AU - Wathen, L AU - Cox, S R AU - Polis, M A AU - Kovacs, J A AU - Falloon, J AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1180 EP - 1188 VL - 170 IS - 5 SN - 0022-1899, 0022-1899 KW - Antigens, CD4 KW - 0 KW - Antiviral Agents KW - Bacterial Toxins KW - CD4-Pseudomonas toxin KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Single-Blind Method KW - Humans KW - Adult KW - Recombinant Proteins -- adverse effects KW - Middle Aged KW - Adolescent KW - Recombinant Proteins -- therapeutic use KW - Antigens, CD4 -- immunology KW - Antiviral Agents -- therapeutic use KW - HIV Infections -- therapy KW - HIV Infections -- immunology KW - Immunotoxins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Exotoxins -- adverse effects KW - Exotoxins -- immunology KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76815032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Use+of+recombinant+soluble+CD4+Pseudomonas+exotoxin%2C+a+novel+immunotoxin%2C+for+treatment+of+persons+infected+with+human+immunodeficiency+virus.&rft.au=Davey%2C+R+T%3BBoenning%2C+C+M%3BHerpin%2C+B+R%3BBatts%2C+D+H%3BMetcalf%2C+J+A%3BWathen%2C+L%3BCox%2C+S+R%3BPolis%2C+M+A%3BKovacs%2C+J+A%3BFalloon%2C+J&rft.aulast=Davey&rft.aufirst=R&rft.date=1994-11-01&rft.volume=170&rft.issue=5&rft.spage=1180&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Xeroderma pigmentosum and related disorders: examining the linkage between defective DNA repair and cancer. AN - 76814987; 7963692 AB - Xeroderma pigmentosum, Cockayne syndrome, the xeroderma pigmentosum-Cockayne syndrome complex, and trichothiodystrophy cells have defects in DNA repair and are associated with clinical and cellular hypersensitivity to ultraviolet radiation (UV). Familial dysplastic nevus syndrome cells have UV hypermutability. Although xeroderma pigmentosum and dysplastic nevus syndrome have markedly increased cancer risk. Cockayne syndrome and trichothiodystrophy do not. At the molecular level, these disorders are associated with several different genetic defects as evidenced by the existence of multiple overlapping complementation groups. Recent progress has been made in identifying the chromosomal location and cloning the defective genes in these disorders. Using plasmid shuttle vectors we have shown abnormal repair and mutagenesis of DNA damaged by 254-nm (UVC) or 295-nm (UVB) radiation or the chemical carcinogen aflatoxin in cells from patients with xeroderma pigmentosum. Although xeroderma pigmentosum cells are defective in repair of all photoproducts, Cockayne syndrome cells appear to be defective in repair of cyclobutane dimers and have normal repair of nondimer photoproducts. DNS cells have post UV plasmid hypermutability. These diseases may serve as models for examining molecular mechanisms of carcinogenesis in humans. JF - The Journal of investigative dermatology AU - Kraemer, K H AU - Levy, D D AU - Parris, C N AU - Gozukara, E M AU - Moriwaki, S AU - Adelberg, S AU - Seidman, M M AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 96S EP - 101S VL - 103 IS - 5 Suppl SN - 0022-202X, 0022-202X KW - Index Medicus KW - Humans KW - Dysplastic Nevus Syndrome -- genetics KW - Cockayne Syndrome -- genetics KW - Hair -- abnormalities KW - Genetic Linkage KW - DNA Repair KW - Xeroderma Pigmentosum -- genetics KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76814987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Xeroderma+pigmentosum+and+related+disorders%3A+examining+the+linkage+between+defective+DNA+repair+and+cancer.&rft.au=Kraemer%2C+K+H%3BLevy%2C+D+D%3BParris%2C+C+N%3BGozukara%2C+E+M%3BMoriwaki%2C+S%3BAdelberg%2C+S%3BSeidman%2C+M+M&rft.aulast=Kraemer&rft.aufirst=K&rft.date=1994-11-01&rft.volume=103&rft.issue=5+Suppl&rft.spage=96S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of oncogenes and tumor suppressor genes in multistage carcinogenesis. AN - 76814947; 7963691 AB - The introduction of the techniques of molecular biology as tools to study skin carcinogenesis has provided more precise localization of biochemical pathways that regulate the tumor phenotype. This approach has identified genetic changes that are characteristic of each of the specific stages of squamous cancer pathogenesis: initiation, exogenous promotion, premalignant progression, and malignant conversion. Initiation can result from mutations in a single gene, and the Harvey allele of the ras gene family has been identified as a frequent site for initiating mutations. Heterozygous activating mutations in c-rasHa are dominant, and affected keratinocytes hyperproliferate and are resistant to signals for terminal differentiation. An important pathway impacted by c-rasHa activation is the protein kinase C (PKC) pathway, a major regulator of keratinocyte differentiation. Increased activity of PKC alpha and suppression of PKC delta by tyrosine phosphorylation contribute to the phenotypic consequences of rasHa gene activation in keratinocytes. Tumor promoters disturb epidermal homeostasis and cause selective clonal expansion of initiated cells to produce multiple benign squamous papillomas. Resistance to differentiation and enhanced growth rate of initiated cells impart a growth advantage when the epidermis is exposed to promoters. The frequency of premalignant progression varies among papillomas, and subpopulations at high risk for progression have been identified. These high-risk papillomas overexpress the alpha 6 beta 4 integrin and are deficient in transforming growth factor beta 1 and beta 2 peptides, two changes associated with a very high proliferation rate in this subset of tumors. The introduction of an oncogenic rasHa gene into epidermal cells derived from transgenic mice with a null mutation in the TGF beta 1 gene have an accelerated rate of malignant progression when examined in vivo. Thus members of the TGF beta gene family contribute a tumor-suppressor function in carcinogenesis. Accelerated malignant progression is also found with v-rasHa transduced keratinocytes from skin of mice with a null mutation in the p53 gene. The similarities in risk for malignant conversion by initiated keratinocytes from TG beta 1 and p53 null geneotypes suggest that a common, growth-related pathway may underly the tumor-suppressive functions of these proteins in the skin carcinogenesis model. JF - The Journal of investigative dermatology AU - Yuspa, S H AU - Długosz, A A AU - Cheng, C K AU - Denning, M F AU - Tennenbaum, T AU - Glick, A B AU - Weinberg, W C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 90S EP - 95S VL - 103 IS - 5 Suppl SN - 0022-202X, 0022-202X KW - Growth Substances KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Genes, ras KW - Animals KW - Neoplasm Staging KW - Humans KW - Tumor Suppressor Protein p53 -- genetics KW - Growth Substances -- physiology KW - Cell Transformation, Neoplastic KW - Oncogenes KW - Genes, Tumor Suppressor KW - Neoplasms, Experimental -- genetics KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76814947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Role+of+oncogenes+and+tumor+suppressor+genes+in+multistage+carcinogenesis.&rft.au=Yuspa%2C+S+H%3BD%C5%82ugosz%2C+A+A%3BCheng%2C+C+K%3BDenning%2C+M+F%3BTennenbaum%2C+T%3BGlick%2C+A+B%3BWeinberg%2C+W+C&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1994-11-01&rft.volume=103&rft.issue=5+Suppl&rft.spage=90S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of mammary tumors in female Sprague-Dawley rats by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and effect of dietary fat. AN - 76813297; 7955086 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat, was determined to be a mammary carcinogen in female Sprague-Dawley rats on a high fat diet. Forty-three-day-old female Sprague-Dawley rats received 10 doses of PhIP (75 mg/kg, p.o., days 1-5 and 8-12). Two days after the last dose of PhIP, animals were placed on a high polyunsaturated fat diet (23.5% corn oil) or a standard low fat diet (5% corn oil). After 25 weeks on the defined diet, mammary tumor incidence (average tumor mass +/- SE) was 53% (5.7 +/- 1.3 g) and 16% (2.4 +/- 0.9 g) in rats on a high fat and standard low fat diet, respectively. The histological differences in mammary gland tumors found in animals on the standard low fat diet and the high fat diet were striking. Mammary gland tumors found in PhIP-treated rats on the low fat diet were all histologically benign. The histopathological changes in these tumors included hypertrophic changes resembling the normal mammary gland, fibrocystic changes, and sclerosing adenosis. However, 80% of the mammary gland tumors found in PhIP-treated rats on a high fat diet were histologically malignant. These tumors had several malignant phenotypes including intraductal carcinoma (papillary, cribriform, and comedotype), tubular adenocarcinoma, and infiltrating duct carcinoma. The data indicate that a high fat diet in combination with a heterocyclic amine carcinogen derived from cooked meat may enhance the incidence and severity of mammary gland cancer. JF - Carcinogenesis AU - Ghoshal, A AU - Preisegger, K H AU - Takayama, S AU - Thorgeirsson, S S AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 2429 EP - 2433 VL - 15 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Dietary Fats KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Imidazoles -- toxicity KW - Cocarcinogenesis KW - Dietary Fats -- adverse effects KW - Carcinogens -- toxicity KW - Dietary Fats -- administration & dosage KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76813297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Induction+of+mammary+tumors+in+female+Sprague-Dawley+rats+by+the+food-derived+carcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+and+effect+of+dietary+fat.&rft.au=Ghoshal%2C+A%3BPreisegger%2C+K+H%3BTakayama%2C+S%3BThorgeirsson%2C+S+S%3BSnyderwine%2C+E+G&rft.aulast=Ghoshal&rft.aufirst=A&rft.date=1994-11-01&rft.volume=15&rft.issue=11&rft.spage=2429&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-22 N1 - Date created - 1994-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Utilization of a fos-lacZ plasmid to investigate the activation of c-fos during cellular senescence and okadaic acid-induced apoptosis. AN - 76813024; 7525690 AB - C-fos is an immediate-early gene that is induced by external stimuli and is possibly involved in initiation of DNA synthesis by such stimuli. In these studies, we used the murine c-fos promoter coupled to a lacZ reporter gene to study fos induction in senescent and quiescent cells. In transfected, quiescent, immortal Syrian hamster embryo (SHE) cells (10W), serum stimulation induced the expression of the fos construct to the same extent that DNA synthesis was stimulated. In contrast, in transfected normal cells that have a finite life span, we observed that the cells failed to display upregulation of fos-lacZ in response to serum in individual cells as they senesced. High doses of the phosphatase inhibitor okadaic acid (160-1000 nM) also induced fos-lacZ expression in quiescent immortal cells; however, induction of DNA synthesis and expression of fos-lacZ were not coordinately induced as a function of okadaic acid concentration. Low concentrations of okadaic acid (0.16 nM) induced DNA synthesis but not fos-lacZ expression, indicating that induction of DNA synthesis by phosphatase inhibitors may bypass, at least quantitatively, the requirement for c-fos induction. At the levels of okadaic acid that induced fos-lacZ expression, cell death, rather than DNA synthesis, was observed. The cells died by apoptosis, thereby implicating a signaling pathway that includes c-fos induction in this process. JF - Journal of gerontology AU - Afshari, C A AU - Bivins, H M AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - B263 EP - B269 VL - 49 IS - 6 SN - 0022-1422, 0022-1422 KW - Carcinogens KW - 0 KW - Ethers, Cyclic KW - RNA, Messenger KW - Okadaic Acid KW - 1W21G5Q4N2 KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Plasmids -- genetics KW - RNA, Messenger -- drug effects KW - RNA, Messenger -- analysis KW - Cell Aging -- genetics KW - DNA -- biosynthesis KW - RNA -- drug effects KW - Cell Aging -- drug effects KW - DNA -- drug effects KW - Blood KW - Cells, Cultured KW - RNA -- isolation & purification KW - Mesocricetus KW - beta-Galactosidase -- genetics KW - Microscopy, Electron KW - Embryo, Mammalian KW - Cricetinae KW - Carcinogens -- pharmacology KW - Genes, Reporter -- genetics KW - Apoptosis -- genetics KW - Apoptosis -- drug effects KW - Genes, fos -- genetics KW - Gene Expression Regulation -- drug effects KW - Genes, fos -- drug effects KW - Ethers, Cyclic -- pharmacology KW - Gene Expression Regulation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76813024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gerontology&rft.atitle=Utilization+of+a+fos-lacZ+plasmid+to+investigate+the+activation+of+c-fos+during+cellular+senescence+and+okadaic+acid-induced+apoptosis.&rft.au=Afshari%2C+C+A%3BBivins%2C+H+M%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1994-11-01&rft.volume=49&rft.issue=6&rft.spage=B263&rft.isbn=&rft.btitle=&rft.title=Journal+of+gerontology&rft.issn=00221422&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The potential for hormonal prevention trials. AN - 76812517; 7954293 AB - Breast and prostate cancer are significant causes of morbidity and mortality and are very similar in etiology, epidemiology, and modalities of treatment. Investigational strategies in the prevention of these malignancies also have strong parallels. The National Cancer Institute is sponsoring several large scale clinical trials involving hormonal manipulation and cancer prevention. In the Breast Cancer Prevention Trial, 16,000 women at high risk for breast cancer are being randomized to receive the antiestrogen agent tamoxifen or placebo for 5 years in an effort to determine if breast cancer development can be inhibited. In a similar trial, the Prostate Cancer Prevention Trial, 18,000 men older than 55 years of age will be randomized to receive finasteride, a 5-alpha-reductase inhibitor, or placebo to determine if inhibition of dihydrotestosterone synthesis in the prostate over a prolonged period will lead to a decreased incidence of prostate cancer. Both clinical trials offer the possibility of demonstrating that a hormonal intervention can decrease an individual's risk of developing breast or prostate cancer. They also have the potential of providing critical information about cancer risk, etiology, screening, and genetics, as well as quantifying the risks and benefits of specific preventive interventions. JF - Cancer AU - Ford, L G AU - Brawley, O W AU - Perlman, J A AU - Nayfield, S G AU - Johnson, K A AU - Kramer, B S AD - Detection and Community Oncology Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 2726 EP - 2733 VL - 74 IS - 9 Suppl SN - 0008-543X, 0008-543X KW - 5-alpha Reductase Inhibitors KW - 0 KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - Finasteride KW - 57GNO57U7G KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Estrogen -- antagonists & inhibitors KW - Randomized Controlled Trials as Topic KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Tamoxifen -- therapeutic use KW - Finasteride -- adverse effects KW - Tamoxifen -- adverse effects KW - Finasteride -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Breast Neoplasms -- metabolism KW - Prostatic Neoplasms -- prevention & control KW - Prostatic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76812517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+potential+for+hormonal+prevention+trials.&rft.au=Ford%2C+L+G%3BBrawley%2C+O+W%3BPerlman%2C+J+A%3BNayfield%2C+S+G%3BJohnson%2C+K+A%3BKramer%2C+B+S&rft.aulast=Ford&rft.aufirst=L&rft.date=1994-11-01&rft.volume=74&rft.issue=9+Suppl&rft.spage=2726&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purification and characterization of the SegA protein of bacteriophage T4, an endonuclease related to proteins encoded by group I introns. AN - 76811703; 7961394 AB - Although not encoded by an intron, the bacteriophage T4 SegA protein shares common amino acid motifs with a family of proteins found within mobile group I introns present in fungi and phage. Each of these intron-encoded proteins is thought to initiate the homing of its own intron by cleaving the intronless DNA at or near the site of insertion. Previously, we have found that SegA also cleaves DNA. In this report, we have purified the SegA protein and characterized this endonuclease activity extensively. SegA protein cleaved circular and linear plasmids, DNA containing unmodified cytosines, and wild-type T4 DNA containing hydroxymethylated, glucosylated cytosines. In all cases, certain sites on the DNA were highly preferred for cleavage, but with increasing protein concentration or time of incubation, cleavage occurred at many sites. SegA cleaving activity was stimulated by the presence of ATP or ATP gamma S. Sequence analysis of three highly preferred cleavage sites did not reveal a simple consensus sequence, suggesting that even among highly preferred sites, SegA tolerates many different sequences. A T4 segA amber mutant that we constructed had no phenotype, and PCR analyses indicated that several T-even-related phages lack the segA gene. Taken together, our results show that SegA is an endonuclease with a hierarchy of site specificity, and these results are consistent with the insertion of segA DNA into the T4 genome some time after the divergence of the closely consistent with the insertion of segA DNA into the T4 genome some time after the divergence of the closely related T-even phages. JF - Journal of bacteriology AU - Sharma, M AU - Hinton, D M AD - Section on Nucleic Acid Biochemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 6439 EP - 6448 VL - 176 IS - 21 SN - 0021-9193, 0021-9193 KW - segA KW - DNA, Viral KW - 0 KW - Recombinant Proteins KW - Viral Proteins KW - Endonucleases KW - EC 3.1.- KW - SegA protein, Enterobacteria phage T4 KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Index Medicus KW - Sequence Homology, Nucleic Acid KW - Amino Acid Sequence KW - Genome, Viral KW - Sequence Analysis, DNA KW - Selection, Genetic KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - T-Phages -- genetics KW - Molecular Sequence Data KW - Substrate Specificity KW - DNA, Viral -- metabolism KW - Endonucleases -- metabolism KW - Bacteriophage T4 -- enzymology KW - Deoxyribonucleases, Type II Site-Specific -- isolation & purification KW - Endonucleases -- isolation & purification KW - Bacteriophage T4 -- genetics KW - Deoxyribonucleases, Type II Site-Specific -- genetics KW - Endonucleases -- genetics KW - Introns -- genetics KW - Deoxyribonucleases, Type II Site-Specific -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76811703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Purification+and+characterization+of+the+SegA+protein+of+bacteriophage+T4%2C+an+endonuclease+related+to+proteins+encoded+by+group+I+introns.&rft.au=Sharma%2C+M%3BHinton%2C+D+M&rft.aulast=Sharma&rft.aufirst=M&rft.date=1994-11-01&rft.volume=176&rft.issue=21&rft.spage=6439&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 - 1994-11-30 N1 - Date created - 1994-11-30 N1 - Date revised - 2017-01-13 N1 - Gene symbol - segA N1 - SuppNotes - Cited By: Cell. 1980 May;20(1):185-97 [6156002] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Cell. 1983 Feb;32(2):379-89 [6297792] Methods Enzymol. 1983;101:78-89 [6310343] Proc Natl Acad Sci U S A. 1984 May;81(10):3049-53 [6328492] Cell. 1983 May;33(1):25-35 [6380756] Proc Natl Acad Sci U S A. 1985 Feb;82(4):1074-8 [3156376] Cell. 1985 Jun;41(2):383-94 [3886163] Cell. 1985 Jun;41(2):395-402 [3886164] J Biol Chem. 1985 Oct 15;260(23):12858-65 [2995395] J Mol Biol. 1985 Nov 20;186(2):231-42 [3003362] J Biol Chem. 1986 Apr 25;261(12):5663-73 [3007520] Cell. 1986 Apr 25;45(2):157-66 [3698096] J Biol Chem. 1986 May 5;261(13):6107-18 [2939071] Cell. 1986 Aug 1;46(3):323 [3731271] Mol Cell Biol. 1986 Dec;6(12):4281-94 [3025649] Methods Enzymol. 1987;154:367-82 [3323813] Nucleic Acids Res. 1988 Feb 11;16(3):1125-34 [2963999] Annu Rev Genet. 1987;21:347-71 [3327469] J Mol Biol. 1988 Apr 20;200(4):665-80 [2842508] Curr Genet. 1988 Sep;14(3):253-64 [3197134] Nucleic Acids Res. 1989 Jan 11;17(1):301-15 [2643081] Cell. 1989 Feb 10;56(3):323-6 [2536590] Cell. 1989 Feb 10;56(3):431-41 [2536593] J Biol Chem. 1989 Aug 25;264(24):14432-9 [2668289] Gene. 1989 Oct 15;82(1):91-114 [2555264] Science. 1989 Dec 1;246(4934):1106-9 [2479980] J Biol Chem. 1990 Apr 25;265(12):6726-33 [2139027] Nucleic Acids Res. 1990 Jul 11;18(13):3763-70 [2165250] Nucleic Acids Res. 1990 Oct 11;18(19):5659-65 [2216759] Mol Gen Genet. 1990 Sep;223(2):288-96 [1701210] Cell. 1991 Jan 11;64(1):9-11 [1898872] J Biol Chem. 1991 Jan 25;266(3):1977-84 [1988456] J Mol Biol. 1991 Mar 20;218(2):293-311 [1849178] Annu Rev Genet. 1990;24:363-85 [2088173] J Mol Biol. 1991 Apr 20;218(4):747-60 [1708831] J Biol Chem. 1991 Sep 25;266(27):18034-44 [1917941] Mol Cell Biol. 1992 Feb;12(2):716-23 [1732740] Nature. 1992 May 28;357(6376):301-6 [1534148] EMBO J. 1992 Jul;11(7):2707-15 [1628629] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6658-62 [1631169] Mol Gen Genet. 1993 Jan;236(2-3):409-14 [8437585] Nucleic Acids Res. 1993 Mar 25;21(6):1500 [8464751] EMBO J. 1993 May;12(5):2141-9 [8491202] Genetics. 1974 Dec;78(4):989-1014 [4455560] J Bacteriol. 1977 Sep;131(3):821-9 [330500] Cell. 1982 Jul;29(3):939-44 [6217898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction. AN - 76811653; 7955094 AB - Incubation of Cr(VI) with ascorbate generated Cr(V), Cr(IV) and ascorbate-derived carbon-centered alkyl radicals, as well as formyl radicals. H2O2 caused generation of hydroxyl radicals (OH) and much higher levels of Cr(V), showing that .OH can be generated via a Cr(IV)-mediated Fenton-like reaction (Cr(IV) + H2O2-->Cr(V) + .OH + OH-). 1,10-Phenanthroline and deferoxamine inhibited the formation of both .OH and Cr(V) from the reaction of Cr(VI) with ascorbate in the presence of H2O2. Electrophoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. .OH radicals generated by Cr(V)- and Cr(IV)-mediated Fenton-like reactions also caused DNA double-strand breaks. HPLC measurements showed that .OH radicals generated by Cr(IV) and Cr(V) from H2O2 caused 2'-deoxyguanine hydroxylation to form 8-hydroxy-2'-deoxyguanine. JF - Carcinogenesis AU - Shi, X AU - Mao, Y AU - Knapton, A D AU - Ding, M AU - Rojanasakul, Y AU - Gannett, P M AU - Dalal, N AU - Liu, K AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 2475 EP - 2478 VL - 15 IS - 11 SN - 0143-3334, 0143-3334 KW - Chromium KW - 0R0008Q3JB KW - Hydroxyl Radical KW - 3352-57-6 KW - Guanine KW - 5Z93L87A1R KW - 8-oxo-7,8-dihydrodeoxyguanine KW - 6957-76-2 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - Hydroxylation KW - Hydroxyl Radical -- metabolism KW - DNA Damage KW - Hydrogen Peroxide -- metabolism KW - Chromium -- metabolism KW - Ascorbic Acid -- metabolism KW - Chromium -- toxicity KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76811653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reaction+of+Cr%28VI%29+with+ascorbate+and+hydrogen+peroxide+generates+hydroxyl+radicals+and+causes+DNA+damage%3A+role+of+a+Cr%28IV%29-mediated+Fenton-like+reaction.&rft.au=Shi%2C+X%3BMao%2C+Y%3BKnapton%2C+A+D%3BDing%2C+M%3BRojanasakul%2C+Y%3BGannett%2C+P+M%3BDalal%2C+N%3BLiu%2C+K&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-11-01&rft.volume=15&rft.issue=11&rft.spage=2475&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-22 N1 - Date created - 1994-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frailty and disability: can growth hormone or other trophic agents make a difference? AN - 76809584; 7963210 JF - Journal of the American Geriatrics Society AU - Hodes, R J AD - National Institute on Aging, Office of the Director, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1208 EP - 1211 VL - 42 IS - 11 SN - 0002-8614, 0002-8614 KW - Estrogens KW - 0 KW - Testosterone KW - 3XMK78S47O KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Growth Hormone KW - 9002-72-6 KW - Growth Hormone-Releasing Hormone KW - 9034-39-3 KW - Index Medicus KW - United States KW - Insulin-Like Growth Factor I -- physiology KW - Age Factors KW - Testosterone -- therapeutic use KW - Estrogens -- therapeutic use KW - Combined Modality Therapy KW - Exercise Therapy KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Drug Therapy, Combination KW - Testosterone -- pharmacology KW - Estrogens -- pharmacology KW - National Institutes of Health (U.S.) KW - Drug Synergism KW - Body Composition -- drug effects KW - Male KW - Female KW - Aging -- physiology KW - Growth Hormone-Releasing Hormone -- therapeutic use KW - Growth Hormone-Releasing Hormone -- pharmacology KW - Growth Hormone -- physiology KW - Growth Hormone -- therapeutic use KW - Frail Elderly KW - Aging -- drug effects KW - Disabled Persons KW - Growth Hormone -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76809584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=Frailty+and+disability%3A+can+growth+hormone+or+other+trophic+agents+make+a+difference%3F&rft.au=Hodes%2C+R+J&rft.aulast=Hodes&rft.aufirst=R&rft.date=1994-11-01&rft.volume=42&rft.issue=11&rft.spage=1208&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-02 N1 - Date created - 1994-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of a marked H2A histone protein in mammalian cells. AN - 76804698; 7957682 AB - Histone protein sequences are highly conserved. In order to determine whether histones with sequences not found in nature would be tolerated in the chromatin of tissue culture cells, a gene for histone H2A.1a was altered by extending the protein coding region with eight amino acids, including three residues for methionine which are lacking in H2A.1a. Isolated clones of HeLa cells transfected with the gene construct were found to produce a novel protein which was resolved from other histone proteins on AUT-AUC two-dimensional gels. One clone, HeLa-B4, in which the novel protein named H2A.E accounted for about 10% of total H2A protein, was studied further. The linkage of H2A.E mRNA concentrations to the rates of DNA and protein synthesis was found to be the same as that of other replication-linked histone mRNA species. The stability of H2A.E in chromatin as well as the partitioning of nascent H2A.E protein between soluble and nuclear fractions was found to be indistinguishable from that of other histone species. This study shows that histone proteins with sequences other than the conserved sequences found in nature may be utilized in tissue culture cells. JF - Experimental cell research AU - Ivanova, V S AU - Bonner, W M AD - Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 63 EP - 67 VL - 215 IS - 1 SN - 0014-4827, 0014-4827 KW - H2A.1a KW - Chromatin KW - 0 KW - Histones KW - RNA, Messenger KW - Index Medicus KW - Clone Cells KW - Chromatin -- metabolism KW - HeLa Cells KW - Humans KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Plasmids KW - RNA, Messenger -- biosynthesis KW - Molecular Weight KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Conserved Sequence KW - Transfection KW - Kinetics KW - Restriction Mapping KW - Electrophoresis, Gel, Two-Dimensional KW - Molecular Sequence Data KW - Time Factors KW - Histones -- biosynthesis KW - Gene Expression KW - Histones -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76804698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Expression+of+a+marked+H2A+histone+protein+in+mammalian+cells.&rft.au=Ivanova%2C+V+S%3BBonner%2C+W+M&rft.aulast=Ivanova&rft.aufirst=V&rft.date=1994-11-01&rft.volume=215&rft.issue=1&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-02 N1 - Date created - 1994-12-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H2A.1a N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ethanol on metarhodopsin II formation is potentiated by phospholipid polyunsaturation. AN - 76790997; 7947679 AB - The role of phospholipids in modulating the effect of ethanol on membrane receptor activation was investigated by studying the extent of metarhodopsin II (MII) formation in vesicles formed POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine) and in native rod outer segment disk membranes as a function of ethanol concentration. The equilibrium concentration of MII, the G protein-activating form of photoactivated rhodopsin, was found to increase as a function of ethanol concentration in all three bilayers. Phospholipid composition had a marked effect on ethanol potency, with the presence of polyunsaturated phospholipid acyl chains increasing ethanol potency by 40%. The effects of ethanol on lipid acyl chain packing in POPC and PDPC were investigated using frequency domain anisotropy decay measurements of the fluorescent membrane probe 1,6-diphenyl-1,3,5-hexatriene. Enhanced formation of MII due to the presence of ethanol was correlated with the effects of ethanol on acyl chain packing properties. These findings support a phospholipid-mediated mechanism for the action of ethanol in modulating integral membrane receptor conformation. JF - Biochemistry AU - Mitchell, D C AU - Litman, B J AD - Section of Fluorescence Studies, NIAAA National Institutes of Health, Bethesda, Maryland 20892-8205. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 12752 EP - 12756 VL - 33 IS - 43 SN - 0006-2960, 0006-2960 KW - Fatty Acids, Unsaturated KW - 0 KW - Liposomes KW - Membrane Lipids KW - Phosphatidylcholines KW - Phospholipids KW - Diphenylhexatriene KW - 1720-32-7 KW - Ethanol KW - 3K9958V90M KW - 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine KW - 59403-54-2 KW - metarhodopsins KW - 60383-01-9 KW - Rhodopsin KW - 9009-81-8 KW - 1-palmitoyl-2-oleoylphosphatidylcholine KW - TE895536Y5 KW - Index Medicus KW - Rod Cell Outer Segment -- metabolism KW - Thermodynamics KW - Fluorescence Polarization KW - Phosphatidylcholines -- chemistry KW - Liposomes -- metabolism KW - Liposomes -- chemistry KW - Cell Membrane -- metabolism KW - Drug Synergism KW - Membrane Lipids -- chemistry KW - Fatty Acids, Unsaturated -- chemistry KW - Phospholipids -- chemistry KW - Ethanol -- pharmacology KW - Rhodopsin -- analogs & derivatives KW - Rhodopsin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76790997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+ethanol+on+metarhodopsin+II+formation+is+potentiated+by+phospholipid+polyunsaturation.&rft.au=Mitchell%2C+D+C%3BLitman%2C+B+J&rft.aulast=Mitchell&rft.aufirst=D&rft.date=1994-11-01&rft.volume=33&rft.issue=43&rft.spage=12752&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asbestos and the mesothelial cell: a molecular trail to mitogenic stimuli and suppressor gene suspects. AN - 76787434; 7946379 JF - American journal of respiratory cell and molecular biology AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 507 EP - 508 VL - 11 IS - 5 SN - 1044-1549, 1044-1549 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Animals KW - Humans KW - Epithelium -- metabolism KW - Epithelium -- drug effects KW - Epithelial Cells KW - Mesothelioma -- etiology KW - Cell Transformation, Neoplastic -- chemically induced KW - Genes, Tumor Suppressor -- physiology KW - Asbestos -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76787434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Asbestos+and+the+mesothelial+cell%3A+a+molecular+trail+to+mitogenic+stimuli+and+suppressor+gene+suspects.&rft.au=Gerwin%2C+B+I&rft.aulast=Gerwin&rft.aufirst=B&rft.date=1994-11-01&rft.volume=11&rft.issue=5&rft.spage=507&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 - 1994-12-15 N1 - Date created - 1994-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition. AN - 76785567; 7946383 AB - Several lines of evidence have suggested that specific (i.e., lymphocyte) immunity plays a role in chemical-induced pulmonary diseases, including asbestosis. To evaluate the influence of cell-mediated immunity in pulmonary inflammation and fibrosis evoked by asbestos fibers, we compared the effects of asbestos in immunodeficient mice (Balb/c nu/nu and severe combined immunodeficient [C3H-SCID]), immunologically normal mice of the same genetic background, and immunodeficient mice reconstituted with syngeneic T lymphocytes. Increases in lavaged cell numbers occurred in asbestos-treated immunodeficient mice compared with asbestos-treated immunocompetent or immunodeficient mice that received T lymphocytes. Differential analysis of the collected cells in treated mice demonstrated a predominantly neutrophilic infiltrate that correlated with increased levels of leukotriene B4 and prostaglandin E2. There were no significant differences between immunocompetent and athymic asbestos-treated mice in bronchoalveolar lavaged total protein. However, asbestos-treated SCID mice revealed a significant increase in protein content and lactate dehydrogenase activity compared with asbestos-treated normal mice, which did not occur in T lymphocyte-reconstituted SCID mice. Fibronectin levels were elevated in asbestos-exposed athymic mice when compared with air-exposed athymic mice or asbestos-exposed immunocompetent mice. Both asbestos-treated athymic and SCID mice showed a significant increase in total lung hydroxyproline when compared with asbestos-treated immunocompetent mice. Lung hydroxyproline was also reduced in asbestos-exposed SCID mice after T lymphocyte reconstitution and, conversely, increased in T cell-depleted Balb/c mice.(ABSTRACT TRUNCATED AT 250 WORDS) JF - American journal of respiratory cell and molecular biology AU - Corsini, E AU - Luster, M I AU - Mahler, J AU - Craig, W A AU - Blazka, M E AU - Rosenthal, G J AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triange Park, North Carolina. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 531 EP - 539 VL - 11 IS - 5 SN - 1044-1549, 1044-1549 KW - Asbestos, Serpentine KW - 0 KW - Fibronectins KW - RNA, Messenger KW - Leukotriene B4 KW - 1HGW4DR56D KW - Interferon-gamma KW - 82115-62-6 KW - Collagen KW - 9007-34-5 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Dinoprostone KW - K7Q1JQR04M KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Animals KW - Interferon-gamma -- genetics KW - Leukotriene B4 -- metabolism KW - RNA, Messenger -- analysis KW - Fibronectins -- metabolism KW - Mice, Nude KW - Mice KW - Bronchoalveolar Lavage Fluid -- immunology KW - Pulmonary Fibrosis -- immunology KW - Mice, Inbred Strains KW - Base Sequence KW - Dinoprostone -- metabolism KW - Molecular Sequence Data KW - Inflammation -- immunology KW - Mice, SCID KW - Bronchoalveolar Lavage Fluid -- cytology KW - Hydroxyproline -- metabolism KW - L-Lactate Dehydrogenase -- metabolism KW - Lung -- immunology KW - Asbestosis -- immunology KW - Collagen -- metabolism KW - Asbestos, Serpentine -- toxicity KW - Lung -- drug effects KW - Lung -- pathology KW - Lung -- metabolism KW - Asbestosis -- metabolism KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76785567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+protective+role+for+T+lymphocytes+in+asbestos-induced+pulmonary+inflammation+and+collagen+deposition.&rft.au=Corsini%2C+E%3BLuster%2C+M+I%3BMahler%2C+J%3BCraig%2C+W+A%3BBlazka%2C+M+E%3BRosenthal%2C+G+J&rft.aulast=Corsini&rft.aufirst=E&rft.date=1994-11-01&rft.volume=11&rft.issue=5&rft.spage=531&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 - 1994-12-15 N1 - Date created - 1994-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The heat-labile enterotoxin of Escherichia coli binds to polylactosaminoglycan-containing receptors in CaCo-2 human intestinal epithelial cells. AN - 76784769; 7947695 AB - The E. coli type I heat-labile enterotoxin (LT-I) shares considerable functional, structural, and immunological homology with cholera toxin (CT). Although the ganglioside GM1 is the sole receptor for CT, LT-I also appears to utilize additional, unique receptors on intestinal cells not recognized by CT. We characterized this second class of LT-I receptors using the human intestinal epithelial cell line, CaCo-2. CaCo-2 cells bound 8-fold more LT-I than CT, and some of these additional LT-I receptors appeared to be functional, as CT-B only partially inhibited LT-I activity at concentrations that completely inhibited CT activity. Membranes from unlabeled or [3H]galactose-labeled cells were incubated with toxin B subunits and extracted with Triton X-100, and the solubilized toxin B-receptor complexes were immunoabsorbed with anti-B bound to protein A-Sepharose. When organic extracts of the complexes were separated by thin-layer chromatography and overlayed with [125I]toxin, both toxins were found to bind only GM1. Separation of the complexes from [3H]galactose-labeled membranes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a series of galactoproteins specifically recognized by LT-I but not by CT. Similar proteins were detected on Western blots probed with [125I]toxin. LT-I activity on intact cells and binding to membranes and the above galactoproteins were enhanced by neuraminidase treatment even in the presence of CT-B. beta-1,4-Galactosidase and endo-beta-1,4-galactosidase, but not beta-1,3-galactosidase, significantly reduced LT-I binding. LT-I binding to fetuin and transferrin exhibited a similar glycosidase sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Orlandi, P A AU - Critchley, D R AU - Fishman, P H AD - Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 12886 EP - 12895 VL - 33 IS - 43 SN - 0006-2960, 0006-2960 KW - Amino Sugars KW - 0 KW - Bacterial Toxins KW - Enterotoxins KW - Escherichia coli Proteins KW - Glycoproteins KW - Polysaccharides KW - Receptors, Peptide KW - galactoproteins KW - heat-labile enterotoxin, E coli KW - lactosaminoglycan KW - G(M1) Ganglioside KW - 37758-47-7 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Galactosidases KW - EC 3.2.1.- KW - Guanylate Cyclase KW - EC 4.6.1.2 KW - Receptors, Guanylate Cyclase-Coupled KW - enterotoxin receptor KW - Index Medicus KW - Glycoproteins -- metabolism KW - Humans KW - Cyclic AMP -- metabolism KW - Cholera Toxin -- pharmacology KW - G(M1) Ganglioside -- metabolism KW - Epithelium -- metabolism KW - Cell Membrane -- metabolism KW - Galactosidases -- pharmacology KW - Cell Line KW - Cholera Toxin -- metabolism KW - Polysaccharides -- analysis KW - Receptors, Peptide -- metabolism KW - Enterotoxins -- metabolism KW - Amino Sugars -- analysis KW - Bacterial Toxins -- pharmacology KW - Intestines -- metabolism KW - Receptors, Peptide -- analysis KW - Guanylate Cyclase -- analysis KW - Guanylate Cyclase -- metabolism KW - Bacterial Toxins -- metabolism KW - Escherichia coli KW - Enterotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76784769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+heat-labile+enterotoxin+of+Escherichia+coli+binds+to+polylactosaminoglycan-containing+receptors+in+CaCo-2+human+intestinal+epithelial+cells.&rft.au=Orlandi%2C+P+A%3BCritchley%2C+D+R%3BFishman%2C+P+H&rft.aulast=Orlandi&rft.aufirst=P&rft.date=1994-11-01&rft.volume=33&rft.issue=43&rft.spage=12886&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical and pharmacokinetic evaluation of long-term therapy with didanosine in children with HIV infection. AN - 76764631; 7936903 AB - Didanosine has demonstrated promising antiviral activity and a tolerable toxicity profile in short term studies. We describe a cohort of HIV-infected children who were treated for a prolonged period of time with didanosine. Children (6 months to 18 years of age) with symptomatic HIV infection or an absolute CD4 count < 0.5 x 10(9) cells/L, received oral didanosine at doses between 20 mg/m2 to 180 mg/m2 every 8 hours. Clinical, immunological, and virological parameters were assessed at least every 2 months. The pharmacokinetics of didanosine were evaluated in 85 patients. Previously untreated children (n = 51) and children who had received prior antiretroviral therapy (n = 52) were enrolled in the study (median time on study 22.6 months; range 2 to 48). The long-term administration of didanosine was well tolerated and no new toxicities were observed. The absolute CD4 count increased by > or = .05 x 10(9) cells/L in 28 of 87 (32%) of patients after 6 months of therapy. Responses were also sustained in 41% of these children after 3 years of therapy. Children entering the study with a CD4 count > 0.1 x 10(9) cells/L (n = 51) had a marked survival advantage (P = .00002) with an estimated survival probability after 3 years of 80% compared to 39% for children with lower CD4 counts. Although the area under the curve of didanosine increased proportionally with the dose, there was considerable interpatient variability at each dose level. There was no apparent relationship between surrogate markers of clinical outcome and plasma drug concentration. Didanosine was well tolerated with chronic administration, and toxicities were uncommon and usually reversible. In 41% of patients, the CD4 count increased and was maintained at the higher level even after years of treatment. JF - Pediatrics AU - Mueller, B U AU - Butler, K M AU - Stocker, V L AU - Balis, F M AU - Brouwers, P AU - Jarosinski, P AU - Husson, R N AU - Lewis, L L AU - Venzon, D AU - Pizzo, P A AD - Pediatric Branch, Warren Grant Magnuson Clinical Center, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 724 EP - 731 VL - 94 IS - 5 SN - 0031-4005, 0031-4005 KW - Antigens, CD4 KW - 0 KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Humans KW - Treatment Outcome KW - Disease Progression KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Didanosine -- therapeutic use KW - Didanosine -- blood KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76764631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Clinical+and+pharmacokinetic+evaluation+of+long-term+therapy+with+didanosine+in+children+with+HIV+infection.&rft.au=Mueller%2C+B+U%3BButler%2C+K+M%3BStocker%2C+V+L%3BBalis%2C+F+M%3BBrouwers%2C+P%3BJarosinski%2C+P%3BHusson%2C+R+N%3BLewis%2C+L+L%3BVenzon%2C+D%3BPizzo%2C+P+A&rft.aulast=Mueller&rft.aufirst=B&rft.date=1994-11-01&rft.volume=94&rft.issue=5&rft.spage=724&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A complex array of positive and negative elements regulates the chicken alpha A-crystallin gene: involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins. AN - 76763496; 7935450 AB - The abundance of crystallins (> 80% of the soluble protein) in the ocular lens provides advantageous markers for selective gene expression during cellular differentiation. Here we show by functional and protein-DNA binding experiments that the chicken alpha A-crystallin gene is regulated by at least five control elements located at sites A (-148 to -139), B (-138 to -132), C (-128 to -101), D (-102 to -93), and E (-56 to -41). Factors interacting with these sites were characterized immunologically and by gel mobility shift experiments. The results are interpreted with the following model. Site A binds USF and is part of a composite element with site B. Site B binds CREB and/or CREM to enhance expression in the lens and binds an AP-1 complex including CREB, Fra2 and/or JunD which interacts with USF on site A to repress expression in fibroblasts. Sites C and E (which is conserved across species) bind Pax-6 in the lens to stimulate alpha A-crystallin promoter activity. These experiments provide the first direct data that Pax-6 contributes to the lens-specific expression of a crystallin gene. Site D (-104 to -93) binds USF and is a negative element. Thus, the data indicate that USF, CREB and/or CREM (or AP-1 factors), and Pax-6 bind a complex array of positive and negative cis-acting elements of the chicken alpha A-crystallin gene to control high expression in the lens and repression in fibroblasts. JF - Molecular and cellular biology AU - Cvekl, A AU - Sax, C M AU - Bresnick, E H AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 7363 EP - 7376 VL - 14 IS - 11 SN - 0270-7306, 0270-7306 KW - Crystallins KW - 0 KW - Cyclic AMP Response Element-Binding Protein KW - DNA-Binding Proteins KW - Eye Proteins KW - Homeodomain Proteins KW - PAX6 Transcription Factor KW - Paired Box Transcription Factors KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Transcription Factors KW - Upstream Stimulatory Factors KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- metabolism KW - Chick Embryo KW - Mutagenesis KW - Promoter Regions, Genetic KW - Base Sequence KW - Chickens KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Transfection KW - Lens, Crystalline -- metabolism KW - Cells, Cultured KW - Models, Genetic KW - DNA -- genetics KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Binding Sites -- genetics KW - DNA-Binding Proteins -- metabolism KW - Transcription Factors -- metabolism KW - Crystallins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76763496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=A+complex+array+of+positive+and+negative+elements+regulates+the+chicken+alpha+A-crystallin+gene%3A+involvement+of+Pax-6%2C+USF%2C+CREB+and%2For+CREM%2C+and+AP-1+proteins.&rft.au=Cvekl%2C+A%3BSax%2C+C+M%3BBresnick%2C+E+H%3BPiatigorsky%2C+J&rft.aulast=Cvekl&rft.aufirst=A&rft.date=1994-11-01&rft.volume=14&rft.issue=11&rft.spage=7363&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 - 1994-11-18 N1 - Date created - 1994-11-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5642-6 [8202541] Cell Growth Differ. 1993 Jan;4(1):49-55 [8424906] EMBO J. 1993 Feb;12(2):501-11 [8440240] Mol Biol Evol. 1993 Jan;10(1):103-26 [8450753] J Biol Chem. 1993 Mar 25;268(9):6777-84 [8454650] J Mol Biol. 1993 Mar 20;230(2):425-35 [8464058] Mol Endocrinol. 1993 Feb;7(2):145-53 [8385737] DNA Cell Biol. 1993 Mar;12(2):183-90 [8471166] Endocr Rev. 1993 Jun;14(3):269-90 [8319595] J Biol Chem. 1993 Sep 5;268(25):18824-34 [8360172] Genes Dev. 1993 Oct;7(10):2048-61 [8406007] Science. 1993 Oct 15;262(5132):395-9 [8211160] Mol Cell Biol. 1993 Dec;13(12):7257-66 [8246948] Mol Cell Biol. 1994 Jan;14(1):456-62 [8264613] J Mol Biol. 1994 Feb 25;236(3):669-78 [8114084] Dev Biol. 1994 Mar;162(1):181-94 [8125186] Adv Enzymol Relat Areas Mol Biol. 1994;69:155-201 [7817868] Mol Cell Biol. 1987 May;7(5):1807-14 [3474517] Science. 1987 Sep 11;237(4820):1324-9 [2888190] Genes Dev. 1987 Oct;1(8):818-28 [2828173] Genes Dev. 1987 Nov;1(9):973-80 [3428603] Differentiation. 1980;17(3):137-49 [7004973] Differentiation. 1981;19(3):134-53 [7030840] Proc Natl Acad Sci U S A. 1982 Apr;79(7):2360-4 [6285380] Cell. 1985 Nov;43(1):165-75 [4075392] DNA. 1988 Jan-Feb;7(1):47-55 [3349904] Annu Rev Biochem. 1988;57:479-504 [3052280] Genes Dev. 1988 Sep;2(9):1144-54 [3192076] J Biol Chem. 1988 Dec 5;263(34):18466-72 [2848037] Mol Cell Biol. 1989 Mar;9(3):1083-91 [2725488] J Biol Chem. 1989 Nov 25;264(33):19837-44 [2584197] Dev Biol. 1990 May;139(1):56-64 [2328840] Trends Neurosci. 1990 May;13(5):184-8 [1693237] Mol Cell Biol. 1990 Jul;10(7):3700-8 [1694016] Adv Cancer Res. 1990;55:1-35 [2166997] Science. 1990 Sep 14;249(4974):1266-72 [2119054] Mol Cell Biol. 1990 Dec;10(12):6192-203 [2147221] Mol Cell Biol. 1991 Mar;11(3):1488-99 [1996106] Mol Endocrinol. 1990 Aug;4(8):1087-94 [2149870] Oncogene. 1991 Apr;6(4):533-42 [1827665] Gene. 1991 Jul 22;103(2):193-200 [1889745] Nature. 1991 Sep 19;353(6341):267-70 [1680220] Mol Cell Biol. 1991 Oct;11(10):5125-36 [1922036] EMBO J. 1991 Dec;10(12):3609-19 [1718739] Cell Growth Differ. 1991 Oct;2(10):525-30 [1751408] Nature. 1991 Dec 19-26;354(6354):522-5 [1684639] Cell. 1991 Dec 20;67(6):1059-74 [1684738] Nature. 1992 Jan 2;355(6355):80-4 [1370576] J Mol Evol. 1991 Dec;33(6):495-505 [1779432] Development. 1991 Oct;113(2):539-50 [1782865] J Biol Chem. 1992 Mar 5;267(7):4277-80 [1537817] Development. 1991 Dec;113(4):1435-49 [1687460] Cell. 1992 May 29;69(5):719-22 [1591773] J Biol Chem. 1992 Jun 25;267(18):12876-84 [1352292] Gene. 1992 Aug 15;117(2):193-200 [1353472] Nucleic Acids Res. 1992 Jul 25;20(14):3701-12 [1641336] Curr Opin Genet Dev. 1992 Aug;2(4):582-8 [1525511] J Mol Evol. 1992 Oct;35(4):337-45 [1404419] Genes Dev. 1992 Nov;6(11):2066-76 [1427072] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449-53 [1438232] Trends Genet. 1992 Oct;8(10):349-55 [1475847] Cell Growth Differ. 1993 Jan;4(1):1-7 [8424902] J Biol Chem. 1994 Mar 18;269(11):8355-61 [8132558] Am J Hum Genet. 1994 May;54(5):801-11 [7909985] Nat Genet. 1992 Nov;2(3):232-9 [1345175] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenicities of Bangkok and Tokyo river waters. AN - 76759332; 7523938 AB - Samples of water from the Chao Phraya river and some connected canals in Bangkok, Thailand, and from the Sumida and Ara rivers in Tokyo, Japan, were tested for mutagenicity using blue rayon to adsorb the mutagens. The samples from the Chao Phraya river and connected canals at sites located 50-150 km from the river mouth taken in May 1993 showed a mutagenicity of 87-1213 revertants per 0.05 g blue rayon extract towards S. typhimurium YG1024 in the presence of S9 mix. Samples from most sites taken in December 1993, which follows the rainy season, showed a lower mutagenicity than those taken in May, possibly due to dilution by the larger volume of water in the river and canals in December. Water samples from the Sumida river were collected in July 1993 and February 1994, and those from the Ara river in January 1994. Mutagenicity of samples from all sites of the Sumida and Ara rivers, which were located 2-30 and 2-20 km, respectively, from the river mouth was also clearly detected in the presence of S9 mix and did not differ much, being 155-748 revertants of YG1024 per 0.05 g blue rayon extract. These results demonstrated that the water in all three rivers contained some frameshift mutagens. JF - Mutation research AU - Kusamran, W R AU - Wakabayashi, K AU - Oguri, A AU - Tepsuwan, A AU - Nagao, M AU - Sugimura, T AD - Biochemistry and Chemical Carcinogenesis Section, National Cancer Institute, Bangkok, Thailand. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 99 EP - 104 VL - 325 IS - 2-3 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Index Medicus KW - Frameshift Mutation KW - Mutagenicity Tests KW - Tokyo KW - Thailand KW - Salmonella typhimurium -- genetics KW - Water Pollution KW - Water Supply UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76759332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Mutagenicities+of+Bangkok+and+Tokyo+river+waters.&rft.au=Kusamran%2C+W+R%3BWakabayashi%2C+K%3BOguri%2C+A%3BTepsuwan%2C+A%3BNagao%2C+M%3BSugimura%2C+T&rft.aulast=Kusamran&rft.aufirst=W&rft.date=1994-11-01&rft.volume=325&rft.issue=2-3&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-18 N1 - Date created - 1994-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humanized antibody directed to the IL-2 receptor beta-chain prolongs primate cardiac allograft survival. AN - 76755571; 7930631 AB - IL-2Rs are expressed by T cells activated in response to foreign histocompatibility Ags but not by normal cells. This difference in IL-2R expression is exploited by blockade of IL-2Rs to achieve immunosuppression. High affinity IL-2Rs involve three subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma. Murine Mik beta 1, a mAb that blocks IL-2 binding to IL-2R beta, was developed as an immunosuppressive agent. There was modest prolongation of cynomolgus cardiac allograft survival in animals treated with murine Mik beta 1 (mean survival 11.8 +/- 1.6 days compared with 8.2 +/- 0.4 days in untreated animals; p = 0.06). However, murine Mik beta 1 is ineffective in recruiting primate effector cells and is neutralized by monkey Abs directed toward the infused Ab. To circumvent these limitations, a humanized form of Mik beta 1, which is a largely human IgG1k Ab, except that murine hypervariable regions are retained, was developed. In vivo plasma survival of humanized Mik beta 1 was threefold longer than simultaneously administered murine Mik beta 1 (terminal t1/2, 104 +/- 10 h vs 37 +/- 2 h). Furthermore, humanized Mik beta 1 manifests Ab-dependent cellular cytotoxicity, an activity that is absent with the parental murine Mik beta 1. Graft survival was significantly prolonged by humanized Mik beta 1 treatment with survivals of 22, 22, 24, 27, 44, and > 300 days (p vs control 0.3) by the addition of humanized anti-Tac, which blocks interaction of IL-2 with IL-2R alpha subunits. There was no toxicity attributable to the use of Mik beta 1 Abs. Thus, humanized Mik beta 1 prolonged cardiac allograft survival in primates without toxicity and may be effective as an adjunct to standard immunosuppressive therapy. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Tinubu, S A AU - Hakimi, J AU - Kondas, J A AU - Bailon, P AU - Familletti, P C AU - Spence, C AU - Crittenden, M D AU - Parenteau, G L AU - Dirbas, F M AU - Tsudo, M AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 4330 EP - 4338 VL - 153 IS - 9 SN - 0022-1767, 0022-1767 KW - Antibodies, Monoclonal KW - 0 KW - Receptors, Interleukin-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Humans KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Transplantation, Homologous -- immunology KW - Heart Transplantation -- immunology KW - Antibodies, Monoclonal -- pharmacokinetics KW - Graft Survival -- immunology KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76755571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Humanized+antibody+directed+to+the+IL-2+receptor+beta-chain+prolongs+primate+cardiac+allograft+survival.&rft.au=Tinubu%2C+S+A%3BHakimi%2C+J%3BKondas%2C+J+A%3BBailon%2C+P%3BFamilletti%2C+P+C%3BSpence%2C+C%3BCrittenden%2C+M+D%3BParenteau%2C+G+L%3BDirbas%2C+F+M%3BTsudo%2C+M&rft.aulast=Tinubu&rft.aufirst=S&rft.date=1994-11-01&rft.volume=153&rft.issue=9&rft.spage=4330&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Primate antibody response to immunotoxin: serological and computer-aided analysis of epitopes on a truncated form of Pseudomonas exotoxin. AN - 76752905; 7927788 AB - NLysPE38 is a 38-kDa derivative of Pseudomonas exotoxin (PE) in which domain Ia (amino acids 1 to 252) and part of domain Ib (365 to 380) are deleted and an 11-amino-acid N-terminal peptide is added. LMB-1 is an immunotoxin in which the monoclonal antibody B3 is coupled to NLysPE38 near its N terminus. LMB-7 is a single-chain immunotoxin in which the Fv fragment of B3 is fused to PE38. To identify the antigenic regions of PE38, 12 polyclonal serum samples from monkeys immunized with the immunotoxins LMB-1 (six monkeys) and LMB-7 (six monkeys) were tested for their reactivity to a panel of 120 synthetic, overlapping peptides representing the amino acid sequence of NLysPE38. The antibody responses to peptides were similar among the 12 serum specimens, identifying several major immunodominant B-cell epitopes. Predominant reactivity was seen in six locations: amino acids 272 to 287, 341 to 359, 504 to 516, 540 to 564, and 573 to 591 and the C-terminal amino acids 591 to 613. The sera did not react with approximately 75% of the peptides. Furthermore, a computer-aided analysis was done to predict the immunologically relevant areas and revealed the same antigenic regions defined by serum reactivity to peptides. Competition enzyme-linked immunosorbent assays and neutralization assays were performed with domain II, III, or III plus Ib of PE38 and confirmed the immunodominance of domain III. To analyze the role of specific amino acids in antibody binding, individual amino acids of PE38 with large accessible surface areas were altered by site-directed mutagenesis. These results also show that the predicted areas of immunogenicity agree with the reactivity of the anti-PE38 antibodies to peptides and to the mutants of PE. JF - Infection and immunity AU - Roscoe, D M AU - Jung, S H AU - Benhar, I AU - Pai, L AU - Lee, B K AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 5055 EP - 5065 VL - 62 IS - 11 SN - 0019-9567, 0019-9567 KW - Antibodies, Bacterial KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Peptides KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Antibody Specificity KW - Animals KW - Pseudomonas aeruginosa -- immunology KW - Base Sequence KW - Macaca fascicularis KW - Molecular Sequence Data KW - Antibodies, Bacterial -- immunology KW - Peptides -- immunology KW - Amino Acid Sequence KW - Epitope Mapping KW - Male KW - Female KW - Immunotoxins -- immunology KW - Exotoxins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76752905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Primate+antibody+response+to+immunotoxin%3A+serological+and+computer-aided+analysis+of+epitopes+on+a+truncated+form+of+Pseudomonas+exotoxin.&rft.au=Roscoe%2C+D+M%3BJung%2C+S+H%3BBenhar%2C+I%3BPai%2C+L%3BLee%2C+B+K%3BPastan%2C+I&rft.aulast=Roscoe&rft.aufirst=D&rft.date=1994-11-01&rft.volume=62&rft.issue=11&rft.spage=5055&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 - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol Methods. 1991 Jun 3;139(2):155-66 [1904463] JAMA. 1993 Jan 6;269(1):78-81 [8416411] J Immunol Methods. 1991 Aug 9;141(2):245-52 [1715369] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8616-20 [1924323] J Clin Oncol. 1991 Dec;9(12):2095-103 [1960550] Cancer Res. 1992 Jan 1;52(1):1-4 [1530765] Annu Rev Biochem. 1992;61:331-54 [1497314] Protein Sci. 1993 Feb;2(2):175-82 [7680266] Int Rev Immunol. 1993;10(2-3):241-50 [8360588] Eur J Cancer. 1993;29A(11):1606-9 [8217369] J Mol Biol. 1971 Feb 14;55(3):379-400 [5551392] Proc Natl Acad Sci U S A. 1975 Jun;72(6):2284-8 [166383] J Biol Chem. 1981 Aug 25;256(16):8579-81 [6267047] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] Infect Immun. 1986 Jun;52(3):756-62 [2423458] Cell. 1987 Jan 16;48(1):129-36 [3098436] Science. 1987 Mar 6;235(4793):1184-90 [3823878] J Biol Chem. 1987 Jun 25;262(18):8707-11 [2885323] J Immunol Methods. 1987 Sep 24;102(2):259-74 [2443575] Science. 1987 Nov 20;238(4830):1098-104 [3317828] J Biol Chem. 1988 Jul 5;263(19):9470-5 [3132465] Biochemistry. 1989 May 30;28(11):4735-49 [2475171] Cell. 1990 May 18;61(4):553-6 [1693095] Mol Immunol. 1990 Oct;27(10):981-93 [1700288] Infect Immun. 1991 Jan;59(1):407-14 [1702764] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3358-62 [2014255] Mol Immunol. 1991 Mar;28(3):201-7 [1708101] Infect Immun. 1993 Dec;61(12):5417-20 [8225617] J Biol Chem. 1994 May 6;269(18):13398-404 [8175770] Cancer Res. 1991 Jul 15;51(14):3781-7 [1648444] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotoxic stress confers preferential and coordinate messenger RNA stability on the five gadd genes. AN - 76748986; 7923213 AB - The growth arrest and DNA damage-inducible (gadd) genes represent a group of five stress-inducible genes that are coordinately regulated at the transcriptional level. Posttranscriptional regulation of gadd153, gadd45, gadd34, gadd33, and gadd7 was studied after exposure to DNA-damaging agents or other growth arrest treatments in hamster cells. Relative transcript levels were measured following treatment with the transcriptional inhibitor actinomycin D. After exposure to methylmethane sulfonate or UV radiation, all five gadd messages demonstrated a coordinate increase in mRNA stability compared to untreated exponentially growing cells. This enhanced stability was not an universal response to genotoxic stress since other DNA damage-inducible genes, such as c-jun and c-fos, did not show an appreciable increase in mRNA half-life. In contrast, induction of growth arrest by media depletion (starvation) or by treatment with the growth inhibitor prostaglandin A2 did not induce such an increase in mRNA stability in all gadd genes. Comparison of overall RNA turnover by 3H labeling of total cellular RNA also indicated that the preferential stabilization of the gadd transcripts by DNA-damaging agents was not an artifactual response due to variations in overall RNA metabolism within each treatment group. However, DNA-damaging agents were ineffective in inducing stabilization of gadd153 mRNA in growth-arrested cells. This suggest that the signal(s) that give rise to gadd mRNA stability may also be affected by the state of cellular proliferation. Together, these results suggest that the global posttranscriptional response of the gadd genes to DNA-damaging agents is specific and unique to actively growing cells, and further implicates the role of the gadd genes in the DNA damage response of cycling cells. JF - Cancer research AU - Jackman, J AU - Alamo, I AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 5656 EP - 5662 VL - 54 IS - 21 SN - 0008-5472, 0008-5472 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Prostaglandins A KW - Proteins KW - RNA, Messenger KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Dactinomycin KW - 1CC1JFE158 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - prostaglandin A2 KW - K6VT5BDY9E KW - Index Medicus KW - Animals KW - Prostaglandins A -- pharmacology KW - Genes, jun -- drug effects KW - CHO Cells KW - Genes, fos -- genetics KW - Genes, fos -- drug effects KW - Genes, jun -- genetics KW - Cricetinae KW - Dactinomycin -- pharmacology KW - RNA, Messenger -- metabolism KW - RNA, Messenger -- drug effects KW - Gene Expression Regulation -- drug effects KW - Proteins -- metabolism KW - Proteins -- genetics KW - DNA Damage -- genetics KW - Methyl Methanesulfonate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76748986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genotoxic+stress+confers+preferential+and+coordinate+messenger+RNA+stability+on+the+five+gadd+genes.&rft.au=Jackman%2C+J%3BAlamo%2C+I%3BFornace%2C+A+J&rft.aulast=Jackman&rft.aufirst=J&rft.date=1994-11-01&rft.volume=54&rft.issue=21&rft.spage=5656&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 - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 gene dosage modifies growth and malignant progression of keratinocytes expressing the v-rasHa oncogene. AN - 76740215; 7923201 AB - Epidermal keratinocyte cultures were established from newborn mice expressing a null mutation in the p53 gene to explore the contribution of p53 to epidermal growth regulation and neoplasia. Keratinocytes were initiated by transduction with a replication-defective retrovirus encoding the v-rasHa oncogene and grafted onto nude mouse hosts. Tumors arising from keratinocytes heterozygous or null for functional p53 in the presence of v-rasHa have growth rates approximately 5-fold higher than those derived from p53(+/+) controls and rapidly form carcinomas, in contrast to the benign phenotype observed in p53(+/+)/v-rasHa grafts. In vitro, p53-deficient keratinocytes with and without v-rasHa expression display decreased responsiveness to the negative growth regulators transforming growth factors beta 1 and beta 2. In combination with v-rasHa, p53-deficient keratinocytes also exhibit decreased responsiveness to elevated Ca2+. These differences between genotypes cannot be attributed to changes in transforming growth factor beta receptor types present or altered levels of epidermal growth factor receptor and are independent of c-myc transcript levels. mRNA expression for the p-53 inducible protein WAF1 correlates with p53 gene dosage, but low levels are still detectable in p53(-/-) keratinocytes. The altered responsiveness of p53 deficient keratinocytes to negative growth regulators may provide a growth advantage to such cells in vivo and render them more susceptible to genetic alterations and malignant conversion. JF - Cancer research AU - Weinberg, W C AU - Azzoli, C G AU - Kadiwar, N AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 5584 EP - 5592 VL - 54 IS - 21 SN - 0008-5472, 0008-5472 KW - p53 KW - v-rasHa KW - Cdkn1a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - RNA, Messenger -- analysis KW - Mice KW - Amino Acid Sequence KW - Calcium -- pharmacology KW - Gene Deletion KW - Cyclins -- analysis KW - Genotype KW - Animals, Newborn KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Transforming Growth Factor beta -- metabolism KW - Genes, myc -- genetics KW - Cell Division -- genetics KW - Keratinocytes -- chemistry KW - Papilloma -- pathology KW - Carcinoma -- chemistry KW - Genes, p53 -- physiology KW - Skin Neoplasms -- pathology KW - Receptor, Epidermal Growth Factor -- analysis KW - Papilloma -- genetics KW - Skin Neoplasms -- metabolism KW - Skin Neoplasms -- genetics KW - Genes, ras -- genetics KW - Carcinoma -- pathology KW - Genes, ras -- physiology KW - Genes, p53 -- genetics KW - Skin Neoplasms -- chemistry KW - Keratinocytes -- metabolism KW - Keratinocytes -- pathology KW - Papilloma -- chemistry KW - Carcinoma -- metabolism KW - Papilloma -- metabolism KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76740215?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=p53+gene+dosage+modifies+growth+and+malignant+progression+of+keratinocytes+expressing+the+v-rasHa+oncogene.&rft.au=Weinberg%2C+W+C%3BAzzoli%2C+C+G%3BKadiwar%2C+N%3BYuspa%2C+S+H&rft.aulast=Weinberg&rft.aufirst=W&rft.date=1994-11-01&rft.volume=54&rft.issue=21&rft.spage=5584&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 - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53; v-rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenic risk of dark vs. light liquor. AN - 76736614; 7927935 AB - A previous report suggested that the cancer risk associated with hard liquor is greater among users of dark liquors, which may contain more potentially carcinogenic compounds than light liquors. To test this hypothesis, we examined alcohol consumption data obtained by interview with 921 cases and 900 controls who participated in 1984-1985 in a population-based case-control study of oral and pharyngeal cancer conducted in 4 areas of the United States. Among heavy liquor drinkers (30+ drinks/week), odds ratios were 13.2 (95% CI = 5.2-33.5) for those who usually drank light liquors vs. 4.6 (95% CI = 2.7-7.9) for those who usually drank dark liquors, with higher risks for light vs. dark liquors at each anatomical subsite. This analysis provides no support for the notion that dark liquors are more carcinogenic than light liquors or that non-ethanolic ingredients of alcoholic beverages are major contributors to the excess risk of oral and pharyngeal cancer. JF - International journal of cancer AU - Day, G L AU - Blot, W J AU - McLaughlin, J K AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/11/01/ PY - 1994 DA - 1994 Nov 01 SP - 319 EP - 321 VL - 59 IS - 3 SN - 0020-7136, 0020-7136 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Pharyngeal Neoplasms -- epidemiology KW - Ethanol -- adverse effects KW - Pharyngeal Neoplasms -- etiology KW - Mouth Neoplasms -- etiology KW - Alcohol Drinking -- adverse effects KW - Ethanol -- chemistry KW - Mouth Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76736614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Carcinogenic+risk+of+dark+vs.+light+liquor.&rft.au=Day%2C+G+L%3BBlot%2C+W+J%3BMcLaughlin%2C+J+K%3BFraumeni%2C+J+F&rft.aulast=Day&rft.aufirst=G&rft.date=1994-11-01&rft.volume=59&rft.issue=3&rft.spage=319&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 - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Demonstration of differential effects of cytokines on mast cells derived from murine bone marrow and peripheral blood mononuclear cells. AN - 76730595; 7523167 AB - Mouse bone marrow (BM) was cultured in the presence of recombinant mouse (rm) interleukin-3 (IL-3), rmIL-4, rmIL-5, rmIL-7, purified mouse (m) IL-9, rmIL-10, recombinant human (rh) macrophage-colony-stimulating factors (M-CSF), rm granulocyte-macrophage colony-stimulating factors (GM-CSF) rm stem cell factor (SCF), rh interferon-alpha (IFN-alpha), rmIFN-gamma, and mNGF to determine which cytokine would give rise to mast cells in murine BM cultures. From a starting population of 1 x 10(7) cells, 1.55 x 10(7) mast cells developed within 14 days in cultures supplemented by rmIL-3. No mast cells were seen at day 14 when any of the other cytokines were present alone, except for rmSCF, which supported the growth of < 0.01% of mast cells observed in IL-3-dependent BM cultures. When rmIL-4, -5, -7, -10, mIL-9, rhM-CSF, rmGM-CSF, rmSCF, rhIFN-alpha, -gamma, or mNGF were added to BM cultures in the presence of rmIL-3, mast cell growth increased 200% with the addition of rmSCF, and 10% when rmIL-4 or IL-9 was added. However, the addition of rhM-CSF, rmGM-CSF, rmIFN-gamma, and mNGF decreased the number of mast cells. Mast cell number, as determined by metachromatic stains, generally approximated the number of Fc epsilon RI+ cells as assessed by FACS analysis. Among the cytokines, only rmIL-4 and rmSCF were able to support the survival of mast cell progenitors in the absence of obvious mast cell proliferation, similarly to rmIL-3. Only rmSCF alone, or in combination with rmIL-3 or -4, supported the growth of mast cells from mouse peripheral blood mononuclear cells (PBMC) where the number of mast cell precursors was about 90 per 10(6) PBMC. With time, mouse BM cells cultured in rmIL-3 became more responsive to rmSCF. Taken together, these data demonstrate that IL-3 is a major early mast cell growth factor, that mast cells become more dependent on SCF with time, and that the effects of IL-3 and SCF are upregulated (IL-4) or downregulated (M-CSF, GM-CSF, IFN-gamma) by both growth factors and proinflammatory cytokines. JF - Experimental hematology AU - Rottem, M AU - Hull, G AU - Metcalfe, D D AD - Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/11// PY - 1994 DA - November 1994 SP - 1147 EP - 1155 VL - 22 IS - 12 SN - 0301-472X, 0301-472X KW - Cytokines KW - 0 KW - Hematopoietic Cell Growth Factors KW - Interleukin-3 KW - Nerve Growth Factors KW - Recombinant Proteins KW - Stem Cell Factor KW - Interleukin-4 KW - 207137-56-2 KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Interferon-gamma KW - 82115-62-6 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Recombinant Proteins -- pharmacology KW - Nerve Growth Factors -- pharmacology KW - Interleukin-3 -- pharmacology KW - Interleukin-4 -- pharmacology KW - Macrophage Colony-Stimulating Factor -- pharmacology KW - Interferon-gamma -- pharmacology KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Cell Survival KW - Cells, Cultured KW - Time Factors KW - Cell Division KW - Bone Marrow Cells KW - Cytokines -- pharmacology KW - Mast Cells -- cytology KW - Leukocytes, Mononuclear -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76730595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+hematology&rft.atitle=Demonstration+of+differential+effects+of+cytokines+on+mast+cells+derived+from+murine+bone+marrow+and+peripheral+blood+mononuclear+cells.&rft.au=Rottem%2C+M%3BHull%2C+G%3BMetcalfe%2C+D+D&rft.aulast=Rottem&rft.aufirst=M&rft.date=1994-11-01&rft.volume=22&rft.issue=12&rft.spage=1147&rft.isbn=&rft.btitle=&rft.title=Experimental+hematology&rft.issn=0301472X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The reproductive toxicity of boric acid. AN - 21256676; 11704915 AB - Previous studies on the reproductive toxicity of boric acid have indicated that male rodents suffer testicular atrophy after treatment. There were, however, no studies of the potential effects on female fertility or on the neonate. In addition, no study described the development of the testicular lesion, thought to be related to the mechanism of toxicity. A Reproductive Assessment by Continuous Breeding (RACB) study using mice exposed to boric acid at 1000, 4500, and 9000 ppm in the diet indicated that there are probably multiple sites of action, although male fertility appears very sensitive. Possible effects on female fertility cannot be separated from potential developmental toxicity and need additional investigation. Decrements in sperm motility were observed at all exposure levels, and testicular atrophy was confirmed in high- and middle-dose-group males. This was investigated further by timed serial-sacrifice studies using 9000 ppm in the diet of rats, which found that the first lesion seen in the testis was an inhibition of spermiation (release of mature spermatids). With continued dosing, this was followed by a disorganization of the normal ordered layering of the seminiferous epithelium, germ cell sloughing and death, and finally, atrophy. Subsequent studies using additional doses (2000, 3000, 4500, 6000, and 9000 ppm) found that it was possible to observe inhibited spermiation that did not progress to atrophy (4500 ppm and below) within the 9-week exposure period.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. A Figure 1. B Figure 1. C Figure 1. D JF - Environmental Health Perspectives AU - Chapin, R E AU - Ku, W W AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Y1 - 1994/11// PY - 1994 DA - Nov 1994 SP - 87 EP - 91 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 102 IS - Suppl 7 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts; Environment Abstracts KW - Diets KW - Testes KW - Mortality KW - Fertility KW - Germ cells KW - Sperm KW - Toxicity KW - Rats KW - Motility KW - breeding KW - Spermatids KW - Breeding KW - Lesions KW - Epithelium KW - boric acid KW - Atrophy KW - Neonates KW - rodents KW - X 24300:Methods KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21256676?accountid=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=The+reproductive+toxicity+of+boric+acid.&rft.au=Chapin%2C+R+E%3BKu%2C+W+W&rft.aulast=Chapin&rft.aufirst=R&rft.date=1994-11-01&rft.volume=102&rft.issue=Suppl+7&rft.spage=87&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 - Testes; Diets; Fertility; Germ cells; Toxicity; Sperm; Motility; Breeding; Spermatids; Atrophy; boric acid; Epithelium; Neonates; Rats; Mortality; breeding; Lesions; rodents ER - TY - JOUR T1 - Peptide-linked 1,3-dialkyl-3-acyltriazenes: gastrin receptor directed antineoplastic alkylating agents. AN - 76833588; 7966139 AB - The gastrin receptor is expressed in various human cancers, such as the adenocarcinoma of the colon. The peptide hormone gastrin and the C-terminal peptides derived from it act as growth factors for these cancers. The hypothesis for the present work was to use the gastrin receptor as a target for appropriately constructed cytotoxic agents. We developed methods to link tetragastrin and pentagastrin by their N-termini to cytotoxic 1-(2-chloroethyl)-3-benzyl-3-succinoyltriazene. These compounds, CBS-4 and CBS-5, respectively, whose complete structures were determined by multinuclear NMR and mass spectrometry, competed effectively with gastrin in an assay using either guinea pig stomach fundus or the rat acinar tumor cell line AR42J as the source of the receptor. CBS-5 was cytotoxic to AR42J cells but was not toxic to A549 human lung cancer cells, which do not express the receptor. JF - Journal of medicinal chemistry AU - Schmidt, B F AU - Hernandez, L AU - Rouzer, C AU - Czerwinski, G AU - Chmurny, G AU - Michejda, C J AD - Molecular Aspects of Drug Design Section, MSL, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/10/28/ PY - 1994 DA - 1994 Oct 28 SP - 3812 EP - 3818 VL - 37 IS - 22 SN - 0022-2623, 0022-2623 KW - Alkylating Agents KW - 0 KW - Antineoplastic Agents KW - Peptides KW - Receptors, Cholecystokinin KW - Triazenes KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Guinea Pigs KW - Humans KW - In Vitro Techniques KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Amino Acid Sequence KW - Male KW - Magnetic Resonance Spectroscopy KW - Triazenes -- pharmacology KW - Alkylating Agents -- pharmacology KW - Triazenes -- chemistry KW - Alkylating Agents -- chemistry KW - Receptors, Cholecystokinin -- drug effects KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76833588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peptide-linked+1%2C3-dialkyl-3-acyltriazenes%3A+gastrin+receptor+directed+antineoplastic+alkylating+agents.&rft.au=Schmidt%2C+B+F%3BHernandez%2C+L%3BRouzer%2C+C%3BCzerwinski%2C+G%3BChmurny%2C+G%3BMichejda%2C+C+J&rft.aulast=Schmidt&rft.aufirst=B&rft.date=1994-10-28&rft.volume=37&rft.issue=22&rft.spage=3812&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 - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the fingers and palm subdomains of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase. AN - 76829743; 7525967 AB - We have analyzed the human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) polymerase domain between amino acids 91 and 157 by site-directed mutagenesis. We have constructed a series of amino acid substitutions using BspMI cassettes, and have assayed the RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant HIV-1 RTs. The regions of HIV-1 RT between amino acids 91 and 119 and between amino acids 151 and 157 lie within the palm subdomain and include part of the polymerase active site. A number of amino acids within these regions have been identified as being directly or indirectly involved with polymerization, since amino acid substitutions at these residues decrease the polymerase activity without affecting RNase H activity. The region of HIV-1 RT between amino acids 120 and 150 lies within the fingers subdomain of the HIV-1 polymerase. We believe that the fingers subdomain plays a role in positioning the template. Many amino acid substitutions in this region decrease or abolish both the polymerase and the RNase H functions. JF - Journal of molecular biology AU - Boyer, P L AU - Ferris, A L AU - Clark, P AU - Whitmer, J AU - Frank, P AU - Tantillo, C AU - Arnold, E AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer and Development Center, Frederick, MD 21702-1201. Y1 - 1994/10/28/ PY - 1994 DA - 1994 Oct 28 SP - 472 EP - 483 VL - 243 IS - 3 SN - 0022-2836, 0022-2836 KW - Amino Acids KW - 0 KW - Polydeoxyribonucleotides KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Polydeoxyribonucleotides -- metabolism KW - Ribonuclease H -- metabolism KW - Protein Binding KW - Amino Acids -- physiology KW - DNA-Directed DNA Polymerase -- metabolism KW - Mutation -- physiology KW - RNA-Directed DNA Polymerase -- chemistry KW - HIV-1 -- enzymology KW - RNA-Directed DNA Polymerase -- metabolism KW - RNA-Directed DNA Polymerase -- genetics KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76829743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Mutational+analysis+of+the+fingers+and+palm+subdomains+of+human+immunodeficiency+virus+type-1+%28HIV-1%29+reverse+transcriptase.&rft.au=Boyer%2C+P+L%3BFerris%2C+A+L%3BClark%2C+P%3BWhitmer%2C+J%3BFrank%2C+P%3BTantillo%2C+C%3BArnold%2C+E%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1994-10-28&rft.volume=243&rft.issue=3&rft.spage=472&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and characterization of recombinant human eosinophil-derived neurotoxin and eosinophil-derived neurotoxin-anti-transferrin receptor sFv. AN - 76752122; 7929408 AB - The gene for the human recombinant eosinophil-derived neurotoxin (rEDN) was synthesized and fused to the gene encoding a single chain antibody (sFv) to the human transferrin receptor (EDNsFv). Both rEDN and EDNsFv were expressed as insoluble proteins in inclusion bodies in Escherichia coli BL21(DE3). Following denaturation and renaturation, EDN and EDNsFv were partially purified by chromatography on heparin-Sepharose. Final purification of EDN was achieved by Sephadex G-100, whereas EDNsFv which contained a 6-histidyl residue carboxyl terminus was highly purified using the metal chelate resin, Ni(2+)-nitriloacetic acid. Whereas the recombinant EDN had ribonuclease activity that was similar to the native protein, the fusion protein had enzymatic activity that was 6-13% that of native EDN. The fusion protein was able to bind to the human transferrin receptor. In contrast to rEDN that had no inherent cytotoxicity to human tumor cells, the EDNsFv fusion protein was cytotoxic to human leukemia cells that express the human transferrin receptor with an IC50, 0.2-1 nM. At 1.3 nM EDNsFv, no cytotoxicity was observed on cells that lack the human transferrin receptor. Free antibody to the human transferrin receptor, E6, inhibited the cytotoxicity of the EDNsFv. Human enzymes may be engineered to acquire cytotoxic properties by fusing them to antibodies. Thus, they may be candidates for the construction of immunofusion proteins that may be less immunogenic than immunotoxins containing bacterial- or plant-derived toxin moieties. JF - The Journal of biological chemistry AU - Newton, D L AU - Nicholls, P J AU - Rybak, S M AU - Youle, R J AD - Biochemistry Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/28/ PY - 1994 DA - 1994 Oct 28 SP - 26739 EP - 26745 VL - 269 IS - 43 SN - 0021-9258, 0021-9258 KW - Antibodies KW - 0 KW - EDNsFv anti-transferrin receptor KW - Immunotoxins KW - Neurotoxins KW - Receptors, Transferrin KW - Recombinant Fusion Proteins KW - Single-Chain Antibodies KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Dose-Response Relationship, Drug KW - Eosinophils -- enzymology KW - Humans KW - Leukemia, Erythroblastic, Acute -- drug therapy KW - Escherichia coli -- genetics KW - Mice KW - Amino Acid Sequence KW - Protein Binding KW - Base Sequence KW - Binding, Competitive KW - Eosinophils -- chemistry KW - Molecular Sequence Data KW - Neurotoxins -- metabolism KW - Immunotoxins -- toxicity KW - Neurotoxins -- genetics KW - Neurotoxins -- pharmacology KW - Immunotoxins -- metabolism KW - Recombinant Fusion Proteins -- toxicity KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Recombinant Fusion Proteins -- pharmacology KW - Immunotoxins -- genetics KW - Receptors, Transferrin -- immunology KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76752122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Expression+and+characterization+of+recombinant+human+eosinophil-derived+neurotoxin+and+eosinophil-derived+neurotoxin-anti-transferrin+receptor+sFv.&rft.au=Newton%2C+D+L%3BNicholls%2C+P+J%3BRybak%2C+S+M%3BYoule%2C+R+J&rft.aulast=Newton&rft.aufirst=D&rft.date=1994-10-28&rft.volume=269&rft.issue=43&rft.spage=26739&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 - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cooperative binding of chromosomal protein HMG-14 to nucleosome cores is reduced by single point mutations in the nucleosomal binding domain. AN - 76840446; 7971283 AB - Mutants of human chromosomal protein HMG-14 were generated by site directed mutagenesis and used to study functional domains in this protein. A replacement of serine by cysteine at position 7 did not affect the binding of the protein to nucleosome cores. The sulfhydryl group in the nucleosome-bound protein is accessible to modifying agents suggesting that position 7 in the protein is not in close contact with either the DNA or the histones in the core particles. Under cooperative binding conditions, replacements of alanine by proline at position 21, or of lysine by cysteine at position 26, decreased the affinity of the protein for nucleosome cores 6.7- and 3-fold respectively. In contrast, the non-cooperative mode of binding was only minimally affected. A replacement of glutamic acid by glutamine at position 76 caused only minor changes in the binding of the protein to the cores. The results indicate that single point mutations, which change either the conformation or change in the nucleosomal binding domain of the protein, significantly reduce the ability of the HMG-14 protein to bind to nucleosome cores. We suggest that in chromatin the protein binds to nucleosomes in a cooperative manner and that upon binding to nucleosomes the protein acquires a distinct conformation. JF - Nucleic acids research AU - Postnikov, Y V AU - Lehn, D A AU - Robinson, R C AU - Friedman, F K AU - Shiloach, J AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10/25/ PY - 1994 DA - 1994 Oct 25 SP - 4520 EP - 4526 VL - 22 IS - 21 SN - 0305-1048, 0305-1048 KW - High Mobility Group Proteins KW - 0 KW - Nucleosomes KW - Recombinant Proteins KW - Sulfhydryl Compounds KW - Glutamic Acid KW - 3KX376GY7L KW - Lysine KW - K3Z4F929H6 KW - Cysteine KW - K848JZ4886 KW - Alanine KW - OF5P57N2ZX KW - Iodoacetamide KW - ZRH8M27S79 KW - Index Medicus KW - Lysine -- chemistry KW - Humans KW - Iodoacetamide -- pharmacology KW - Gene Expression KW - Escherichia coli -- genetics KW - Alanine -- chemistry KW - Structure-Activity Relationship KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cysteine -- chemistry KW - Recombinant Proteins -- metabolism KW - Sulfhydryl Compounds -- chemistry KW - Molecular Sequence Data KW - Protein Conformation KW - High Mobility Group Proteins -- chemistry KW - High Mobility Group Proteins -- genetics KW - Nucleosomes -- metabolism KW - Point Mutation KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76840446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=The+cooperative+binding+of+chromosomal+protein+HMG-14+to+nucleosome+cores+is+reduced+by+single+point+mutations+in+the+nucleosomal+binding+domain.&rft.au=Postnikov%2C+Y+V%3BLehn%2C+D+A%3BRobinson%2C+R+C%3BFriedman%2C+F+K%3BShiloach%2C+J%3BBustin%2C+M&rft.aulast=Postnikov&rft.aufirst=Y&rft.date=1994-10-25&rft.volume=22&rft.issue=21&rft.spage=4520&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-19 N1 - Date created - 1994-12-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] EMBO J. 1992 Dec;11(12):4497-506 [1425584] Cell. 1993 Sep 10;74(5):887-98 [8374955] EMBO J. 1993 Oct;12(10):3855-64 [8404854] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] J Biol Chem. 1980 Apr 25;255(8):3673-84 [7364765] Science. 1980 Sep 26;209(4464):1534-6 [7433974] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] Eur J Biochem. 1982 Oct;127(2):429-36 [6216108] J Biol Chem. 1983 Nov 10;258(21):13221-9 [6226664] Chromosoma. 1984;90(5):355-65 [6439496] Exp Cell Res. 1986 Mar;163(1):95-102 [3510889] Methods Enzymol. 1987;155:537-58 [2828876] J Biol Chem. 1989 Jan 25;264(3):1799-803 [2912984] J Biol Chem. 1989 Feb 25;264(6):3421-7 [2563381] J Mol Biol. 1989 Apr 5;206(3):451-63 [2716057] J Biol Chem. 1990 Apr 5;265(10):5736-46 [2180934] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7405-9 [2170977] J Biol Chem. 1990 Nov 25;265(33):20077-80 [2243079] Nucleic Acids Res. 1991 Jun 11;19(11):3115-21 [2057367] Cell. 1992 Nov 27;71(5):777-89 [1330326] Genes Dev. 1993 Aug;7(8):1521-34 [8339930] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transfer of a constitutive viral promoter-cystic fibrosis transmembrane conductance regulator cDNA to human epithelial cells conveys resistance to down-regulation of cAMP-regulated Cl- secretion in the presence of inflammatory stimuli. AN - 76839196; 7526342 AB - The expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be down-regulated by inflammatory stimuli such as phorbol myristate acetate (PMA). Since the respiratory manifestations of cystic fibrosis (CF) are characterized by intense chronic airway inflammation very early in life, successful gene therapy for CF will require that expression of the transferred normal CFTR gene be resistant to down-regulation by inflammatory mediators. To evaluate the concept that a viral promoter--human CFTR cDNA unit would be resistant to this form of down-regulation, a retrovirus promoter (5' long terminal repeat of the Moloney murine leukemia virus)--human CFTR cDNA unit was transferred to T84 human colon carcinoma cell line using a retrovirus vector. Exposure of the retrovirus-modified T84 cells to PMA resulted in down-regulation of the endogenous CFTR mRNA transcripts (6.5 kb), but did not affect the level of exogenous CFTR transcripts (8.0 kb). Importantly, in parallel with the persistence of the exogenous CFTR transcripts, the modified cells still maintained cAMP-regulated CI- secretion in the presence of PMA. These in vitro data suggest that a constitutive viral promoter--CFTR cDNA unit should be resistant to modulation by inflammatory stimuli, a likely requirement for successful gene therapy for CF. JF - Nucleic acids research AU - Kobayashi, N AU - Rosenthal, E R AU - Yoshimura, K AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10/25/ PY - 1994 DA - 1994 Oct 25 SP - 4470 EP - 4476 VL - 22 IS - 21 SN - 0305-1048, 0305-1048 KW - Chlorides KW - 0 KW - DNA, Complementary KW - Membrane Proteins KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Colforsin KW - 1F7A44V6OU KW - Cyclic AMP KW - E0399OZS9N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Promoter Regions, Genetic KW - Colforsin -- pharmacology KW - DNA, Complementary -- genetics KW - Blotting, Northern KW - Tumor Cells, Cultured KW - Gene Transfer Techniques KW - Blotting, Southern KW - Genetic Vectors KW - Epithelium -- metabolism KW - Repetitive Sequences, Nucleic Acid KW - Colonic Neoplasms KW - Cyclic AMP -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Moloney murine leukemia virus -- genetics KW - Gene Expression Regulation -- drug effects KW - Chlorides -- metabolism KW - Membrane Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76839196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Transfer+of+a+constitutive+viral+promoter-cystic+fibrosis+transmembrane+conductance+regulator+cDNA+to+human+epithelial+cells+conveys+resistance+to+down-regulation+of+cAMP-regulated+Cl-+secretion+in+the+presence+of+inflammatory+stimuli.&rft.au=Kobayashi%2C+N%3BRosenthal%2C+E+R%3BYoshimura%2C+K%3BCrystal%2C+R+G&rft.aulast=Kobayashi&rft.aufirst=N&rft.date=1994-10-25&rft.volume=22&rft.issue=21&rft.spage=4470&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-19 N1 - Date created - 1994-12-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1992 Aug 15;267(23):16056-60 [1379589] Science. 1991 Jul 12;253(5016):202-5 [1712984] Cell. 1991 Sep 6;66(5):1027-36 [1716180] J Clin Invest. 1992 Jan;89(1):339-49 [1370301] Cell. 1992 Jan 10;68(1):143-55 [1370653] Cell. 1992 Feb 21;68(4):809-18 [1371239] Mol Cell Biol. 1992 Apr;12(4):1872-8 [1372390] J Clin Invest. 1992 May;89(5):1478-84 [1569186] Science. 1992 May 8;256(5058):774-9 [1375392] J Biol Chem. 1992 Jun 25;267(18):12742-52 [1377674] Nucleic Acids Res. 1992 Jun 25;20(12):3233-40 [1377820] J Clin Invest. 1992 Oct;90(4):1296-301 [1357002] Am J Respir Cell Mol Biol. 1992 Nov;7(5):485-91 [1384582] Am J Physiol. 1993 Jan;264(1 Pt 1):C161-8 [7679250] Nature. 1993 Mar 18;362(6417):250-5 [7681548] Nat Genet. 1992 Aug;1(5):321-7 [1284548] Nat Genet. 1992 Sep;2(1):13-20 [1284640] J Biol Chem. 1993 Jul 5;268(19):13935-9 [7686146] J Biol Chem. 1993 Jul 25;268(21):15336-9 [7687995] Cell. 1993 Oct 22;75(2):207-16 [7691415] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Somatic Cell Genet. 1981 Sep;7(5):603-16 [7292260] Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Science. 1986 Dec 19;234(4783):1552-7 [3491428] Nature. 1987 Dec 24-31;330(6150):752-4 [2447502] Nature. 1988 Jan 28;331(6154):358-60 [2448645] Science. 1989 Jun 16;244(4910):1351-3 [2472005] Science. 1989 Sep 8;245(4922):1059-65 [2772657] Science. 1989 Sep 8;245(4922):1066-73 [2475911] J Virol. 1990 Feb;64(2):543-50 [2104942] Proc Natl Acad Sci U S A. 1990 May;87(10):4012-6 [1692630] Am J Physiol. 1990 Aug;259(2 Pt 1):C358-64 [1696431] Cell. 1990 Sep 21;62(6):1227-33 [1698126] J Biol Chem. 1990 Oct 5;265(28):17285-93 [2170370] Nature. 1990 Sep 27;347(6291):358-63 [1699126] Cell. 1990 Nov 16;63(4):827-34 [1699669] Lancet. 1991 Feb 16;337(8738):392-4 [1671425] Science. 1991 Feb 8;251(4994):679-82 [1704151] Cell. 1991 Feb 22;64(4):681-91 [1705179] J Biol Chem. 1991 May 15;266(14):9140-4 [1709163] J Biol Chem. 1991 Jun 5;266(16):10319-23 [2037584] Genomics. 1991 May;10(1):214-28 [1710598] Science. 1992 Sep 18;257(5077):1701-4 [1382316] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylphosphonodiester substitution near the conserved CA dinucleotide in the HIV LTR alters both extent of 3'-processing and choice of nucleophile by HIV-1 integrase. AN - 76839157; 7971274 AB - We present evidence suggesting that the 3'-processing activity of HIV-1 integrase is dramatically affected by electrostatic and/or steric perturbations 3' to the conserved CA dinucleotide. When the phosphodiester bond 3' to the scissile phosphodiester is replaced by a methylphosphonodiester linkage, 3'-processing decreases by two orders of magnitude. This block of cleavage can be somewhat overcome by increasing the pH of the reaction. Labeling of the substrates at the 3'-end revealed blockage of water and glycerol, but stimulation of the viral DNA 3'-hydroxyl, acting as the nucleophile with the methylphosphonodiester substrate. Interestingly, a circular trinucleotide was formed using the phosphodiester and methylphosphonodiester substrates when the terminal nucleotide was 3'-deoxyadenosine but not 2'-deoxyadenosine. Mutagenesis of the enzyme active site has previously been shown to alter the choice of nucleophile in the 3'-processing reaction. Taken together, the results in this study suggest that 'mutagenesis' of the DNA backbone can also alter the choice of nucleophile. JF - Nucleic acids research AU - Mazumder, A AU - Gupta, M AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/10/25/ PY - 1994 DA - 1994 Oct 25 SP - 4441 EP - 4448 VL - 22 IS - 21 SN - 0305-1048, 0305-1048 KW - DNA, Viral KW - 0 KW - Deoxyadenosines KW - Oligodeoxyribonucleotides KW - Organophosphorus Compounds KW - Manganese KW - 42Z2K6ZL8P KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - cordycepin KW - GZ8VF4M2J8 KW - 2'-deoxyadenosine KW - P582C98ULC KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - AIDS/HIV KW - Stereoisomerism KW - Hydrogen-Ion Concentration KW - Deoxyadenosines -- chemistry KW - Deoxyadenosines -- metabolism KW - Structure-Activity Relationship KW - Base Sequence KW - Conserved Sequence KW - Kinetics KW - Molecular Sequence Data KW - Substrate Specificity KW - Electrochemistry KW - DNA, Viral -- metabolism KW - HIV-1 -- genetics KW - HIV Long Terminal Repeat KW - Oligodeoxyribonucleotides -- chemistry KW - Organophosphorus Compounds -- chemistry KW - HIV-1 -- enzymology KW - Oligodeoxyribonucleotides -- metabolism KW - DNA Nucleotidyltransferases -- chemistry KW - DNA Nucleotidyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76839157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Methylphosphonodiester+substitution+near+the+conserved+CA+dinucleotide+in+the+HIV+LTR+alters+both+extent+of+3%27-processing+and+choice+of+nucleophile+by+HIV-1+integrase.&rft.au=Mazumder%2C+A%3BGupta%2C+M%3BPommier%2C+Y&rft.aulast=Mazumder&rft.aufirst=A&rft.date=1994-10-25&rft.volume=22&rft.issue=21&rft.spage=4441&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-19 N1 - Date created - 1994-12-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1994 Mar;68(3):1468-74 [8107210] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11633-7 [8265600] Trends Genet. 1993 Dec;9(12):433-8 [8122311] J Virol. 1994 Jun;68(6):3558-69 [8189495] J Virol. 1994 Jun;68(6):3896-907 [8189526] Annu Rev Biochem. 1994;63:133-73 [7526778] Cell. 1984 Jul;37(3):1043-52 [6204767] Virology. 1984 Sep;137(2):358-70 [6091334] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6461-5 [6208550] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7885-9 [6083562] Biochemistry. 1985 Jul 16;24(15):4041-6 [2413882] Cell. 1987 May 8;49(3):347-56 [3032450] Anticancer Drug Des. 1987 Oct;2(2):117-28 [3329522] Cell. 1988 Aug 12;54(4):497-504 [3401925] Cell. 1989 Jul 14;58(1):47-54 [2546673] J Virol. 1989 Dec;63(12):5319-27 [2555556] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5119-23 [2164223] J Acquir Immune Defic Syndr. 1990;3(9):839-51 [2166782] Cell. 1990 Aug 24;62(4):829-37 [2167180] Cell. 1990 Oct 5;63(1):87-95 [2170022] J Virol. 1990 Nov;64(11):5626-7 [2214029] J Virol. 1990 Nov;64(11):5656-9 [2214031] Science. 1990 Sep 28;249(4976):1555-8 [2171144] Nucleic Acids Res. 1990 Oct 25;18(20):6045-7 [2235486] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] J Virol. 1991 Sep;65(9):4636-44 [1870194] Cell. 1991 Dec 20;67(6):1211-21 [1760846] Nucleic Acids Res. 1991 Dec 25;19(24):6691-8 [1662361] Science. 1992 Feb 7;255(5045):723-6 [1738845] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3458-62 [1533044] J Virol. 1992 Jun;66(6):3593-601 [1374809] Antisense Res Dev. 1991 Fall;1(3):243-54 [1821645] J Biol Chem. 1992 Oct 25;267(30):21273-6 [1383220] J Mol Biol. 1993 Mar 5;230(1):111-23 [8450529] Nucleic Acids Res. 1993 Jul 25;21(15):3373-7 [8346016] J Biomol Struct Dyn. 1993 Jun;10(6):1023-45 [8357540] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8499-503 [8378323] J Virol. 1993 Dec;67(12):7077-87 [8230431] Biochemistry. 1994 Mar 8;33(9):2349-55 [8117693] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets. AN - 76784055; 7938008 AB - The NADPH oxidase responsible for generation of superoxide anion and related microbicidal oxidants by phagocytes is assembled from at least five distinct proteins. Two are cytosolic components (p47-phox and p67-phox) that contain Src homology 3 (SH3) domains and associate with a transmembrane cytochrome b558 upon activation. We show here that the SH3 domains of p47-phox bind to proline-rich sequences in p47-phox itself and the p22-phox subunit of cytochrome b558. Binding of the p47-phox SH3 domains to p22-phox was abolished by a mutation in one proline-rich sequence (Pro156-->Gln) noted in a distinct form of chronic granulomatous disease and was inhibited by a short proline-rich synthetic peptide corresponding to residues 149-162 of p22-phox. Expression of mutated p22-phox did not restore oxidase activity to p22-phox-deficient B cells and did not enable p22-phox-dependent translocation of p47-phox to membranes in phorbol ester-stimulated cells. We also show that the cytosolic oxidase components associate with one another through the C-terminal SH3 domain of p67-phox and a proline-rich C-terminal sequence in p47-phox. These SH3 target sites conform to consensus features deduced from SH3 binding sites in other systems. We propose a model in which the oxidase complex assembles through a mechanism involving SH3 domains of both cytosolic proteins and cognate proline-rich targets in other oxidase components. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Leto, T L AU - Adams, A G AU - de Mendez, I AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10/25/ PY - 1994 DA - 1994 Oct 25 SP - 10650 EP - 10654 VL - 91 IS - 22 SN - 0027-8424, 0027-8424 KW - Cytochrome b Group KW - 0 KW - DNA Primers KW - Phosphoproteins KW - Recombinant Proteins KW - neutrophil cytosol factor 67K KW - cytochrome b558 KW - 9064-78-2 KW - Proline KW - 9DLQ4CIU6V KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - NADPH Oxidase KW - EC 1.6.3.1 KW - neutrophil cytosolic factor 1 KW - NADPH Dehydrogenase KW - EC 1.6.99.1 KW - Index Medicus KW - Cytochrome b Group -- metabolism KW - Animals KW - Genes, src KW - Recombinant Proteins -- biosynthesis KW - Spodoptera KW - Humans KW - B-Lymphocytes -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Point Mutation KW - Sequence Homology, Amino Acid KW - Enzyme Activation KW - Amino Acid Sequence KW - Granulomatous Disease, Chronic -- genetics KW - Protein Binding KW - Binding Sites KW - Polymerase Chain Reaction KW - Transfection KW - Granulomatous Disease, Chronic -- metabolism KW - Consensus Sequence KW - Cell Line KW - NADPH Dehydrogenase -- metabolism KW - NADH, NADPH Oxidoreductases -- biosynthesis KW - Phagocytes -- enzymology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76784055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assembly+of+the+phagocyte+NADPH+oxidase%3A+binding+of+Src+homology+3+domains+to+proline-rich+targets.&rft.au=Leto%2C+T+L%3BAdams%2C+A+G%3Bde+Mendez%2C+I&rft.aulast=Leto&rft.aufirst=T&rft.date=1994-10-25&rft.volume=91&rft.issue=22&rft.spage=10650&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 - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1992 Oct 30;71(3):359-62 [1423600] J Biol Chem. 1992 Sep 25;267(27):19072-4 [1326544] Nature. 1993 May 6;363(6424):83-5 [8479540] Nature. 1993 May 6;363(6424):85-8 [8479541] Biochemistry. 1993 Jun 1;32(21):5711-7 [8504089] EMBO J. 1993 Jul;12(7):2625-34 [7687537] Cell. 1993 Oct 8;75(1):25-36 [8402898] Immunogenetics. 1994;39(4):272-5 [8119734] Cell. 1994 Mar 11;76(5):933-45 [7510218] J Biol Chem. 1994 Jun 10;269(23):16326-32 [8206939] Nature. 1986 Jul 3-9;322(6074):32-8 [2425263] Proc Natl Acad Sci U S A. 1988 May;85(10):3319-23 [3368442] Science. 1989 Jul 28;245(4916):409-12 [2547247] Proc Natl Acad Sci U S A. 1989 Sep;86(18):7195-9 [2550933] J Clin Invest. 1990 Mar;85(3):714-21 [2155923] Science. 1990 May 11;248(4956):727-30 [1692159] J Biol Chem. 1990 May 25;265(15):8745-50 [2160466] J Biol Chem. 1990 Nov 15;265(32):19910-5 [2246268] J Clin Invest. 1991 Jan;87(1):352-6 [1985107] J Biol Chem. 1991 Oct 15;266(29):19812-8 [1918085] Nature. 1991 Oct 17;353(6345):668-70 [1922386] Science. 1991 Dec 6;254(5037):1512-5 [1660188] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11231-5 [1763037] J Biol Chem. 1992 May 25;267(15):10215-8 [1316893] Science. 1992 Jun 5;256(5062):1459-62 [1318579] Science. 1992 Aug 7;257(5071):803-6 [1379745] J Biol Chem. 1992 Aug 25;267(24):16767-70 [1512217] Science. 1993 Feb 19;259(5098):1157-61 [8438166] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic effects of a chimeric protein consisting of tetanus toxin light chain and anthrax toxin lethal factor in non-neuronal cells. AN - 76747262; 7929330 AB - The light chain of tetanus toxin is a zinc endoprotease that inhibits neurotransmitter release by selective proteolysis of the synaptic vesicle-associated protein synaptobrevin/vesicle-associated membrane protein. Cellubrevin is a homologue of synaptobrevin that is found in most cell types and is also a substrate for tetanus toxin. The lack of receptors for tetanus toxin on most cell types has made studies of tetanus toxin action in non-neuronal cells difficult. To characterize tetanus toxin effects in non-neuronal cells, a fusion protein consisting of the 254 amino-terminal amino acids of lethal factor (LF) of anthrax toxin and tetanus toxin light chain (LC) was prepared. This protein (LF-LC) inhibited evoked glycine release from primary spinal cord neurons at concentrations between 1.0 and 100 ng/ml. LF-LC was cytotoxic to RAW 264.7, ANA-1 cells (mouse macrophage cell lines), and Chinese hamster ovary cells in a dose-dependent manner. These effects required the presence of protective antigen, the receptor binding component of anthrax toxin. In contrast, LF-LC was not cytotoxic to RBL-2H3, Vero, or mouse hybridoma cell lines. Mutagenesis of conserved amino acids (His237 and Glu234) in the zinc-binding motif of LC resulted in fusion proteins having no biological activity. LF-LC did not inhibit regulated secretion of serotonin in RBL-2H3 cells or constitutive secretion in any non-neuronal cell lines as measured in several different assays. We suggest that the cytotoxic effects of LF-LC result from inhibition of a specific intracellular membrane fusion event mediated by cellubrevin. JF - The Journal of biological chemistry AU - Arora, N AU - Williamson, L C AU - Leppla, S H AU - Halpern, J L AD - Laboratory of Microbial Ecology, NIDR, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/21/ PY - 1994 DA - 1994 Oct 21 SP - 26165 EP - 26171 VL - 269 IS - 42 SN - 0021-9258, 0021-9258 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Recombinant Fusion Proteins KW - Tetanus Toxin KW - anthrax toxin KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Neurons -- drug effects KW - Zinc -- metabolism KW - Molecular Sequence Data KW - CHO Cells KW - Mice KW - Cricetinae KW - Tetanus Toxin -- toxicity KW - Bacterial Toxins -- toxicity KW - Recombinant Fusion Proteins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76747262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxic+effects+of+a+chimeric+protein+consisting+of+tetanus+toxin+light+chain+and+anthrax+toxin+lethal+factor+in+non-neuronal+cells.&rft.au=Arora%2C+N%3BWilliamson%2C+L+C%3BLeppla%2C+S+H%3BHalpern%2C+J+L&rft.aulast=Arora&rft.aufirst=N&rft.date=1994-10-21&rft.volume=269&rft.issue=42&rft.spage=26165&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 - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Helicobacter and human cancer. AN - 76753737; 7932804 JF - Journal of the National Cancer Institute AU - Nightingale, T E AU - Gruber, J AD - Biological Carcinogenesis Branch, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/10/19/ PY - 1994 DA - 1994 Oct 19 SP - 1505 EP - 1509 VL - 86 IS - 20 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Stomach Neoplasms -- microbiology KW - Neoplasms, Experimental -- microbiology KW - Liver Neoplasms -- microbiology KW - Animals KW - Humans KW - Helicobacter pylori KW - Helicobacter Infections -- complications KW - Neoplasms -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76753737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Helicobacter+and+human+cancer.&rft.au=Nightingale%2C+T+E%3BGruber%2C+J&rft.aulast=Nightingale&rft.aufirst=T&rft.date=1994-10-19&rft.volume=86&rft.issue=20&rft.spage=1505&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 - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Capillaritis (purpura simplex) associated with use of aminoglutethimide in Cushing's syndrome. AN - 77725995; 7847422 JF - American journal of hospital pharmacy AU - Stratakis, C A AU - Chrousos, G P AD - National Institutes of Health/Georgetown University Fellowship Program, Bethesda, MD. Y1 - 1994/10/15/ PY - 1994 DA - 1994 Oct 15 SP - 2589 EP - 2591 VL - 51 IS - 20 SN - 0002-9289, 0002-9289 KW - Aminoglutethimide KW - 0O54ZQ14I9 KW - Index Medicus KW - Humans KW - Middle Aged KW - Time Factors KW - Female KW - Purpura -- chemically induced KW - Drug Eruptions -- etiology KW - Cushing Syndrome -- drug therapy KW - Aminoglutethimide -- therapeutic use KW - Aminoglutethimide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77725995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hospital+pharmacy&rft.atitle=Capillaritis+%28purpura+simplex%29+associated+with+use+of+aminoglutethimide+in+Cushing%27s+syndrome.&rft.au=Stratakis%2C+C+A%3BChrousos%2C+G+P&rft.aulast=Stratakis&rft.aufirst=C&rft.date=1994-10-15&rft.volume=51&rft.issue=20&rft.spage=2589&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hospital+pharmacy&rft.issn=00029289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-09 N1 - Date created - 1995-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NF-kappa B/Rel family members are physically associated phosphoproteins. AN - 76860314; 7980409 AB - We performed radioimmunoprecipitation followed by serial immunoblots to show that, in the unstimulated Jurkat T cell line, the NF-kappa B/Rel family proteins, p80-c-Rel, p105-NF-kappa B, p65-NF-kappa B, p50-NF-kappa B and p36-I kappa B alpha, can be detected as complexes using antisera against c-Rel, p105-NF-kappa B or p65-NF-kappa B. p36-I kappa B alpha and p105, both known inhibitors of NF-kappa B function, can physically associate with NF-kappa B/Rel family members, but not with each other. In vivo and in vitro phosphorylation experiments demonstrated that NF-kappa B/Rel family members, including p105, c-Rel, p50, p65 (for the first time for p50 and p65) and p36-I kappa B alpha are also phosphoproteins. Phosphoserine and phosphothreonine residues were identified in these proteins isolated from unstimulated Jurkat cells. Both unphosphorylated and hyperphosphorylated forms of p36-I kappa B alpha were found in the complexes, suggesting that hyperphosphorylated I kappa B alpha is still capable of associating with the NF-kappa B/Rel family members. After stimulation with phorbol 12-myristate 13-acetate and phytohaemagglutinin for 10 min, p105-NF-kappa B and p50-NF-kappa B, but not p36-I kappa B, were highly phosphorylated. Phosphopeptide mapping of p105 showed that phorbol ester/phytohaemagglutinin stimulation may change p105 phosphorylation qualitatively. JF - The Biochemical journal AU - Li, C C AU - Korner, M AU - Ferris, D K AU - Chen, E AU - Dai, R M AU - Longo, D L AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp., NCI-Frederick Cancer Research and Development Center 21702-1201. Y1 - 1994/10/15/ PY - 1994 DA - 1994 Oct 15 SP - 499 EP - 506 VL - 303 ( Pt 2) SN - 0264-6021, 0264-6021 KW - Immune Sera KW - 0 KW - NF-kappa B KW - Proto-Oncogene Proteins KW - Transcription Factors KW - Transcription Factor RelB KW - 147337-75-5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Peptide Mapping KW - Electrophoresis, Polyacrylamide Gel KW - Immune Sera -- immunology KW - Cross Reactions KW - Molecular Weight KW - Blotting, Western KW - Phosphorylation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - T-Lymphocytes -- drug effects KW - Cell Line KW - Radioimmunoprecipitation Assay KW - NF-kappa B -- chemistry KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- immunology KW - NF-kappa B -- immunology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76860314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=NF-kappa+B%2FRel+family+members+are+physically+associated+phosphoproteins.&rft.au=Li%2C+C+C%3BKorner%2C+M%3BFerris%2C+D+K%3BChen%2C+E%3BDai%2C+R+M%3BLongo%2C+D+L&rft.aulast=Li&rft.aufirst=C&rft.date=1994-10-15&rft.volume=303+%28+Pt+2%29&rft.issue=&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-30 N1 - Date created - 1994-11-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] Cell. 1992 Oct 16;71(2):243-53 [1423592] Cell. 1986 Aug 29;46(5):705-16 [3091258] J Virol. 1987 Sep;61(9):2684-90 [3039162] Oncogene. 1992 Nov;7(11):2095-104 [1437141] EMBO J. 1993 Jan;12(1):213-22 [8428580] Science. 1993 Mar 26;259(5103):1912-5 [8096091] Genes Dev. 1993 Apr;7(4):705-18 [8458581] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532-6 [8460169] Mol Cell Biol. 1993 Jun;13(6):3301-10 [8497253] J Virol. 1993 Jul;67(7):4205-13 [8510222] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2479-83 [3357877] Cell. 1988 Apr 22;53(2):211-7 [3129195] Science. 1988 Oct 28;242(4878):540-6 [3140380] J Virol. 1988 Dec;62(12):4730-6 [2846883] Oncogene. 1989 Jun;4(6):677-83 [2543940] J Biol Chem. 1989 Jul 25;264(21):12562-7 [2787319] Cell. 1989 Jul 28;58(2):227-9 [2665943] J Virol. 1990 Feb;64(2):584-91 [2153225] Virology. 1990 Mar;175(1):149-60 [2155506] Nature. 1990 Apr 12;344(6267):678-82 [2157987] Cell. 1990 Apr 20;61(2):255-65 [2184941] Oncogene. 1990 Aug;5(8):1109-15 [2202947] Genes Dev. 1990 Nov;4(11):1975-84 [2125960] Biochim Biophys Acta. 1991 Apr 16;1072(1):63-80 [2018779] Oncogene. 1991 Apr;6(4):615-26 [1851550] Cell. 1991 Jun 28;65(7):1281-9 [1829648] Genes Dev. 1991 Aug;5(8):1464-76 [1907941] Science. 1991 Sep 13;253(5025):1268-71 [1891714] Mol Cell Biol. 1991 Dec;11(12):5867-77 [1944267] J Biol Chem. 1992 Jan 5;267(1):239-46 [1309735] Trends Genet. 1991 Oct;7(10):318-22 [1781029] Trends Biochem Sci. 1992 Apr;17(4):135-40 [1533967] EMBO J. 1992 Aug;11(8):3003-9 [1639070] Nature. 1992 Aug 13;358(6387):597-9 [1501714] J Biol Chem. 1977 Feb 10;252(3):1102-6 [320200] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted deletion of the TGF-beta 1 gene causes rapid progression to squamous cell carcinoma. AN - 76815160; 7958907 AB - To study the contribution of autocrine and paracrine TGF-beta 1 to tumor progression in a well-defined system of multistage carcinogenesis, keratinocytes with a targeted deletion of the TGF-beta 1 gene were initiated in vitro with the v-rasHa oncogene and their in vivo tumorigenic properties were determined by skin grafting initiated cells onto athymic mice in combination with either wild-type or null dermal fibroblasts. Grafts of v-rasHa-initiated null keratinocytes progressed rapidly to multifocal squamous cell carcinomas within dysplastic papillomas irrespective of the fibroblast genotype, whereas the initiated control genotypes formed well-differentiated papillomas. Malignant progression was not associated with mutations in the c-rasHa gene, alterations in p53 protein, or loss of responsiveness to TGF-beta 1. The tumor cell labeling index was elevated in grafts of initiated null keratinocytes with wild-type fibroblasts compared to tumors of other genotypes. However, labeling index in all tumors was reduced when TGF-beta 1 null fibroblasts formed the stroma. The null tumor cells could not accumulate TGF-beta 1 from the host, but grafts of uninitiated null keratinocytes, which formed a normal epidermis, became TGF-beta 1 positive even though they did not express TGF-beta 1 mRNA. These results demonstrate that autocrine TGF-beta 1 suppresses the frequency and rate of malignant progression, and that autocrine and paracrine TGF-beta 1 can have opposing effects on tumor cell proliferation. The lack of paracrine inhibition of tumor cell progression appears to result from the inability of tumor cells to localize host-derived TGF-beta 1 by a mechanism that operates in normal cells. JF - Genes & development AU - Glick, A B AU - Lee, M M AU - Darwiche, N AU - Kulkarni, A B AU - Karlsson, S AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/15/ PY - 1994 DA - 1994 Oct 15 SP - 2429 EP - 2440 VL - 8 IS - 20 SN - 0890-9369, 0890-9369 KW - TGF-beta 1 KW - c-ras KW - p53 KW - v-rasHa KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - RNA, Messenger KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - DNA Primers -- genetics KW - Gene Expression KW - Skin Transplantation KW - Mice, Nude KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Genes, ras KW - Polymerase Chain Reaction KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Genes, p53 KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Keratinocytes -- metabolism KW - Cell Division KW - Skin Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- pathology KW - Skin Neoplasms -- etiology KW - Carcinoma, Squamous Cell -- genetics KW - Skin Neoplasms -- pathology KW - Transforming Growth Factor beta -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76815160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=Targeted+deletion+of+the+TGF-beta+1+gene+causes+rapid+progression+to+squamous+cell+carcinoma.&rft.au=Glick%2C+A+B%3BLee%2C+M+M%3BDarwiche%2C+N%3BKulkarni%2C+A+B%3BKarlsson%2C+S%3BYuspa%2C+S+H&rft.aulast=Glick&rft.aufirst=A&rft.date=1994-10-15&rft.volume=8&rft.issue=20&rft.spage=2429&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-02 N1 - Date created - 1994-12-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TGF-beta 1; c-ras; p53; v-rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - National Cancer Institute (phase II) study of high-grade glioma treated with accelerated hyperfractionated radiation and iododeoxyuridine: results in anaplastic astrocytoma. AN - 76745313; 7928489 AB - We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m2 per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-down field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity. JF - International journal of radiation oncology, biology, physics AU - Sullivan, F J AU - Herscher, L L AU - Cook, J A AU - Smith, J AU - Steinberg, S M AU - Epstein, A H AU - Oldfield, E H AU - Goffman, T E AU - Kinsella, T J AU - Mitchell, J B AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/10/15/ PY - 1994 DA - 1994 Oct 15 SP - 583 EP - 590 VL - 30 IS - 3 SN - 0360-3016, 0360-3016 KW - Radiation-Sensitizing Agents KW - 0 KW - Idoxuridine KW - LGP81V5245 KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Astrocytoma -- radiotherapy KW - Astrocytoma -- surgery KW - Glioblastoma -- radiotherapy KW - Brain Neoplasms -- surgery KW - Brain Neoplasms -- radiotherapy KW - Glioblastoma -- surgery KW - Idoxuridine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76745313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=National+Cancer+Institute+%28phase+II%29+study+of+high-grade+glioma+treated+with+accelerated+hyperfractionated+radiation+and+iododeoxyuridine%3A+results+in+anaplastic+astrocytoma.&rft.au=Sullivan%2C+F+J%3BHerscher%2C+L+L%3BCook%2C+J+A%3BSmith%2C+J%3BSteinberg%2C+S+M%3BEpstein%2C+A+H%3BOldfield%2C+E+H%3BGoffman%2C+T+E%3BKinsella%2C+T+J%3BMitchell%2C+J+B&rft.aulast=Sullivan&rft.aufirst=F&rft.date=1994-10-15&rft.volume=30&rft.issue=3&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-03 N1 - Date created - 1994-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure. AN - 76739775; 7923161 AB - Isoprene, the 2-methyl analogue of 1,3-butadiene, is a high production chemical used largely in the manufacture of synthetic rubber and is the major endogenous hydrocarbon exhaled in human breath. Thirteen-week inhalation toxicology studies of isoprene were conducted in male and female F344 rats and B6C3F1 mice at exposure concentrations of 0, 70, 220, 700, 2200, and 7000 ppm (6 h/day; 5 days/week). In addition, 26-week inhalation studies at the same exposure levels, followed by a 26-week recovery period, were conducted in male rats and mice. The 13-week exposures produced no discernible exposure-related toxic effects in rats. Interstitial cell hyperplasia of the testis was observed in all male rats in the 7000 ppm group after 26 weeks of exposure; following the 26-week recovery period the only effect in rats was a marginal increase in benign testicular interstitial cell tumors. In mice, isoprene induced toxic and carcinogenic effects at multiple organ sites. Following the 26-week exposure and 26-week recovery periods, incidences of neoplastic lesions in the liver, lung, forestomach, and harderian gland were significantly increased. Neoplastic effects were observed at 700 ppm and higher exposures. Non-neoplastic lesions in mice exposed to isoprene included spinal cord degeneration, testicular atrophy, degeneration of the olfactory epithelium, and epithelial hyperplasia of the forestomach. A partial hindlimb paralysis and a nonresponsive macrocytic anemia were also seen in mice. Most of the toxic and carcinogenic effects caused by isoprene, as well as the species' difference in response, had been observed after inhalation exposures to 1,3-butadiene. JF - Cancer research AU - Melnick, R L AU - Sills, R C AU - Roycroft, J H AU - Chou, B J AU - Ragan, H A AU - Miller, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10/15/ PY - 1994 DA - 1994 Oct 15 SP - 5333 EP - 5339 VL - 54 IS - 20 SN - 0008-5472, 0008-5472 KW - Butadienes KW - 0 KW - Hemiterpenes KW - Pentanes KW - isoprene KW - 0A62964IBU KW - Index Medicus KW - Animals KW - Sex Factors KW - Testis -- pathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Rats KW - Hyperplasia -- chemically induced KW - Rats, Inbred F344 KW - Testis -- drug effects KW - Stomach Neoplasms -- chemically induced KW - Harderian Gland -- drug effects KW - Lung Neoplasms -- chemically induced KW - Administration, Inhalation KW - Time Factors KW - Female KW - Male KW - Neoplasms, Multiple Primary -- pathology KW - Carcinoma -- pathology KW - Butadienes -- toxicity KW - Adenoma -- chemically induced KW - Butadienes -- administration & dosage KW - Neoplasms, Multiple Primary -- chemically induced KW - Adenoma -- pathology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76739775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isoprene%2C+an+endogenous+hydrocarbon+and+industrial+chemical%2C+induces+multiple+organ+neoplasia+in+rodents+after+26+weeks+of+inhalation+exposure.&rft.au=Melnick%2C+R+L%3BSills%2C+R+C%3BRoycroft%2C+J+H%3BChou%2C+B+J%3BRagan%2C+H+A%3BMiller%2C+R+A&rft.aulast=Melnick&rft.aufirst=R&rft.date=1994-10-15&rft.volume=54&rft.issue=20&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 - 1994-11-03 N1 - Date created - 1994-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metal oxyanion stabilization of the rat glucocorticoid receptor is independent of thiols. AN - 76751787; 7929266 AB - The ability of sodium molybdate, both to stabilize the steroid binding activity of glucocorticoid receptors and to prevent the activation of receptor-steroid complexes to a DNA binding species, has long been thought to involve thiols. Two receptor thiols in particular, Cys-656 and Cys-661 of rat receptors, have been suspected. The requirements for the action of molybdate, as well as two other metal oxyanions (tungstate and vanadate) known to exert the same effects as molybdate, have now been examined with receptors in which these thiols, or a third cysteine in the steroid binding cavity (Cys-640), have been mutated to serine. No mutation prevented any metal oxyanion from either stabilizing steroid-free receptors or blocking the activation of complexes for binding to nonspecific or specific DNA sequences. Thus, Cys-640, Cys-656, and Cys-661 are not required for any of the effects of molybdate, tungstate, or vanadate with rat glucocorticoid receptors. Studies with hybrid receptors, and with a 16-kDa steroid binding core fragment containing only 3 cysteines at positions 640, 656, and 661, indicated that no cysteine of the rat receptor was needed to maintain responsiveness to molybdate. Even when all of the thiol groups in crude cytosol were blocked by reaction with excess methyl methanethiol-sulfonate, each metal oxyanion was still able to stabilize the steroid binding of receptors. These results argue that molybdate, tungstate, and vanadate each interact with the receptor or an associated nonreceptor protein(s) in a manner that does not require thiols. An indirect mechanism of molybdate action was evaluated in light of the recent report that the whole cell actions are mediated by increased levels of intracellular cGMP. Under cell-free conditions, however, the effects of molybdate could not be reproduced by cGMP derivatives. Evidence consistent with a direct effect was that molybdate, tungstate, or vanadate each modified the kinetics of proteolysis of wild type receptors at 0 degrees C by trypsin, presumably due to induced conformational changes of the receptor. This alteration of trypsin digestion constitutes yet another effect of metal oxyanions on the glucocorticoid receptor. JF - The Journal of biological chemistry AU - Modarress, K J AU - Cavanaugh, A H AU - Chakraborti, P K AU - Simons, S S AD - Steroid Hormones Section, NIDDK/LMCB, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/14/ PY - 1994 DA - 1994 Oct 14 SP - 25621 EP - 25628 VL - 269 IS - 41 SN - 0021-9258, 0021-9258 KW - Affinity Labels KW - 0 KW - Anions KW - Peptide Fragments KW - Receptors, Glucocorticoid KW - Sulfhydryl Compounds KW - Tungsten Compounds KW - molybdate KW - 14259-85-9 KW - methyl methanethiosulfonate KW - 2949-92-0 KW - Vanadates KW - 3WHH0066W5 KW - Dexamethasone KW - 7S5I7G3JQL KW - Molybdenum KW - 81AH48963U KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Trypsin KW - EC 3.4.21.4 KW - Cyclic GMP KW - H2D2X058MU KW - Cysteine KW - K848JZ4886 KW - dexamethasone 21-methanesulfonate KW - O9S11FMA79 KW - tungstate KW - SW0Y0WQ46I KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Cysteine -- metabolism KW - Sulfhydryl Compounds -- metabolism KW - Cysteine -- genetics KW - Anions -- pharmacology KW - Methyl Methanesulfonate -- analogs & derivatives KW - Structure-Activity Relationship KW - Methyl Methanesulfonate -- pharmacology KW - Rats KW - Base Sequence KW - Molecular Sequence Data KW - Trypsin -- metabolism KW - Mutation KW - Cyclic GMP -- analogs & derivatives KW - Dexamethasone -- analogs & derivatives KW - Tungsten Compounds -- pharmacology KW - Receptors, Glucocorticoid -- drug effects KW - Dexamethasone -- metabolism KW - Molybdenum -- pharmacology KW - Vanadates -- pharmacology KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76751787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metal+oxyanion+stabilization+of+the+rat+glucocorticoid+receptor+is+independent+of+thiols.&rft.au=Modarress%2C+K+J%3BCavanaugh%2C+A+H%3BChakraborti%2C+P+K%3BSimons%2C+S+S&rft.aulast=Modarress&rft.aufirst=K&rft.date=1994-10-14&rft.volume=269&rft.issue=41&rft.spage=25621&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 - 1994-11-17 N1 - Date created - 1994-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells. Activation of P-glycoprotein as a putative mechanism. AN - 76782899; 7945444 AB - Since P-glycoprotein (P-gp) in normal tissues may serve as a cellular defense mechanism against naturally occurring xenobiotics, we considered whether physiologically active components of commonly ingested plant foods could influence P-gp function. To examine this possibility, a series of flavonoids commonly found in plant foods was tested for their ability to modulate [14C]Adriamycin ([14C]ADR) accumulation and efflux in P-gp-expressing HCT-15 colon cells. Many flavonoids, in the micromolar range, inhibited the accumulation of [14C]ADR. Detailed experiments utilizing flavonoids with the greatest activity in reducing [14C]ADR accumulation, i.e. galangin, kaempferol, and quercetin, revealed that the efflux of [14C]ADR is increased markedly in the presence of these compounds. Flavonoid-induced stimulation of efflux was rapid and was blocked by the multidrug-resistant (MDR) reversal agents verapamil, vinblastine, and quinidine. The magnitude of flavonoid-stimulated efflux in sodium butyrate-treated cells with a 4-fold induction of P-gp protein was similar to that in uninduced cells. [3H]Azidopine photoaffinity labeling of P-gp in crude membrane preparations revealed mild to no competition for binding by flavonoids possessing either activity or inactivity in reducing ADR accumulation. Although flavonoid hydrophobicity was found to be unrelated to flavonoid activity in altering [14C]ADR accumulation, certain structural features were associated with enhancement or diminution of activity. Finally, the significance of flavonoid-related reduction of [14C]ADR accumulation was underscored in cell growth studies, showing partial protection by quercetin against ADR-induced growth inhibition. It is concluded that certain naturally occurring plant flavonoids may acutely upregulate the apparent activity of P-gp. JF - Biochemical pharmacology AU - Critchfield, J W AU - Welsh, C J AU - Phang, J M AU - Yeh, G C AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, NIH, Frederick, MD 21702. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 1437 EP - 1445 VL - 48 IS - 7 SN - 0006-2952, 0006-2952 KW - Butyrates KW - 0 KW - Flavonoids KW - Kaempferols KW - P-Glycoprotein KW - Butyric Acid KW - 107-92-6 KW - galangin KW - 142FWE6ECS KW - Vinblastine KW - 5V9KLZ54CY KW - kaempferol KW - 731P2LE49E KW - Doxorubicin KW - 80168379AG KW - Quercetin KW - 9IKM0I5T1E KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Vinblastine -- pharmacology KW - Drug Interactions KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Butyrates -- pharmacology KW - Cell Division -- drug effects KW - Diet KW - Verapamil -- pharmacology KW - Cell Line KW - Structure-Activity Relationship KW - Doxorubicin -- metabolism KW - P-Glycoprotein -- metabolism KW - Quercetin -- analogs & derivatives KW - Doxorubicin -- toxicity KW - Flavonoids -- pharmacology KW - Quercetin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76782899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Modulation+of+adriamycin+accumulation+and+efflux+by+flavonoids+in+HCT-15+colon+cells.+Activation+of+P-glycoprotein+as+a+putative+mechanism.&rft.au=Critchfield%2C+J+W%3BWelsh%2C+C+J%3BPhang%2C+J+M%3BYeh%2C+G+C&rft.aulast=Critchfield&rft.aufirst=J&rft.date=1994-10-07&rft.volume=48&rft.issue=7&rft.spage=1437&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BRCA1 mutations in primary breast and ovarian carcinomas. AN - 76776943; 7939630 AB - Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele. JF - Science (New York, N.Y.) AU - Futreal, P A AU - Liu, Q AU - Shattuck-Eidens, D AU - Cochran, C AU - Harshman, K AU - Tavtigian, S AU - Bennett, L M AU - Haugen-Strano, A AU - Swensen, J AU - Miki, Y AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 120 EP - 122 VL - 266 IS - 5182 SN - 0036-8075, 0036-8075 KW - BRCA1 KW - BRCA1 Protein KW - 0 KW - Neoplasm Proteins KW - Transcription Factors KW - Index Medicus KW - Chromosomes, Human, Pair 17 KW - Base Sequence KW - Alleles KW - Age of Onset KW - Humans KW - Heterozygote KW - Adult KW - Molecular Sequence Data KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Breast Neoplasms -- genetics KW - Ovarian Neoplasms -- genetics KW - Genes, Tumor Suppressor KW - Neoplasm Proteins -- genetics KW - Germ-Line Mutation KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76776943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=BRCA1+mutations+in+primary+breast+and+ovarian+carcinomas.&rft.au=Futreal%2C+P+A%3BLiu%2C+Q%3BShattuck-Eidens%2C+D%3BCochran%2C+C%3BHarshman%2C+K%3BTavtigian%2C+S%3BBennett%2C+L+M%3BHaugen-Strano%2C+A%3BSwensen%2C+J%3BMiki%2C+Y&rft.aulast=Futreal&rft.aufirst=P&rft.date=1994-10-07&rft.volume=266&rft.issue=5182&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-08 N1 - Date created - 1994-11-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - BRCA1 N1 - Genetic sequence - U14680; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 14-3-3: modulators of signaling proteins? AN - 76769410; 7939645 JF - Science (New York, N.Y.) AU - Morrison, D AD - Molecular Mechanisms of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research Development Center, MD 21702-1201. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 56 EP - 57 VL - 266 IS - 5182 SN - 0036-8075, 0036-8075 KW - 14-3-3 Proteins KW - 0 KW - Antigens, Polyomavirus Transforming KW - BMH1 protein, S cerevisiae KW - Fungal Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Saccharomyces cerevisiae Proteins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Fusion Proteins, bcr-abl KW - EC 2.7.10.2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Index Medicus KW - Animals KW - Fungal Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Fusion Proteins, bcr-abl -- metabolism KW - Enzyme Activation KW - Proto-Oncogene Proteins -- metabolism KW - Antigens, Polyomavirus Transforming -- metabolism KW - Adenosine Diphosphate Ribose -- metabolism KW - Yeasts -- metabolism KW - Proteins -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76769410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=14-3-3%3A+modulators+of+signaling+proteins%3F&rft.au=Morrison%2C+D&rft.aulast=Morrison&rft.aufirst=D&rft.date=1994-10-07&rft.volume=266&rft.issue=5182&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-08 N1 - Date created - 1994-11-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 1994 Oct 7;266(5182):126-9 [7939632] Science. 1994 Oct 7;266(5182):129-33 [7939633] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for participation of calcineurin in potentiation of agonist-stimulated cyclic AMP formation by the calcium-mobilizing hormone, angiotensin II. AN - 76751832; 7929124 AB - Angiotensin II (AII) receptors are known to interact with two distinct guanine nucleotide binding proteins, Gq/11 and Gi, in rat adrenal glomerulosa cells to activate phospholipase C and to inhibit adenylate cyclase, respectively. However, in cultured bovine glomerulosa cells AII potentiates rather than inhibits the stimulatory effect of adrenocorticotropin (ACTH) on cAMP levels. This effect of AII was partially mimicked by phorbol 12-myristate 13-acetate (PMA) and was partially inhibited by staurosporine or depletion of protein kinase C but was unaffected by pertussis toxin treatment. No potentiation was detectable in disrupted cells or in membrane preparations. In intact glomerulosa cells, treatment with cyclosporin A or FK506 completely inhibited AII- or PMA-induced potentiation of cAMP production without affecting the response to ACTH. In COS-7 cells transfected with the rat AT1 receptor, AII caused 2-3-fold enhancement of the ACTH-induced cAMP response, an effect that was partially reproduced by PMA. These potentiating actions of AII and PMA were prevented by preincubation with cyclosporin A or FK506, and the latter effect was abolished by rapamycin. These results implicate the Ca2+- and calmodulin-dependent protein phosphatase, calcineurin, in AII-induced enhancement of adenylate cyclase activity in both adrenal glomerulosa and transfected COS-7 cells. The finding that AII enhances ACTH-stimulated production of cAMP by a second messenger-mediated mechanism that involves the participation of calcineurin reveals an additional mode of cross-talk between pathways activated by Ca(2+)-mobilizing and cAMP-generating receptors. JF - The Journal of biological chemistry AU - Baukal, A J AU - Hunyady, L AU - Catt, K J AU - Balla, T AD - Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 24546 EP - 24549 VL - 269 IS - 40 SN - 0021-9258, 0021-9258 KW - Calmodulin-Binding Proteins KW - 0 KW - Receptors, Angiotensin KW - Angiotensin II KW - 11128-99-7 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcineurin KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Receptors, Angiotensin -- analysis KW - Animals KW - Cattle KW - Cells, Cultured KW - Adrenocorticotropic Hormone -- pharmacology KW - GTP-Binding Proteins -- physiology KW - Protein Kinase C -- physiology KW - Drug Synergism KW - Cyclic AMP -- biosynthesis KW - Calmodulin-Binding Proteins -- physiology KW - Phosphoprotein Phosphatases -- physiology KW - Calcium -- physiology KW - Angiotensin II -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76751832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+participation+of+calcineurin+in+potentiation+of+agonist-stimulated+cyclic+AMP+formation+by+the+calcium-mobilizing+hormone%2C+angiotensin+II.&rft.au=Baukal%2C+A+J%3BHunyady%2C+L%3BCatt%2C+K+J%3BBalla%2C+T&rft.aulast=Baukal&rft.aufirst=A&rft.date=1994-10-07&rft.volume=269&rft.issue=40&rft.spage=24546&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidation of hemoglobin and the enhancement produced by nitroblue tetrazolium. AN - 76751264; 7929164 AB - The autoxidation of hemoglobin as a function of oxygen pressure and the effect of added nitroblue tetrazolium have been studied. It has been shown that the enhanced autoxidation at intermediate oxygen pressures can only be partially explained by the outer-sphere reaction of oxygen with deoxygenated chains. An additional enhancement associated with the properties of partially oxygenated hemoglobins has been attributed to the mobility on the distal side of the heme which facilitates the nucleophilic displacement of bound oxygen by the distal histidine. Nitroblue tetrazolium, in addition to reacting with the superoxide formed during autoxidation, is shown to oxidize directly both deoxygenated and oxygenated hemoglobin in two steps, proceeding through the one-electron reduced intermediate, a tetrazolinyl radical. Even though the oxygenated chains are oxidized by nitroblue tetrazolium, much less overall reduction of nitroblue tetrazolium is observed at high oxygen pressures. This phenomenon is attributed to the reoxidation by oxygen of both the tetrazolinyl radical and the formazan. The reaction with nitroblue tetrazolium is also found to contribute to enhanced oxidation at intermediate oxygen pressures. This behavior is explained by the two-electron reaction with nitroblue tetrazolium and the oxygen dependence of the various processes involved in the reaction of nitroblue tetrazolium. JF - The Journal of biological chemistry AU - Abugo, O O AU - Rifkind, J M AD - Molecular Dynamics Section, National Institute on Aging, Baltimore, Maryland 21224. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 24845 EP - 24853 VL - 269 IS - 40 SN - 0021-9258, 0021-9258 KW - Hemoglobins KW - 0 KW - Oxidants KW - Nitroblue Tetrazolium KW - 298-83-9 KW - Index Medicus KW - Oxidation-Reduction KW - Humans KW - Oxidants -- metabolism KW - Hemoglobins -- metabolism KW - Nitroblue Tetrazolium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76751264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidation+of+hemoglobin+and+the+enhancement+produced+by+nitroblue+tetrazolium.&rft.au=Abugo%2C+O+O%3BRifkind%2C+J+M&rft.aulast=Abugo&rft.aufirst=O&rft.date=1994-10-07&rft.volume=269&rft.issue=40&rft.spage=24845&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. AN - 76751218; 7929152 AB - Synergistic sites in the central cell-adhesive domain of fibronectin (FN) substantially enhance cell adhesion mediated by the alpha 5 beta 1 integrin receptor for fibronectin. We characterized a critical minimal sequence needed for synergistic activity using site-directed mutagenesis and homology scanning using intramolecular chimeras. The minimal cell-binding domain of FN consisting of the 9th and 10th type III FN repeat was expressed in an Escherichia coli expression system. This protein retained high biological activity when assayed using a competitive inhibition assay for FN-mediated adhesion of baby hamster kidney or HT-1080 cells. In contrast, a construct consisting of the 8th and 10th repeat displayed very low biological activity. By replacing various portions of the 8th repeat with homologous 9th repeat segments, we mapped the synergistic region to the center of the 9th repeat. When a very short peptide sequence, Pro-His-Ser-Arg-Asn (PHSRN), from the 9th repeat was substituted for the homologous pentapeptide site in the 8th repeat sequence, the recombinant protein showed markedly enhanced activity. Further mutagenesis analysis suggested that the arginine residue of this pentapeptide sequence is important for function. We also identified a weaker adjacent synergy region other than the PHSRN region. Epitope mapping of an anti-FN monoclonal antibody that inhibits FN-mediated adhesion identified the same critical regions. A synthetic peptide containing the PHSRN sequence showed neither competitive inhibitory activity in solution nor synergy with a soluble RGD-containing peptide. However, when the same synthetic peptide was positioned via a covalent bond at the corresponding site of the normally inactive 8th repeat, it mediated an enhancement of adhesive activity. These results identify a pentapeptide site that synergistically enhances the cell-adhesive activity of the FN RGD sequence. JF - The Journal of biological chemistry AU - Aota, S AU - Nomizu, M AU - Yamada, K M AD - Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10/07/ PY - 1994 DA - 1994 Oct 07 SP - 24756 EP - 24761 VL - 269 IS - 40 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Fibronectins KW - Oligopeptides KW - Recombinant Proteins KW - arginyl-glycyl-aspartic acid KW - 78VO7F77PN KW - Index Medicus KW - Base Sequence KW - Recombinant Proteins -- pharmacology KW - Humans KW - Molecular Sequence Data KW - Oligopeptides -- pharmacology KW - Amino Acid Sequence KW - Epitope Mapping KW - Structure-Activity Relationship KW - Fibronectins -- chemistry KW - Cell Adhesion -- drug effects KW - Fibronectins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76751218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+short+amino+acid+sequence+Pro-His-Ser-Arg-Asn+in+human+fibronectin+enhances+cell-adhesive+function.&rft.au=Aota%2C+S%3BNomizu%2C+M%3BYamada%2C+K+M&rft.aulast=Aota&rft.aufirst=S&rft.date=1994-10-07&rft.volume=269&rft.issue=40&rft.spage=24756&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of leukemia following treatment for non-Hodgkin's lymphoma. AN - 76717136; 8089863 AB - There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected. JF - Journal of the National Cancer Institute AU - Travis, L B AU - Curtis, R E AU - Stovall, M AU - Holowaty, E J AU - van Leeuwen, F E AU - Glimelius, B AU - Lynch, C F AU - Hagenbeek, A AU - Li, C Y AU - Banks, P M AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/10/05/ PY - 1994 DA - 1994 Oct 05 SP - 1450 EP - 1457 VL - 86 IS - 19 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Registries KW - Logistic Models KW - Dose-Response Relationship, Drug KW - Humans KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- therapy KW - Lymphoma, Non-Hodgkin -- radiotherapy KW - Leukemia, Radiation-Induced -- etiology KW - Leukemia, Myeloid, Acute -- etiology KW - Leukemia, Myeloid, Acute -- chemically induced KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Neoplasms, Second Primary -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76717136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Risk+of+leukemia+following+treatment+for+non-Hodgkin%27s+lymphoma.&rft.au=Travis%2C+L+B%3BCurtis%2C+R+E%3BStovall%2C+M%3BHolowaty%2C+E+J%3Bvan+Leeuwen%2C+F+E%3BGlimelius%2C+B%3BLynch%2C+C+F%3BHagenbeek%2C+A%3BLi%2C+C+Y%3BBanks%2C+P+M&rft.aulast=Travis&rft.aufirst=L&rft.date=1994-10-05&rft.volume=86&rft.issue=19&rft.spage=1450&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 - 1994-10-18 N1 - Date created - 1994-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spermidine potentiates dizocilpine-induced impairment of learning performance by rats in a 14-unit T-maze. AN - 77721665; 7843267 AB - The NMDA receptor, a ligand-gated ion channel complex, has been reported to be involved in memory processes. Learning is impaired following administration of dizocilpine, a non-competitive antagonist of the NMDA receptor. Polyamines, such as spermine and spermidine, interact with the NMDA receptor to enhance binding of dizocilpine, which blocks the ion channel. The present study assessed action of polyamines as modulators of learning via NMDA receptor activation. Dizocilpine (0.05 mg/kg) was given i.p. before maze learning, at a dose that produced a slight, nonsignificant impairment of maze learning. Pretreatment with 80 mg/kg but not 15 or 40 mg/kg spermidine (i.p.) before dizocilpine impaired maze learning compared to saline controls. Administration of 80 mg/kg spermidine without dizocilpine did not impair maze learning. The results are consistent with the view that systemic injection of a polyamine can modulate learning processes involving the NMDA receptor. JF - European journal of pharmacology AU - Shimada, A AU - Spangler, E L AU - London, E D AU - Ingram, D K AD - Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994/10/03/ PY - 1994 DA - 1994 Oct 03 SP - 293 EP - 300 VL - 263 IS - 3 SN - 0014-2999, 0014-2999 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Spermidine KW - U87FK77H25 KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Rats, Inbred F344 KW - Analysis of Variance KW - Memory -- drug effects KW - Drug Synergism KW - Male KW - Maze Learning -- drug effects KW - Spermidine -- administration & dosage KW - Spermidine -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Dizocilpine Maleate -- toxicity KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Dizocilpine Maleate -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77721665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Spermidine+potentiates+dizocilpine-induced+impairment+of+learning+performance+by+rats+in+a+14-unit+T-maze.&rft.au=Shimada%2C+A%3BSpangler%2C+E+L%3BLondon%2C+E+D%3BIngram%2C+D+K&rft.aulast=Shimada&rft.aufirst=A&rft.date=1994-10-03&rft.volume=263&rft.issue=3&rft.spage=293&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 - 1995-03-03 N1 - Date created - 1995-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. AN - 85276599; pmid-7747758 AB - To determine the spectrum of manifestations in neurofibromatosis 2 (NF2) and to assess possible heterogeneity, we evaluated 63 affected individuals from 32 families. Work-up included skin and neurologic examinations, audiometry, a complete ophthalmology examination with slit-lamp biomicroscopy of the lens and fundus, and gadolinium-enhanced MRI of the brain and, in some, of the spine. Mean age-at-onset in 58 individuals was 20.3 years; initial symptoms resulted from vestibular schwannomas (44.4%), other CNS tumors (22.2%), skin tumors (12.7%), and ocular manifestations including cataracts and retinal hamartomas (12.7%). Five asymptomatic individuals were diagnosed through screening. Vestibular schwannomas were documented in 62 individuals (98.4%); other findings included cataracts (81.0%), skin tumors (67.7%), spinal tumors (67.4%), and meningiomas (49.2%). Usually, clinical manifestations and course were similar within families but differed among families. To assess possible heterogeneity, we assigned affected individuals to three proposed subtypes (representing mild, intermediate, and severe NF2) based on age-at-onset, presence or absence of CNS tumors other than vestibular schwannomas, and presence or absence of retinal hamartomas. Comparisons among the three subtypes for many clinical parameters demonstrated that patients in the mild subtype differed from those in the other two subtypes for most parameters, but that none of the parameters distinguished patients in the intermediate subtype from those in the severe subtype. Thus, there are likely two rather than three subtypes of NF2. Classification of patients to subtype may aid in counseling about long-term prognosis and in formulating individualized guidelines for medical surveillance. JF - American Journal of Medical Genetics AU - Parry, D M AU - Eldridge, R AU - Kaiser-Kupfer, M I AU - Bouzas E A AU - Pikus, A AU - Patronas, N AD - Clinical Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892. PY - 1994 SP - 450 EP - 461 VL - 52 IS - 4 SN - 0148-7299, 0148-7299 KW - Pedigree KW - Support, U.S. Gov't, P.H.S. KW - Skin KW - Age of Onset KW - Eye Diseases KW - Human KW - Cranial Nerve Neoplasms KW - Neurilemmoma KW - Aged KW - Child KW - Skin Neoplasms KW - Neurofibromatosis 2 KW - Pregnancy KW - Brain Neoplasms KW - Adult KW - Middle Age KW - Meningioma KW - Adolescent KW - Family Health KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Neurofibromatosis+2+%28NF2%29%3A+clinical+characteristics+of+63+affected+individuals+and+clinical+evidence+for+heterogeneity.&rft.au=Parry%2C+D+M%3BEldridge%2C+R%3BKaiser-Kupfer%2C+M+I%3BBouzas+E+A%3BPikus%2C+A%3BPatronas%2C+N&rft.aulast=Parry&rft.aufirst=D&rft.date=1994-10-01&rft.volume=52&rft.issue=4&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2. AN - 85239172; pmid-7942846 AB - X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available, polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at theta = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3' to exon 50 of the dystrophin gene) and at DXS1068 (5' to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5'DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described. JF - American Journal of Human Genetics AU - Lalwani, A K AU - Brister, J R AU - Fex, J AU - Grundfast, K M AU - Pikus, A T AU - Ploplis, B AU - San, Agustin T AU - Skarka, H AU - Wilcox, E R AD - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892. PY - 1994 SP - 685 EP - 694 VL - 55 IS - 4 SN - 0002-9297, 0002-9297 KW - Pedigree KW - Linkage (Genetics) KW - Promoter Regions (Genetics) KW - Audiometry KW - Human KW - Brain KW - Dystrophin KW - Hearing Loss, Sensorineural KW - Chromosome Mapping KW - Polymerase Chain Reaction KW - Muscular Dystrophies KW - Heterozygote Detection KW - Lod Score KW - Recombination, Genetic KW - Case Report KW - Male KW - Female KW - X Chromosome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Human+Genetics&rft.atitle=A+new+nonsyndromic+X-linked+sensorineural+hearing+impairment+linked+to+Xp21.2.&rft.au=Lalwani%2C+A+K%3BBrister%2C+J+R%3BFex%2C+J%3BGrundfast%2C+K+M%3BPikus%2C+A+T%3BPloplis%2C+B%3BSan%2C+Agustin+T%3BSkarka%2C+H%3BWilcox%2C+E+R&rft.aulast=Lalwani&rft.aufirst=A&rft.date=1994-10-01&rft.volume=55&rft.issue=4&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Human+Genetics&rft.issn=00029297&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Development of hepatocellular carcinoma among patients with chronic liver disease due to hepatitis C viral infection. AN - 85204425; pmid-7528758 AB - Although chronic infection with hepatitis C (HCV) and B viruses (HBV) are important risk factors for hepatocellular carcinoma (HCC), their relative roles in causing liver cancer remain poorly defined, particularly in developed Western countries. Thirty-one patients with HCC seen at the Clinical Center of the National Institutes of Health between 1986 and 1992 were evaluated serologically for evidence of HBV and HCV infection: antibodies to HBV and HCV and hepatitis B surface antigen (HBsAg) were detected by conventional immunoassays, and HCV RNA and HBV DNA were detected by polymerase chain reaction (PCR). Serologic evidence of HBV infection was found in 18 patients (56%), 17 with antibodies, 16 with HBV DNA, and 14 with HBsAg. Evidence of HCV infection was found in 10 patients (32%), seven of whom also had HCV RNA. One patient had both anti-HCV and HBsAg. In comparison to patients with HBV-related HCC, those with HCV-related cancer were older and more likely to be white, to have been born in the United States, to have a history of parenteral exposure, and to have cirrhosis. In two patients in whom the course of hepatitis C could be traced from its onset, hepatocellular carcinoma developed after 5 years in one and after 9 years in another case. Thus chronic HCV infection is a common etiology of cirrhosis among United States patients with HCC, often as a late complication of intravenous drug abuse or blood transfusion. JF - Journal of Clinical Gastroenterology AU - Di Bisceglie A M AU - Simpson, L H AU - Lotze, M T AU - Hoofnagle, J H AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892. PY - 1994 SP - 222 EP - 226 VL - 19 IS - 3 SN - 0192-0790, 0192-0790 KW - Hepatitis B Surface Antigens KW - Hepacivirus KW - Hepatitis, Chronic KW - Carcinoma, Hepatocellular KW - Human KW - Hepatitis Antibodies KW - Aged KW - Hepatitis B Virus KW - RNA, Viral KW - Liver Neoplasms KW - Hepatitis B Antibodies KW - Adult KW - Hepatitis B KW - Middle Age KW - Hepatitis C Antibodies KW - Hepatitis C KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85204425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Gastroenterology&rft.atitle=Development+of+hepatocellular+carcinoma+among+patients+with+chronic+liver+disease+due+to+hepatitis+C+viral+infection.&rft.au=Di+Bisceglie+A+M%3BSimpson%2C+L+H%3BLotze%2C+M+T%3BHoofnagle%2C+J+H&rft.aulast=Di+Bisceglie+A+M&rft.aufirst=&rft.date=1994-10-01&rft.volume=19&rft.issue=3&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A membrane motor model for the fast motility of the outer hair cell. AN - 85156873; pmid-7963034 AB - A model is presented for describing the membrane potential-dependent motility of the outer hair cell. This model assumes that the motility is due to conformational changes of motor molecules in the plasma membrane. Two kinds of experimental observations, elasticity of the cell and stretch dependence of the motor molecule, are important for characterize this motility by the model. The motor molecule can be described by a two-state model which has electrical and mechanical components in the free energy. The electrical component is due to the charge transferred across the membrane and the mechanical component is due to a change in membrane area in the two states. It can be shown that the elastic element and the motor element are connected in series. Thus the apparent strain of the cell is represented by the sum of true elastic strain and changes due to motor molecules. This model predicts the amplitude of the movement and the force produced by the motility. The model predicts the force produced under isometric condition is about 0.1 nN/mV, in agreement with values estimated from in vivo conditions. The effect of an elastic load attached to the cell is also discussed. JF - The Journal of the Acoustical Society of America AU - Iwasa, Kuni H AD - National Institute on Deafness and Other Communication Disorders PY - 1994 SP - 2216 EP - 2224 VL - 96 IS - 4 SN - 0001-4966, 0001-4966 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85156873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Acoustical+Society+of+America&rft.atitle=A+membrane+motor+model+for+the+fast+motility+of+the+outer+hair+cell.&rft.au=Iwasa%2C+Kuni+H&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=1994-10-01&rft.volume=96&rft.issue=4&rft.spage=2216&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Toxicokinetics of oxazepam in rats and mice. AN - 77804312; 7884653 AB - The comparative toxicokinetics of oxazepam were studied in F344 rats, B6C3F1 mice, and Swiss-Webster mice of both sexes after an i.v. dose of 20 mg/kg and oral gavage doses of 50, 200, and 400 mg/kg. In addition, the toxicokinetics of oxazepam in a 3-week dosed-feed study of male B6C3F1 mice at 125 and 2500 ppm were also investigated. Results indicated that the elimination of oxazepam from plasma after i.v. injection in both rats and mice were first-order and could be best described by a two-compartment model with a terminal elimination half-life of 4-5 h for rats and 5-7 h for mice. After oral gavage dosing the peak oxazepam plasma concentrations in most rodents were reached within 2-3.5 h. At all doses studied, female rodents had significantly higher plasma concentrations than males. Absorption of oxazepam was significantly extended at higher oral doses of 200 and 400 mg/kg. At 50 mg/kg, the bioavailability of oxazepam in rats ( 80%). The bioavailability of oxazepam in both B6C3F1 and Swiss-Webster mice decreased with increasing dose. A dose proportionality of Cmax was not observed in rats and mice after gavage doses of 50, 200, and 400 mg/kg. Plasma concentrations of oxazepam in the dosed-feed study increased with the concentration of oxazepam in the feed, a quasi-steady-state of plasma concentrations of oxazepam was reached after approximately 4 days ad libitum exposure. In B6C3F1 mice, the estimated relative bioavailability of oxazepam from dosed feed (relative to gavage study at 50 mg/kg) was about 43%. JF - Journal of pharmaceutical sciences AU - Yuan, J AU - Goehl, T J AU - Hong, L AU - Clark, J AU - Murrill, E AU - Moore, R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1373 EP - 1379 VL - 83 IS - 10 SN - 0022-3549, 0022-3549 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Rats KW - Evaluation Studies as Topic KW - Mice, Inbred Strains KW - Animals KW - Rats, Inbred F344 KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Mice KW - Models, Biological KW - Male KW - Female KW - Drug Administration Routes KW - Enteral Nutrition KW - Oxazepam -- toxicity KW - Oxazepam -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77804312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+sciences&rft.atitle=Toxicokinetics+of+oxazepam+in+rats+and+mice.&rft.au=Yuan%2C+J%3BGoehl%2C+T+J%3BHong%2C+L%3BClark%2C+J%3BMurrill%2C+E%3BMoore%2C+R&rft.aulast=Yuan&rft.aufirst=J&rft.date=1994-10-01&rft.volume=83&rft.issue=10&rft.spage=1373&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans. AN - 77794330; 7894496 AB - Genetic susceptibility factors may play a role in determining adverse effects of exposure to environmental toxins. As a preliminary step to a molecular epidemiological study in a population exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), we investigated 20 healthy Caucasian volunteers with a set of putative susceptibility markers including a CYP1A1 Msp I restriction fragment length genetic polymorphism (RFLP), CYP1A1 mRNA expression, and ethoxyresorufin-O-deethylase (EROD) activity in cultured and mitogen-activated blood lymphocytes. Both basal (p = 0.008) and induced (p = 0.0001) EROD activity was significantly higher among persons with a mutation in one or both alleles of the CYP1A1 gene (variant CYP1A1 genotype). Induction in vitro by TCDD significantly increased EROD activity in both variant and wild-type CYP1A1 subjects; however, the absolute increase was greater in subjects with variant genotypes. An additive interaction between genotype and TCDD induction was suggested. Expression of CYP1A1 mRNA, both basal and induced, did not vary significantly across the genotypes. JF - Pharmacogenetics AU - Landi, M T AU - Bertazzi, P A AU - Shields, P G AU - Clark, G AU - Lucier, G W AU - Garte, S J AU - Cosma, G AU - Caporaso, N E AD - Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 242 EP - 246 VL - 4 IS - 5 SN - 0960-314X, 0960-314X KW - CYP1A1 KW - DNA Primers KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP1A1 KW - Index Medicus KW - Polymorphism, Genetic KW - Humans KW - Cytochrome P-450 Enzyme System -- metabolism KW - Genotype KW - Base Sequence KW - Oxidoreductases -- metabolism KW - Adult KW - Polychlorinated Dibenzodioxins -- toxicity KW - Molecular Sequence Data KW - Lymphocytes -- enzymology KW - Enzyme Induction KW - Middle Aged KW - Female KW - Male KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - RNA, Messenger -- genetics KW - Aryl Hydrocarbon Hydroxylases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77794330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Association+between+CYP1A1+genotype%2C+mRNA+expression+and+enzymatic+activity+in+humans.&rft.au=Landi%2C+M+T%3BBertazzi%2C+P+A%3BShields%2C+P+G%3BClark%2C+G%3BLucier%2C+G+W%3BGarte%2C+S+J%3BCosma%2C+G%3BCaporaso%2C+N+E&rft.aulast=Landi&rft.aufirst=M&rft.date=1994-10-01&rft.volume=4&rft.issue=5&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP1A1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of gene expression of amyloid precursor protein (APP) in activated human lymphoblastoid cells and lymphocytes. AN - 77787001; 7702710 AB - To understand the possible role of amyloid precursor protein (APP) in human lymphocytes, and the regulation of APP gene expression in this cell type, we determined levels of cellular APP protein and of mRNA in human T-cell-derived Jurkat cells that were treated with lectin, phorbol ester, and calcium ionophore. We also related these levels to cell aggregation and adhesion. Cell-cell aggregation and cell-plastic adhesion were observed over a 24-h period after incubating cells for 2 h with phytohemagglutinin or phorbol myristate acetate. Cells treated with a calcium ionophore showed no aggregation or adhesion. Western blots indicated no obvious alteration in the level of cellular APP with different treatments. Northern blots showed a significant transient increase of APP mRNA after incubation with the calcium ionophore, whereas phorbol ester treatment showed a slight increase of APP mRNA. We analyzed the level of APP mRNA in human peripheral T cells which had been separated from peripheral lymphocytes. The level increased transiently by up to threefold after treatment with calcium ionophore plus phorbol esters. These data suggest that cell-cell aggregation and cell-matrix adhesion by human lymphocytes are not associated with an increased level of cellular APP protein or of mRNA. JF - Molecular and chemical neuropathology AU - Fukuyama, R AU - Murakawa, Y AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892. PY - 1994 SP - 93 EP - 101 VL - 23 IS - 2-3 SN - 1044-7393, 1044-7393 KW - Amyloid beta-Protein Precursor KW - 0 KW - RNA, Messenger KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Blotting, Western KW - Blotting, Northern KW - Cell Adhesion -- physiology KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Aggregation -- physiology KW - RNA, Messenger -- biosynthesis KW - Lymphocyte Activation -- physiology KW - Amyloid beta-Protein Precursor -- biosynthesis KW - Lymphocytes -- metabolism KW - Gene Expression -- physiology KW - Amyloid beta-Protein Precursor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77787001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+chemical+neuropathology&rft.atitle=Induction+of+gene+expression+of+amyloid+precursor+protein+%28APP%29+in+activated+human+lymphoblastoid+cells+and+lymphocytes.&rft.au=Fukuyama%2C+R%3BMurakawa%2C+Y%3BRapoport%2C+S+I&rft.aulast=Fukuyama&rft.aufirst=R&rft.date=1994-10-01&rft.volume=23&rft.issue=2-3&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Molecular+and+chemical+neuropathology&rft.issn=10447393&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-08 N1 - Date created - 1995-05-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Mol Chem Neuropathol 1995 Feb-Apr;24(2-3):319 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Requirement for metabolic activation of acetylaminofluorene to induce multidrug gene expression. AN - 77784271; 7889850 AB - Previously we have demonstrated that several xenobiotics can induce multidrug (mdr) gene expression in cultures of primary isolated hepatocytes. One of the best of these xenobiotic inducers in rat hepatocytes is 2-acetylaminofluorene (2-AAF), which induces mdr expression by an enhancement of mdr gene transcription. In all species studied to date, AAF is extensively and variously metabolized. In this study we have sought to determine if AAF per se or a metabolite is responsible for mediating the increase in mdr gene transcription and expression. This study demonstrates that AAF per se is not active, but that the effect of AAF we have observed on mdr gene transcription and expression in the rat is due to the formation of a reactive metabolite(s). Our data indicate that this reactive metabolite is probably N-acetoxy-2-aminofluorene or the sulfate ester of N-hydroxy-AAF. The requirement for the formation of one of these metabolites may explain the differences in species response to AAF, in terms of mdr gene expression, that we have observed. We hypothesize that the mechanism by which mdr gene transcription is increased in response to AAF involves a covalent interaction between a reactive metabolite and an mdr gene regulatory protein. Our current work is concerned with the exploration of this hypothesis. JF - Environmental health perspectives AU - Gant, T W AU - Schrenk, D AU - Silverman, J A AU - Thorgeirsson, S S AD - National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 209 EP - 212 VL - 102 Suppl 6 SN - 0091-6765, 0091-6765 KW - mdr KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Biotransformation KW - Liver -- cytology KW - Liver -- drug effects KW - Liver -- metabolism KW - Gene Expression Regulation -- drug effects KW - 2-Acetylaminofluorene -- pharmacokinetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77784271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Requirement+for+metabolic+activation+of+acetylaminofluorene+to+induce+multidrug+gene+expression.&rft.au=Gant%2C+T+W%3BSchrenk%2C+D%3BSilverman%2C+J+A%3BThorgeirsson%2C+S+S&rft.aulast=Gant&rft.aufirst=T&rft.date=1994-10-01&rft.volume=102+Suppl+6&rft.issue=&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-19 N1 - Date created - 1995-04-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1987 May;84(9):3004-8 [3472246] Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9 [2432605] Cancer Res. 1987 Nov 1;47(21):5577-83 [2889526] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7701-5 [2890168] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735-8 [2444983] J Natl Cancer Inst. 1988 Mar 2;80(1):14-20 [2892943] Proc Natl Acad Sci U S A. 1988 May;85(10):3580-4 [3368466] J Natl Cancer Inst. 1988 Nov 2;80(17):1383-6 [2845109] Carcinogenesis. 1988 Nov;9(11):1995-2002 [3180338] J Natl Cancer Inst. 1989 Jan 18;81(2):116-24 [2562856] Proc Natl Acad Sci U S A. 1989 Jan;86(2):695-8 [2563168] Mol Cell Biol. 1989 Mar;9(3):1346-50 [2471060] J Biol Chem. 1989 Jul 15;264(20):11693-8 [2568355] J Biol Chem. 1989 Jul 15;264(20):12053-62 [2473069] Science. 1989 Sep 8;245(4922):1066-73 [2475911] FASEB J. 1989 Dec;3(14):2583-92 [2574119] J Biol Chem. 1990 Jan 5;265(1):221-6 [1967174] J Natl Cancer Inst. 1990 Feb 7;82(3):193-8 [1967320] Mol Carcinog. 1991;4(6):499-509 [1686552] Cancer Treat Res. 1991;57:101-19 [1686712] Cancer Treat Res. 1991;57:187-208 [1686717] Science. 1992 Apr 10;256(5054):232-4 [1348873] FASEB J. 1992 Jun;6(9):2660-6 [1377140] J Biol Chem. 1992 Jul 5;267(19):13535-9 [1618854] J Biol Chem. 1992 Sep 5;267(25):18093-9 [1381362] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6 [1356264] Nature. 1990 Jul 26;346(6282):362-5 [1973824] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6258-62 [2166952] Biochem J. 1990 Dec 1;272(2):281-95 [1980062] Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):547-51 [1671173] Cell Growth Differ. 1990 Feb;1(2):57-62 [1982215] Blood. 1991 Aug 1;78(3):586-92 [1859877] Gene. 1991 Oct 15;106(2):229-36 [1682220] Biochem Pharmacol. 1992 Feb 4;43(3):393-401 [1311577] Pharmacol Rev. 1973 Mar;25(1):1-66 [4571258] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Cancer Res. 1983 Jan;43(1):28-34 [6401166] Cancer Res. 1983 Sep;43(9):4413-9 [6135505] Science. 1983 Sep 23;221(4617):1285-8 [6137059] Drug Metab Rev. 1984;15(4):753-839 [6437779] Nature. 1985 Aug 29-Sep 4;316(6031):817-9 [2863759] J Clin Oncol. 1986 May;4(5):626-38 [3701386] Nature. 1986 Oct 23-29;323(6090):728-31 [3022150] Nature. 1986 Dec 4-10;324(6096):485-9 [2878368] Science. 1987 May 29;236(4805):1120-2 [3576227] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro but not in vivo inhibition of CYP2D6 by phenethyl isothiocyanate (PEITC), a constituent of watercress. AN - 77770890; 7894500 JF - Pharmacogenetics AU - Caporaso, N AU - Whitehouse, J AU - Monkman, S AU - Boustead, C AU - Issaq, H AU - Fox, S AU - Morse, M A AU - Idle, J R AU - Chung, F L AD - Genetic Epidemiology Branch, National Cancer Institute, Rockville, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 275 EP - 280 VL - 4 IS - 5 SN - 0960-314X, 0960-314X KW - Anticarcinogenic Agents KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Isothiocyanates KW - phenethyl isothiocyanate KW - 6U7TFK75KV KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Debrisoquin KW - X31CDK040E KW - Index Medicus KW - Debrisoquin -- metabolism KW - Microsomes, Liver -- metabolism KW - Humans KW - Microsomes, Liver -- enzymology KW - Adult KW - Male KW - Female KW - Plants -- chemistry KW - Isothiocyanates -- pharmacology KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Anticarcinogenic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77770890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+but+not+in+vivo+inhibition+of+CYP2D6+by+phenethyl+isothiocyanate+%28PEITC%29%2C+a+constituent+of+watercress.&rft.au=Caporaso%2C+N%3BWhitehouse%2C+J%3BMonkman%2C+S%3BBoustead%2C+C%3BIssaq%2C+H%3BFox%2C+S%3BMorse%2C+M+A%3BIdle%2C+J+R%3BChung%2C+F+L&rft.aulast=Caporaso&rft.aufirst=N&rft.date=1994-10-01&rft.volume=4&rft.issue=5&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expanding the potential of restriction endonucleases: use of hapaxoterministic enzymes. AN - 77767057; 7856834 AB - A new class of restriction endonucleases called hapaxoterministic enzymes, hapaxomers for short, has been defined. A hapaxomer cleaves DNA outside the recognition site or within an interrupted "palindrome" at bases which are not specified producing fragments with asymmetric, staggered ends. Such termini are unique; in the general case, the protrusions of a fragment obtained with the aid of a hapaxomer cannot self-hybridize, nor can the fragment be ligated to the vast majority of other fragments produced by the same enzyme. When the fragments generated by a hapaxoterministic enzyme are mixed, they can reassemble in only one configuration--that of the original structure from which they were derived. Hapaxomers, then, are characterized not by their recognition sites, which may be symmetric or asymmetric, but by their cleavage sites. The ability to reunite once-contiguous fragments efficiently means that hapaxomers cleaving DNA at many locations are virtually equivalent to restriction enzymes cutting at unique sites. These properties can be exploited for applications such as site-specific mutagenesis or the isolation of large intact DNA fragments. JF - Analytical biochemistry AU - Berger, S L AD - Section on Genes and Gene Products, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1 EP - 8 VL - 222 IS - 1 SN - 0003-2697, 0003-2697 KW - DNA KW - 9007-49-2 KW - DNA Restriction Enzymes KW - EC 3.1.21.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - DNA Restriction Enzymes -- metabolism KW - DNA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77767057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Expanding+the+potential+of+restriction+endonucleases%3A+use+of+hapaxoterministic+enzymes.&rft.au=Berger%2C+S+L&rft.aulast=Berger&rft.aufirst=S&rft.date=1994-10-01&rft.volume=222&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Anal Biochem 1995 Feb 10;225(1):195 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence. AN - 77765117; 7882928 AB - Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages of the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify. JF - Environmental health perspectives 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. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 19 EP - 23 VL - 102 Suppl 5 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Genes, Tumor Suppressor KW - Humans KW - Time Factors KW - Mutation KW - Cell Division -- genetics KW - Lung Neoplasms -- etiology KW - Asbestos -- pharmacokinetics KW - Carcinogens, Environmental -- adverse effects KW - Lung Neoplasms -- genetics KW - Asbestos -- adverse effects KW - Carcinogens, Environmental -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77765117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+and+molecular+mechanisms+of+asbestos+carcinogenicity%3A+implications+for+biopersistence.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=1994-10-01&rft.volume=102+Suppl+5&rft.issue=&rft.spage=19&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1984 Jun;37(2):357-8 [6327062] Cancer Res. 1984 May;44(5):2170-80 [6324999] Carcinogenesis. 1985 Mar;6(3):473-5 [3978760] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3884-8 [2987952] Cancer Genet Cytogenet. 1986 Feb 15;20(3-4):191-201 [3943062] Nature. 1986 Apr 24-30;320(6064):695-9 [3754619] Cancer Res. 1986 Nov;46(11):5795-802 [3756923] Hereditas. 1986;105(2):233-9 [3818338] Am J Pathol. 1987 Feb;126(2):343-9 [3826298] Cancer Genet Cytogenet. 1987 Nov;29(1):75-9 [3478131] Cancer Res. 1988 Jan 1;48(1):142-7 [3334988] Cancer Genet Cytogenet. 1988 Jul 15;33(2):251-74 [3164248] Carcinog Compr Surv. 1989;11:165-86 [2646015] Important Adv Oncol. 1989;:41-60 [2651296] Am J Pathol. 1989 May;134(5):979-91 [2541616] Cancer Res. 1989 Jul 1;49(13):3598-601 [2567206] IARC Sci Publ. 1989;(90):54-73 [2663719] Int J Cancer. 1989 Aug 15;44(2):256-60 [2474517] Cancer Genet Cytogenet. 1989 Aug;41(1):33-9 [2766251] Cancer Res. 1989 Nov 1;49(21):6118-22 [2790824] Science. 1990 Feb 9;247(4943):707-10 [2300822] Carcinogenesis. 1990 Apr;11(4):673-81 [2323006] Cancer Genet Cytogenet. 1990 May;46(1):135-7 [2331678] Cell. 1990 Jun 1;61(5):759-67 [2188735] Cell. 1991 Jan 25;64(2):235-48 [1988146] Genes Chromosomes Cancer. 1989 Nov;1(2):148-54 [2487155] Am J Ind Med. 1992;21(2):253-73 [1536158] Cancer Genet Cytogenet. 1992 Mar;59(1):57-61 [1555192] Environ Health Perspect. 1993 Apr;100:9-20 [8354184] Science. 1976 Oct 1;194(4260):23-8 [959840] Acta Cytol. 1978 Sep-Oct;22(5):398-401 [281850] Cancer Res. 1984 Nov;44(11):5017-22 [6091868] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents. AN - 77765082; 7889840 AB - In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2-AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for 4 weeks produced an increase in DNA adduct formation during the first 2 weeks, followed by a plateau, which presumably occurred because the rate of adduct removal offset the rate of adduct formation. The quantity of DNA adducts present at equilibrium correlated directly with the carcinogen concentration; therefore, when exposure was continued for 4 weeks, DNA adducts that reflected the plateau level at each dose could be expressed as a function of dose. Liver and bladder DNA adduct profiles thus obtained during administration of multiple doses of 2-AAF (to female mice) and 4-ABP (to male and female mice) were compared to profiles for tumor incidences obtained during lifetime exposures to the same doses. These experiments demonstrated similar profiles for DNA adduct formation and tumorigenesis in liver. In the bladder, DNA adducts were linear, but tumors only appeared at the higher doses in conjunction with cell proliferation. In addition to these aromatic amines, similar data are available for aflatoxin B1, diethylnitrosamine, and (methylnitrosamino)-1-(3-pyridyl)-1-butanone (also known as nicotine-derived nitrosoketone). Of the nine different biological situations (carcinogen/species/sex/organ) for which data are available, correlations between steady-state DNA adduct levels and tumorigenic response at the different doses were linear in five of the nine biological models.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Poirier, M C AU - Beland, F A AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 161 EP - 165 VL - 102 Suppl 6 SN - 0091-6765, 0091-6765 KW - Aminobiphenyl Compounds KW - 0 KW - Carcinogens KW - DNA Adducts KW - 4-biphenylamine KW - 16054949HJ KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - Incidence KW - Mice KW - Time Factors KW - Male KW - Female KW - 2-Acetylaminofluorene -- toxicity KW - Urinary Bladder Neoplasms -- chemistry KW - DNA Adducts -- analysis KW - Aminobiphenyl Compounds -- toxicity KW - Liver Neoplasms -- chemistry KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77765082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+adduct+measurements+and+tumor+incidence+during+chronic+carcinogen+exposure+in+rodents.&rft.au=Poirier%2C+M+C%3BBeland%2C+F+A&rft.aulast=Poirier&rft.aufirst=M&rft.date=1994-10-01&rft.volume=102+Suppl+6&rft.issue=&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-19 N1 - Date created - 1995-04-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1991 May;12(5):895-900 [2029755] Carcinogenesis. 1990 Dec;11(12):2133-5 [2124951] Prog Clin Biol Res. 1992;374:79-92 [1620719] Cancer Res. 1970 Mar;30(3):559-76 [4915745] Food Cosmet Toxicol. 1974 Oct;12(5-6):681-5 [4375655] Cancer Res. 1978 Jun;38(6):1479-96 [348302] J Environ Pathol Toxicol. 1979 Dec;3(1-2):1-148 [547011] Carcinogenesis. 1984 Dec;5(12):1591-6 [6499111] Eur J Cancer Clin Oncol. 1985 Jul;21(7):865-73 [2995043] Cancer Res. 1986 Mar;46(3):1280-4 [3943097] Carcinogenesis. 1986 Jun;7(6):853-8 [3085966] Cancer Res. 1987 Mar 15;47(6):1577-81 [3815358] Cancer Res. 1987 Nov 15;47(22):6058-65 [3664508] Environ Health Perspect. 1987 Dec;76:57-63 [3447904] Biochem Biophys Res Commun. 1988 Apr 29;152(2):843-8 [3365254] Adv Cancer Res. 1988;50:25-70 [3287845] Cancer Res. 1989 Dec 15;49(24 Pt 1):6985-8 [2582440] Cancer Res. 1990 Jun 15;50(12):3772-80 [2340522] Toxicol Appl Pharmacol. 1990 Jun 1;104(1):79-93 [2360210] Cancer Res. 1991 Dec 1;51(23 Pt 2):6415-51 [1933906] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suspected determinants of enrollment into detoxification and methadone maintenance treatment among injecting drug users. AN - 77742711; 7851280 AB - Our primary aim in this study has been to evaluate selected conditions thought to influence the entry of injecting drug users (IDU) into detoxification and methadone maintenance programs, making use of a prospective study design to strengthen a cross-sectional investigation of these conditions. To begin our investigation, we analyzed cross-sectionally gathered data on 2879 IDUs who had been recruited through extensive community outreach efforts and who were interviewed at the time of recruitment. We then tested our hypotheses about suspected determinants of entry into treatment by analyzing prospectively gathered data on 1039 active drug users who had no recent history of being treated for drug problems. Among these 1039 IDUs (a subset of the initial cross-sectional sample), 144 entered a detoxification program between their recruitment interview and their next follow-up interview, conducted about six months after recruitment (range: 3.5-9.5 months) and 64 entered a methadone maintenance program during that observation interval. Using multiple logistic regression analyses, we found that a recent drug overdose, relatively higher frequency of injecting drugs, and a history of prior arrest or treatment were independent predictors of entry into detoxification. Being married or living with a partner, being female, a lengthy duration of drug use (> 10 years), and a history of prior treatment were independent predictors of entry into methadone maintenance. These findings shed light on what appears to be a different profile of suspected determinants of entry into a detoxification treatment versus methadone maintenance treatment, and help to clarify some potential differences between treated and untreated drug users that ought to be considered when evaluating results of investigations with IDU participants recruited solely from treatment settings. JF - Drug and alcohol dependence AU - Schütz, C G AU - Rapiti, E AU - Vlahov, D AU - Anthony, J C AD - National Institute on Drug Abuse/Intramural Research Program, Etiology Branch, Baltimore, MD 21224. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 129 EP - 138 VL - 36 IS - 2 SN - 0376-8716, 0376-8716 KW - Amphetamine KW - CK833KGX7E KW - Cocaine KW - I5Y540LHVR KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Opioid-Related Disorders -- rehabilitation KW - Baltimore -- epidemiology KW - HIV Infections -- prevention & control KW - Adult KW - Patient Admission -- statistics & numerical data KW - Heroin Dependence -- rehabilitation KW - Heroin Dependence -- psychology KW - Adolescent KW - Male KW - Social Environment KW - HIV Infections -- transmission KW - Opioid-Related Disorders -- psychology KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology KW - Cross-Sectional Studies KW - Opioid-Related Disorders -- epidemiology KW - Prospective Studies KW - Heroin Dependence -- epidemiology KW - Risk Factors KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Substance-Related Disorders -- epidemiology KW - Methadone -- therapeutic use KW - Urban Population -- statistics & numerical data KW - Patient Acceptance of Health Care KW - Substance Abuse, Intravenous -- rehabilitation KW - Substance Abuse, Intravenous -- epidemiology KW - Substance Abuse, Intravenous -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77742711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Suspected+determinants+of+enrollment+into+detoxification+and+methadone+maintenance+treatment+among+injecting+drug+users.&rft.au=Sch%C3%BCtz%2C+C+G%3BRapiti%2C+E%3BVlahov%2C+D%3BAnthony%2C+J+C&rft.aulast=Sch%C3%BCtz&rft.aufirst=C&rft.date=1994-10-01&rft.volume=36&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-15 N1 - Date created - 1995-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids. AN - 77733777; 7851278 AB - We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms. JF - Drug and alcohol dependence AU - Cheskin, L J AU - Fudala, P J AU - Johnson, R E AD - National Institute on Drug Abuse's Intramural Research Program, Baltimore, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 115 EP - 121 VL - 36 IS - 2 SN - 0376-8716, 0376-8716 KW - Buprenorphine KW - 40D3SCR4GZ KW - Clonidine KW - MN3L5RMN02 KW - Index Medicus KW - Baltimore KW - Drug Administration Schedule KW - Substance Withdrawal Syndrome -- rehabilitation KW - Substance Abuse Treatment Centers KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Clonidine -- administration & dosage KW - Clonidine -- adverse effects KW - Buprenorphine -- administration & dosage KW - Opioid-Related Disorders -- rehabilitation KW - Heroin Dependence -- rehabilitation KW - Buprenorphine -- adverse effects KW - Urban Population UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77733777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=A+controlled+comparison+of+buprenorphine+and+clonidine+for+acute+detoxification+from+opioids.&rft.au=Cheskin%2C+L+J%3BFudala%2C+P+J%3BJohnson%2C+R+E&rft.aulast=Cheskin&rft.aufirst=L&rft.date=1994-10-01&rft.volume=36&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-15 N1 - Date created - 1995-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the testicular effects of 2-methoxyethanol (ME) in rats and guinea pigs. AN - 77726839; 7859828 AB - Glycol ethers produce both hemato- and testicular toxicity in animals, which is dependent on both the alkyl chain length and animal species used. Ethylene glycol monobutyl ether (2-butoxyethanol, BE) causes hemolytic anemia in rats but not in guinea pigs, and red blood cells from both guinea pigs and humans are minimally affected in vitro by the active metabolite 2-butoxyacetic acid. This demonstrates the importance of animal species selection for assessing human risk to BE exposure. 2-Methoxyethanol (ME) produces testicular lesions in rats characterized primarily by the degeneration of spermatocytes undergoing meiotic division with minimal or no hemolytic changes. Because of the differential hemolytic response to BE between rats and guinea pigs, the present study addressed whether the testicular response to ME was similarly dichotomous. Adult rats or guinea pigs were given a single dose of either 200 or 300 mg ME/kg by gavage, and testicular and hemolytic changes were assessed 24 hr after treatment. Testis histology in rats showed dose-dependent degeneration of dividing spermatocytes in stage XIV tubules as expected, with only minimal hemolytic changes, also as expected. In contrast, no testicular or hemolytic effects were observed in guinea pigs 24 hr after either single ME dose. In a subsequent study, a single dose or multiple (3 daily) doses of 200 mg ME/kg were given, and animals were examined at 4 days after the start of treatment. Testes from rats given both single and multiple ME doses showed, as expected, tubules depleted of spermatocytes and early spermatids. In guinea pigs, spermatocyte degeneration was observed in stage III/IV tubules for both dosing schemes, but was much less severe and widespread and differed from rats in morphological characteristics, specifically in the appearance of nuclear chromatin degeneration. In the rat, degenerating spermatocytes showed uniformly condensed and dispersed chromatin, while in the guinea pig they showed marked chromatin condensation at the nuclear periphery. No hemolytic changes were observed in either species or dosing scheme. In summary, although ME-associated testicular lesions were observed in both species, they differed significantly in onset, characteristics, and severity. Both the nature of the differential testicular response to ME and a comparison to the in vitro human testicular response to the active metabolite 2-methoxyacetic acid are subjects of future study. JF - Experimental and molecular pathology AU - Ku, W W AU - Ghanayem, B I AU - Chapin, R E AU - Wine, R N AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 119 EP - 133 VL - 61 IS - 2 SN - 0014-4800, 0014-4800 KW - Ethylene Glycols KW - 0 KW - methyl cellosolve KW - EK1L6XWI56 KW - Index Medicus KW - Rats KW - Erythrocytes -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Guinea Pigs KW - Spermatozoa -- drug effects KW - Spermatozoa -- pathology KW - Species Specificity KW - Male KW - Spermatozoa -- ultrastructure KW - Ethylene Glycols -- toxicity KW - Testis -- drug effects KW - Testis -- pathology KW - Testis -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77726839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+molecular+pathology&rft.atitle=Comparison+of+the+testicular+effects+of+2-methoxyethanol+%28ME%29+in+rats+and+guinea+pigs.&rft.au=Ku%2C+W+W%3BGhanayem%2C+B+I%3BChapin%2C+R+E%3BWine%2C+R+N&rft.aulast=Ku&rft.aufirst=W&rft.date=1994-10-01&rft.volume=61&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Experimental+and+molecular+pathology&rft.issn=00144800&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-21 N1 - Date created - 1995-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of carcinogenicity and cellular proliferation induced by mutagenic noncarcinogens vs carcinogens. III. Organophosphate pesticides vs tris(2,3-dibromopropyl)phosphate. AN - 77724590; 7835536 AB - Our laboratory has been examining the mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce carcinogenesis in 2-year rodent bioassays. Previous studies indicated that some mutagenic hepatocarcinogens increased cell proliferation in the target organ, the liver, while other structurally related mutagens that were noncarcinogenic failed to do so. We demonstrate in this report that another mutagenic carcinogen, tris(2,3-dibromopropyl phosphate), increased cell proliferation that was localized in the outer medulla of the kidney. This was also the target site for carcinogenesis in a 2-year bioassay and is another example of the association between chemically induced cell proliferation and carcinogenesis. This study also reports the absence of increased cell proliferation in the liver or kidney after exposure in the diet to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos following dietary exposure for 2 weeks at the same dose levels and routes of exposure that did not increase the tumor incidence in either organ in 2-year carcinogenesis assays. The present studies support the tenet that chemically induced cell proliferation may be a necessary prerequisite for chemical carcinogenesis, since in rat liver and kidney there was neither cell proliferation after 2 weeks nor tumor development after 2 years dietary exposure to the mutagenic organophosphate insecticides dimethoate, dioxathion, and dichlorvos. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Cunningham, M L AU - Elwell, M R AU - Matthews, H B AD - Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 363 EP - 369 VL - 23 IS - 3 SN - 0272-0590, 0272-0590 KW - Insecticides KW - 0 KW - Mutagens KW - Organophosphates KW - Pyrimidines KW - tris(2,3-dibromopropyl)phosphate KW - 126-72-7 KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Liver -- pathology KW - Kidney -- pathology KW - Liver -- drug effects KW - DNA Damage KW - Kidney -- drug effects KW - Pyrimidines -- pharmacology KW - Male KW - Insecticides -- toxicity KW - Kidney Neoplasms -- chemically induced KW - Organophosphates -- toxicity KW - Liver Neoplasms -- chemically induced KW - Cell Division -- drug effects KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77724590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Relationship+of+carcinogenicity+and+cellular+proliferation+induced+by+mutagenic+noncarcinogens+vs+carcinogens.+III.+Organophosphate+pesticides+vs+tris%282%2C3-dibromopropyl%29phosphate.&rft.au=Cunningham%2C+M+L%3BElwell%2C+M+R%3BMatthews%2C+H+B&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1994-10-01&rft.volume=23&rft.issue=3&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-01 N1 - Date created - 1995-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bilateral adrenal hemorrhage and adrenal insufficiency in a patient with lymphomatous adrenal infiltration following administration of a fusion toxin (DAB486 interleukin-2). AN - 77722818; 7834123 AB - DAB486IL-2 is a novel fusion toxin in which the ADP-ribosyltransferase and membrane-translocating domains of diphtheria toxin have been combined with the interleukin-2 (IL-2) gene, creating a recombinant protein capable of selectively intoxicating cells bearing the high-affinity IL-2 receptor. Clinical activity has been documented in Hodgkin disease and the non-Hodgkin lymphomas; toxicities have been minimal and include mild hepatic transaminitis, proteinuria, and hypersensitivity reactions. In this report, a patient with tumor-stage cutaneous T-cell lymphoma developed clinical adrenal failure with bilateral adrenal hemorrhage and necrosis 7 weeks after completing a 5-day course of treatment with DAB486IL-2. The relationship of fusion toxin therapy to the development of this unusual toxicity is discussed. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Cohen, R AU - Jaffe, E S AU - Stetler-Stevenson, M A AU - Sausville, E A AU - DeNigris, E C AU - Woodworth, T AU - Foss, F M AD - National Cancer Institute-Navy Medical Oncology Branch, Bethesda, Maryland. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 229 EP - 233 VL - 16 IS - 3 SN - 1067-5582, 1067-5582 KW - DAB(486)-interleukin 2 KW - 0 KW - Diphtheria Toxin KW - Immunotoxins KW - Interleukin-2 KW - Recombinant Fusion Proteins KW - Index Medicus KW - Neoplasm Invasiveness KW - Recombinant Fusion Proteins -- adverse effects KW - Necrosis -- etiology KW - Humans KW - Adrenal Insufficiency -- etiology KW - Aged KW - Adrenal Gland Neoplasms -- pathology KW - Lymphoma, T-Cell, Cutaneous -- pathology KW - Recombinant Fusion Proteins -- therapeutic use KW - Adrenal Gland Neoplasms -- therapy KW - Male KW - Lymphoma, T-Cell, Cutaneous -- therapy KW - Interleukin-2 -- pharmacology KW - Interleukin-2 -- adverse effects KW - Hemorrhage -- pathology KW - Immunotoxins -- adverse effects KW - Diphtheria Toxin -- pharmacology KW - Immunotoxins -- therapeutic use KW - Diphtheria Toxin -- adverse effects KW - Adrenal Gland Diseases -- pathology KW - Hemorrhage -- etiology KW - Adrenal Gland Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77722818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=Bilateral+adrenal+hemorrhage+and+adrenal+insufficiency+in+a+patient+with+lymphomatous+adrenal+infiltration+following+administration+of+a+fusion+toxin+%28DAB486+interleukin-2%29.&rft.au=Cohen%2C+R%3BJaffe%2C+E+S%3BStetler-Stevenson%2C+M+A%3BSausville%2C+E+A%3BDeNigris%2C+E+C%3BWoodworth%2C+T%3BFoss%2C+F+M&rft.aulast=Cohen&rft.aufirst=R&rft.date=1994-10-01&rft.volume=16&rft.issue=3&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-27 N1 - Date created - 1995-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T cell activation and increases in protein kinase C activity enhance retinoic acid-induced gene transcription. AN - 77722794; 7854354 AB - Retinoic acid (RA) has profound effects on cell growth and differentiation. Its receptors are members of the steroid/thyroid hormone receptor superfamily, which regulates nuclear transcription and gene expression by binding specific response elements. Protein kinase C (PKC) is activated during signal transduction initiated by a variety of membrane receptors. Using a RA-responsive element and reporter gene construct transfected into a T cell, we found: 1) T cell activation and PKC activators enhance transactivation by RA, 2) down-regulation of PKC protein has little effect on RA transactivation but abolishes superinduction by phorbol ester, which is restored by cotransfection of a PKC alpha-expression vector, and 3) cotransfection of dominant-negative c-jun does not prevent superinduction by phorbol ester. Together, these data demonstrate that PKC can modulate RA signal transduction, apparently without involvement of AP-1, and provide a new example of cross-talk between signal transduction pathways. JF - Molecular endocrinology (Baltimore, Md.) AU - Yang, Y AU - Minucci, S AU - Zand, D J AU - Ozato, K AU - Ashwell, J D AD - Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1370 EP - 1376 VL - 8 IS - 10 SN - 0888-8809, 0888-8809 KW - c-jun KW - Antibodies KW - 0 KW - Antigens, CD3 KW - Transcription Factor AP-1 KW - Tretinoin KW - 5688UTC01R KW - Luciferases KW - EC 1.13.12.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Hybridomas KW - Transcription Factor AP-1 -- metabolism KW - Luciferases -- metabolism KW - Transcriptional Activation -- drug effects KW - Mice KW - Plasmids KW - Antigens, CD3 -- immunology KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Antibodies -- pharmacology KW - Molecular Sequence Data KW - Genes, Reporter KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Drug Synergism KW - Luciferases -- genetics KW - Cell Line KW - Genes, jun KW - Protein Kinase C -- metabolism KW - Lymphocyte Activation KW - Tretinoin -- pharmacology KW - Transcription, Genetic -- drug effects KW - Protein Kinase C -- genetics KW - T-Lymphocytes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77722794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=T+cell+activation+and+increases+in+protein+kinase+C+activity+enhance+retinoic+acid-induced+gene+transcription.&rft.au=Yang%2C+Y%3BMinucci%2C+S%3BZand%2C+D+J%3BOzato%2C+K%3BAshwell%2C+J+D&rft.aulast=Yang&rft.aufirst=Y&rft.date=1994-10-01&rft.volume=8&rft.issue=10&rft.spage=1370&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-13 N1 - Date created - 1995-03-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-jun N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells. AN - 77722376; 7834198 AB - 1. Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration-dependent (1-100 microM) manner. At 10 microM nicotine, the IC50 value for strychnine is approximately 30 microM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3. Strychnine competes with nicotine in its effect, but not modify the apparent positive cooperatively of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release. 4. These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. JF - British journal of pharmacology AU - Kuijpers, G A AU - Vergara, L A AU - Calvo, S AU - Yadid, G AD - Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 471 EP - 478 VL - 113 IS - 2 SN - 0007-1188, 0007-1188 KW - Catecholamines KW - 0 KW - Nicotinic Antagonists KW - Receptors, Glycine KW - Strychnine KW - H9Y79VD43J KW - Calcium KW - SY7Q814VUP KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Calcium -- metabolism KW - Animals KW - Cattle KW - Catecholamines -- metabolism KW - Glycine -- pharmacology KW - Cells, Cultured KW - Membrane Potentials -- drug effects KW - Receptors, Glycine -- drug effects KW - Receptors, Glycine -- antagonists & inhibitors KW - Enterochromaffin Cells -- drug effects KW - Adrenal Medulla -- drug effects KW - Adrenal Medulla -- cytology KW - Strychnine -- pharmacology KW - Adrenal Medulla -- metabolism KW - Enterochromaffin Cells -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77722376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Inhibitory+effect+of+strychnine+on+acetylcholine+receptor+activation+in+bovine+adrenal+medullary+chromaffin+cells.&rft.au=Kuijpers%2C+G+A%3BVergara%2C+L+A%3BCalvo%2C+S%3BYadid%2C+G&rft.aulast=Kuijpers&rft.aufirst=G&rft.date=1994-10-01&rft.volume=113&rft.issue=2&rft.spage=471&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-01 N1 - Date created - 1995-03-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Synapse. 1990;5(3):190-200 [2160740] Eur J Pharmacol. 1990 Jan 17;175(3):365-6 [2157604] EMBO J. 1990 Dec;9(13):4391-8 [1702381] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4860-4 [2052567] Proc Biol Sci. 1992 Apr 22;248(1321):35-40 [1355909] J Neurosci. 1992 Oct;12(10):3935-45 [1403091] Eur J Pharmacol. 1992 Oct 20;221(2-3):389-91 [1426016] J Neurosci. 1993 Feb;13(2):596-604 [7678857] FEBS Lett. 1993 Jul 26;327(2):241-6 [8335115] FASEB J. 1993 Sep;7(12):1171-8 [8375616] Neurosci Lett. 1993 Aug 20;158(2):139-42 [8233086] Neurochem Res. 1993 Oct;18(10):1051-5 [8255354] Neuron. 1994 Jan;12(1):167-77 [7507338] Acta Physiol Scand Suppl. 1955;33(118):45-56 [14398342] Arch Int Pharmacodyn Ther. 1961 Apr 1;131:123-50 [13682839] Br J Pharmacol. 1991 Nov;104(3):760-4 [1797336] J Physiol. 1991;440:67-83 [1804982] Nature. 1967 Dec 2;216(5118):922-3 [6074971] Life Sci. 1967 Dec 1;6(23):2515-7 [6080569] Exp Brain Res. 1968;6(1):1-18 [5721755] Int J Neuropharmacol. 1969 Mar;8(2):191-4 [5783005] Nature. 1970 Dec 5;228(5275):917-22 [4921376] Brain Res. 1970 Mar 17;18(3):542-4 [5511229] Exp Brain Res. 1971 Jun 29;12(5):547-65 [5093729] Proc Natl Acad Sci U S A. 1973 Oct;70(10):2832-6 [4200724] J Neurochem. 1974 Oct;23(4):617-23 [4430907] Acta Physiol Lat Am. 1974;24(2):124-33 [4451123] J Gen Physiol. 1977 Jun;69(6):897-914 [302320] J Gen Physiol. 1977 Jun;69(6):915-26 [302321] Biophys J. 1979 Jul;27(1):57-73 [233569] J Neurosci. 1981 Mar;1(3):259-70 [6114995] Eur J Biochem. 1983 Apr 5;131(3):519-25 [6301811] Neurosci Lett. 1980 Jan;16(1):91-5 [6302570] Physiol Rev. 1984 Oct;64(4):1103-61 [6208567] Proc Natl Acad Sci U S A. 1984 Nov;81(22):7224-7 [6095276] Brain Res Bull. 1985 Nov;15(5):473-86 [2998565] J Physiol. 1986 Jan;370:395-407 [2420978] Mol Pharmacol. 1986 Dec;30(6):590-7 [3023812] Nature. 1987 Jul 16-22;328(6127):215-20 [3037383] Nature. 1987 Jul 16-22;328(6127):221-7 [3037384] J Gen Physiol. 1988 Aug;92(2):145-59 [2459299] J Biol Chem. 1989 Jan 15;264(2):698-705 [2910860] Neurosci Lett. 1989 Jul 17;102(1):82-6 [2550855] Pharmacol Biochem Behav. 1990 Apr;35(4):833-40 [1693213] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternate 5' exons in the rat brain-derived neurotrophic factor gene: differential patterns of expression across brain regions. AN - 77721267; 7854051 AB - Brain-derived neurotrophic factor (BDNF) enhances the survival of dopaminergic neurons and protects them from neurotoxins in vitro. This trophic factor might thus be of therapeutic value for the treatment of Parkinsonian syndromes. The rat BDNF gene consists of several upstream noncoding exons that are alternatively spliced to a common coding exon. To investigate BDNF 5' exons expressed in the adult rat brain, we subjected RNA from cerebellum to 5'-RACE analysis and compared the resulting clones to previously reported 5' exon sequences from rat brain and hippocampus. In addition to known 5' exons, we isolated a BDNF transcript with a novel 5' sequence representing yet another alternate upstream exon in this gene. Quantitative PCR analysis of BDNF mRNAs containing each of the five upstream exons indicated that each of the alternate transcripts is most abundant in the hippocampus, intermediate in the substantia nigra and cerebellum and least abundant in the striatum. However, the magnitude of these differences in expression varied considerably suggesting that BDNF gene transcription in the mature brain is regulated by alternate promoters that are differentially active across regions. JF - Brain research. Molecular brain research AU - Bishop, J F AU - Mueller, G P AU - Mouradian, M M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 225 EP - 232 VL - 26 IS - 1-2 SN - 0169-328X, 0169-328X KW - Brain-Derived Neurotrophic Factor KW - 0 KW - DNA Primers KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Index Medicus KW - Animals KW - Corpus Striatum -- metabolism KW - Hippocampus -- metabolism KW - Transcription, Genetic KW - Organ Specificity KW - Cerebellum -- metabolism KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Nerve Growth Factors -- biosynthesis KW - Alternative Splicing KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Exons KW - Nerve Tissue Proteins -- biosynthesis KW - Brain -- metabolism KW - Nerve Tissue Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77721267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alternate+5%27+exons+in+the+rat+brain-derived+neurotrophic+factor+gene%3A+differential+patterns+of+expression+across+brain+regions.&rft.au=Bishop%2C+J+F%3BMueller%2C+G+P%3BMouradian%2C+M+M&rft.aulast=Bishop&rft.aufirst=J&rft.date=1994-10-01&rft.volume=26&rft.issue=1-2&rft.spage=225&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 - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - S76758; GENBANK; S76759; S76760; S76799; S76757 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol and magnesium. Introduction to the symposium. AN - 77718493; 7847585 JF - Alcoholism, clinical and experimental research AU - Zakhari, S AU - Altura, B M AD - Biomedical Research Branch, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20892-7003. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1037 EP - 1039 VL - 18 IS - 5 SN - 0145-6008, 0145-6008 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Rats KW - Animals KW - Risk Factors KW - Humans KW - Magnesium -- physiology KW - Alcohol Withdrawal Delirium -- physiopathology KW - Magnesium Deficiency -- physiopathology KW - Alcoholism -- physiopathology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77718493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Alcohol+and+magnesium.+Introduction+to+the+symposium.&rft.au=Zakhari%2C+S%3BAltura%2C+B+M&rft.aulast=Zakhari&rft.aufirst=S&rft.date=1994-10-01&rft.volume=18&rft.issue=5&rft.spage=1037&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebrovascular disease in children. AN - 77717259; 7839810 AB - Stroke although rare in children, is an important cause of morbidity in the paediatric age group. Over a period of 8 years, 43 children (17 boys and 26 girls) in the age groups of 1-16 years (mean 8.02 yrs) presented with stroke which constituted 10% of all strokes in the young and 0.7% of all paediatric admissions. The chief clinical features were hemiplegia (86%), convulsions (27%), fever (23%), dysphasia (23%), headache (11%) and altered level of consciousness (11%). Routine laboratory tests were non-contributory. Cranial computerized tomography (CCT) on 21 patients was abnormal in 95% and was useful in revealing the extent of infarction. Infarction was confined to middle cerebral artery territory, often involving basal ganglionic structures and was associated with focal or diffuse atrophy. Angiograms were abnormal in 78% of the patients (18/23) and were complimentary to the CCT. Etiological factors identified were: Moya-moya disease 6, arteritis 5, fibromuscular dysplasia 2, scorpion sting 2, and venous sinus thrombosis and small vessel occlusion one each. Though 23% of the patients had fever at onset, no obvious evidence of systemic or CNS infection was noticed. Stroke in children continues to pose a diagnostic challenge. JF - Acta neurologica Scandinavica AU - Nagaraja, D AU - Verma, A AU - Taly, A B AU - Kumar, M V AU - Jayakumar, P N AD - Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 251 EP - 255 VL - 90 IS - 4 SN - 0001-6314, 0001-6314 KW - Index Medicus KW - Animals KW - Moyamoya Disease -- complications KW - Humans KW - Arteritis -- complications KW - Tomography, X-Ray Computed KW - Scorpion Stings -- complications KW - Child KW - Sinus Thrombosis, Intracranial -- diagnosis KW - Sinus Thrombosis, Intracranial -- complications KW - Arteritis -- diagnosis KW - Scorpion Stings -- diagnosis KW - Child, Preschool KW - Infant KW - Cerebral Angiography KW - Moyamoya Disease -- diagnosis KW - Fibromuscular Dysplasia -- diagnosis KW - Fibromuscular Dysplasia -- complications KW - Scorpions KW - Adolescent KW - Male KW - Female KW - Cerebrovascular Disorders -- diagnosis KW - Cerebrovascular Disorders -- etiology KW - Cerebral Infarction -- diagnosis KW - Cerebral Infarction -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77717259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+neurologica+Scandinavica&rft.atitle=Cerebrovascular+disease+in+children.&rft.au=Nagaraja%2C+D%3BVerma%2C+A%3BTaly%2C+A+B%3BKumar%2C+M+V%3BJayakumar%2C+P+N&rft.aulast=Nagaraja&rft.aufirst=D&rft.date=1994-10-01&rft.volume=90&rft.issue=4&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Acta+neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-28 N1 - Date created - 1995-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic hyperpolarization of liver by ethanol: the importance of Mg2+ and H+ in determining impermeant intracellular anionic charge and energy of metabolic reactions. AN - 77716143; 7531402 JF - Alcoholism, clinical and experimental research AU - Veech, R L AU - Gates, D N AU - Crutchfield, C AU - Gitomer, W L AU - Kashiwaya, Y AU - King, M T AU - Wondergem, R AD - Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville MD 20852-1823. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1040 EP - 1056 VL - 18 IS - 5 SN - 0145-6008, 0145-6008 KW - Ion Channels KW - 0 KW - Ethanol KW - 3K9958V90M KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Software KW - Animals KW - Liver -- physiopathology KW - Ethanol -- pharmacokinetics KW - Hydrogen-Ion Concentration KW - Humans KW - Membrane Potentials -- physiology KW - Magnesium -- physiology KW - Energy Metabolism -- physiology KW - Liver Diseases, Alcoholic -- physiopathology KW - Ion Channels -- physiology KW - Acid-Base Equilibrium -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77716143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Metabolic+hyperpolarization+of+liver+by+ethanol%3A+the+importance+of+Mg2%2B+and+H%2B+in+determining+impermeant+intracellular+anionic+charge+and+energy+of+metabolic+reactions.&rft.au=Veech%2C+R+L%3BGates%2C+D+N%3BCrutchfield%2C+C%3BGitomer%2C+W+L%3BKashiwaya%2C+Y%3BKing%2C+M+T%3BWondergem%2C+R&rft.aulast=Veech&rft.aufirst=R&rft.date=1994-10-01&rft.volume=18&rft.issue=5&rft.spage=1040&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trichloroethanol potentiation of gamma-aminobutyric acid-activated chloride current in mouse hippocampal neurones. AN - 77710019; 7834208 AB - 1. The action of 2,2,2-trichloroethanol on gamma-aminobutyric acid (GABA)-activated Cl- current was studied in mouse hippocampal neurones in tissue culture by use of whole-cell patch-clamp recording. 2. Trichloroethanol increased the amplitude of currents activated by 1 microM GABA or 0.1 microM muscimol. Trichloroethanol, 1-25 mM, potentiated current activated by 1 microM GABA in a concentration-dependent manner with an EC50 of 3.0 +/- 1.4 mM and a maximal response (Emax) of 576 +/- 72% of control. 3. Trichloroethanol potentiated currents activated by GABA concentrations or = 10 microM. Despite marked potentiation of currents activated by low concentrations of GABA, trichloroethanol did not significantly alter the EC50, slope, or Emax of the GABA concentration-response curve. 4. Trichloroethanol, 5 mM, potentiated GABA-activated current in neurones in which ethanol, 10-500 mM, did not. The effect of trichloroethanol was not altered by the putative ethanol antagonist, Ro 15-4513. Trichloroethanol did not potentiate currents activated by pentobarbitone. 5. In the absence of exogenous GABA, trichloroethanol at concentrations > or = 2.5 mM activated a current that appeared to be carried by Cl- as its reversal potential changed with changes in the Cl- gradient and as it was inhibited by the GABAA antagonists, bicuculline methiodide and picrotoxin. 6. Since trichloroethanol is thought to be the active metabolite of chloral hydrate and other chloral derivative anaesthetics, potentiation of the GABA-activated current in central nervous system neurones by trichloroethanol may contribute to the sedative/hypnotic effects of these agents. JF - British journal of pharmacology AU - Peoples, R W AU - Weight, F F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcholism, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 555 EP - 563 VL - 113 IS - 2 SN - 0007-1188, 0007-1188 KW - Chloride Channels KW - 0 KW - GABA-A Receptor Antagonists KW - Receptors, GABA-A KW - Muscimol KW - 2763-96-4 KW - Ethanol KW - 3K9958V90M KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Ethylene Chlorohydrin KW - 753N66IHAN KW - 2,2,2-trichloroethanol KW - AW835AJ62N KW - Pentobarbital KW - I4744080IR KW - Index Medicus KW - Animals KW - Patch-Clamp Techniques KW - Ethanol -- pharmacology KW - Cells, Cultured KW - Up-Regulation -- drug effects KW - Receptors, GABA-A -- metabolism KW - Mice KW - Drug Synergism KW - Muscimol -- pharmacology KW - Pentobarbital -- pharmacology KW - Neurons -- metabolism KW - Ethylene Chlorohydrin -- antagonists & inhibitors KW - gamma-Aminobutyric Acid -- pharmacology KW - Neurons -- drug effects KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - gamma-Aminobutyric Acid -- physiology KW - Ethylene Chlorohydrin -- analogs & derivatives KW - Chloride Channels -- metabolism KW - Chloride Channels -- drug effects KW - Ethylene Chlorohydrin -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77710019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Trichloroethanol+potentiation+of+gamma-aminobutyric+acid-activated+chloride+current+in+mouse+hippocampal+neurones.&rft.au=Peoples%2C+R+W%3BWeight%2C+F+F&rft.aulast=Peoples&rft.aufirst=R&rft.date=1994-10-01&rft.volume=113&rft.issue=2&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-01 N1 - Date created - 1995-03-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Prog Neurobiol. 1991;36(3):171-94 [1673253] Neuron. 1990 Jun;4(6):919-28 [1694446] J Physiol. 1972 Jun;223(3):803-14 [5045741] Nature. 1975 Apr 24;254(5502):703-5 [1124130] Adv Biochem Psychopharmacol. 1975;(14):131-51 [242199] Nature. 1975 Dec 18;258(5536):625-7 [1207741] Clin Pharmacokinet. 1977 Mar-Apr;2(2):93-109 [16715] Nature. 1977 Sep 22;269(5626):342-4 [561893] Nature. 1978 Feb 9;271(5645):563-4 [563985] Am J Physiol. 1978 Aug;235(2):E97-102 [686171] J Physiol. 1978 Jul;280:355-72 [690885] Science. 1980 Jul 25;209(4455):507-9 [6248961] Science. 1980 Aug 8;209(4457):708-10 [7394531] Biochem Pharmacol. 1980 Nov 1;29(21):3011-6 [7458951] Mol Pharmacol. 1981 Jan;19(1):49-55 [7207463] Brain Res. 1981 Mar 23;209(1):177-88 [6260300] J Neurophysiol. 1981 Apr;45(4):621-31 [6262463] Nature. 1990 Aug 16;346(6285):648-51 [2166916] Neuron. 1990 Nov;5(5):703-11 [1699569] Eur J Pharmacol. 1990 Oct 2;187(1):127-30 [1703076] Brain Res. 1991 Jan 11;538(2):319-23 [1901506] J Physiol. 1992 Apr;449:279-93 [1326046] Nature. 1993 Jan 28;361(6410):356-9 [7678923] J Pharmacol Exp Ther. 1993 Mar;264(3):1097-103 [8383736] J Neurochem. 1993 Apr;60(4):1548-53 [7681105] Anesthesiology. 1993 Apr;78(4):757-76 [8385426] Br J Pharmacol. 1993 Mar;108(3):711-6 [8385534] J Neurochem. 1993 May;60(5):1972-5 [8386229] J Pharmacol Exp Ther. 1993 May;265(2):771-6 [8496823] Neuron. 1994 Jan;12(1):61-71 [8292360] Proc Natl Acad Sci U S A. 1981 Nov;78(11):7180-4 [6273918] Brain Res. 1981 Dec 28;230(1-2):434-8 [6797680] J Neurosci. 1982 Jul;2(7):889-94 [6284887] J Physiol. 1982 Nov;332:299-314 [6296374] Br J Pharmacol. 1984 Sep;83(1):57-68 [6091828] Brain Res. 1984 Dec 10;323(2):287-92 [6098342] J Physiol. 1985 Mar;360:367-86 [2580971] Br J Pharmacol. 1985 Jul;85(3):675-81 [2992670] Q J Exp Physiol. 1985 Jul;70(3):313-28 [2994165] Science. 1986 May 23;232(4753):1004-7 [2422758] Proc Natl Acad Sci U S A. 1986 Jun;83(11):4071-5 [2424017] Prog Neurobiol. 1987;28(3):197-276 [2883706] J Physiol. 1987 May;386:485-501 [2445967] Gaoxiong Yi Xue Ke Xue Za Zhi. 1987 May;3(5):346-53 [3482999] J Pharmacol Exp Ther. 1988 Aug;246(2):558-64 [2457076] J Physiol. 1988 Feb;396:515-33 [2900892] Nature. 1988 Sep 1;335(6185):76-9 [2842688] Adv Biochem Psychopharmacol. 1988;45:247-61 [2902744] J Pharmacol Exp Ther. 1988 Dec;247(3):1012-7 [2849653] Nature. 1989 Apr 13;338(6216):582-5 [2538761] FASEB J. 1989 May;3(7):1850-4 [2541038] Brain Res. 1988 Jun 7;451(1-2):376-80 [3251598] Brain Res. 1989 Sep 25;498(1):181-4 [2551455] J Physiol. 1989 Mar;410:479-99 [2477526] J Neurophysiol. 1989 Nov;62(5):1018-27 [2573696] Pharmacol Rev. 1989 Jun;41(2):143-210 [2558391] Mol Pharmacol. 1990 Feb;37(2):263-70 [1689453] Brain Res. 1990 Jan 22;507(2):332-6 [2186844] Neuron. 1991 Jul;7(1):27-33 [1712603] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accumulation of polychlorinated dibenzo-p-dioxins and dibenzofurans in liver of control laboratory rats. AN - 77706715; 7835546 AB - Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls belong to a class of compounds, the polyhalogenated aromatic hydrocarbons (PHAHs), which are ubiquitous environmental contaminants. Due to the existence of a common mechanism of action, i.e., binding to the Ah receptor, the activity of members of this class of compounds is generally expressed relative to the prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as toxic equivalency factors (TEFs). In the present studies we examined the presence of liver of untreated PCDFs in standard laboratory feed and in the liver of untreated rats at three different ages (60, 140, and 200 days) in terms of concentration and in toxic equivalents (TEQs, TEF x concentration). Feed was shown to contain trace amounts of PCDDs and PCDFs and control rat liver was shown to contain several PCDD and PCDF congeners in terms of concentration of congener and concentration of TEQs contributed by that congener. The total concentration of TEQs increased with increasing age in rat liver, going from 20 ppt TEQ at 60 days to 78 ppt TEQ at 200 days of age. This accumulation in dioxin-like activity was due primarily to PCDFs. In particular the congener 2,3,4,7,8-pentachlorodibenzofuran accrued in untreated rat liver accounting for approximately 80% of the total TEQ at 200 days of age. These studies affirm the pervasive presence of PHAHs and suggest prudence in evaluating chronic rat studies in which interference from background levels of PCDDs and PCDFs may be a factor. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Vanden Heuvel, J P AU - Clark, G C AU - Tritscher, A m AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 465 EP - 469 VL - 23 IS - 3 SN - 0272-0590, 0272-0590 KW - Benzofurans KW - 0 KW - Dibenzofurans, Polychlorinated KW - Polychlorinated Dibenzodioxins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Age Factors KW - Cytochrome P-450 Enzyme System -- physiology KW - Female KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- pharmacokinetics KW - Benzofurans -- pharmacokinetics KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77706715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Accumulation+of+polychlorinated+dibenzo-p-dioxins+and+dibenzofurans+in+liver+of+control+laboratory+rats.&rft.au=Vanden+Heuvel%2C+J+P%3BClark%2C+G+C%3BTritscher%2C+A+m%3BLucier%2C+G+W&rft.aulast=Vanden+Heuvel&rft.aufirst=J&rft.date=1994-10-01&rft.volume=23&rft.issue=3&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-01 N1 - Date created - 1995-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiretroviral therapy for infection due to human immunodeficiency virus in children. AN - 77105917; 11361369 JF - Pediatric AIDS and HIV infection AU - Pizzo, P A AU - Wilfert, C AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 273 EP - 295 VL - 5 IS - 5 SN - 1045-5418, 1045-5418 KW - Antiviral Agents KW - 0 KW - Reverse Transcriptase Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Drug Therapy, Combination KW - Treatment Failure KW - Humans KW - Child KW - Antiviral Agents -- therapeutic use KW - Acquired Immunodeficiency Syndrome -- virology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Antiviral Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77105917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+AIDS+and+HIV+infection&rft.atitle=Antiretroviral+therapy+for+infection+due+to+human+immunodeficiency+virus+in+children.&rft.au=Pizzo%2C+P+A%3BWilfert%2C+C&rft.aulast=Pizzo&rft.aufirst=P&rft.date=1994-10-01&rft.volume=5&rft.issue=5&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Pediatric+AIDS+and+HIV+infection&rft.issn=10455418&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-11 N1 - Date created - 1995-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase antimutator allele. AN - 76949455; 7828810 AB - We have previously isolated mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants have a mutation in the dnaE gene, encoding the alpha subunit of DNA polymerase III. They were isolated in a mismatch-repair-defective mutL background, in which mutations can be considered to represent uncorrected DNA replication errors. In the present study we analyze the effect of one of these alleles, dnaE911, on spontaneous mutagenesis in a mismatch-repair-proficient background. In this background, spontaneous mutations may be the sum of uncorrected replication errors and mutations resulting from other pathways. Hence, the effect of the dnaE allele may provide insights into the contribution of uncorrected DNA replication errors to spontaneous mutation. The data show that dnaE911 decreases the level of Rifr, lacI and galK mutations in this background by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lacI gene reveals that this effect has a clear specificity. Transversions are decreased by approximately 3-fold, whereas transitions, frameshifts, deletions and duplications remain essentially unchanged. Among the transversions, A.T-->T.A are affected most strongly (approximately 6-fold). In addition to this effect on transversions within the lacI gene, one previously recognized A.T-->G.C base-pair substitution hotspot in the lac operator is also reduced (approximately 5-fold). The data are discussed in the light of the role of DNA replication errors in spontaneous mutation, as well as other possible explanations for the observed antimutator effects. JF - Genetics AU - Oller, A R AU - Schaaper, R M AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 263 EP - 270 VL - 138 IS - 2 SN - 0016-6731, 0016-6731 KW - dnaE KW - dnaE911 KW - galK KW - lacI KW - Oligodeoxyribonucleotides KW - 0 KW - DNA Polymerase III KW - EC 2.7.7.- KW - DNA polymerase III, alpha subunit KW - Index Medicus KW - Genotype KW - Frameshift Mutation KW - Genes, Bacterial KW - Base Sequence KW - Genes, Dominant KW - Point Mutation KW - Molecular Sequence Data KW - Sequence Deletion KW - DNA Polymerase III -- genetics KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Mutation KW - DNA Polymerase III -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76949455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Spontaneous+mutation+in+Escherichia+coli+containing+the+dnaE911+DNA+polymerase+antimutator+allele.&rft.au=Oller%2C+A+R%3BSchaaper%2C+R+M&rft.aulast=Oller&rft.aufirst=A&rft.date=1994-10-01&rft.volume=138&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-21 N1 - Date created - 1995-02-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - dnaE; dnaE911; galK; lacI N1 - SuppNotes - Cited By: J Mol Biol. 1986 May 20;189(2):273-84 [3018259] Nature. 1969 Mar 22;221(5186):1128-32 [4975273] Proc Natl Acad Sci U S A. 1989 Jul;86(14):5345-9 [2501784] Environ Mol Mutagen. 1990;16(3):143-8 [2209571] J Biol Chem. 1991 Oct 15;266(29):19127-30 [1918028] Genetics. 1991 Oct;129(2):317-26 [1660424] Environ Mol Mutagen. 1991;18(4):224-30 [1748083] Annu Rev Genet. 1991;25:229-53 [1812808] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7022-5 [1495996] J Biol Chem. 1994 Jan 7;269(1):438-46 [8276833] J Biol Chem. 1994 Feb 25;269(8):5635-43 [8119900] Gene. 1985;39(2-3):181-9 [4092929] Cell. 1984 Jun;37(2):675-82 [6373019] Microbiol Rev. 1984 Mar;48(1):60-93 [6371470] Mol Gen Genet. 1983;189(1):113-7 [6574304] Mol Gen Genet. 1975 Nov 3;141(1):23-40 [765723] J Biol Chem. 1987 Dec 5;262(34):16267-70 [2824485] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients. AN - 76947297; 7826903 AB - It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The extent to which GM-CSF can increase the actual delivered dose intensity of combination chemotherapy over multiple cycles of therapy to patients with advanced breast cancer has not been well defined. We conducted a phase I/II study of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) in combination with GM-CSF in patients with locally advanced and metastatic breast cancer to study the acute and cumulative toxicities, anti-tumor activity and dose-intensity achievable with this regimen. Eighty-one patients with newly diagnosed stages IIB, III and IV breast cancer who were previously untreated with chemotherapy and who had measurable disease received multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered every three weeks. FLAC plus GM-CSF as associated with significant cumulative hematologic toxicity. Ninety-eight percent of patients developed grade 4 neutropenia; 29% of all cycles administered required hospitalization for fever and neutropenia; 41% and 22% of cycles required red blood cell and platelet transfusions, respectively. Other significant toxicities with E. coli-derived GM-CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of patients; and vascular thromboses. The average delivered dose intensities over all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100% and 83% for LABC and metastatic patients, respectively. There were 23% (6/26) pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54) clinical CR's in the stage IV patients. The median survival of the LABC patients has not been reached (> 26 months) and is 30 months for the stage IV patients. The administration of multiple cycles of FLAC plus E. coli-derived GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression, especially thrombocytopenia, as well as significant clinical toxicity. A modest increase in FLAC dose intensity over the starting doses was achievable with the addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF must be balanced by its considerable cost and alteration in patients' quality of life due to toxicity. Combination hematopoietic growth factor strategies may be able to reduce the toxicity of FLAC and to allow further increase dose intensity. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - O'Shaughnessy, J A AU - Denicoff, A M AU - Venzon, D J AU - Danforth, D AU - Pierce, L J AU - Frame, J N AU - Bastian, A AU - Ghosh, B AU - Goldspiel, B AU - Miller, L AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 709 EP - 716 VL - 5 IS - 8 SN - 0923-7534, 0923-7534 KW - Recombinant Proteins KW - 0 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Regression Analysis KW - Doxorubicin -- adverse effects KW - Neoplasm Staging KW - Leucovorin -- administration & dosage KW - Humans KW - Hypotension -- etiology KW - Neutropenia -- prevention & control KW - Neutropenia -- chemically induced KW - Leucovorin -- adverse effects KW - Aged KW - Doxorubicin -- administration & dosage KW - Cyclophosphamide -- adverse effects KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Survival Rate KW - Adult KW - Recombinant Proteins -- adverse effects KW - Escherichia coli KW - Middle Aged KW - Dyspnea -- etiology KW - Recombinant Proteins -- therapeutic use KW - Remission Induction KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76947297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=A+dose+intensity+study+of+FLAC+%285-fluorouracil%2C+leucovorin%2C+doxorubicin%2C+cyclophosphamide%29+chemotherapy+and+Escherichia+coli-derived+granulocyte-macrophage+colony-stimulating+factor+%28GM-CSF%29+in+advanced+breast+cancer+patients.&rft.au=O%27Shaughnessy%2C+J+A%3BDenicoff%2C+A+M%3BVenzon%2C+D+J%3BDanforth%2C+D%3BPierce%2C+L+J%3BFrame%2C+J+N%3BBastian%2C+A%3BGhosh%2C+B%3BGoldspiel%2C+B%3BMiller%2C+L&rft.aulast=O%27Shaughnessy&rft.aufirst=J&rft.date=1994-10-01&rft.volume=5&rft.issue=8&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and stomach cancer in a cohort of Swedish men. AN - 76919947; 7810549 AB - Using the Cancer-Environment Registry of Sweden, which links the 1960 census information on employment with cancer incidence data from 1961-1979, we conducted a systematic, population-based assessment of stomach cancer incidence by industry and occupation for men in Sweden. Nearly 17,000 stomach cancer cases were diagnosed during the 19 years of follow-up. Stomach cancer incidence was elevated among miners and quarrymen, farmers and fishermen, and craftsmen and production workers. Men who held white collar jobs, including professional and technical, administrative and management, clerical, and sales jobs, had a reduction in stomach cancer incidence. Examination of specific jobs revealed generally elevated rates of stomach cancer among men who may be exposed to dusty work environments, such as quarry workers, stone cutters, circular and plane operators, construction workers, crane operators, heavy laborers, and shop and construction metal workers. These occupational associations mostly were observed for stomach cancers of noncardia origin, and no significant associations were found with cardia cancers. We had no information on dietary or other potential confounding factors and cannot make inferences about the role of occupation per se, but the current findings support those of earlier investigations and add to the evidence of a small but significant occupational role in stomach carcinogenesis. JF - American journal of industrial medicine AU - Chow, W H AU - McLaughlin, J K AU - Malker, H S AU - Weiner, J A AU - Ericsson, J L AU - Stone, B J AU - Blot, W J AD - National Cancer Institute, Division of Cancer Etiology, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 511 EP - 520 VL - 26 IS - 4 SN - 0271-3586, 0271-3586 KW - Dust KW - 0 KW - Index Medicus KW - Registries KW - Risk Factors KW - Humans KW - Sweden -- epidemiology KW - Incidence KW - Follow-Up Studies KW - Workplace KW - Poisson Distribution KW - Dust -- adverse effects KW - Male KW - Occupational Diseases -- epidemiology KW - Stomach Neoplasms -- epidemiology KW - Occupations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76919947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupation+and+stomach+cancer+in+a+cohort+of+Swedish+men.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BMalker%2C+H+S%3BWeiner%2C+J+A%3BEricsson%2C+J+L%3BStone%2C+B+J%3BBlot%2C+W+J&rft.aulast=Chow&rft.aufirst=W&rft.date=1994-10-01&rft.volume=26&rft.issue=4&rft.spage=511&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 - 1995-01-31 N1 - Date created - 1995-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coadministration of fluvoxamine increases serum concentrations of haloperidol. AN - 76911194; 7806690 AB - Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine. JF - Journal of clinical psychopharmacology AU - Daniel, D G AU - Randolph, C AU - Jaskiw, G AU - Handel, S AU - Williams, T AU - Abi-Dargham, A AU - Shoaf, S AU - Egan, M AU - Elkashef, A AU - Liboff, S AD - Clinical Brain Disorders Branch, NIMH Neuroscience Center at Saint Elizabeths, Washington, D.C. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 340 EP - 343 VL - 14 IS - 5 SN - 0271-0749, 0271-0749 KW - Benztropine KW - 1NHL2J4X8K KW - Haloperidol KW - J6292F8L3D KW - Fluvoxamine KW - O4L1XPO44W KW - Index Medicus KW - Benztropine -- adverse effects KW - Drug Administration Schedule KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Benztropine -- pharmacokinetics KW - Drug Therapy, Combination KW - Benztropine -- administration & dosage KW - Psychiatric Status Rating Scales KW - Adult KW - Neurologic Examination -- drug effects KW - Cross-Over Studies KW - Middle Aged KW - Chronic Disease KW - Male KW - Haloperidol -- adverse effects KW - Fluvoxamine -- adverse effects KW - Schizophrenia -- blood KW - Haloperidol -- pharmacokinetics KW - Haloperidol -- administration & dosage KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Fluvoxamine -- pharmacokinetics KW - Fluvoxamine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Coadministration+of+fluvoxamine+increases+serum+concentrations+of+haloperidol.&rft.au=Daniel%2C+D+G%3BRandolph%2C+C%3BJaskiw%2C+G%3BHandel%2C+S%3BWilliams%2C+T%3BAbi-Dargham%2C+A%3BShoaf%2C+S%3BEgan%2C+M%3BElkashef%2C+A%3BLiboff%2C+S&rft.aulast=Daniel&rft.aufirst=D&rft.date=1994-10-01&rft.volume=14&rft.issue=5&rft.spage=340&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 - 1995-02-01 N1 - Date created - 1995-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heavy drinking and the risk of occupational injury. AN - 76895867; 7999210 AB - This study evaluated the association between the frequency of heavy drinking and the risk of occupational injury, using nationally representative data from the 1988 National Health Interview Survey (NHIS). The sample consisted of 29,192 adults who were employed at some time during the year preceding the NHIS interview. Overall, 7.2% reported an on-the-job injury during the preceding year, but the rates were higher--about 13%--for those employed as skilled or unskilled laborers or who reported engaging in repeated strenuous physical activity at work. Slightly more than one-fourth of the employed adults reported at least one occasion of drinking five or more drinks during the preceding year. After adjusting for the effects of age, gender, education, occupation, and strenuous job activity, the odds of occupational injury increased with frequency of heavy drinking, with odds ratios varying from 1.08 (one occasion of heavy drinking) to 1.74 (daily heavy drinking). Odds ratios were decreased slightly by the inclusion of smoking as a control variable, indicating that some of the excess risk of injury among heavy drinkers may reflect their greater propensity to take health-related risks rather than direct effects of ethanol. The odds ratios also were slightly lower when the analysis was restricted to current drinkers, suggesting that the risk of work injury was increased by light or moderate as well as heavy drinking. JF - Accident; analysis and prevention AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 655 EP - 665 VL - 26 IS - 5 SN - 0001-4575, 0001-4575 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Smoking -- adverse effects KW - Smoking -- epidemiology KW - Risk Factors KW - Adult KW - Health Surveys KW - Middle Aged KW - Adolescent KW - Bias (Epidemiology) KW - Occupations KW - United States -- epidemiology KW - Female KW - Male KW - Wounds and Injuries -- epidemiology KW - Wounds and Injuries -- etiology KW - Accidents, Occupational -- statistics & numerical data KW - Alcohol Drinking -- adverse effects KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76895867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Accident%3B+analysis+and+prevention&rft.atitle=Heavy+drinking+and+the+risk+of+occupational+injury.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1994-10-01&rft.volume=26&rft.issue=5&rft.spage=655&rft.isbn=&rft.btitle=&rft.title=Accident%3B+analysis+and+prevention&rft.issn=00014575&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-20 N1 - Date created - 1995-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The design and test of a new volume coil for high field imaging. AN - 76888710; 7997115 AB - A major problem in the development of high field (> 100 MHz) large volume (> 6000 cm3) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B1 homogeneity. JF - Magnetic resonance in medicine AU - Wen, H AU - Chesnick, A S AU - Balaban, R S AD - Laboratory of Cardiac Energetics, NHLBI, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 492 EP - 498 VL - 32 IS - 4 SN - 0740-3194, 0740-3194 KW - Index Medicus KW - Equipment Design KW - Models, Structural KW - Radiation Protection KW - Humans KW - Head -- anatomy & histology KW - Magnetic Resonance Imaging -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76888710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+resonance+in+medicine&rft.atitle=The+design+and+test+of+a+new+volume+coil+for+high+field+imaging.&rft.au=Wen%2C+H%3BChesnick%2C+A+S%3BBalaban%2C+R+S&rft.aulast=Wen&rft.aufirst=H&rft.date=1994-10-01&rft.volume=32&rft.issue=4&rft.spage=492&rft.isbn=&rft.btitle=&rft.title=Magnetic+resonance+in+medicine&rft.issn=07403194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Magn Reson Med. 1988 Sep;8(1):104-9 [3173064] Radiology. 1988 Dec;169(3):811-6 [3187004] NMR Biomed. 1990 Feb;3(1):31-45 [2390452] Magn Reson Med. 1992 Jan;23(1):37-45 [1734182] Magn Reson Med. 1991 Nov;22(1):159-66 [1798390] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5675-9 [1608978] Magn Reson Med. 1993 Feb;29(2):277-9 [8429797] Magn Reson Med. 1993 May;29(5):713-6 [8505911] J Magn Reson. 2011 Dec;213(2):329-43 [22152352] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-human immunodeficiency virus type 1 activity of hydroxyurea in combination with 2',3'-dideoxynucleosides. AN - 76836407; 7969058 AB - The effects of hydroxyurea (HU), an inhibitor of ribonucleotide reductase, on the replication of human immunodeficiency virus type 1 (HIV-1) in activated peripheral blood mononuclear cells were studied. The inhibition of HIV-1 replication by HU alone was dose dependent, with a 90% inhibitory concentration of 0.4 mM, a plasma concentration tolerated by patients with oncological diseases. HU at lower concentrations ( 50%. Analyses using high performance liquid chromatography and enzymatic assays suggested that the greater degree of potentiation by HU of the action of ddl, compared with the other dideoxynucleosides, is due to the more effective inhibition by HU of dATP synthesis, compared with the synthesis of the other deoxynucleoside triphosphates (dGTP, dTTP, and dCTP). The present study suggests that, for appropriate agents, pharmacological reduction of deoxynucleoside triphosphate levels represents a potential therapeutic approach for inhibition of HIV-1 replication. JF - Molecular pharmacology AU - Gao, W Y AU - Johns, D G AU - Mitsuya, H AD - Experimental Retrovirology Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 767 EP - 772 VL - 46 IS - 4 SN - 0026-895X, 0026-895X KW - Antiviral Agents KW - 0 KW - Dideoxynucleosides KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - Didanosine KW - K3GDH6OH08 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - AIDS/HIV KW - Virus Replication -- drug effects KW - Cells, Cultured KW - Humans KW - Zidovudine -- pharmacology KW - Zalcitabine -- pharmacology KW - Drug Synergism KW - Didanosine -- pharmacology KW - Dideoxynucleosides -- pharmacology KW - Antiviral Agents -- pharmacology KW - Hydroxyurea -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76836407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-human+immunodeficiency+virus+type+1+activity+of+hydroxyurea+in+combination+with+2%27%2C3%27-dideoxynucleosides.&rft.au=Gao%2C+W+Y%3BJohns%2C+D+G%3BMitsuya%2C+H&rft.aulast=Gao&rft.aufirst=W&rft.date=1994-10-01&rft.volume=46&rft.issue=4&rft.spage=767&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 - 1994-12-06 N1 - Date created - 1994-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in lung cancers from Japanese mustard gas workers. AN - 76824673; 7955036 AB - Mustard gas (MG) is a mutagenic and carcinogenic alkylating agent, and is a known risk factor for occupational lung cancer. Our hypothesis is that lung cancers from MG workers contain mutations (G:C to A:T transitions) as the result of MG-produced DNA promutagenic adducts in the p53 tumor suppressor gene. We analyzed 12 primary lung cancers from Japanese MG factory workers and 12 lung cancers from non-exposed individuals. Genomic DNA was isolated from archival paraffin-embedded tissues. Exons 5-8 were amplified by polymerase chain reaction using p53-specific primers, and sequenced by dideoxy termination methods. Six out of 12 lung cancers from MG workers contained a total of eight somatic point mutations: two cases had double G:C to A:T transitions; one had a G:C to T:A transversion; one case had an A:T to G:C transition; and two cases had single base deletions. Four of the six mutated purines occurred on the non-transcribed, DNA-coding strand. Out of 12 unexposed cases, there were six single base mutations in six cancers, and no double mutations. The p53 mutational frequency in the MG-exposed cases is similar to the non-exposed controls and the usual smoking-related lung cancers reported previously. However, the distinctive double mutations (G:C to A:T transition) observed in two cases are unusual and may be related to MG exposure. JF - Carcinogenesis AU - Takeshima, Y AU - Inai, K AU - Bennett, W P AU - Metcalf, R A AU - Welsh, J A AU - Yonehara, S AU - Hayashi, Y AU - Fujihara, M AU - Yamakido, M AU - Akiyama, M AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2075 EP - 2079 VL - 15 IS - 10 SN - 0143-3334, 0143-3334 KW - p53 KW - Codon KW - 0 KW - DNA, Neoplasm KW - Mustard Gas KW - T8KEC9FH9P KW - Index Medicus KW - DNA Damage KW - Exons KW - Humans KW - Aged KW - DNA, Neoplasm -- drug effects KW - Japan -- epidemiology KW - Aged, 80 and over KW - Point Mutation KW - Case-Control Studies KW - DNA, Neoplasm -- genetics KW - Middle Aged KW - Male KW - Occupational Diseases -- genetics KW - Lung Neoplasms -- epidemiology KW - Genes, p53 -- drug effects KW - Mustard Gas -- adverse effects KW - Lung Neoplasms -- genetics KW - Occupational Diseases -- epidemiology KW - Lung Neoplasms -- chemically induced KW - Occupational Diseases -- chemically induced KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76824673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+lung+cancers+from+Japanese+mustard+gas+workers.&rft.au=Takeshima%2C+Y%3BInai%2C+K%3BBennett%2C+W+P%3BMetcalf%2C+R+A%3BWelsh%2C+J+A%3BYonehara%2C+S%3BHayashi%2C+Y%3BFujihara%2C+M%3BYamakido%2C+M%3BAkiyama%2C+M&rft.aulast=Takeshima&rft.aufirst=Y&rft.date=1994-10-01&rft.volume=15&rft.issue=10&rft.spage=2075&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ras proto-oncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice. AN - 76823788; 7955063 AB - The frequency and mutation spectra of proto-oncogene activation in hepatocellular neoplasms induced by tetrachloroethylene, trichloroethylene and dichloroacetic acid were examined to help define the molecular basis for their carcinogenicity. H-ras codon 61 activation was not significantly different among dichloroacetic acid- and trichloroethylene-induced and combined historical and concurrent control hepatocellular tumors (62%, 51% and 69% respectively). The mutation spectra of H-ras codon 61 mutations showed a significant decrease in AAA and increase in CTA mutations for dichloroacetic acid- and trichloroethylene-induced tumors when compared to combined controls. The H-ras codon 61 mutation frequency for tetrachloroethylene-induced tumors was significantly lower (24%) than that of combined controls and also that of the two other chemicals. Mutations at codons 13 and 117 plus a second exon insert contributed 4% to the total H-ras frequencies for trichloroethylene and tetrachloroethylene. There was also a higher incidence of K-ras activation (13%) in tetrachloroethylene-induced tumors than in the other chemically induced or control tumors. Four liver tumors were found to contain insertions of additional bases within the second exon of K- or H-ras. These findings suggest that exposure to dichloroacetic acid, trichloroethylene and tetrachloroethylene provides a selective growth advantage to spontaneously occurring mutations in codon 61 of H-ras and, at the same time, is responsible for a small number of unique molecular lesions suggestive of either a random genotoxic mode of action or a non-specific result of secondary DNA damage. However, the absence of ras activation in many of the liver neoplasms suggests that alternative mechanisms are also important in B6C3F1 mouse hepatocarcinogenesis. JF - Carcinogenesis AU - Anna, C H AU - Maronpot, R R AU - Pereira, M A AU - Foley, J F AU - Malarkey, D E AU - Anderson, M W AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2255 EP - 2261 VL - 15 IS - 10 SN - 0143-3334, 0143-3334 KW - c-jun KW - c-myc KW - ras KW - Codon KW - 0 KW - Trichloroethylene KW - 290YE8AR51 KW - Dichloroacetic Acid KW - 9LSH52S3LQ KW - Tetrachloroethylene KW - TJ904HH8SN KW - Index Medicus KW - Animals KW - Exons KW - Mice KW - Mice, Nude KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Base Sequence KW - Carcinogenicity Tests KW - Molecular Sequence Data KW - Mutation KW - Cell Transformation, Neoplastic -- genetics KW - Male KW - Liver Neoplasms, Experimental -- genetics KW - Dichloroacetic Acid -- toxicity KW - Genes, ras -- drug effects KW - Liver Neoplasms, Experimental -- chemically induced KW - Tetrachloroethylene -- toxicity KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Trichloroethylene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76823788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=ras+proto-oncogene+activation+in+dichloroacetic+acid-%2C+trichloroethylene-+and+tetrachloroethylene-induced+liver+tumors+in+B6C3F1+mice.&rft.au=Anna%2C+C+H%3BMaronpot%2C+R+R%3BPereira%2C+M+A%3BFoley%2C+J+F%3BMalarkey%2C+D+E%3BAnderson%2C+M+W&rft.aulast=Anna&rft.aufirst=C&rft.date=1994-10-01&rft.volume=15&rft.issue=10&rft.spage=2255&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-jun; c-myc; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Fpg protein, a DNA repair enzyme, is inhibited by the biomediator nitric oxide in vitro and in vivo. AN - 76823740; 7955043 AB - Nitric oxide has been shown to be a mediator molecule in the regulation of many physiological functions. However, this small diatomic molecule in the presence of O2 generates reactive intermediates which modify DNA bases and inactive enzymes at high concentrations (100 microM). We report that NO generated by 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA/NO, Et2NN(O)NO-Na+), a compound known to release NO in a predictable manner, caused irreversible damage at physiological concentrations to the zinc finger-containing DNA repair enzyme formamidopyrimidine-DNA glycolyase (Fpg protein). The inhibition of the enzyme activity was DEA/NO dose and time dependent with IC50s with respect to total NO released from this compound of approximately 110 and approximately 120 mumol/l respectively. This inhibitory effect by P3 was not reversible over time in the presence of reducing agents and/or Zn2+. Nitrite and diethylamine, the nitrogenous products of the decomposition of DEA/NO, did not inhibit the enzyme. The presence of 500 micrograms/ml bovine serum albumin did not protect the protein from the inhibitory effects of DEA/NO, however, the presence of 10 mM cysteine did dramatically abate the inhibition of the Fpg protein by DEA/NO. Other DNA glycosylases tested were not inhibited by exposure to these concentrations of NO. These results, together with reports of site-directed mutagenesis of this protein, suggest that the cysteine residues contained within the zinc finger motif of the Fpg protein are the primary sites of NO interaction. Our studies were then extended to intact cells. The Fpg protein activity was decreased following treatment in vivo when Escherichia coli MH321 (acr A-) cells were treated with DEA/NO. Furthermore, the Fapy-DNA glycosylase activity in H4 cells, a rat hepatoma line, was decreased when intact cells were incubated with DEA/NO. JF - Carcinogenesis AU - Wink, D A AU - Laval, J AD - Chemistry Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2125 EP - 2129 VL - 15 IS - 10 SN - 0143-3334, 0143-3334 KW - Escherichia coli Proteins KW - 0 KW - Hydrazines KW - Nitrogen Oxides KW - Nitric Oxide KW - 31C4KY9ESH KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - DNA-formamidopyrimidine glycosylase, E coli KW - DNA Ligases KW - EC 6.5.1.- KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Macrophages -- enzymology KW - Animals KW - Hydrazines -- pharmacology KW - DNA Ligases -- antagonists & inhibitors KW - Kinetics KW - Neutrophils -- enzymology KW - DNA Ligases -- metabolism KW - DNA Repair -- drug effects KW - N-Glycosyl Hydrolases -- metabolism KW - Nitric Oxide -- pharmacology KW - Nitric Oxide -- physiology KW - N-Glycosyl Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76823740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Fpg+protein%2C+a+DNA+repair+enzyme%2C+is+inhibited+by+the+biomediator+nitric+oxide+in+vitro+and+in+vivo.&rft.au=Wink%2C+D+A%3BLaval%2C+J&rft.aulast=Wink&rft.aufirst=D&rft.date=1994-10-01&rft.volume=60&rft.issue=4&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Praxis+der+Kinderpsychologie+und+Kinderpsychiatrie&rft.issn=00327034&rft_id=info:doi/10.13109%2Fprkk.2011.60.4.253 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: potential implications for the syndrome of inappropriate vasopressin secretion. AN - 76814373; 7962300 AB - We recently demonstrated that sc administered interleukin-6 (IL-6) strongly stimulates the human hypothalamic-pituitary-adrenal (HPA) axis, with mild toxicity and no hypotensive effects. In this study, we evaluated the response of the human HPA axis to escalating iv doses of recombinant IL-6 in six patients with cancer and good performance status who received daily, every 8 h, three equal doses of 0.3-30 micrograms/kg IL-6. The plasma levels of IL-6 assayed by a specific enzyme-linked immunosorbent assay during the 4 h following the first IL-6 injection were elevated for 2-4 h, proportionally to the amount of injected IL-6. Administration of the cytokine was followed by marked elevations of plasma ACTH (53.0-98.6 pmol/L) and cortisol (824.9-1729.9 nmol/L) independently of the IL-6 dose administered, suggesting that the doses employed were at the top of the dose-response curve for these hormones. Interestingly, plasma arginine vasopressin (AVP) levels were also elevated during the 2 h after IL-6 injection in all patients who received a dose of 3 micrograms/kg or more, suggesting that IL-6 activated the magnocellular AVP-secreting neurons and that it might be involved in the syndrome of inappropriate AVP secretion. Cortisol elevations with peaks similar to those observed after the first injection of IL-6 were also detected in plasma sampled every 2 h after the second and third injections, suggesting that there was no rapid tachyphylaxis in response to IL-6 administration. Plasma IL-1 beta and tumor necrosis factor-alpha concentrations, assayed by specific enzyme-linked immunosorbent assays during the 4 h after the first IL-6 injection, were either within the normal range or undetectable, confirming in vitro observations that IL-6 does not stimulate IL-1 beta or tumor necrosis factor-alpha secretion and suggesting that it exerts its effect on the HPA axis and AVP secretion independently of them. We conclude that IL-6 is a potent stimulator of the human HPA axis and a secretagogue of magnocellular AVP secretion, which might be employed as a challenge test of the axis and the magnocellular AVP neuron. JF - The Journal of clinical endocrinology and metabolism AU - Mastorakos, G AU - Weber, J S AU - Magiakou, M A AU - Gunn, H AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 934 EP - 939 VL - 79 IS - 4 SN - 0021-972X, 0021-972X KW - Cytokines KW - 0 KW - Interleukin-6 KW - Recombinant Proteins KW - Arginine Vasopressin KW - 113-79-1 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Cytokines -- blood KW - Corticotropin-Releasing Hormone -- blood KW - Circadian Rhythm KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Hydrocortisone -- blood KW - Female KW - Adrenocorticotropic Hormone -- blood KW - Hypothalamo-Hypophyseal System -- physiology KW - Hypothalamo-Hypophyseal System -- drug effects KW - Arginine Vasopressin -- blood KW - Arginine Vasopressin -- secretion KW - Interleukin-6 -- pharmacology KW - Inappropriate ADH Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76814373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypothalamic-pituitary-adrenal+axis+activation+and+stimulation+of+systemic+vasopressin+secretion+by+recombinant+interleukin-6+in+humans%3A+potential+implications+for+the+syndrome+of+inappropriate+vasopressin+secretion.&rft.au=Mastorakos%2C+G%3BWeber%2C+J+S%3BMagiakou%2C+M+A%3BGunn%2C+H%3BChrousos%2C+G+P&rft.aulast=Mastorakos&rft.aufirst=G&rft.date=1994-10-01&rft.volume=79&rft.issue=4&rft.spage=934&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 - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Endocrinol Metab. 1994 Oct;79(4):932-3 [7962299] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion by polychlorinated biphenyls of lung and liver tumors in mice. AN - 76812851; 7955061 AB - Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been seen between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcinogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitrosodimethylamine (NDMA), were promoted by later treatment with Aroclor 1254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated lung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multiplicities of lung tumors were enhanced four-fold by PCBs at 28 and 52 weeks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA-PCB groups. Liver tumors first occurred in significant numbers at 52 weeks and only in mice receiving both NDMA and PCBs. As for the lung, at 72 weeks the incidence was high in both the NDMA-only and NDMA-PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive association between lung tumor numbers at 28 weeks and relative percentage of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by triggering the early appearance of latent initiated tumors otherwise presenting in old age. JF - Carcinogenesis AU - Anderson, L M AU - Logsdon, D AU - Ruskie, S AU - Fox, S D AU - Issaq, H J AU - Kovatch, R M AU - Riggs, C M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Ft Detrick, MD 21702-1201. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2245 EP - 2248 VL - 15 IS - 10 SN - 0143-3334, 0143-3334 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Body Burden KW - Mice KW - Male KW - Female KW - Polychlorinated Biphenyls -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76812851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Promotion+by+polychlorinated+biphenyls+of+lung+and+liver+tumors+in+mice.&rft.au=Anderson%2C+L+M%3BLogsdon%2C+D%3BRuskie%2C+S%3BFox%2C+S+D%3BIssaq%2C+H+J%3BKovatch%2C+R+M%3BRiggs%2C+C+M&rft.aulast=Anderson&rft.aufirst=L&rft.date=1994-10-01&rft.volume=15&rft.issue=10&rft.spage=2245&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High dietary retinoic acid prevents malignant conversion of skin papillomas induced by a two-stage carcinogenesis protocol in female SENCAR mice. AN - 76807654; 7955082 AB - We have previously reported that high dietary retinoic acid (RA; 30 micrograms/g diet) inhibits carcinoma formation in a two-stage skin carcinogenesis protocol, using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as the tumor-promoter in female SENCAR mice. We next asked whether switching the diets from high to control levels of RA and vice versa would influence carcinoma formation. Mice at 3 weeks of age were initiated with DMBA (20 micrograms) once, followed by 20 weekly applications of TPA (2 micrograms). At 3 weeks of age mice were weaned onto a diet containing either 3 (control) or 30 (high) micrograms RA/g diet. Half of the mice from either dietary group were switched to the other diet at 20 weeks of age, when papilloma formation was at its peak. These four groups are designated RA 3 micrograms, RA 30 micrograms, RA 3/30 micrograms and RA 30/3 micrograms groups. As previously found, papilloma formation (including incidence and yield) was not significantly affected by dietary treatment. However, high dietary RA inhibited carcinoma formation; specifically cumulative carcinoma incidence (18.5-23.1% versus 50%) and yield (0.19-0.23 versus 0.68) were significantly lower (P < 0.05) in the high dietary RA treatment groups than the RA 3 micrograms control group, as was the carcinoma conversion efficiency (2.1-3.8% versus 9.4%). The beneficial effect on carcinoma formation was still evident when excess RA was given late during the carcinogenesis process (i.e. the RA 3/30 micrograms group). Moreover, a residual effect of excess RA was also seen after the dietary RA was switched to the control level at 20 weeks of age, when papilloma yield was highest (i.e. the RA 30/3 micrograms group). It is therefore concluded that the chemopreventive effect of high dietary RA on skin carcinogenesis induced by a two-stage carcinogenesis protocol with DMBA and TPA resides mainly at the step of conversion from benign papillomas to malignant carcinomas. JF - Carcinogenesis AU - Chen, L C AU - Sly, L AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2383 EP - 2386 VL - 15 IS - 10 SN - 0143-3334, 0143-3334 KW - Anticarcinogenic Agents KW - 0 KW - Tretinoin KW - 5688UTC01R KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Mice KW - Mice, Inbred SENCAR KW - Male KW - Female KW - Pregnancy KW - Anticarcinogenic Agents -- therapeutic use KW - Papilloma -- prevention & control KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- prevention & control KW - Papilloma -- chemically induced KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76807654?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=High+dietary+retinoic+acid+prevents+malignant+conversion+of+skin+papillomas+induced+by+a+two-stage+carcinogenesis+protocol+in+female+SENCAR+mice.&rft.au=Chen%2C+L+C%3BSly%2C+L%3BDe+Luca%2C+L+M&rft.aulast=Webb&rft.aufirst=C.&rft.date=2011-12-01&rft.volume=16&rft.issue=4&rft.spage=e236&rft.isbn=&rft.btitle=&rft.title=Eating+and+Weight+Disorders&rft.issn=11244909&rft_id=info:doi/10.1007%2FBF03327466 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidation of 1,1-dimethylhydrazine (UDMH) in aqueous solution with air and hydrogen peroxide. AN - 76803420; 7953474 AB - The degradation of 1,1-dimethylhydrazine (UDMH), a component of some rocket fuels, was investigated using atmospheric oxygen and hydrogen peroxide. The reactions were carried out in the presence and absence of copper catalysis and at varying pH. Reactions were also carried out in the presence of hydrazine, a constituent, along with UDMH, of the rocket fuel Aerozine-50. In the presence of copper, UDMH was degraded by air passed through the solution; the efficiency of degradation increased as the pH increased but the carcinogen N-nitrosodimethylamine (NDMA) was formed at neutral and alkaline pH. Oxidation was not seen in the absence of copper. Production of NDMA occurred even at copper concentrations of < 1 ppm. Oxidation of UDMH with hydrogen peroxide also gave rise to NDMA. When copper was absent degradation of UDMH did not occur at acid pH but when copper was present some degradation occurred at all pH levels investigated. The production of NDMA occurred mostly at neutral and alkaline pH. In general, higher concentrations of hydrogen peroxide and copper favored the production of NDMA. Dimethylamine, methanol, formaldehyde dimethylhydrazone, formaldehyde hydrazone, and tetramethyltetrazene were also produced. The last three compounds were tested and found to be mutagenic. JF - Chemosphere AU - Lunn, G AU - Sansone, E B AD - PRI/DynCorp, Environmental Control and Research Program, NCI-Frederich Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1577 EP - 1590 VL - 29 IS - 7 SN - 0045-6535, 0045-6535 KW - Dimethylhydrazines KW - 0 KW - dimazine KW - 4WPQ90N53J KW - Copper KW - 789U1901C5 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - Mutagenicity Tests KW - Salmonella typhimurium -- drug effects KW - Dimethylhydrazines -- pharmacology KW - Dimethylhydrazines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76803420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Oxidation+of+1%2C1-dimethylhydrazine+%28UDMH%29+in+aqueous+solution+with+air+and+hydrogen+peroxide.&rft.au=Lunn%2C+G%3BSansone%2C+E+B&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-10-01&rft.volume=29&rft.issue=7&rft.spage=1577&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-22 N1 - Date created - 1994-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunochemical methods of studying the mechanism of diclofenac-induced hepatitis. AN - 76792162; 7945484 JF - Arthritis and rheumatism AU - Pohl, L R AU - Martin, J L AU - Hargus, S J AD - NHLBI, NIH, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1557 VL - 37 IS - 10 SN - 0004-3591, 0004-3591 KW - Antibodies KW - 0 KW - Diclofenac KW - 144O8QL0L1 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Liver -- metabolism KW - Mice KW - Liver -- chemistry KW - Diclofenac -- analysis KW - Chemical and Drug Induced Liver Injury -- etiology KW - Diclofenac -- adverse effects KW - Immunohistochemistry -- methods KW - Chemical and Drug Induced Liver Injury -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76792162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Immunochemical+methods+of+studying+the+mechanism+of+diclofenac-induced+hepatitis.&rft.au=Pohl%2C+L+R%3BMartin%2C+J+L%3BHargus%2C+S+J&rft.aulast=Pohl&rft.aufirst=L&rft.date=1994-10-01&rft.volume=37&rft.issue=10&rft.spage=1557&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-14 N1 - Date created - 1994-11-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Republished From: Arthritis Rheum. 1994 Jul;37(7):1112 [8024621] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P-glycoprotein-mediated multidrug resistance in normal and neoplastic hematopoietic cells. AN - 76790646; 7948302 AB - The multidrug transporter, P-glycoprotein (P-gp), is expressed by CD34-positive bone marrow cells, which include hematopoietic stem cells, and in other cells in the bone marrow and peripheral blood, including some lymphoid cells. Multidrug resistance mediated by P-gp appears to be a major impediment to successful treatment of acute myeloid leukemias and multiple myelomas. However, the impact of P-gp expression on prognosis has to be confirmed in several other hematopoietic neoplasms. The role of P-gp in normal and malignant hematopoiesis and clinical attempts to circumvent multidrug resistance in hematopoietic malignancies are reviewed. The recent transduction of the MDR1 gene into murine hematopoietic cells, which protects them from toxic effects of chemotherapy, suggests that MDR1 gene therapy may help prevent myelosuppression following chemotherapy. JF - Annals of hematology AU - Licht, T AU - Pastan, I AU - Gottesman, M AU - Herrmann, F AD - National Cancer Institute, NIH, Laboratory of Molecular Biology, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 159 EP - 171 VL - 69 IS - 4 SN - 0939-5555, 0939-5555 KW - MDR1 KW - P-Glycoprotein KW - 0 KW - Index Medicus KW - Multiple Myeloma -- pathology KW - Humans KW - Lymphoma -- pathology KW - Lymphoma -- physiopathology KW - Multiple Myeloma -- physiopathology KW - Leukemia -- pathology KW - P-Glycoprotein -- physiology KW - Drug Resistance, Multiple -- physiology KW - Hematopoietic Stem Cells -- cytology KW - Hematopoietic Stem Cells -- physiology KW - Leukemia -- physiopathology KW - Hematopoietic Stem Cells -- drug effects KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76790646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Golden%2C+Claire+Rachel&rft.aulast=Golden&rft.aufirst=Claire&rft.date=2014-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=978-1-303-53275-7&rft.btitle=&rft.title=The+relationship+between+disordered+eating+and+coping+styles%3A+Presentation+of+disordered+eating+in+ethnically+diverse+female+college+students&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of differentiation and covalent binding to proteins by the synthetic retinoids Ch55 and Am80. AN - 76789938; 7944409 AB - all-trans-Retinoic acid (RA) is a potent inducer in vitro of the differentiation of the human acute myeloid leukemia cell line HL60. A mechanism for RA-induced differentiation of HL60 cells may involve retinoylation (RA acylation) which is a post-translational modification of proteins occurring in many eukaryotic cell lines. Here, we found that differentiation by the synthetic retinoid (E)4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]-benzoic acid (Ch55) was dose-dependent in serum-free medium. The synthetic retinoid 4(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarbamoyl) benzoic acid (Am80) did not induce differentiation. Ch55 bound covalently to proteins of HL60 cells. In contrast, covalent binding of Am80 to HL60 proteins was much lower. Two-dimensional gel electrophoresis patterns of proteins labeled covalently by RA and Ch55 were different with few proteins labeled by both retinoids. The level of retinoylation was increased by Am80 and combinations of RA with either Ch55 or Am80 synergistically induced differentiation of HL60 cells. These results suggest that covalent modification of proteins by a retinoid may play a role in inducing differentiation of HL60 cells. In addition, the synergy seen with combinations of RA and either Ch55 or Am80 suggests that some synthetic retinoids may be active because they displace RA from intracellular sites or because they inhibit RA catabolism. JF - Archives of biochemistry and biophysics AU - Takahashi, N AU - Breitman, T R AD - Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 82 EP - 89 VL - 314 IS - 1 SN - 0003-9861, 0003-9861 KW - Benzoates KW - 0 KW - Chalcones KW - Neoplasm Proteins KW - Tetrahydronaphthalenes KW - tamibarotene KW - 08V52GZ3H9 KW - Tretinoin KW - 5688UTC01R KW - Chalcone KW - 5S5A2Q39HX KW - 3,5-di-tert-butylchalcone 4'-carboxylic acid KW - 95906-67-5 KW - Index Medicus KW - Tretinoin -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - Electrophoresis, Gel, Two-Dimensional KW - Tretinoin -- metabolism KW - Leukemia, Promyelocytic, Acute KW - Drug Synergism KW - Neoplasm Proteins -- metabolism KW - Tetrahydronaphthalenes -- metabolism KW - Tetrahydronaphthalenes -- pharmacology KW - Protein Binding -- drug effects KW - Benzoates -- metabolism KW - Chalcone -- analogs & derivatives KW - Chalcone -- pharmacology KW - Cell Differentiation -- drug effects KW - Benzoates -- pharmacology KW - Chalcone -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76789938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+differentiation+and+covalent+binding+to+proteins+by+the+synthetic+retinoids+Ch55+and+Am80.&rft.au=Takahashi%2C+N%3BBreitman%2C+T+R&rft.aulast=Takahashi&rft.aufirst=N&rft.date=1994-10-01&rft.volume=314&rft.issue=1&rft.spage=82&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 - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characteristics of HPRT-mutant T cell lines in a lupus patient treated with cyclophosphamide. AN - 76788470; 7945481 AB - This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC. JF - Arthritis and rheumatism AU - Wood, G M AU - Dawisha, S AU - Gourley, M AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1548 EP - 1552 VL - 37 IS - 10 SN - 0004-3591, 0004-3591 KW - Receptors, Antigen, T-Cell KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infusions, Intravenous KW - Humans KW - Adult KW - Receptors, Antigen, T-Cell -- analysis KW - Mutation KW - Female KW - Cell Line KW - Lupus Erythematosus, Systemic -- pathology KW - Cyclophosphamide -- administration & dosage KW - CD8-Positive T-Lymphocytes -- pathology KW - Lupus Erythematosus, Systemic -- drug therapy KW - CD8-Positive T-Lymphocytes -- chemistry KW - CD4-Positive T-Lymphocytes -- pathology KW - CD4-Positive T-Lymphocytes -- chemistry KW - Hypoxanthine Phosphoribosyltransferase -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76788470?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Characteristics+of+HPRT-mutant+T+cell+lines+in+a+lupus+patient+treated+with+cyclophosphamide.&rft.au=Wood%2C+G+M%3BDawisha%2C+S%3BGourley%2C+M&rft.aulast=Wood&rft.aufirst=G&rft.date=1994-10-01&rft.volume=37&rft.issue=10&rft.spage=1548&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-14 N1 - Date created - 1994-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination paclitaxel (Taxol) and doxorubicin therapy for metastatic breast cancer. AN - 76788165; 7939757 AB - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a very active agent for the treatment of breast cancer, with associated complete response rates of 12% in patients with minimally pretreated metastatic disease. Simultaneous paclitaxel and doxorubicin administration by 72-hour continuous infusion in patients with previously untreated metastatic breast cancer has yielded an overall response rate of 72% with 8% complete responses. No alterations in paclitaxel or doxorubicin pharmacokinetics were observed when the drugs were administered alone versus in combination. Two phase I studies from the M.D. Anderson Cancer Center (Houston, TX) and the University of Indiana (Indianapolis, IN) have shown that administration of a 24-hour paclitaxel infusion prior to doxorubicin results in a significantly higher incidence of mucositis than the reverse sequence. Preliminary pharmacokinetic studies from M.D. Anderson suggest that peak plasma concentration and clearance of doxorubicin are altered by pretreatment with 24-hour paclitaxel. In contrast, in an ongoing phase I study at the Istituto Nazionale Tumori in Milan, Italy, no differences in toxicities have been observed with the combination of intravenous bolus doxorubicin and 3-hour infusional paclitaxel administered by either sequence. Preclinical in vitro and in vivo studies suggest that the combination of paclitaxel and doxorubicin is associated with no or minimal additive antitumor effects. The modest complete response rates that have been observed in patients with metastatic breast cancer to date are in agreement with these observations. A randomized study of paclitaxel versus doxorubicin versus intravenous bolus doxorubicin followed by 24-hour paclitaxel is now being conducted by the Eastern Cooperative Oncology Group. JF - Seminars in oncology AU - O'Shaughnessy, J A AU - Fisherman, J S AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 19 EP - 23 VL - 21 IS - 5 Suppl 8 SN - 0093-7754, 0093-7754 KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Neoplasm Metastasis KW - Clinical Trials as Topic KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- drug therapy KW - Doxorubicin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76788165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Sitnikov%2C+Lilya&rft.aulast=Sitnikov&rft.aufirst=Lilya&rft.date=2015-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=978-1-321-06861-0&rft.btitle=&rft.title=Emotion+regulation+strategies+in+binge+eating+disorder%3A+Rumination%2C+distress+tolerance%2C+and+expectancies+for+eating&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-08 N1 - Date created - 1994-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphic admixture typing in human ethnic populations. AN - 76785493; 7942857 AB - A panel of 257 RFLP loci was selected on the basis of high heterozygosity in Caucasian DNA surveys and equivalent spacing throughout the human genome. Probes from each locus were used in a Southern blot survey of allele frequency distribution for four human ethnic groups: Caucasian, African American, Asian (Chinese), and American Indian (Cheyenne). Nearly all RFLP loci were polymorphic in each group, albeit with a broad range of differing allele frequencies (delta). The distribution of frequency differences (delta values) was used for three purposes: (1) to provide estimates for genetic distance (differentiation) among these ethnic groups, (2) to revisit with a large data set the proportion of human genetic variation attributable to differentiation within ethnic groups, and (3) to identify loci with high delta values between recently admixed populations of use in mapping by admixture linkage disequilibrium (MALD). Although most markers display significant allele frequency differences between ethnic groups, the overall genetic distances between ethnic groups were small (.066-.098), and < 10% of the measured overall molecular genetic diversity in these human samples can be attributed to "racial" differentiation. The median delta values for pairwise comparisons between groups fell between .15 and .20, permitting identification of highly informative RFLP loci for MALD disease association studies. JF - American journal of human genetics AU - Dean, M AU - Stephens, J C AU - Winkler, C AU - Lomb, D A AU - Ramsburg, M AU - Boaze, R AU - Stewart, C AU - Charbonneau, L AU - Goldman, D AU - Albaugh, B J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 788 EP - 808 VL - 55 IS - 4 SN - 0002-9297, 0002-9297 KW - DNA Probes KW - 0 KW - Genetic Markers KW - DNA KW - 9007-49-2 KW - Index Medicus KW - United States KW - Biometry KW - Humans KW - Asian Continental Ancestry Group -- genetics KW - Indians, North American -- genetics KW - Alleles KW - African Continental Ancestry Group -- genetics KW - Blotting, Southern KW - Cells, Cultured KW - DNA -- blood KW - DNA -- genetics KW - China -- ethnology KW - Genetic Variation KW - Gene Frequency KW - Polymorphism, Restriction Fragment Length KW - European Continental Ancestry Group -- genetics KW - Chromosome Mapping KW - Ethnic Groups -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76785493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+genetics&rft.atitle=Polymorphic+admixture+typing+in+human+ethnic+populations.&rft.au=Dean%2C+M%3BStephens%2C+J+C%3BWinkler%2C+C%3BLomb%2C+D+A%3BRamsburg%2C+M%3BBoaze%2C+R%3BStewart%2C+C%3BCharbonneau%2C+L%3BGoldman%2C+D%3BAlbaugh%2C+B+J&rft.aulast=Dean&rft.aufirst=M&rft.date=1994-10-01&rft.volume=55&rft.issue=4&rft.spage=788&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-25 N1 - Date created - 1994-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Hum Genet. 1980 May;32(3):314-31 [6247908] Am J Hum Genet. 1994 Oct;55(4):809-24 [7942858] Theor Popul Biol. 1983 Apr;23(2):183-201 [6612631] Genetics. 1983 Oct;105(2):437-60 [6628982] In Vitro. 1984 Nov;20(11):856-8 [6519667] Genetics. 1985 Sep;111(1):147-64 [4029609] Am J Phys Anthropol. 1985 Oct;68(2):149-55 [2998196] Science. 1986 Feb 28;231(4741):992-5 [3003917] N Engl J Med. 1986 Jul 24;315(4):209-14 [2941687] Nature. 1987 Jan 1-7;325(6099):31-6 [3025745] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23 [3194414] J Acquir Immune Defic Syndr. 1988;1(1):2-7 [3063804] Am J Hum Genet. 1989 Mar;44(3):388-96 [2916582] Am J Hum Genet. 1989 Mar;44(3):397-401 [2563634] N Engl J Med. 1989 Oct 26;321(17):1141-8 [2477702] Am J Hum Genet. 1990 Mar;46(3):613-23 [1968708] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):839-43 [1992475] Gene Geogr. 1987 Apr;1(1):47-64 [2908691] Science. 1991 Sep 27;253(5027):1503-7 [1840702] Genomics. 1992 Feb;12(2):241-53 [1740333] Nature. 1992 Oct 29;359(6398):794-801 [1436057] Science. 1992 Nov 20;258(5086):1300-1 [1455222] Science. 1993 Jan 15;259(5093):312-3 [8420001] Science. 1993 Jan 29;259(5095):639-46 [8430313] Hum Mol Genet. 1993 Aug;2(8):1123-8 [8401493] Science. 1993 Oct 1;262(5130):43-6 [8211127] Science. 1993 Oct 1;262(5130):47-8 [8211128] Sci Am. 1993 Dec;269(6):78-83 [8266061] J Hered. 1994 Jan-Feb;85(1):59-63 [8120361] Lancet. 1981 Nov 21;2(8256):1129-33 [6118576] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping by admixture linkage disequilibrium in human populations: limits and guidelines. AN - 76780744; 7942858 AB - Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees. JF - American journal of human genetics AU - Stephens, J C AU - Briscoe, D AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, National Institutes of Health, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 809 EP - 824 VL - 55 IS - 4 SN - 0002-9297, 0002-9297 KW - Genetic Markers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Feasibility Studies KW - Alleles KW - Polymorphism, Genetic KW - Genetic Techniques KW - Models, Genetic KW - Humans KW - DNA -- genetics KW - Cohort Studies KW - Guidelines as Topic KW - False Positive Reactions KW - Gene Frequency KW - Hominidae -- genetics KW - Genetic Diseases, Inborn -- genetics KW - Genetic Diseases, Inborn -- epidemiology KW - Linkage Disequilibrium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76780744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+genetics&rft.atitle=Mapping+by+admixture+linkage+disequilibrium+in+human+populations%3A+limits+and+guidelines.&rft.au=Stephens%2C+J+C%3BBriscoe%2C+D%3BO%27Brien%2C+S+J&rft.aulast=Stephens&rft.aufirst=J&rft.date=1994-10-01&rft.volume=55&rft.issue=4&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-25 N1 - Date created - 1994-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Hum Genet. 1991 Jul;49(1):106-11 [1676559] Science. 1990 Oct 12;250(4978):237-44 [2218527] J Hered. 1994 Jan-Feb;85(1):59-63 [8120361] Nat Genet. 1992 Nov;2(3):204-11 [1345170] Am J Hum Genet. 1994 Oct;55(4):788-808 [7942857] Nature. 1971 Apr 2;230(5292):335-6 [5549412] Genetics. 1973 Sep;75(1):213-9 [4762877] Theor Popul Biol. 1975 Oct;8(2):184-201 [1198351] Lancet. 1981 Nov 21;2(8256):1129-33 [6118576] Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:1-13 [3472706] Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:49-62 [2884068] Proc Natl Acad Sci U S A. 1988 May;85(9):3071-4 [3362862] Nature. 1988 Jun 23;333(6175):710 [3386713] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23 [3194414] Am J Hum Genet. 1989 Mar;44(3):388-96 [2916582] Am J Hum Genet. 1989 Mar;44(3):397-401 [2563634] Science. 1989 Sep 8;245(4922):1073-80 [2570460] Am J Hum Genet. 1990 Sep;47(3):499-514 [1975479] Hum Mol Genet. 1993 Aug;2(8):1123-8 [8401493] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flunarizine for treatment of partial seizures: results of a concentration-controlled trial. AN - 76778320; 7936231 AB - The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%). JF - Neurology AU - Pledger, G W AU - Sackellares, J C AU - Treiman, D M AU - Pellock, J M AU - Wright, F S AU - Mikati, M AU - Sahlroot, J T AU - Tsay, J Y AU - Drake, M E AU - Olson, L AD - NINDS Epilepsy Branch, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1830 EP - 1836 VL - 44 IS - 10 SN - 0028-3878, 0028-3878 KW - Carbamazepine KW - 33CM23913M KW - Phenytoin KW - 6158TKW0C5 KW - Flunarizine KW - R7PLA2DM0J KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Carbamazepine -- therapeutic use KW - Drug Therapy, Combination KW - Half-Life KW - Phenytoin -- therapeutic use KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Flunarizine -- pharmacokinetics KW - Flunarizine -- adverse effects KW - Epilepsy -- drug therapy KW - Flunarizine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76778320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Flunarizine+for+treatment+of+partial+seizures%3A+results+of+a+concentration-controlled+trial.&rft.au=Pledger%2C+G+W%3BSackellares%2C+J+C%3BTreiman%2C+D+M%3BPellock%2C+J+M%3BWright%2C+F+S%3BMikati%2C+M%3BSahlroot%2C+J+T%3BTsay%2C+J+Y%3BDrake%2C+M+E%3BOlson%2C+L&rft.aulast=Pledger&rft.aufirst=G&rft.date=1994-10-01&rft.volume=28&rft.issue=4&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Health+Education+%26+Behavior&rft.issn=10901981&rft_id=info:doi/10.1177%2F109019810102800405 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-16 N1 - Date created - 1994-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Angiotensin II maintains, but does not mediate, isoproterenol-induced cardiac hypertrophy in rats. AN - 76776720; 7524366 AB - The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance. JF - The American journal of physiology AU - Golomb, E AU - Abassi, Z A AU - Cuda, G AU - Stylianou, M AU - Panchal, V R AU - Trachewsky, D AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - H1496 EP - H1506 VL - 267 IS - 4 Pt 2 SN - 0002-9513, 0002-9513 KW - c-fos KW - Actins KW - 0 KW - Biphenyl Compounds KW - DNA Primers KW - Imidazoles KW - RNA, Messenger KW - Tetrazoles KW - Angiotensin II KW - 11128-99-7 KW - Hydralazine KW - 26NAK24LS8 KW - Methyldopa KW - 56LH93261Y KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Captopril KW - 9G64RSX1XD KW - Myosins KW - EC 3.6.4.1 KW - Losartan KW - JMS50MPO89 KW - Isoproterenol KW - L628TT009W KW - Labetalol KW - R5H8897N95 KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Transcription, Genetic -- drug effects KW - Heart -- drug effects KW - Myocardium -- metabolism KW - RNA, Messenger -- biosynthesis KW - Rats KW - RNA -- metabolism KW - Molecular Sequence Data KW - Hydroxyproline -- metabolism KW - Male KW - Myosins -- biosynthesis KW - Dose-Response Relationship, Drug KW - Methyldopa -- pharmacology KW - DNA -- metabolism KW - Captopril -- pharmacology KW - Polymerase Chain Reaction KW - Rats, Sprague-Dawley KW - Base Sequence KW - Hydralazine -- pharmacology KW - Genes, fos KW - Blood Pressure -- drug effects KW - Labetalol -- pharmacology KW - Actins -- biosynthesis KW - Heart -- physiopathology KW - Tetrazoles -- pharmacology KW - Imidazoles -- pharmacology KW - Cardiomegaly -- chemically induced KW - Biphenyl Compounds -- pharmacology KW - Cardiomegaly -- drug therapy KW - Cardiomegaly -- physiopathology KW - Isoproterenol -- pharmacology KW - Angiotensin II -- pharmacology KW - Angiotensin II -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76776720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Angiotensin+II+maintains%2C+but+does+not+mediate%2C+isoproterenol-induced+cardiac+hypertrophy+in+rats.&rft.au=Golomb%2C+E%3BAbassi%2C+Z+A%3BCuda%2C+G%3BStylianou%2C+M%3BPanchal%2C+V+R%3BTrachewsky%2C+D%3BKeiser%2C+H+R&rft.aulast=Golomb&rft.aufirst=E&rft.date=1994-10-01&rft.volume=267&rft.issue=4+Pt+2&rft.spage=H1496&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-18 N1 - Date created - 1994-11-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficient homologous recombination of Ty1 element cDNA when integration is blocked. AN - 76766044; 7523854 AB - Integration of the yeast retrotransposon Ty1 into the genome requires the self-encoded integrase (IN) protein and specific terminal nucleotides present on full-length Ty1 cDNA. Ty1 mutants with defects in IN, the conserved termini of Ty1 cDNA, or priming plus-strand DNA synthesis, however, were still able to efficiently insert into the genome when the elements were expressed from the GAL1 promoter present on a multicopy plasmid. As with normal transposition, formation of the exceptional insertions required an RNA intermediate, Ty1 reverse transcriptase, and Ty1 protease. In contrast to Ty1 transposition, at least 70% of the chromosomal insertions consisted of complex multimeric Ty1 elements. Ty1 cDNA was transferred to the inducing plasmid as well as to the genome, and transfer required the recombination and repair gene RAD52. Furthermore, multimeric insertions occurred without altering the levels of total Ty1 RNA, virus-like particle-associated RNA or cDNA, Ty1 capsid proteins, or IN. These results suggest that Ty1 cDNA is utilized much more efficiently for homologous recombination when IN-mediated integration is blocked. JF - Molecular and cellular biology AU - Sharon, G AU - Burkett, T J AU - Garfinkel, D J AD - Laboratory of Eukaryotic Gene Expression, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 6540 EP - 6551 VL - 14 IS - 10 SN - 0270-7306, 0270-7306 KW - DNA Transposable Elements KW - 0 KW - DNA, Complementary KW - DNA, Fungal KW - DNA-Binding Proteins KW - Fungal Proteins KW - RAD52 protein, S cerevisiae KW - Rad52 DNA Repair and Recombination Protein KW - Saccharomyces cerevisiae Proteins KW - Histidine KW - 4QD397987E KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Genetic Linkage KW - DNA, Complementary -- genetics KW - Histidine -- biosynthesis KW - DNA-Binding Proteins -- genetics KW - Gene Rearrangement KW - Fungal Proteins -- genetics KW - Mutagenesis KW - Endopeptidases -- genetics KW - Base Sequence KW - Histidine -- genetics KW - Molecular Sequence Data KW - DNA Nucleotidyltransferases -- genetics KW - Repetitive Sequences, Nucleic Acid -- genetics KW - RNA-Directed DNA Polymerase -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Recombination, Genetic KW - DNA, Fungal -- genetics KW - DNA Transposable Elements -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76766044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficient+homologous+recombination+of+Ty1+element+cDNA+when+integration+is+blocked.&rft.au=Sharon%2C+G%3BBurkett%2C+T+J%3BGarfinkel%2C+D+J&rft.aulast=Sharon&rft.aufirst=G&rft.date=1994-10-01&rft.volume=14&rft.issue=10&rft.spage=6540&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 - 1994-10-21 N1 - Date created - 1994-10-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1992 Mar;11(3):1155-64 [1312462] Cell. 1991 Oct 18;67(2):355-64 [1655280] Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3236-40 [1314382] Genetics. 1992 Jul;131(3):519-29 [1321064] Nature. 1992 Aug 27;358(6389):717 [1324434] Genetics. 1992 Aug;131(4):833-50 [1325387] Nature. 1993 Jan 14;361(6408):170-3 [8380627] Cell. 1993 Apr 23;73(2):347-60 [8477448] Gene. 1994 Feb 11;139(1):19-26 [8112584] Gene. 1994 Feb 11;139(1):9-18 [8112595] Mol Cell Biol. 1994 Jul;14(7):4485-92 [7516468] Cell. 1980 Oct;21(3):599-600 [6254661] Nature. 1982 Aug 26;298(5877):815-9 [6287274] Gene. 1982 Dec;20(3):441-9 [6299901] Cell. 1983 Jun;33(2):563-73 [6345000] Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 [6091052] Cell. 1984 Dec;39(3 Pt 2):675-82 [6096019] Mol Gen Genet. 1984;197(2):345-6 [6394957] Cell. 1985 Mar;40(3):491-500 [2982495] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3756-60 [3889913] Cell. 1985 Sep;42(2):507-17 [2411424] Nucleic Acids Res. 1985 Dec 9;13(23):8587-601 [3001645] Gene. 1986;42(2):133-9 [3015727] Science. 1986 Dec 19;234(4783):1582-5 [3538420] Mol Cell Biol. 1986 Nov;6(11):3575-81 [3025601] Cell. 1987 Apr 10;49(1):111-9 [3030564] Mol Gen Genet. 1987 May;207(2-3):421-9 [3039300] Microbiol Rev. 1988 Mar;52(1):70-102 [3280967] Mol Cell Biol. 1988 Apr;8(4):1421-31 [2454391] Mol Cell Biol. 1988 Apr;8(4):1432-42 [2837641] Mol Cell Biol. 1988 May;8(5):2257-60 [3290654] Cell. 1988 Sep 23;54(7):955-66 [2843295] Cell. 1989 Mar 24;56(6):911-3 [2647305] Science. 1989 Jun 16;244(4910):1346-8 [2544026] Gene. 1989 Apr 15;77(1):51-9 [2744487] Gene. 1989 Apr 15;77(1):61-8 [2744488] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717-21 [2481313] Mol Gen Genet. 1990 Jan;220(2):213-21 [2157950] Genes Dev. 1990 Mar;4(3):324-30 [2159935] Mol Cell Biol. 1990 Jun;10(6):2695-702 [2160583] Mol Cell Biol. 1990 Jun;10(6):2882-92 [2160587] Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):936-40 [1846969] Methods Enzymol. 1991;194:319-29 [2005796] Mol Gen Genet. 1991 Apr;226(1-2):145-53 [1851946] J Virol. 1991 Sep;65(9):4573-81 [1714514] Mol Cell Biol. 1992 Apr;12(4):1613-20 [1372387] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitrite-induced mutations in a forward mutation assay: influence of nitrite concentration and pH. AN - 76764927; 7523928 AB - The mutagenicity of sodium nitrite at three pHs (7.4, 6.4 and 5.4) has been investigated by treating a shuttle vector plasmid in vitro and assaying for mutations within the supF target gene following replication of the damaged plasmid in human Ad293 cells. Mutation frequency increased with increasing nitrite concentration and decreasing pH. Among treatments from which a significant number of mutants could be collected, the most commonly induced mutations were GC-->AT transitions (44-56% of total mutations), followed by GC-->TA transversions (24-30%). The types of mutations induced at different nitrite concentrations and different pH's were similar, though some differences in their distribution throughout the supF gene were noted. These results provide information on the types of mutations that may be produced following the processing of nitrite-induced DNA damage in human cells. JF - Mutation research AU - Routledge, M N AU - Mirsky, F J AU - Wink, D A AU - Keefer, L K AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 341 EP - 346 VL - 322 IS - 4 SN - 0027-5107, 0027-5107 KW - supF KW - Mutagens KW - 0 KW - DNA KW - 9007-49-2 KW - Sodium Nitrite KW - M0KG633D4F KW - Index Medicus KW - Mutagenicity Tests KW - Base Sequence KW - Cells, Cultured KW - Hydrogen-Ion Concentration KW - Humans KW - Molecular Sequence Data KW - Genes, Viral KW - Plasmids KW - DNA -- drug effects KW - Mutagens -- toxicity KW - Sodium Nitrite -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76764927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Nitrite-induced+mutations+in+a+forward+mutation+assay%3A+influence+of+nitrite+concentration+and+pH.&rft.au=Routledge%2C+M+N%3BMirsky%2C+F+J%3BWink%2C+D+A%3BKeefer%2C+L+K%3BDipple%2C+A&rft.aulast=Routledge&rft.aufirst=M&rft.date=1994-10-01&rft.volume=322&rft.issue=4&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. AN - 76760818; 7931470 AB - We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. Ninety patients with previously untreated extensive-stage SCLC fulfilled criteria for randomization to standard-dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m2 on days 1 to 3 and cisplatin 80 mg/m2 on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m2 on days 1 to 5 and cisplatin 27 mg/m2 on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients. Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to those randomized to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Ihde, D C AU - Mulshine, J L AU - Kramer, B S AU - Steinberg, S M AU - Linnoila, R I AU - Gazdar, A F AU - Edison, M AU - Phelps, R M AU - Lesar, M AU - Phares, J C AD - National Cancer Institute-Navy Medical Oncology Branch, Uniformed Services University of the Health Sciences, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2022 EP - 2034 VL - 12 IS - 10 SN - 0732-183X, 0732-183X KW - Etoposide KW - 6PLQ3CP4P3 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Drug Administration Schedule KW - Neoplasm Staging KW - Humans KW - Aged KW - Cisplatin -- administration & dosage KW - Prospective Studies KW - Survival Rate KW - Etoposide -- administration & dosage KW - Leukopenia -- chemically induced KW - Adult KW - Weight Loss -- drug effects KW - Thrombocytopenia -- chemically induced KW - Etoposide -- adverse effects KW - Middle Aged KW - Cisplatin -- adverse effects KW - Female KW - Male KW - Remission Induction KW - Proportional Hazards Models KW - Carcinoma, Small Cell -- pathology KW - Carcinoma, Small Cell -- mortality KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76760818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Prospective+randomized+comparison+of+high-dose+and+standard-dose+etoposide+and+cisplatin+chemotherapy+in+patients+with+extensive-stage+small-cell+lung+cancer.&rft.au=Ihde%2C+D+C%3BMulshine%2C+J+L%3BKramer%2C+B+S%3BSteinberg%2C+S+M%3BLinnoila%2C+R+I%3BGazdar%2C+A+F%3BEdison%2C+M%3BPhelps%2C+R+M%3BLesar%2C+M%3BPhares%2C+J+C&rft.aulast=Ihde&rft.aufirst=D&rft.date=1994-10-01&rft.volume=12&rft.issue=10&rft.spage=2022&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. AN - 76759447; 7931473 AB - This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Foss, F M AU - Ihde, D C AU - Linnoila, I R AU - Fischmann, A B AU - Schechter, G P AU - Cotelingam, J D AU - Steinberg, S M AU - Ghosh, B C AU - Stocker, J L AU - Bastian, A AD - National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2051 EP - 2059 VL - 12 IS - 10 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Interferon-alpha KW - Recombinant Proteins KW - interferon alfa-2a KW - 47RRR83SK7 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Drug Administration Schedule KW - Disease-Free Survival KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Remission Induction KW - Skin Neoplasms -- drug therapy KW - Sezary Syndrome -- drug therapy KW - Vidarabine -- analogs & derivatives KW - Mycosis Fungoides -- therapy KW - Interferon-alpha -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Sezary Syndrome -- therapy KW - Skin Neoplasms -- therapy KW - Vidarabine -- administration & dosage KW - Mycosis Fungoides -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76759447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+II+trial+of+fludarabine+phosphate+and+interferon+alfa-2a+in+advanced+mycosis+fungoides%2FS%C3%A9zary+syndrome.&rft.au=Foss%2C+F+M%3BIhde%2C+D+C%3BLinnoila%2C+I+R%3BFischmann%2C+A+B%3BSchechter%2C+G+P%3BCotelingam%2C+J+D%3BSteinberg%2C+S+M%3BGhosh%2C+B+C%3BStocker%2C+J+L%3BBastian%2C+A&rft.aulast=Foss&rft.aufirst=F&rft.date=1994-10-01&rft.volume=12&rft.issue=10&rft.spage=2051&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy. AN - 76759430; 7523607 AB - To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. Thirty-three patients with diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and ProMACE-MOPP (P2 = .04). Adult patients with diffuse small non-cleaved-cell non-Burkitt's lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma). JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Longo, D L AU - Duffey, P L AU - Jaffe, E S AU - Raffeld, M AU - Hubbard, S M AU - Fisher, R I AU - Wittes, R E AU - DeVita, V T AU - Young, R C AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2153 EP - 2159 VL - 12 IS - 10 SN - 0732-183X, 0732-183X KW - Cytarabine KW - 04079A1RDZ KW - Bleomycin KW - 11056-06-7 KW - Procarbazine KW - 35S93Y190K KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Mechlorethamine -- administration & dosage KW - Disease-Free Survival KW - Bleomycin -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Vincristine -- administration & dosage KW - Prognosis KW - Aged KW - Doxorubicin -- administration & dosage KW - Cytarabine -- administration & dosage KW - Procarbazine -- administration & dosage KW - Survival Rate KW - Etoposide -- administration & dosage KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Remission Induction KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- mortality KW - Lymphoma, Non-Hodgkin -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76759430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diffuse+small+noncleaved-cell%2C+non-Burkitt%27s+lymphoma+in+adults%3A+a+high-grade+lymphoma+responsive+to+ProMACE-based+combination+chemotherapy.&rft.au=Longo%2C+D+L%3BDuffey%2C+P+L%3BJaffe%2C+E+S%3BRaffeld%2C+M%3BHubbard%2C+S+M%3BFisher%2C+R+I%3BWittes%2C+R+E%3BDeVita%2C+V+T%3BYoung%2C+R+C&rft.aulast=Longo&rft.aufirst=D&rft.date=1994-10-01&rft.volume=12&rft.issue=10&rft.spage=2153&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Clin Oncol 1996 Jun;14(6):1969 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In situ and suspension protocols for chemically-induced mutation at the tk locus in L5178Y MOLY cells: dose response and colony size distribution. AN - 76759279; 7523923 AB - We used EMS up to concentrations of 0.25 microliters/ml (292 micrograms/ml) to induce mutations at the tk locus in L5178Y MOLY cells, measured the cellular response by the in situ mutation assay protocol and compared these results to those obtained in a concomitant suspension assay. EMS induced mutagenic responses with both protocols. The mutant fraction for the solvent control was 89 mutants per million viable colonies for the suspension protocol and 426 mutations per million viable cells plated for the in situ protocol. These numbers increase to 447 and 2073 respectively, with 0.25 microliter/ml EMS treatment. Sizing curves indicated that the in situ protocol detected a greater proportion of smaller colonies than did the suspension protocol. Not only were the number of small colonies greater than large colonies in the in situ protocol, but their rate of increase was also slightly higher than that of the large colonies. The in situ protocol also reduces the time and cost of experimentally performing the assay compared to the suspension protocol. In this paper we compare the use of the suspension and in situ protocols to measure chemically-induced mutations and demonstrate that the latter method detects a larger fraction of induced mutations at the tk locus in L5178Y MOLY cells. JF - Mutation research AU - Spencer, D L AU - Caspary, W J AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 291 EP - 300 VL - 322 IS - 4 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Index Medicus KW - Clone Cells KW - Animals KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Mice KW - Cell Division KW - Mutagenicity Tests -- methods KW - Mutagens -- toxicity KW - Ethyl Methanesulfonate -- toxicity KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76759279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Eating+and+Weight+Disorders&rft.atitle=Orthorexic+eating+behaviour+as+a+coping+strategy+in+patients+with+anorexia+nervosa&rft.au=Barthels%2C+Friederike%3BMeyer%2C+Frank%3BHuber%2C+Thomas%3BPietrowsky%2C+Reinhard&rft.aulast=Barthels&rft.aufirst=Friederike&rft.date=2016-10-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Eating+and+Weight+Disorders&rft.issn=11244909&rft_id=info:doi/10.1007%2Fs40519-016-0329-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma. AN - 76757943; 7930733 AB - Human monocytes are important effector cells in host defenses against Aspergillus hyphae, and as elutriated monocytes (EHM) they may be transfused in large quantities to leukopenic patients with invasive aspergillosis. The antifungal activity of EHM against Aspergillus hyphae was compared with that of polymorphonuclear leukocytes (PMNL). The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on superoxide anion (O2-) release and on hyphal damage caused by EHM against unopsonized A. fumigatus hyphae was investigated. EHM had antihyphal activity comparable to that of PMNL. GM-CSF significantly augmented O2- release by EHM in response to PMA. Also, both GM-CSF and IFN-gamma significantly enhanced the antifungal activity of EHM compared with untreated controls. Thus, EHM have demonstrable antifungal activity against Aspergillus hyphae that may be increased by GM-CSF and IFN-gamma, suggesting their potential therapeutic role in immune reconstitution of effector cells. JF - The Journal of infectious diseases AU - Roilides, E AU - Holmes, A AU - Blake, C AU - Venzon, D AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 894 EP - 899 VL - 170 IS - 4 SN - 0022-1899, 0022-1899 KW - Antifungal Agents KW - 0 KW - Recombinant Proteins KW - Superoxides KW - 11062-77-4 KW - Interferon-gamma KW - 82115-62-6 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Adult KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Superoxides -- blood KW - Aspergillus fumigatus -- isolation & purification KW - Monocytes -- physiology KW - Monocytes -- drug effects KW - Interferon-gamma -- pharmacology KW - Neutrophils -- physiology KW - Monocytes -- microbiology KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Neutrophils -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76757943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Antifungal+activity+of+elutriated+human+monocytes+against+Aspergillus+fumigatus+hyphae%3A+enhancement+by+granulocyte-macrophage+colony-stimulating+factor+and+interferon-gamma.&rft.au=Roilides%2C+E%3BHolmes%2C+A%3BBlake%2C+C%3BVenzon%2C+D%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Roilides&rft.aufirst=E&rft.date=1994-10-01&rft.volume=170&rft.issue=4&rft.spage=894&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-01 N1 - Date created - 1994-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Optimization of recombinant t-PA secretion from seeded vascular grafts. AN - 76757298; 7934027 AB - Seeding of vascular grafts with genetically engineered endothelial cells (EC) secreting anticoagulant or fibrinolytic agents offers a potential means of improving patency rates. Prior to the initiation of in vivo studies, we examined cell retention and tissue plasminogen activator (t-PA) secretion from small-diameter synthetic graft segments seeded with sheep venous EC genetically engineered to secrete human t-PA. Following retroviral-mediated gene transfer, EC were seeded at varying densities onto 4-mm-diameter synthetic graft segments of different composition, achieving confluent coverage of all materials. t-PA production from seeded grafts was evaluated under both static conditions and after flow exposure, for up to 3 days after seeding. t-PA secretion varied directly with increasing seeding density for all graft types, reaching a maximum of 20 ng/cm2/24 hr. t-PA secretion correlated highly with the number of seeded cells as determined by measurement of DNA from lysates of seeded grafts (r2 = 0.90, P < 0.0001). For all graft types tested, approximately 50% of seeded cells were retained after exposure to flow in vitro. Retained EC remained viable as determined by t-PA secretion. The rate of t-PA secretion from collagen-impregnated Dacron grafts was higher than that obtained with other materials both under static conditions and after flow exposure. This higher rate was most likely due to the higher surface area presented by the Dacron grafts. These data demonstrate that small-diameter prosthetic graft materials can be coated with a layer of EC that (i) remains metabolically active and capable of secreting a fibrinolytic agent, and (ii) remains adherent to the graft surface after exposure to flow. These experiments provide a foundation for in vivo studies in which grafts are seeded with EC genetically engineered to increase local fibrinolysis. JF - The Journal of surgical research AU - Shayani, V AU - Newman, K D AU - Dichek, D A AD - Molecular Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 495 EP - 504 VL - 57 IS - 4 SN - 0022-4804, 0022-4804 KW - Polycarboxylate Cement KW - 0 KW - Polyethylene Terephthalates KW - Recombinant Proteins KW - polycarbonate KW - 25766-59-0 KW - Urethane KW - 3IN71E75Z5 KW - Polytetrafluoroethylene KW - 9002-84-0 KW - DNA KW - 9007-49-2 KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- secretion KW - Genetic Engineering KW - Sheep KW - Humans KW - DNA -- analysis KW - Regional Blood Flow KW - Cell Survival KW - Tissue Plasminogen Activator -- secretion KW - Endothelium, Vascular -- secretion KW - Endothelium, Vascular -- cytology KW - Blood Vessel Prosthesis KW - Endothelium, Vascular -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76757298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+research&rft.atitle=Optimization+of+recombinant+t-PA+secretion+from+seeded+vascular+grafts.&rft.au=Shayani%2C+V%3BNewman%2C+K+D%3BDichek%2C+D+A&rft.aulast=Shayani&rft.aufirst=V&rft.date=1994-10-01&rft.volume=57&rft.issue=4&rft.spage=495&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+surgical+research&rft.issn=00224804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-07 N1 - Date created - 1994-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of purine analogs: a review. AN - 76756458; 7931492 AB - The purine analogs, fludarabine, cladribine, and pentostatin, are active against a broad spectrum of indolent lymphoid malignancies. They also have similar toxicities, including myelosuppression, immunosuppression, and sporadic neurotoxicity. This review compares the spectrum of neurotoxicity of each of these agents. Now that these drugs are commercially available and are being widely used, physicians should be aware of potentially serious side effects that may be encountered. The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the fall of 1993. In addition, case records from National Cancer Institute (NCI) Group C protocols were reviewed for fludarabine in chronic lymphocytic leukemia (CLL), and cladribine and pentostatin in hairy cell leukemia (HCL), as well as adverse drug reactions reported to the NCI from January 1980 through September 1993. At higher than recommended doses, life-threatening and fatal neurotoxicity were encountered with all three drugs. At the recommended doses, each agent induced neurotoxicity in approximately 15% of patients, mostly mild and reversible. However, severe neurologic complications were reported; these were occasionally delayed, sometimes fatal, but often at least partially reversible. The doses of these three agents should not be increased above the recommended levels. Development of moderate or worse neurotoxicity should result in discontinuation of that drug. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AU - Vena, D A AU - Foss, F M AU - Sorensen, J M AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2216 EP - 2228 VL - 12 IS - 10 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Purine Nucleosides KW - Pentostatin KW - 395575MZO7 KW - Cladribine KW - 47M74X9YT5 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Vidarabine -- analogs & derivatives KW - Cladribine -- adverse effects KW - Pentostatin -- adverse effects KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Nervous System Diseases -- chemically induced KW - Vidarabine -- adverse effects KW - Male KW - Female KW - Purine Nucleosides -- adverse effects KW - Nervous System -- drug effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76756458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cognitive+and+Behavioral+Practice&rft.atitle=Developing+an+acceptance-based+behavioral+treatment+for+binge+eating+disorder%3A+Rationale+and+challenges&rft.au=Juarascio%2C+Adrienne+S.%3BManasse%2C+Stephanie+M.%3BSchumacher%2C+Leah%3BEspel%2C+Hallie%3BForman%2C+Evan+M.&rft.aulast=Juarascio&rft.aufirst=Adrienne&rft.date=2016-02-24&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Cognitive+and+Behavioral+Practice&rft.issn=10777229&rft_id=info:doi/10.1016%2Fj.cbpra.2015.12.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of adenylylcyclase by protein kinase C in human neurotumor SK-N-MC cells: evidence that the alpha isozyme mediates both potentiation and desensitization. AN - 76755971; 7931287 AB - Exposure of human SK-N-MC neurotumor cells to 4 beta-phorbol 12-myristate 13-acetate (PMA) increased isoproterenol stimulation of cyclic AMP levels by severalfold. This potentiation was blocked by inhibitors of protein kinase C (PKC) and did not occur in cells in which PKC had been down-regulated. PMA treatment also enhanced the stimulation by dopamine, cholera toxin, and forskolin. Thus, the effect of PMA on the adenylylcyclase system was postreceptor and involved either the guanine nucleotide binding regulatory (G) proteins or the cyclase itself. As PMA treatment did not impair the inhibition of isoproterenol stimulation by neuropeptide Y, an involvement of the inhibitory G protein Gi was unlikely. Cholate extracts of membranes from control and PMA-treated cells were equally effective in the reconstitution of adenylylcyclase activity in S49 cyc- membranes, which lack the stimulatory G protein subunit Gs alpha; thus, Gs did not appear to be the target of PMA action. Membranes from PMA-treated cells exhibited increased adenylylcyclase activity to all stimulators including Mn2+ and Mn2+ plus forskolin. In addition, activity was increased when control membranes were incubated with ATP and purified PKC from rat brain. This is consistent with a direct effect of PKC on the adenylylcyclase catalyst in SK-N-MC cells. PMA treatment also resulted in a shift to less sensitivity in the K(act) for isoproterenol but not for dopamine or CGP-12177 (a beta 3-adrenergic agonist) stimulation. Thus, the beta 1 but not the D1 or beta 3 receptors were being desensitized by PKC activation. Analysis of SK-N-MC cells by western blotting with antibodies against different PKC isozymes revealed that both the alpha and zeta isozymes were present in these cells. Whereas PKC-alpha was activated and translocated from cytosol to membrane by phorbol esters, the zeta isozyme was not. Thus, PKC-alpha, which has been implicated in desensitization in other cell lines, also appears to potentiate adenylylcyclase activity. JF - Journal of neurochemistry AU - Zhou, X M AU - Curran, P AU - Baumgold, J AU - Fishman, P H AD - Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 1361 EP - 1370 VL - 63 IS - 4 SN - 0022-3042, 0022-3042 KW - Adrenergic beta-Antagonists KW - 0 KW - Alkaloids KW - Aluminum Compounds KW - Isoenzymes KW - Neuropeptide Y KW - Propanolamines KW - Colforsin KW - 1F7A44V6OU KW - tetrafluoroaluminate KW - 21340-02-3 KW - Manganese KW - 42Z2K6ZL8P KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Staurosporine KW - H88EPA0A3N KW - Isoproterenol KW - L628TT009W KW - Sphingosine KW - NGZ37HRE42 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Fluorides KW - Q80VPU408O KW - CGP 12177 KW - R89UMZ82MJ KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Manganese -- pharmacology KW - Dopamine -- pharmacology KW - Humans KW - Neuropeptide Y -- pharmacology KW - Cholera Toxin -- pharmacology KW - Fluorides -- pharmacology KW - Neuroblastoma KW - Rats KW - Brain -- enzymology KW - Colforsin -- pharmacology KW - Tumor Cells, Cultured KW - Kinetics KW - GTP-Binding Proteins -- metabolism KW - Alkaloids -- pharmacology KW - Aluminum Compounds -- pharmacology KW - Sphingosine -- pharmacology KW - Cell Membrane -- metabolism KW - Drug Synergism KW - Propanolamines -- pharmacology KW - Adrenergic beta-Antagonists -- pharmacology KW - Cell Line KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Cyclic AMP -- metabolism KW - Adenylyl Cyclases -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Isoproterenol -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76755971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Modulation+of+adenylylcyclase+by+protein+kinase+C+in+human+neurotumor+SK-N-MC+cells%3A+evidence+that+the+alpha+isozyme+mediates+both+potentiation+and+desensitization.&rft.au=Zhou%2C+X+M%3BCurran%2C+P%3BBaumgold%2C+J%3BFishman%2C+P+H&rft.aulast=Zhou&rft.aufirst=X&rft.date=1994-10-01&rft.volume=63&rft.issue=4&rft.spage=1361&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-01 N1 - Date created - 1994-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic transformation of the Lyme disease agent Borrelia burgdorferi with coumarin-resistant gyrB. AN - 76753450; 7928965 AB - No useful method to genetically manipulate Borrelia burgdorferi, the causative agent of Lyme disease, has been developed previously. We have used resistance to the coumarin antibiotic coumermycin A1, an inhibitor of DNA gyrase, as a genetic marker to monitor the transformation of B. burgdorferi by electroporation. Introduction of site-directed mutations into the gyrB gene demonstrated that transformation was successful, provided evidence that homologous recombination occurs on the chromosome, and established that mutations at Arg-133 of DNA gyrase B confer coumermycin A1 resistance in B. burgdorferi. The coumermycin A1-resistant gyrB marker and genetic transformation can now be applied toward dissecting the physiology and pathogenesis of the Lyme disease agent on a molecular genetic level. JF - Journal of bacteriology AU - Samuels, D S AU - Mach, K E AU - Garon, C F AD - Laboratory of Vectors and Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 6045 EP - 6049 VL - 176 IS - 19 SN - 0021-9193, 0021-9193 KW - gyrB KW - Aminocoumarins KW - 0 KW - Anti-Bacterial Agents KW - Coumarins KW - DNA, Bacterial KW - Genetic Markers KW - Topoisomerase II Inhibitors KW - DNA Gyrase KW - EC 5.99.1.3 KW - DNA Topoisomerases, Type II KW - coumermycin KW - PCH9QZ1IIH KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Genetic Markers -- genetics KW - Base Sequence KW - Electroporation KW - Coumarins -- pharmacology KW - DNA, Bacterial -- genetics KW - Restriction Mapping KW - Drug Resistance, Microbial -- genetics KW - Molecular Sequence Data KW - Borrelia burgdorferi Group -- enzymology KW - DNA Topoisomerases, Type II -- genetics KW - Transformation, Genetic KW - Anti-Bacterial Agents -- pharmacology KW - Borrelia burgdorferi Group -- drug effects KW - Borrelia burgdorferi Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76753450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+transformation+of+the+Lyme+disease+agent+Borrelia+burgdorferi+with+coumarin-resistant+gyrB.&rft.au=Samuels%2C+D+S%3BMach%2C+K+E%3BGaron%2C+C+F&rft.aulast=Samuels&rft.aufirst=D&rft.date=1994-10-01&rft.volume=176&rft.issue=19&rft.spage=6045&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 - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gyrB N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8860-4 [1656457] J Clin Invest. 1991 Jul;88(1):82-92 [2056133] J Bacteriol. 1992 Jun;174(11):3766-74 [1592827] FEMS Microbiol Lett. 1992 Apr 1;71(1):109-13 [1624107] FEMS Microbiol Lett. 1992 Apr 1;71(1):15-8 [1624108] Infect Immun. 1992 Aug;60(8):3098-104 [1639477] Mol Microbiol. 1992 Jun;6(12):1617-24 [1323022] J Exp Med. 1992 Sep 1;176(3):799-809 [1339462] Mol Microbiol. 1992 Oct;6(20):3031-40 [1479892] FEMS Microbiol Lett. 1992 Dec 1;78(2-3):245-50 [1490605] Antimicrob Agents Chemother. 1993 Jan;37(1):46-50 [8381639] Biochemistry. 1993 Mar 16;32(10):2717-24 [8383523] Science. 1993 Jun 11;260(5114):1610-6 [8503006] Mol Microbiol. 1993 May;8(5):967-80 [8102774] FEMS Microbiol Lett. 1993 Jul 15;111(1):109-14 [8359672] Mol Microbiol. 1993 Aug;9(4):681-6 [8231802] J Clin Microbiol. 1993 Oct;31(10):2577-83 [8253952] J Gen Microbiol. 1993 Oct;139(10):2445-9 [8254314] J Bacteriol. 1994 May;176(10):3072-5 [8188609] Mol Microbiol. 1993 Dec;10(5):917-22 [7934868] Proc Natl Acad Sci U S A. 1976 Dec;73(12):4474-8 [794878] Proc Natl Acad Sci U S A. 1978 Dec;75(12):5960-3 [153529] Proc Natl Acad Sci U S A. 1978 Oct;75(10):4838-42 [368801] Annu Rev Biochem. 1981;50:879-910 [6267993] Nucleic Acids Res. 1981 Aug 11;9(15):3589-603 [6269086] Science. 1982 Jun 18;216(4552):1317-9 [7043737] N Engl J Med. 1983 Mar 31;308(13):733-40 [6828118] N Engl J Med. 1983 Mar 31;308(13):740-2 [6828119] Science. 1987 Jul 24;237(4813):409-11 [3603026] J Clin Microbiol. 1987 Nov;25(11):2054-8 [3693538] Biochemistry. 1988 Apr 5;27(7):2253-9 [2838070] N Engl J Med. 1989 Aug 31;321(9):586-96 [2668764] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5969-73 [2762306] Res Microbiol. 1989 Oct;140(8):507-16 [2696058] J Basic Microbiol. 1990;30(3):209-24 [2164580] J Bacteriol. 1990 Nov;172(11):6602-4 [2228977] Zentralbl Bakteriol. 1990 Oct;274(1):28-39 [1979740] J Bacteriol. 1991 Jan;173(2):642-8 [1846146] Crit Rev Biochem Mol Biol. 1991;26(3-4):335-75 [1657531] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The presence of an active S-adenosylmethionine decarboxylase gene increases the growth defect observed in Saccharomyces cerevisiae mutants unable to synthesize putrescine, spermidine, and spermine. AN - 76751600; 7929015 AB - Saccharomyces cerevisiae spe1 delta SPE2 mutants (lacking ornithine decarboxylase) and spe1 delta spe2 delta mutants (lacking both ornithine decarboxylase and S-adenosylmethionine decarboxylase) are equally unable to synthesize putrescine, spermidine, and spermine and require spermidine or spermine for growth in amine-free media. The cessation of growth, however, occurs more rapidly in spe1 delta SPE2 cells than in SPE1 spe2 delta or spe1 delta spe2 delta cells. Since spe1 delta SPE2 cells can synthesize decarboxylated adenosylmethionine (dcAdoMet), these data indicate that dcAdoMet may be toxic to amine-deficient cells. JF - Journal of bacteriology AU - Balasundaram, D AU - Xie, Q W AU - Tabor, C W AU - Tabor, H AD - Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 6407 EP - 6409 VL - 176 IS - 20 SN - 0021-9193, 0021-9193 KW - SPE1 KW - SPE2 KW - Polyamines KW - 0 KW - Spermine KW - 2FZ7Y3VOQX KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Adenosylmethionine Decarboxylase KW - EC 4.1.1.50 KW - Spermidine KW - U87FK77H25 KW - Putrescine KW - V10TVZ52E4 KW - Index Medicus KW - Spermine -- biosynthesis KW - Ornithine Decarboxylase -- genetics KW - Putrescine -- biosynthesis KW - Spermidine -- biosynthesis KW - Saccharomyces cerevisiae -- genetics KW - Genes, Fungal -- genetics KW - Adenosylmethionine Decarboxylase -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Polyamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76751600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Eating+Behaviors&rft.atitle=Positive+cognitive+coping+strategies+and+binge+eating+in+college+women&rft.au=Kelly%2C+Nichole+R.%3BLydecker%2C+Janet+A.%3BMazzeo%2C+Suzanne+E.&rft.aulast=Kelly&rft.aufirst=Nichole&rft.date=2012-08-01&rft.volume=13&rft.issue=3&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Eating+Behaviors&rft.issn=14710153&rft_id=info:doi/10.1016%2Fj.eatbeh.2012.03.012 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - SPE1; SPE2 N1 - SuppNotes - Cited By: Clin Chem. 1975 Nov;21(12):1721-4 [1182991] Biochem Pharmacol. 1993 Aug 3;46(3):471-81 [8347171] J Bacteriol. 1980 Jun;142(3):791-9 [6991493] J Chromatogr. 1982 Feb 12;227(2):349-68 [6801066] Eur J Biochem. 1982 Apr;123(3):499-504 [6804235] Biochem J. 1982 Feb 15;202(2):519-26 [6807294] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Methods Enzymol. 1983;101:202-11 [6310324] Biochem J. 1984 Nov 15;224(1):29-38 [6439194] Mol Cell Biol. 1985 Jan;5(1):161-6 [3885007] Biochemistry. 1986 Jan 28;25(2):379-84 [3006760] Yeast. 1986 Sep;2(3):163-7 [3333305] Biochem Biophys Res Commun. 1989 Aug 15;162(3):1409-16 [2669750] Yeast. 1990 Nov-Dec;6(6):455-60 [2080662] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5872-6 [2062864] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4693-7 [8506320] J Bacteriol. 1978 Apr;134(1):208-13 [348678] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the eosinophil granule proteins recognized by the activation-specific antibody EG2. AN - 76749295; 7930947 AB - Monoclonal antibodies EG1 and EG2 have the unique ability to distinguish the storage from the secreted forms of the eosinophil cationic protein (ECP). EG2 has been used extensively as a marker for activated, secreting eosinophils, despite the fact that no biochemical differences between the storage and secreted forms of ECP have been identified. We have determined that the activation-specific EG2 detects only one of three distinct glycosylated forms of ECP (18 kDa); in contrast, both EG1 and polyclonal anti-ECP antiserum can detect three glycosylated forms of this protein (18, 20, and 22 kDa). We have also determined that EG2 detects fully deglycosylated ECP as well as fully deglycosylated eosinophil-derived neurotoxin. Our results indicate that activation-specific EG2 recognizes a polypeptide epitope that is masked in the higher-molecular-weight, more heavily glycosylated forms of ECP. These findings suggest that deglycosylation may occur in conjunction with activation and secretion; alternatively, the 18-kDa form of ECP may be present in the storage granule of resting eosinophils but may remain undetected in an inaccessible location or conformation. JF - Journal of leukocyte biology AU - Rosenberg, H F AU - Tiffany, H L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 502 EP - 506 VL - 56 IS - 4 SN - 0741-5400, 0741-5400 KW - Antibodies, Monoclonal KW - 0 KW - Blood Proteins KW - Eosinophil Granule Proteins KW - Neurotoxins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Index Medicus KW - Sequence Alignment KW - Humans KW - Molecular Sequence Data KW - Cytoplasmic Granules -- chemistry KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Antibodies, Monoclonal -- immunology KW - Eosinophils -- chemistry KW - Blood Proteins -- metabolism KW - Neurotoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76749295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=Characterization+of+the+eosinophil+granule+proteins+recognized+by+the+activation-specific+antibody+EG2.&rft.au=Rosenberg%2C+H+F%3BTiffany%2C+H+L&rft.aulast=Rosenberg&rft.aufirst=H&rft.date=1994-10-01&rft.volume=56&rft.issue=4&rft.spage=502&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-02 N1 - Date created - 1994-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Small chimeric toxins containing only transforming growth factor alpha and domain III of Pseudomonas exotoxin with good antitumor activity in mice. AN - 76748831; 7923133 AB - Chimeric toxins composed of transforming growth factor alpha (TGF alpha) fused to mutant forms of Pseudomonas exotoxin (PE) bind to the epidermal growth factor receptor and kill cells bearing epidermal growth factor receptors. Initially, the binding domain (Ia; amino acids 1-252) of PE was deleted and replaced with TGF alpha to make TGF alpha-PE40 in which TGF alpha is fused to domains II, Ib, and III of PE (amino acids 253-613). That drug is currently undergoing clinical study for the intravesical therapy of bladder cancer. To generate smaller molecules that would have increased tumor penetration, several deletion mutants were constructed. In one of these, TGF alpha was inserted near the carboxyl terminus of PE, and residues in domains II and Ib of PE (amino acids 253-279 and 365-380) were deleted so that the chimeric toxin did not need to be cleaved by an intracellular protease to be activated (Theuer et al., J. Biol. Chem., 267: 16872-16877, 1992). We have now constructed chimeric toxins which contain only domain III, yet still exhibit high cytotoxic activity on epidermal growth factor receptor-containing cells and produce substantial tumor regressions in mice bearing a human xenograft. The high cytotoxic activity of these severely truncated toxins provides new insights on the proposed functions of domains II and III of PE. JF - Cancer research AU - Kihara, A AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/10/01/ PY - 1994 DA - 1994 Oct 01 SP - 5154 EP - 5159 VL - 54 IS - 19 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Exotoxins KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - transforming growth factor type alpha-Pseudomonas exotoxin A KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Drug Stability KW - Animals KW - Base Sequence KW - Receptor, Epidermal Growth Factor -- metabolism KW - Humans KW - Molecular Sequence Data KW - Mice, Nude KW - Mice KW - Receptor, Epidermal Growth Factor -- analysis KW - Neoplasms, Experimental -- drug therapy KW - Adenosine Diphosphate Ribose -- metabolism KW - Female KW - Structure-Activity Relationship KW - Transforming Growth Factor alpha -- toxicity KW - Exotoxins -- pharmacology KW - Exotoxins -- metabolism KW - Transforming Growth Factor alpha -- pharmacology KW - Recombinant Fusion Proteins -- pharmacology KW - Exotoxins -- toxicity KW - Transforming Growth Factor alpha -- metabolism KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76748831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Small+chimeric+toxins+containing+only+transforming+growth+factor+alpha+and+domain+III+of+Pseudomonas+exotoxin+with+good+antitumor+activity+in+mice.&rft.au=Kihara%2C+A%3BPastan%2C+I&rft.aulast=Kihara&rft.aufirst=A&rft.date=1994-10-01&rft.volume=54&rft.issue=19&rft.spage=5154&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 - 1994-11-03 N1 - Date created - 1994-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychosocial and diagnostic characteristics of individuals initiating domestic violence. AN - 76746094; 7931207 JF - The Journal of nervous and mental disease AU - Bitler, D A AU - Linnoila, M AU - George, D T AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 583 EP - 585 VL - 182 IS - 10 SN - 0022-3018, 0022-3018 KW - Abridged Index Medicus KW - Index Medicus KW - Stress Disorders, Post-Traumatic -- epidemiology KW - Stress Disorders, Post-Traumatic -- psychology KW - Humans KW - Antisocial Personality Disorder -- psychology KW - Borderline Personality Disorder -- epidemiology KW - Spouse Abuse -- statistics & numerical data KW - Alcoholism -- psychology KW - Comorbidity KW - Disruptive, Impulse Control, and Conduct Disorders -- epidemiology KW - Antisocial Personality Disorder -- epidemiology KW - Panic Disorder -- psychology KW - Panic Disorder -- epidemiology KW - Aggression -- psychology KW - Disruptive, Impulse Control, and Conduct Disorders -- psychology KW - Adult KW - Alcohol Drinking -- psychology KW - Borderline Personality Disorder -- psychology KW - Middle Aged KW - Male KW - Female KW - Spouse Abuse -- psychology KW - Mental Disorders -- epidemiology KW - Domestic Violence -- statistics & numerical data KW - Mental Disorders -- psychology KW - Domestic Violence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76746094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nervous+and+mental+disease&rft.atitle=Psychosocial+and+diagnostic+characteristics+of+individuals+initiating+domestic+violence.&rft.au=Bitler%2C+D+A%3BLinnoila%2C+M%3BGeorge%2C+D+T&rft.aulast=Bitler&rft.aufirst=D&rft.date=1994-10-01&rft.volume=182&rft.issue=10&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nervous+and+mental+disease&rft.issn=00223018&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-26 N1 - Date created - 1994-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of trypsin-like cleavage at arginine 192 in the enzymatic and cytotonic activities of Escherichia coli heat-labile enterotoxin. AN - 76742218; 7927684 AB - Previous studies of cholera toxin and Escherichia coli heat-labile enterotoxin have suggested that proteolytic cleavage plays an important role in the expression of ADP-ribosyltransferase activity and toxicity. Specifically, several studies have implicated a trypsin-like cleavage at arginine 192, which lies within an exposed region subtended by a disulfide bond in the intact A subunit, in toxicity. To investigate the role of this modification in the enzymatic and cytotonic properties of heat-labile enterotoxin, the response of purified, recombinant A subunit to tryptic activation and the effect of substituting arginine 192 with glycine on the activities of the holotoxin were examined. The recombinant A subunit of heat-labile enterotoxin exhibited significant levels of ADP-ribosyltransferase activity that were only nominally increased (approximately twofold) by prior limited trypsinolysis. The enzymatic activity also did not appear to be affected by auto-ADP-ribosylation that occurs during the high-level synthesis of the recombinant A subunit in E. coli. A mutant form of the holotoxin containing the arginine 192-to-glycine substitution exhibited levels of cytotonic activity for CHO cells that were similar to that of the untreated, wild-type holotoxin but exhibited a marked delay in the ability to increase intracellular levels of cyclic AMP in Caco-2 cells. The results indicate that trypsin-like cleavage of the A subunit of E. coli heat-labile enterotoxin at arginine 192 is not requisite to the expression of enzymatic activity by the A subunit and further reveal that this modification, although it enhances the biological and enzymatic activities of the toxin, is not absolutely required for the enterotoxin to elicit cytotonic effects. JF - Infection and immunity AU - Grant, C C AU - Messer, R J AU - Cieplak, W AD - Laboratory of Vectors and Pathogens, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 4270 EP - 4278 VL - 62 IS - 10 SN - 0019-9567, 0019-9567 KW - Bacterial Toxins KW - 0 KW - Enterotoxins KW - Escherichia coli Proteins KW - Recombinant Proteins KW - heat-labile enterotoxin, E coli KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Cyclic AMP KW - E0399OZS9N KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Cyclic AMP -- biosynthesis KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - CHO Cells KW - Adenosine Diphosphate Ribose -- metabolism KW - Structure-Activity Relationship KW - Cricetinae KW - Enterotoxins -- chemistry KW - Bacterial Toxins -- isolation & purification KW - Enterotoxins -- isolation & purification KW - ADP Ribose Transferases -- metabolism KW - Bacterial Toxins -- chemistry KW - Escherichia coli -- enzymology KW - Bacterial Toxins -- toxicity KW - Enterotoxins -- toxicity KW - Trypsin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76742218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+trypsin-like+cleavage+at+arginine+192+in+the+enzymatic+and+cytotonic+activities+of+Escherichia+coli+heat-labile+enterotoxin.&rft.au=Grant%2C+C+C%3BMesser%2C+R+J%3BCieplak%2C+W&rft.aulast=Grant&rft.aufirst=C&rft.date=1994-10-01&rft.volume=62&rft.issue=10&rft.spage=4270&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 - 1994-11-04 N1 - Date created - 1994-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 1991 Sep;59(9):2870-9 [1908825] J Clin Invest. 1978 Aug;62(2):281-5 [209060] Infect Immun. 1992 Feb;60(2):428-34 [1730472] J Biol Chem. 1979 Jul 10;254(13):5855-61 [221485] Infect Immun. 1979 Jun;24(3):760-9 [89088] J Bacteriol. 1979 Sep;139(3):850-8 [383697] J Biol Chem. 1979 Dec 10;254(23):11993-9 [227885] J Clin Microbiol. 1980 Jan;11(1):35-40 [6986402] J Infect Dis. 1980 Jan;141(1):64-70 [6988518] J Biol Chem. 1980 Aug 25;255(16):7835-7 [7400150] Proc Natl Acad Sci U S A. 1982 May;79(9):2976-80 [7045877] J Biol Chem. 1982 Oct 25;257(20):12148-52 [6288709] J Bacteriol. 1984 Feb;157(2):637-42 [6363391] J Biol Chem. 1984 Jan 25;259(2):696-8 [6582062] Infect Immun. 1984 Sep;45(3):558-60 [6432694] Microbiol Rev. 1984 Sep;48(3):199-221 [6436655] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Proc Natl Acad Sci U S A. 1985 Feb;82(4):1074-8 [3156376] DNA. 1985 Apr;4(2):165-70 [3996185] J Biol Chem. 1985 Dec 25;260(30):16187-91 [3934172] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] J Bacteriol. 1987 Mar;169(3):1352-7 [3546273] J Bacteriol. 1988 May;170(5):2208-11 [3129402] Nucleic Acids Res. 1988 Jul 11;16(13):6127-45 [3041370] J Bacteriol. 1989 Sep;171(9):4945-52 [2670900] J Biol Chem. 1989 Dec 15;264(35):21066-72 [2512288] J Biol Chem. 1990 Nov 25;265(33):20678-85 [2122978] Trends Biochem Sci. 1990 Dec;15(12):483-6 [2077689] Nucleic Acids Res. 1991 Jan 11;19(1):184 [2011503] J Clin Invest. 1991 May;87(5):1780-6 [1902492] Infect Immun. 1994 Feb;62(2):333-40 [8300195] Infect Immun. 1992 Feb;60(2):497-502 [1730481] J Biol Chem. 1992 Aug 15;267(23):16335-40 [1644818] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277-81 [1438214] Microbiol Rev. 1992 Dec;56(4):622-47 [1480112] J Biol Chem. 1993 Feb 5;268(4):2590-4 [8381410] J Biol Chem. 1993 Jun 5;268(16):12010-6 [8389369] Infect Immun. 1993 Aug;61(8):3282-6 [8392970] J Biol Chem. 1993 Dec 15;268(35):26461-5 [8253774] Science. 1974 Feb 15;183(4125):656-7 [4810267] Infect Immun. 1974 Aug;10(2):320-7 [4368545] Immunochemistry. 1976 Jul;13(7):605-11 [955672] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5440-2 [202956] Infect Immun. 1991 Nov;59(11):4266-70 [1937784] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pulmonary response of Fischer 344 rats to acute nose-only inhalation of indium trichloride. AN - 76740262; 7925195 AB - We have previously shown that rats dosed intratracheally with indium trichloride (InCl3) develop severe lung damage and fibrosis. However, it is not clear what pulmonary effects would result following accidental occupational exposure to low concentrations of indium by inhalation. The present study uses a model of acute lung injury based on single 1-hr nose-only exposures to 0.2, 2.0, or 20 mg InCl3/m3. Exposure to 0.2 mg InCl3/m3 was capable of initiating an inflammatory response. Seven days following inhalation of 20 mg InCl3/m3 the total cell number, fibronectin, and TNF alpha levels in the bronchial alveolar lavage fluid were 8, 40, and 5 times higher than the control, respectively. Commensurate with the level of lung injury 7 days after exposure, an acute restrictive lung lesion and increased airway responsiveness to acetylcholine were observed. Forty-two days after exposure a compensatory increase in lung volume and carbon monoxide diffusing capacity in the 20 mg InCl3/m3 group suggested recovery from the lung injury. Lung collagen levels were increased in a concentration-dependent manner 42 days postexposure. These data indicate that inhalation of InCl3/m3 causes acute inflammatory changes in the lung. JF - Environmental research AU - Blazka, M E AU - Tepper, J S AU - Dixon, D AU - Winsett, D W AU - O'Connor, R W AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 68 EP - 83 VL - 67 IS - 1 SN - 0013-9351, 0013-9351 KW - Aerosols KW - 0 KW - Fibronectins KW - Tumor Necrosis Factor-alpha KW - Indium KW - 045A6V3VFX KW - indium trichloride KW - 31JB8MKF8Z KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Respiratory Function Tests KW - Animals KW - Total Lung Capacity -- drug effects KW - Random Allocation KW - Multivariate Analysis KW - Rats KW - Fibronectins -- analysis KW - Rats, Inbred F344 KW - Hydroxyproline -- analysis KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Tumor Necrosis Factor-alpha -- analysis KW - Administration, Inhalation KW - Bronchoalveolar Lavage Fluid -- cytology KW - Female KW - Organ Size -- drug effects KW - Indium -- toxicity KW - Lung -- chemistry KW - Lung -- drug effects KW - Lung -- physiopathology KW - Indium -- analysis KW - Indium -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76740262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Pulmonary+response+of+Fischer+344+rats+to+acute+nose-only+inhalation+of+indium+trichloride.&rft.au=Blazka%2C+M+E%3BTepper%2C+J+S%3BDixon%2C+D%3BWinsett%2C+D+W%3BO%27Connor%2C+R+W%3BLuster%2C+M+I&rft.aulast=Blazka&rft.aufirst=M&rft.date=1994-10-01&rft.volume=67&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lymphocyte depletion during treatment with intensive chemotherapy for cancer. AN - 76732529; 7919339 AB - Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens. JF - Blood AU - Mackall, C L AU - Fleisher, T A AU - Brown, M R AU - Magrath, I T AU - Shad, A T AU - Horowitz, M E AU - Wexler, L H AU - Adde, M A AU - McClure, L L AU - Gress, R E AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/10/01/ PY - 1994 DA - 1994 Oct 01 SP - 2221 EP - 2228 VL - 84 IS - 7 SN - 0006-4971, 0006-4971 KW - Antineoplastic Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Count KW - Dose-Response Relationship, Drug KW - Humans KW - Opportunistic Infections -- immunology KW - Adult KW - Child KW - Adolescent KW - Time Factors KW - Immunophenotyping KW - Cyclophosphamide -- administration & dosage KW - Lymphocyte Depletion KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76732529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lymphocyte+depletion+during+treatment+with+intensive+chemotherapy+for+cancer.&rft.au=Mackall%2C+C+L%3BFleisher%2C+T+A%3BBrown%2C+M+R%3BMagrath%2C+I+T%3BShad%2C+A+T%3BHorowitz%2C+M+E%3BWexler%2C+L+H%3BAdde%2C+M+A%3BMcClure%2C+L+L%3BGress%2C+R+E&rft.aulast=Mackall&rft.aufirst=C&rft.date=1994-10-01&rft.volume=84&rft.issue=7&rft.spage=2221&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-07 N1 - Date created - 1994-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct and overlapping direct effects of macrophage inflammatory protein-1 alpha and transforming growth factor beta on hematopoietic progenitor/stem cell growth. AN - 76730994; 7919333 AB - Both transforming growth factor beta (TGF beta) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been shown to be multifunctional regulators of hematopoiesis that can either inhibit or enhance the growth of hematopoietic progenitor cells (HPC). We report here the spectrum of activities of these two cytokines on different hematopoietic progenitor and stem cell populations, and whether these effects are direct or indirect. MIP-1 alpha enhances interleukin-3 (IL-3)/and granulocyte-macrophage colony-stimulating factor (GM-CSF)/induced colony formation of normal bone marrow progenitor cells (BMC) and lineage-negative (Lin-) progenitors, but has no effect on G-CSF or CSF-1/induced colony formation. Similarly, TGF beta enhances GM-CSF/induced colony formation of normal BMC and Lin- progenitors. In contrast, TGF beta inhibits IL-3/ and CSF-1/induced colony formation of Lin- progenitors. The effects of MIP-1 alpha and TGF beta on the growth of Lin- progenitors were direct and correlate with colony formation in soft agar. Separation of the Lin- cells into Thy-1 and Thy-1lo subsets showed that the growth of Thy-1lo Lin- cells is directly inhibited by MIP-1 alpha and TGF beta regardless of the cytokine used to stimulate growth (IL-3), GM-CSF, or CSF-1). In contrast, two other stem cell populations (0% to 15% Höechst 33342/Rhodamine 123 [Hö/Rh123] and Lin-Sca-1+ cells) were markedly inhibited by TGF beta and unaffected by MIP-1 alpha. Furthermore, MIP-1 alpha has no effect on high proliferative potential colony-forming cells 1 or 2 (HPP-CFC/1 or /2) colony formation in vitro, whereas TGF beta inhibits both HPP-CFC/1 and HPP-CFC/2. Thus, MIP-1 alpha and TGF beta are direct bidirectional regulators of HPC growth, whose effects are dependent on other growth factors present as well as the maturational state of the HPC assayed. The spectrum of their inhibitory and enhancing activities shows overlapping yet distinct effects. JF - Blood AU - Keller, J R AU - Bartelmez, S H AU - Sitnicka, E AU - Ruscetti, F W AU - Ortiz, M AU - Gooya, J M AU - Jacobsen, S E AD - Biological Carcinogenesis and Development Program, Program Resources, Inc/DynCorp, National Cancer Institute (NCI)-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/10/01/ PY - 1994 DA - 1994 Oct 01 SP - 2175 EP - 2181 VL - 84 IS - 7 SN - 0006-4971, 0006-4971 KW - Antigens, Thy-1 KW - 0 KW - Biomarkers KW - Chemokine CCL3 KW - Chemokine CCL4 KW - Cytokines KW - Macrophage Inflammatory Proteins KW - Monokines KW - Transforming Growth Factor beta KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Biomarkers -- analysis KW - Antigens, Thy-1 -- analysis KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Immunophenotyping KW - Female KW - Transforming Growth Factor beta -- pharmacology KW - Cytokines -- pharmacology KW - Hematopoiesis -- drug effects KW - Hematopoietic Stem Cells -- cytology KW - Monokines -- pharmacology KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76730994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+and+overlapping+direct+effects+of+macrophage+inflammatory+protein-1+alpha+and+transforming+growth+factor+beta+on+hematopoietic+progenitor%2Fstem+cell+growth.&rft.au=Keller%2C+J+R%3BBartelmez%2C+S+H%3BSitnicka%2C+E%3BRuscetti%2C+F+W%3BOrtiz%2C+M%3BGooya%2C+J+M%3BJacobsen%2C+S+E&rft.aulast=Keller&rft.aufirst=J&rft.date=1994-10-01&rft.volume=84&rft.issue=7&rft.spage=2175&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-07 N1 - Date created - 1994-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preferential primary-response gene expression in promotion-resistant versus promotion-sensitive JB6 cells. AN - 76721212; 7916993 AB - The 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequence (TIS) genes are a set of primary response genes induced in Swiss 3T3 cells by TPA. They include three transcription factors, a prostaglandin synthase, and three proteins of unknown function. To ascertain which, if any TIS genes might be involved in tumor promotion, we examined the expression of these genes in response to tumor promoters in transformation promotion-sensitive (P+) and -resistant (P-) JB6 murine epidermal cells, a model used to identify events relevant to promotion. A subset of TIS genes (TIS1, TIS10, and TIS21) was preferentially induced by TPA in P-cells. In addition, TIS1 and TIS21 mRNAs were preferentially induced in P-cells by epidermal growth factor, another transformation promoter that distinguishes P+ from P-cells. TIS1 and TIS21 protein levels were also greater in TPA-treated P-cells than P+ cells. Forskolin, a cAMP-elevating anti-promoter, increased TPA-induced levels of TIS1, TIS10, and TIS21 mRNAs in P+ cells, ruling in potential roles for these genes in modulating tumor promotion. The anti-promoters fluocinolone acetonide, retinoic acid, and superoxide dismutase did not enhance TPA-induced levels of TIS1 and TIS21 mRNAs in P+ cells, suggesting that these inhibitors may act on other promotion-relevant genes. TIS1 encodes a member of the steroid receptor superfamily. TIS1 encodes a protein of unknown function with strong sequence similarity to BTG1, a proposed "anti-proliferative gene" (Rouault JP, Rimokh R, Tessa C, et al., EMBO J 11:1663-1670, 1992). Preferential induction by multiple promoters of these TIS genes in P-cells and enhancement of their induction in P+ cells by the anti-promoter forskolin make TIS1 and TIS21 candidates for promotion suppressor genes. JF - Molecular carcinogenesis AU - Cmarik, J L AU - Herschman, H AU - Colburn, N H AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 115 EP - 124 VL - 11 IS - 2 SN - 0899-1987, 0899-1987 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - Immediate-Early Proteins KW - Proteins KW - Tristetraprolin KW - Zfp36 protein, mouse KW - Epidermal Growth Factor KW - 62229-50-9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Multigene Family KW - Gene Expression KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Mice, Inbred BALB C KW - Proteins -- genetics KW - Carcinogens -- pharmacology KW - Genes KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preferential+primary-response+gene+expression+in+promotion-resistant+versus+promotion-sensitive+JB6+cells.&rft.au=Cmarik%2C+J+L%3BHerschman%2C+H%3BColburn%2C+N+H&rft.aulast=Cmarik&rft.aufirst=J&rft.date=1994-10-01&rft.volume=11&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-16 N1 - Date created - 1994-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asbestos stimulates IL-8 production from human lung epithelial cells. AN - 76714691; 8089496 AB - Studies have indicated that soluble products, including chemotactic factors, released by activated lung macrophages and fibroblasts are critical mediators in the pathogenesis of asbestos-induced pulmonary fibrosis. We provide evidence that mediators produced by lung epithelial cells in response to asbestos may also contribute to lung disease. In the present study, the carcinogenic and fibrogenic fibers, chrysotile and crocidolite asbestos, were shown to directly stimulate the human pulmonary type-II epithelial cell line, A549, and to a lesser degree primary human bronchial epithelial cells, to elicit the chemotactic cytokine IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. That the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by cytokines was confirmed by using membrane-stabilizing agents and protein synthesis inhibitors. Stimulation was not observed with nonfibrogenic fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to stimulate the release of TNF, IL-1 beta, or monocyte chemoattractant protein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 alpha, probably preformed, was released in human bronchial epithelial cells. These data suggest that epithelial cells may, in addition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in particular, in the neutrophilic infiltration that is commonly observed after asbestos exposure. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Rosenthal, G J AU - Germolec, D R AU - Blazka, M E AU - Corsini, E AU - Simeonova, P AU - Pollock, P AU - Kong, L Y AU - Kwon, J AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/10/01/ PY - 1994 DA - 1994 Oct 01 SP - 3237 EP - 3244 VL - 153 IS - 7 SN - 0022-1767, 0022-1767 KW - Asbestos, Serpentine KW - 0 KW - Interleukin-1 KW - Interleukin-8 KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Abridged Index Medicus KW - Index Medicus KW - Interleukin-1 -- pharmacology KW - Bronchi -- cytology KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Gene Expression KW - Epithelium -- immunology KW - RNA, Messenger -- genetics KW - Bronchi -- immunology KW - L-Lactate Dehydrogenase -- metabolism KW - Cell Line KW - Lung -- immunology KW - Interleukin-8 -- biosynthesis KW - Lung -- cytology KW - Interleukin-8 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76714691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Asbestos+stimulates+IL-8+production+from+human+lung+epithelial+cells.&rft.au=Rosenthal%2C+G+J%3BGermolec%2C+D+R%3BBlazka%2C+M+E%3BCorsini%2C+E%3BSimeonova%2C+P%3BPollock%2C+P%3BKong%2C+L+Y%3BKwon%2C+J%3BLuster%2C+M+I&rft.aulast=Rosenthal&rft.aufirst=G&rft.date=1994-10-01&rft.volume=153&rft.issue=7&rft.spage=3237&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-14 N1 - Date created - 1994-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Representation of older patients in cancer treatment trials. AN - 76708002; 8087794 AB - In 1990, the five leading causes of cancer death in men aged 65 and older were carcinomas of the lung, prostate, colon and rectum, and pancreas, and leukemia. For women in this age group, the five leading causes of cancer death were carcinomas of the lung, breast, colon and rectum, pancreas, and ovary. To determine the representation of the elderly in clinical trials, the 1992 accrual of the National Cancer Institute (NCI)-sponsored Clinical Cooperative Group treatment trials (which included more than 8000 elderly patients) for the aforementioned sites was compared with the 1990 incidence data from the NCI's Surveillance, Epidemiology, and End Results program. Of the male patients enrolled in the trials, an average of 39% were older than 65 (47.3% lung, 79.5% prostate, 47.5% colorectal, 45.6% pancreas, and 9.6% leukemia); whereas 25.9% of all women enrolled in trials were 65 or older (43.6% lung, 17.3% breast, 46.2% colorectal, 59.6% pancreas, and 35.4% ovary). With respect to incidence, older patients generally are underrepresented in cancer treatment trials. With the exception of the data on prostate cancer, each of the comparisons using the Z statistic gave probability values of less than 0.01. The most significant discrepancies between incidence and participation in cancer treatment protocols were noted for leukemia in males and breast cancer in females. Possible explanations for these findings include (1) a research focus on aggressive therapy, which may be unacceptably toxic to the elderly; (2) presence of comorbidity in the elderly; (3) fewer trials available specifically aimed at older patients; (4) limited expectations for long term benefits on the part of physicians, relatives, and the patients themselves; and (5) a lack of financial, logistic, and social support for the participation of elderly patients in clinical trials. Recognizing this situation, NCI recently sponsored a number of trials that specifically target the elderly. This paper describes the status of all major Phase II and III clinical trials that recently were closed, still are active, or now are in review that address the clinical care of this important segment of the U.S. population. JF - Cancer AU - Trimble, E L AU - Carter, C L AU - Cain, D AU - Freidlin, B AU - Ungerleider, R S AU - Friedman, M A AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/10/01/ PY - 1994 DA - 1994 Oct 01 SP - 2208 EP - 2214 VL - 74 IS - 7 Suppl SN - 0008-543X, 0008-543X KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Prostatic Neoplasms -- epidemiology KW - Clinical Trials, Phase II as Topic KW - Clinical Trials, Phase III as Topic KW - Humans KW - Rectal Neoplasms -- epidemiology KW - Breast Neoplasms -- epidemiology KW - Research Design KW - Registries KW - Colonic Neoplasms -- epidemiology KW - Lung Neoplasms -- epidemiology KW - National Institutes of Health (U.S.) KW - Incidence KW - Pancreatic Neoplasms -- epidemiology KW - Middle Aged KW - Female KW - Male KW - Ovarian Neoplasms -- epidemiology KW - Neoplasms -- mortality KW - Neoplasms -- epidemiology KW - Clinical Trials as Topic KW - Aged KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76708002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Representation+of+older+patients+in+cancer+treatment+trials.&rft.au=Trimble%2C+E+L%3BCarter%2C+C+L%3BCain%2C+D%3BFreidlin%2C+B%3BUngerleider%2C+R+S%3BFriedman%2C+M+A&rft.aulast=Trimble&rft.aufirst=E&rft.date=1994-10-01&rft.volume=74&rft.issue=7+Suppl&rft.spage=2208&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Monocyte maturation controls expression of equine infectious anemia virus. AN - 76703484; 8083967 AB - In vivo, equine infectious anemia virus (EIAV) replicates in tissues rich in macrophages, and it is widely believed that the tissue macrophage is the principal, if not sole, cell within the host that replicates virus. No viral replication has been detected in circulating peripheral blood monocytes. However, proviral DNA can be detected in these cells, and monocytes may serve as a reservoir for the virus. In this study, an in vitro model was developed to clarify the role of monocyte maturation in regulating EIAV expression. Freshly isolated, nonadherent equine peripheral blood monocytes were infected with a macrophage-tropic strain of EIAV, and expression of EIAV was monitored in cells held as nonadherent monocytes and cells allowed to adhere and differentiate into macrophages. A 2- to 3-day delay in viral antigen expression was observed in the nonadherent cells. This restriction of viral expression in monocytes was supported by nuclear run-on studies demonstrating that on day 5 postinfection, the level of actively transcribed viral messages was 4.7-fold lower in monocyte cultures than in macrophage cultures. Electrophoretic mobility shift assays identified three regions of the U3 enhancer that interacted with nuclear extracts from normal equine macrophages. Each region contained the core binding motif of a family of transcription factors that includes the product of the proto-oncogene ets. Antibodies to the Ets family member PU.1 caused a supershifting of retarded bands in an electrophoretic mobility shift assay. Transfection studies of ets motif mutants demonstrated that the U3 ets sites were important in the regulation of EIAV transcription in macrophages. Interactions between the ets motif and nuclear extracts from freshly isolated, nonadherent monocytes, macrophages adherent for 1 or 2 days, or macrophages adherent for 5 days gave different patterns of retarded bands, although the binding specificities were similar with all three extracts. The different complexes formed by monocyte and macrophage nuclear extracts may explain the enhanced ability of mature macrophages to support EIAV expression. JF - Journal of virology AU - Maury, W AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 6270 EP - 6279 VL - 68 IS - 10 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - Guanosine Triphosphate KW - 86-01-1 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Cell Nucleus -- metabolism KW - Humans KW - Horses KW - Transcription, Genetic KW - Plasmids KW - Chloramphenicol O-Acetyltransferase -- analysis KW - Glucosephosphate Dehydrogenase -- biosynthesis KW - Guanosine Triphosphate -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Glucosephosphate Dehydrogenase -- analysis KW - Transfection KW - Cells, Cultured KW - Molecular Sequence Data KW - Virus Replication KW - Macrophages -- microbiology KW - Infectious Anemia Virus, Equine -- metabolism KW - Gene Expression Regulation, Viral KW - Monocytes -- physiology KW - Enhancer Elements, Genetic KW - Infectious Anemia Virus, Equine -- genetics KW - Macrophages -- physiology KW - Monocytes -- microbiology KW - Infectious Anemia Virus, Equine -- physiology KW - Repetitive Sequences, Nucleic Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76703484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Monocyte+maturation+controls+expression+of+equine+infectious+anemia+virus.&rft.au=Maury%2C+W&rft.aulast=Maury&rft.aufirst=W&rft.date=1994-10-01&rft.volume=68&rft.issue=10&rft.spage=6270&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 - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1991 Nov;65(11):5782-9 [1920616] J Virol. 1993 Nov;67(11):6586-95 [8411361] Mol Cell Biol. 1993 Nov;13(11):7163-9 [8413305] J Virol. 1994 Jan;68(1):298-307 [8254741] Mol Cell Biol. 1994 Jan;14(1):373-81 [8264604] Mol Cell Biol. 1994 Jan;14(1):840-50 [8264651] Virology. 1994 May 1;200(2):632-42 [8178449] Mol Cell Biol. 1992 Jan;12(1):368-78 [1729611] J Virol. 1992 Apr;66(4):2067-75 [1548752] Mol Cell Biol. 1992 Jul;12(7):2967-75 [1620109] J Virol. 1992 Oct;66(10):5906-13 [1382143] Virology. 1973 Apr;52(2):456-67 [4705382] Am J Pathol. 1971 Feb;62(2):283-94 [4322275] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9934-8 [1409722] J Am Vet Med Assoc. 1979 Apr 1;174(7):727-33 [218920] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Infect Immun. 1983 Jul;41(1):67-73 [6862634] J Immunol Methods. 1983 Aug 12;62(1):31-7 [6875265] Methods Enzymol. 1983;101:582-98 [6888276] Rev Infect Dis. 1985 Jan-Feb;7(1):83-8 [2984759] Proc Natl Acad Sci U S A. 1985 Oct;82(20):7086-90 [2996004] Virology. 1985 Nov;147(1):231-6 [2998068] J Virol. 1986 Apr;58(1):67-74 [3005660] Nature. 1986 Jul 10-16;322(6075):130-6 [2425264] Science. 1986 Jul 11;233(4760):215-9 [3014648] Science. 1986 Sep 5;233(4768):1089-93 [3016903] Mol Cell Biol. 1987 Aug;7(8):2735-44 [3670291] J Biol Chem. 1988 Jun 25;263(18):8671-6 [3379039] J Virol. 1988 Oct;62(10):3779-88 [3047430] Adv Vet Sci Comp Med. 1988;32:129-48 [2461057] J Virol. 1989 Jun;63(6):2492-6 [2470916] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974-8 [2762307] J Gen Virol. 1989 Oct;70 ( Pt 10):2661-72 [2677236] J Virol. 1989 Dec;63(12):5194-200 [2555550] Cell. 1990 Apr 6;61(1):113-24 [2180582] J Virol. 1990 Apr;64(4):1616-24 [2157047] AIDS. 1990 Mar;4(3):221-8 [2112397] J Acquir Immune Defic Syndr. 1990;3(7):658-68 [2161920] Virus Res. 1990 Jun;16(2):175-83 [2166980] J Virol. 1991 Mar;65(3):1605-10 [1847479] J Infect Dis. 1991 May;163(5):976-88 [2019773] J Med Primatol. 1992 Feb-May;21(2-3):74-81 [1433270] J Acquir Immune Defic Syndr. 1992 Oct;5(10):1009-15 [1333528] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):357-61 [8419941] AIDS Res Hum Retroviruses. 1993 Jan;9(1):69-76 [8427715] Eur J Pharmacol. 1993 Jan 26;231(1):61-8 [8383063] J Biol Chem. 1993 Mar 5;268(7):5014-20 [8095266] J Virol. 1993 Apr;67(4):2064-74 [8383228] EMBO J. 1993 Mar;12(3):1169-78 [8458329] J Virol. 1993 Jul;67(7):3885-90 [8389910] Arch Virol. 1993;131(3-4):335-47 [8102229] J Virol. 1993 Sep;67(9):5175-86 [7688819] J Virol. 1993 Sep;67(9):5522-8 [8350410] Mol Cell Biol. 1993 Sep;13(9):5276-89 [8355682] J Virol. 1991 Nov;65(11):6242-51 [1717720] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The high transforming potency of erbB-2 and ret is associated with phosphorylation of paxillin and a 23 kDa protein. AN - 76703098; 7916147 AB - Two-dimensional gel maps of proteins phosphorylated by the epidermal growth factor receptor (EGFR) and erbB-2 kinases were obtained, to investigate the molecular basis of the different biological properties of these two molecules. Several proteins were phosphorylated by EGFR or erbB-2 with different stoichiometry. Differences were either quantitative or qualitative. In NIH3T3 cells, erbB-2 is 100-fold more transforming than EGFR. In the same cell line several proteins were preferentially phosphorylated by erbB-2, as compared to EGFR. To identify which of these substrates might be directly involved in mitogenic signaling, we obtained two-dimensional maps of proteins phosphorylated on tyrosine by EGFR/ret and an EGFR/erbB-2TK chimeric receptors. Both these chimerae behaved indistinguishably from erbB-2 in a number of bioassays and potently transformed NIH3T3 cells. Paxillin and a 23 kDa substrate were invariably phosphorylated to higher stoichiometry whenever potent mitogenic and transforming signals were activated. We propose that paxillin and the 23 kDa substrate are important elements in the erbB-2 and ret-activated mitogenic and transforming signaling. JF - Oncogene AU - Romano, A AU - Wong, W T AU - Santoro, M AU - Wirth, P J AU - Thorgeirsson, S S AU - Di Fiore, P P AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 2923 EP - 2933 VL - 9 IS - 10 SN - 0950-9232, 0950-9232 KW - erbB-2 KW - ret KW - Cytoskeletal Proteins KW - 0 KW - Drosophila Proteins KW - Paxillin KW - Phosphoproteins KW - Proteins KW - Proto-Oncogene Proteins KW - Pxn protein, mouse KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-ret KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Epidermal Growth Factor KW - Receptor, ErbB-2 KW - Ret oncogene protein, Drosophila KW - Ret protein, mouse KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Amino Acid Sequence KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Proteins -- metabolism KW - Phosphorylation KW - Electrophoresis, Gel, Two-Dimensional KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Sequence Homology, Amino Acid KW - Signal Transduction KW - Cell Transformation, Neoplastic KW - Cell Division KW - Receptor, Epidermal Growth Factor -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Cytoskeletal Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76703098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+high+transforming+potency+of+erbB-2+and+ret+is+associated+with+phosphorylation+of+paxillin+and+a+23+kDa+protein.&rft.au=Romano%2C+A%3BWong%2C+W+T%3BSantoro%2C+M%3BWirth%2C+P+J%3BThorgeirsson%2C+S+S%3BDi+Fiore%2C+P+P&rft.aulast=Romano&rft.aufirst=A&rft.date=1994-10-01&rft.volume=9&rft.issue=10&rft.spage=2923&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Gene symbol - erbB-2; ret N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcription of the human T-cell lymphotropic virus type I promoter by an alpha-amanitin-resistant polymerase. AN - 76697754; 7521915 AB - The human T-lymphotropic virus type I (HTLV-I) promoter contains the structural features of a typical RNA polymerase II (pol II) template. The promoter contains a TATA box 30 bp upstream of the transcription initiation site and binding sites for several pol II transcription factors, and long poly(A)+ RNA is synthesized from the integrated HTLV-I proviral DNA in vivo. Consistent with these characteristics, HTLV-I transcription activity was reconstituted in vitro by using TATA-binding protein, TFIIA, recombinant TFIIB, TFIIE, and TFIIF, TFIIH, and pol II. Transcription of the HTLV-I promoter in the reconstituted system requires RNA pol II. In HeLa whole cell extracts, however, the HTLV-I long terminal repeat also contains an overlapping transcription unit (OTU). HTLV-I OTU transcription is initiated at the same nucleotide site as the RNA isolated from the HTLV-I-infected cell line MT-2 but was not inhibited by the presence of alpha-amanitin at concentrations which inhibited the adenovirus major late pol II promoter (6 micrograms/ml). HTLV-I transcription was inhibited when higher concentrations of alpha-amanitin (60 micrograms/ml) were used, in the range of a typical pol III promoter (VA-I). Neutralization and depletion experiments with three distinct pol II antibodies demonstrate that RNA pol II is not required for HTLV-I OTU transcription. Antibodies to basal transcription factors TATA-binding protein and TFIIB, but not TFIIIC, inhibited HTLV-I OTU transcription. These observations suggest that the HTLV-I long terminal repeat contains overlapping promoters, a typical pol II promoter and a unique pol III promoter which requires a distinct set of transcription factors. JF - Journal of virology AU - Piras, G AU - Kashanchi, F AU - Radonovich, M F AU - Duvall, J F AU - Brady, J N AD - Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/10// PY - 1994 DA - October 1994 SP - 6170 EP - 6179 VL - 68 IS - 10 SN - 0022-538X, 0022-538X KW - Amanitins KW - 0 KW - RNA, Messenger KW - RNA, Viral KW - Recombinant Proteins KW - Transcription Factor TFIIA KW - Transcription Factor TFIIB KW - Transcription Factors KW - Transcription Factors, TFII KW - transcription factor TFIIE KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - RNA Polymerase II KW - EC 2.7.7.- KW - transcription factor TFIIF KW - EC 3.6.4.12 KW - Index Medicus KW - AIDS/HIV KW - HeLa Cells KW - Humans KW - RNA, Viral -- biosynthesis KW - Drug Resistance, Microbial KW - Blotting, Western KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Proviruses -- genetics KW - Repetitive Sequences, Nucleic Acid KW - TATA Box KW - Proviruses -- metabolism KW - RNA Polymerase II -- metabolism KW - Human T-lymphotropic virus 1 -- genetics KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Poly A -- biosynthesis KW - Transcription, Genetic KW - Human T-lymphotropic virus 1 -- metabolism KW - Amanitins -- toxicity KW - RNA -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76697754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcription+of+the+human+T-cell+lymphotropic+virus+type+I+promoter+by+an+alpha-amanitin-resistant+polymerase.&rft.au=Piras%2C+G%3BKashanchi%2C+F%3BRadonovich%2C+M+F%3BDuvall%2C+J+F%3BBrady%2C+J+N&rft.aulast=Piras&rft.aufirst=G&rft.date=1994-10-01&rft.volume=68&rft.issue=10&rft.spage=6170&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 - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1992 Oct 16;71(2):221-30 [1423590] Cell. 1992 Dec 11;71(6):1015-28 [1458533] Cell. 1992 Dec 11;71(6):1055-64 [1458536] Nucleic Acids Res. 1992 Nov 25;20(22):5889-98 [1461721] Nucleic Acids Res. 1992 Dec 25;20(24):6451-4 [1480467] Nucleic Acids Res. 1993 Feb 25;21(4):1013-8 [8451168] Genes Dev. 1993 Jul;7(7B):1291-308 [8330735] J Virol. 1993 Oct;67(10):6087-95 [8371355] J Biol Chem. 1993 Oct 5;268(28):21225-31 [8407959] Oncogene. 1993 Nov;8(11):3029-36 [8414503] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112-6 [3022280] EMBO J. 1986 Nov;5(11):2883-8 [3024966] Cell. 1987 Apr 10;49(1):47-56 [3030566] Nature. 1988 Jun 23;333(6175):776-8 [2838755] Science. 1988 Jul 1;241(4861):89-92 [2838905] J Biol Chem. 1988 Jul 25;263(21):10048-51 [3292520] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526-30 [2847164] EMBO J. 1988 Dec 20;7(13):4179-84 [2468487] Mol Cell Biol. 1988 Dec;8(12):5581-7 [2854202] Oncogene Res. 1989;4(1):39-46 [2470009] Mol Cell Biol. 1989 Apr;9(4):1733-45 [2786141] J Biol Chem. 1989 Jul 5;264(19):11511-20 [2472398] J Biol Chem. 1983 Oct 10;258(19):11968-73 [6194159] Cell. 1984 Feb;36(2):241-7 [6692471] J Biol Chem. 1984 Feb 25;259(4):2236-42 [6321464] Science. 1984 Jul 27;225(4660):381-5 [6330891] Virology. 1984 Dec;139(2):340-5 [6097028] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277-81 [2986109] CRC Crit Rev Biochem. 1985;18(1):31-90 [3893883] J Virol. 1987 Jul;61(7):2175-81 [3035218] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653-7 [3035544] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5389-93 [3037548] Cell. 1987 Dec 24;51(6):1001-8 [3690658] Nature. 1988 Feb 11;331(6156):540-3 [2829028] Science. 1970 Oct 23;170(3956):447-9 [4918258] Eur J Biochem. 1974 May 15;44(2):421-36 [4209621] Cell. 1992 Dec 11;71(6):1029-40 [1458534] Cell. 1992 Dec 11;71(6):1041-53 [1458535] N Engl J Med. 1988 May 5;318(18):1141-7 [2896300] EMBO J. 1988 Feb;7(2):519-23 [2835230] Genes Dev. 1993 Nov;7(11):2246-57 [8224850] Nature. 1970 Jan 3;225(5227):60-2 [5410195] Biochem Biophys Res Commun. 1970 Jan 6;38(1):165-71 [4907405] Biochim Biophys Acta. 1974 Jun 27;353(2):160-84 [4601749] Proc Natl Acad Sci U S A. 1975 Jan;72(1):348-52 [1054509] Annu Rev Biochem. 1975;44:613-38 [1094919] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 [6933441] J Biol Chem. 1980 Dec 25;255(24):11992-6 [7440580] J Biol Chem. 1982 Mar 10;257(5):2613-8 [6174508] Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031-5 [6979048] Biochemistry. 1982 Jun 22;21(13):3097-101 [7104312] Proc Natl Acad Sci U S A. 1982 Nov;79(22):6899-902 [6294664] Science. 1982 Feb 19;215(4535):975-8 [6760397] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618-22 [6304725] Science. 1985 Aug 16;229(4714):675-9 [2992082] Cell. 1985 Sep;42(2):599-610 [3896517] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6502-6 [2995968] J Biol Chem. 1985 Dec 5;260(28):15304-10 [3905793] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558-62 [3018737] Nature. 1989 Oct 5;341(6241):410-4 [2477704] Cell. 1989 Dec 22;59(6):1081-92 [2598261] J Biol Chem. 1990 Jan 5;265(1):499-505 [2403565] Mol Cell Biol. 1989 Nov;9(11):4731-7 [2689863] Genes Dev. 1989 Oct;3(10):1534-44 [2482226] Science. 1990 Mar 2;247(4946):1082-4 [2309119] J Biol Chem. 1990 May 15;265(14):8237-42 [2186038] Genes Dev. 1990 Mar;4(3):313-23 [2186966] EMBO J. 1990 Aug;9(8):2537-42 [2196176] Mol Cell Biol. 1990 Aug;10(8):4192-201 [2370863] Annu Rev Biochem. 1990;59:711-54 [2197989] J Exp Med. 1990 Sep 1;172(3):759-65 [2388034] EMBO J. 1990 Oct;9(10):3137-44 [2209540] Proc Natl Acad Sci U S A. 1990 Nov;87(22):8687-91 [2247437] Science. 1991 Jan 25;251(4992):424-6 [1989075] J Virol. 1991 Mar;65(3):1420-6 [1847461] Cell. 1991 Feb 22;64(4):727-37 [1671761] EMBO J. 1991 Jul;10(7):1853-62 [2050122] J Virol. 1991 Aug;65(8):4525-8 [2072462] Genes Dev. 1991 Aug;5(8):1477-89 [1869050] Nature. 1991 Aug 22;352(6337):689-95 [1876184] J Virol. 1991 Oct;65(10):5513-23 [1895400] Nucleic Acids Res. 1991 Sep 25;19(18):5045-52 [1923771] EMBO J. 1991 Dec;10(12):3795-803 [1935901] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10004-8 [1946417] Nature. 1991 Dec 5;354(6352):369-73 [1956398] Virology. 1992 Feb;186(2):764-9 [1733110] Nature. 1992 Jan 30;355(6359):461-4 [1734283] Nature. 1992 Jan 30;355(6359):464-7 [1734284] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1949-53 [1542692] Cell. 1992 Mar 6;68(5):965-76 [1547496] Mol Cell Biol. 1992 May;12(5):1986-96 [1569936] Curr Opin Cell Biol. 1992 Jun;4(3):488-95 [1497921] Cell. 1992 Oct 2;71(1):5-7 [1394431] Genes Dev. 1992 Oct;6(10):1940-9 [1398071] J Biol Chem. 1992 Oct 5;267(28):20204-11 [1400338] Cell. 1992 Oct 16;71(2):211-20 [1423589] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of lung immunity after intratracheal instillation of benzo(a)pyrene AN - 15846223; 4014351 AB - Benzo(a)pyrene (B(a)P) has been shown to suppress systemic immunity in experimental animals, which may contribute to the growth of the chemical-induced tumors. However, its effects on lung immunity after inhalation, a common route for human exposure in urban areas, has not been determined. These studies examine intratracheal B(a)P instillation on lung natural killer (NK) cell activity, alveolar macrophage (AM) functions, and susceptibility to tumor cell challenge in Fischer 344 (F-344) rats. Adult female F-344 rats were given a single intratracheal instillation of 0, 10, 20, or 40 mg B(a)P/kg body weight as a suspension, and lung NK cell activity and AM functions were examined 7, 21, or 100 d later. Although exposure to B(a)P did not alter cell recovery after lavage, histologic changes were observed as evidenced by granulomatous inflammation and squamous metaplasia. There was a slight but significant suppression of H sub(2)O sub(2) and nitric oxide (NO) release from alveolar macrophages of treated animals as well as NK cell activity from the lung digest. A marked suppression of tumor necrosis factor- alpha (TNF alpha ) and interleukin (IL-1) secretion in LPS-and/or cytokine-activated alveolar macrophages occurred. The suppressive effects were generally more severe on Day 7 after exposure than on Days 21 or 100, although IL-1 remained depressed through Day 100 after exposure. B(a)P exposure allowed for the increased growth of MADB106 metastatic tumor cells in the lung. These tumor cells were shown to be highly sensitive to lysis by immune-mediators, including TNF alpha . Taken together, these results indicated that NK cell activity and particularly secretory products produced by AM are sensitive targets for instilled B(a)P, and altered lung immunity may play a role in allowing for the growth of lung tumors. (DBO) JF - American Journal of Respiratory and Critical Care Medicine AU - Kong, Ling-Yuan AU - Luster, MI AU - Dixon, D AU - O'Grady, J AU - Rosenthal, G J AD - NIEHS, P.O. Box 12233, MD C1-04, Research Triangle Park, NC 27709, USA Y1 - 1994/10// PY - 1994 DA - Oct 1994 SP - 1123 EP - 1124 VL - 150 IS - 4 SN - 1073-449X, 1073-449X KW - benzo(a)pyrene KW - rats KW - Toxicology Abstracts KW - lung KW - immunity KW - immunotoxicity KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/15846223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Inhibition+of+lung+immunity+after+intratracheal+instillation+of+benzo%28a%29pyrene&rft.au=Kong%2C+Ling-Yuan%3BLuster%2C+MI%3BDixon%2C+D%3BO%27Grady%2C+J%3BRosenthal%2C+G+J&rft.aulast=Kong&rft.aufirst=Ling-Yuan&rft.date=1994-10-01&rft.volume=150&rft.issue=4&rft.spage=1123&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - lung; immunity; immunotoxicity ER - TY - JOUR T1 - The Value of Amniotic Fluid Interleukin-6, White Blood Cell Count, and Gram Stain in the Diagnosis of Microbial Invasion of the Amniotic Cavity in Patients at Term AN - 1356934732; 18052091 AB - PROBLEM: Subclinical microbial invasion of the amniotic cavity occurs in 18.8% of women with term labor and intact membranes and in 34% of patients with term PROM and is a risk factor for the development of puerperal infection related morbidity. Although amniotic fluid white blood cell count, interleukin-6 determination, and Gram stain examination have been used for the diagnosis of intrauterine infection in patients with preterm labor and preterm premature rupture of membranes, no information is available about the accuracy and specific cut-off values for these tests in patients at term. The purpose of this study was to compare the performance of the amniotic fluid Gram stain examination, white blood cell count, and interleukin-6 determination in the identification of microbial invasion of the amniotic cavity in patients at term with and without PROM. METHOD: Amniotic fluid was retrieved from 148 patients with term gestations (90 patients with spontaneous labor and intact membranes and 58 patients with PROM). Samples were cultured for bacteria and Mycoplasma species. Amniotic fluid Gram stain, white blood cell count, and interleukin-6 determinations (ELISA, sensitivity: 43 pg/ml) were performed in all samples. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. Analysis was conducted using Mann-Whitney U test, Fisher's exact test, receiver operating characteristic curves and logistic regression. RESULTS: Patients with spontaneous labor and intact membranes: The prevalence of microbial invasion of amniotic cavity in this group was 15.6% (14/90). The most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determination (sensitivity for: interleukin-6 greater than or equal to 5.7 ng/ml = 86%, white blood cell count greater than or equal to 20 cells/mm3 = 64%, Gram stain = 28%). The most specific test was the Gram stain of the amniotic fluid (specificity for: Gram stain = 84%, interleukin-6 = 79% and white blood cell count = 63%). Multiple logistic regression demonstrated that amniotic fluid interleukin-6 concentration was the only covariate that retained statistical significance when intrauterine infection was used as outcome variable. Patients with PROM: The prevalence of a positive amniotic fluid culture in this group was 39.7% (23/58). Logistic regression demonstrated that only interleukin-6 retained a significant relationship with the results of amniotic culture when all variables were entered simultaneously into a model to predict amniotic fluid culture results. The most sensitive tests for the detection of intrauterine infection were interleukin-6 determination and white blood cell count (sensitivity for interleukin-6 greater than or equal to 3.4 ng/ml and white blood cell count greater than or equal to 20 cells/mm3 = 69.6% for both). The most specific test was Gram stain (97.1%). CONCLUSIONS: Amniotic fluid interleukin-6 determination is the best rapid test for the detection of microbial invasion of the amniotic cavity in patients at term with and without PROM. When this test is not available, amniotic fluid Gram stain and white blood cell count represent valid diagnostic tools to assess the microbial state of amniotic cavity. JF - American Journal of Reproductive Immunology AU - Gomez, Ricardo AU - Romero, Roberto AU - Galasso, Maurizio AU - Behnke, Ernesto AU - Insunza, Alvaro AU - Cotton, David B AD - Perinatology Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland Y1 - 1994/10// PY - 1994 DA - Oct 1994 SP - 200 EP - 210 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 32 IS - 3 SN - 1046-7408, 1046-7408 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - Interleukin 6 KW - Amniotic fluid KW - Cavities KW - Enzyme-linked immunosorbent assay KW - Statistics KW - Leukocytes KW - Rupture KW - Cell culture KW - Infection KW - Morbidity KW - Gram stain KW - Risk factors KW - Gestation KW - Puerperal infection KW - Microorganisms KW - Regression analysis KW - Mycoplasma KW - F 06935:Development, Aging & Organ Systems KW - A 01300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1356934732?accountid=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=American+Journal+of+Reproductive+Immunology&rft.atitle=The+Value+of+Amniotic+Fluid+Interleukin-6%2C+White+Blood+Cell+Count%2C+and+Gram+Stain+in+the+Diagnosis+of+Microbial+Invasion+of+the+Amniotic+Cavity+in+Patients+at+Term&rft.au=Gomez%2C+Ricardo%3BRomero%2C+Roberto%3BGalasso%2C+Maurizio%3BBehnke%2C+Ernesto%3BInsunza%2C+Alvaro%3BCotton%2C+David+B&rft.aulast=Gomez&rft.aufirst=Ricardo&rft.date=1994-10-01&rft.volume=32&rft.issue=3&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Reproductive+Immunology&rft.issn=10467408&rft_id=info:doi/10.1111%2Fj.1600-0897.1994.tb01115.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-05-01 N1 - Last updated - 2015-09-03 N1 - SubjectsTermNotLitGenreText - Amniotic fluid; Interleukin 6; Cavities; Enzyme-linked immunosorbent assay; Statistics; Leukocytes; Rupture; Cell culture; Infection; Morbidity; Gram stain; Risk factors; Gestation; Regression analysis; Microorganisms; Puerperal infection; Mycoplasma DO - http://dx.doi.org/10.1111/j.1600-0897.1994.tb01115.x ER - TY - JOUR T1 - Conformationally locked nucleoside analogues. Synthesis of dideoxycarbocyclic nucleoside analogues structurally related to neplanocin C. AN - 76753373; 7932567 AB - The glycon moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme northern and southern conformations as defined by the pseudorotation cycle. The concept of preparing rigid nucleoside analogues with the glycon conformation locked in one of these two extremes was tested with the synthesis of some cyclopropane-fused dideoxycarbocyclic nucleosides, similar to the well-known class of anti-HIV active dideoxynucleosides. The new compounds described here are dideoxynucleoside analogues of the fermentation product neplanocin C (6) which exhibits a typical northern geometry for its 6-oxabicyclo[3.1.0]hexane pseudosugar moiety. However, in view of the lability of the epoxide ring in this system, the equivalent cyclopropane-fused bicyclo[3.1.0]hexane system was used instead to prepare the corresponding dideoxynucleoside analogues bearing all the common bases [(+/-)-9-13]. Due to the well-documented preference of unrestricted bicyclo[3.1.0]hexane systems to exist exclusively in a boat conformation, the resulting nucleosides are structurally locked in a typical northern conformation similar to that of neplanocin C. The locked northern conformation in these nucleosides remained unchanged in solution in the 20-80 degrees C temperature range according to variable temperature 1H NMR studies. For the synthesis of these compounds, racemic trans-1-[(benzyloxy)methyl]-4-hydroxybicyclo[3.1.0]hexane [(+/-)-18] was prepared by a samarium-promoted cyclopropanation reaction with the antecedent cyclopentenol. All of the bases were incorporated under Mitsunobu conditions and converted to the desired final products following a standard methodology. Anti-HIV evaluation revealed that only the adenosine analogue (+/-)-9 possessed enough activity to warrant resolution into its optical antipodes. This was realized by chiral HPLC chromatography to give the individual enantiomers (-)-32 and (+)-33. Adenosine deaminase was used to identify isomer (+)-33 as the enantiomer with the "natural" configuration which was solely responsible for the observed biological activity and toxicity of (+/-)-9. It is possible that the exclusive northern conformation adopted by these nucleosides reduces their substrate affinity for the various activating kinases, except in the case of the adenosine analogue. JF - Journal of medicinal chemistry AU - Rodriguez, J B AU - Marquez, V E AU - Nicklaus, M C AU - Mitsuya, H AU - Barchi, J J AD - Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/09/30/ PY - 1994 DA - 1994 Sep 30 SP - 3389 EP - 3399 VL - 37 IS - 20 SN - 0022-2623, 0022-2623 KW - 1-(hydroxymethyl)-4-(6-amino-9-purinyl)bicyclo(3.1.0)hexane KW - 0 KW - Antiviral Agents KW - Bridged Bicyclo Compounds KW - Nucleosides KW - neplanocin C KW - 72877-48-6 KW - Adenosine Deaminase KW - EC 3.5.4.4 KW - Adenine KW - JAC85A2161 KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Adenosine Deaminase -- metabolism KW - Stereoisomerism KW - Computer Simulation KW - Models, Molecular KW - Adenosine -- chemistry KW - Adenosine -- analogs & derivatives KW - Temperature KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Magnetic Resonance Spectroscopy KW - HIV -- drug effects KW - Bridged Bicyclo Compounds -- pharmacology KW - Bridged Bicyclo Compounds -- chemical synthesis KW - Antiviral Agents -- chemical synthesis KW - Adenine -- metabolism KW - Antiviral Agents -- pharmacology KW - Adenine -- chemical synthesis KW - Bridged Bicyclo Compounds -- metabolism KW - Nucleosides -- chemistry KW - Nucleic Acid Conformation KW - Adenine -- analogs & derivatives KW - Adenine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76753373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conformationally+locked+nucleoside+analogues.+Synthesis+of+dideoxycarbocyclic+nucleoside+analogues+structurally+related+to+neplanocin+C.&rft.au=Rodriguez%2C+J+B%3BMarquez%2C+V+E%3BNicklaus%2C+M+C%3BMitsuya%2C+H%3BBarchi%2C+J+J&rft.aulast=Rodriguez&rft.aufirst=J&rft.date=1994-09-30&rft.volume=37&rft.issue=20&rft.spage=3389&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 - 1994-11-03 N1 - Date created - 1994-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerance of the bladder to intraoperative radiation in a canine model: a five-year follow-up. AN - 76745227; 7928460 AB - Late effects of intraoperative radiation therapy (IORT) on bladder were investigated in a canine model. After laporatomy and cystotomy in adult female foxhounds weighing 25-35 kg, 12 MeV electrons were delivered intraoperatively to a 5 cm circular bladder field which included the trigone and both uretero-vesicle junctions. Each animal received doses of 0, 20, 25, 30, 35, or 40 Gy. All the dogs were followed 5 years postoperatively. An unoperated dog receiving no surgery or radiation treatment was followed as a control. Close clinical monitoring was performed with regular cystometrics and intravenous pyelography. Animals were killed as scheduled with complete necropsies, including histopathology, with special attention to genitourinary structures. There were no acute or late bladder complications detected clinically in any animal. The dog receiving 30 Gy IORT developed rhabdomyosarcoma in the treatment field at 58 months. On follow-up testing over 5 years, there was no loss of bladder contractility on cystometry, and mild changes in the ureters on intravenous pyleography when animals receiving IORT were compared with baseline pretreatment values or with control animals. Histologically, a difference was evident between irradiated and unirradiated animals, but the changes were not clearly dose-related. Intraoperative radiation therapy may by safely delivered to the canine bladder with few acute or chronic complications. It is an approach which has potential for clinical use and should continue to be explored in human clinical trials. JF - International journal of radiation oncology, biology, physics AU - DeLuca, A M AU - Johnstone, P A AU - Ollayos, C W AU - Bacher, J D AU - Terrill, R E AU - Kinsella, T J AU - Sindelar, W F AD - National Cancer Institute, Radiation Biology Branch, Bethesda, MD 20892. Y1 - 1994/09/30/ PY - 1994 DA - 1994 Sep 30 SP - 339 EP - 345 VL - 30 IS - 2 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Animals KW - Dogs KW - Radiography KW - Intraoperative Period KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Urinary Bladder Neoplasms -- radiotherapy KW - Female KW - Urinary Bladder -- pathology KW - Radiation Tolerance KW - Urinary Bladder -- radiation effects KW - Urinary Bladder -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76745227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Tolerance+of+the+bladder+to+intraoperative+radiation+in+a+canine+model%3A+a+five-year+follow-up.&rft.au=DeLuca%2C+A+M%3BJohnstone%2C+P+A%3BOllayos%2C+C+W%3BBacher%2C+J+D%3BTerrill%2C+R+E%3BKinsella%2C+T+J%3BSindelar%2C+W+F&rft.aulast=DeLuca&rft.aufirst=A&rft.date=1994-09-30&rft.volume=30&rft.issue=2&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-03 N1 - Date created - 1994-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of toxicity of cypenhymustine, a new anticancer compound, in mice. AN - 76740498; 7923104 AB - The toxicity of cypenhymustine, a potential anticancer compound 1 (Cancer Letters, 70 (1993) 1-6), was assessed in normal as well as in Ehrlich ascites carcinoma (EAC), Sarcoma-180 (S-180) and Dalton's lymphoma (DL)-bearing Swiss male mice by measuring drug-induced changes in (1) hematological parameters and (2) femoral bone marrow cellularity on day 9 following drug treatment at the optimum dose of 3.0 mg/kg body weight from days 1 to 7. Detailed studies were also made by noting sequential changes in the above parameters in normal and EAC-bearing mice on days 12, 15, 18 and 21, respectively. The results indicate that the compound did not adversely affect hematopoiesis. From the sequential studies, it was observed that after a mild initial decrease in hematological counts, particularly in EAC-bearing treated mice, normalcy was reached within 11-14 days after termination of drug therapy. Drug induced hepatotoxicity and nephrotoxicity were also sequentially evaluated in normal and EAC-bearing mice on days 9, 12 and 15 but no such toxicities were detected. Also, body weight, skin and hair texture, and behavioural pattern (food and water intake and activity) did not reflect any toxic reaction in the host mice at this optimum dose. JF - Cancer letters AU - Sadhu, U AU - Ghosh, M AU - Bhattacharya, S AU - Dutta, S AU - Das, H AU - Sanyal, U AD - Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994/09/30/ PY - 1994 DA - 1994 Sep 30 SP - 65 EP - 72 VL - 85 IS - 1 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents KW - 0 KW - Hemoglobins KW - Hydantoins KW - Nitrogen Mustard Compounds KW - cypenhymustine KW - 150380-35-1 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Alkaline Phosphatase KW - EC 3.1.3.1 KW - Index Medicus KW - Animals KW - Erythrocyte Count -- drug effects KW - Chemical and Drug Induced Liver Injury KW - Platelet Count -- drug effects KW - Mice KW - Liver Diseases -- enzymology KW - Kidney Diseases -- enzymology KW - Blood Urea Nitrogen KW - Alkaline Phosphatase -- blood KW - Femur KW - Bone Marrow Cells KW - Leukocyte Count -- drug effects KW - Aspartate Aminotransferases -- blood KW - Alanine Transaminase -- blood KW - Hemoglobins -- metabolism KW - Thrombocytosis -- chemically induced KW - Body Weight -- drug effects KW - Bone Marrow -- drug effects KW - Drug Evaluation, Preclinical KW - Male KW - Kidney Diseases -- chemically induced KW - Hydantoins -- toxicity KW - Antineoplastic Agents -- toxicity KW - Nitrogen Mustard Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76740498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Evaluation+of+toxicity+of+cypenhymustine%2C+a+new+anticancer+compound%2C+in+mice.&rft.au=Sadhu%2C+U%3BGhosh%2C+M%3BBhattacharya%2C+S%3BDutta%2C+S%3BDas%2C+H%3BSanyal%2C+U&rft.aulast=Sadhu&rft.aufirst=U&rft.date=1994-09-30&rft.volume=85&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard. AN - 76778536; 7937793 AB - G2 arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes. We investigated the possibility that this might be due to a suppression of cdc25C phosphatase activity. cdc25C from interphase cells migrated as a 54- to 57-kDa doublet in SDS gels and exhibited basal phosphatase activity. cdc25C from mitotic cells migrated as a 66-kDa hyperphosphorylated species and exhibited elevated phosphatase activity. cdc25C hyperphosphorylation and activation were mediated by cdc2, supporting the view of a cdc2-cdc25C autocatalytic feedback loop. Immunofluorescence and cell fractionation studies suggested cdc2-cdc25C interaction occurred within the cytoplasm. Cells arrested in G2 phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species. Our findings suggest that checkpoints guarding against mitotic entry in the presence of unreplicated or damaged DNA suppress formation of the cdc2-cdc25C autocatalytic feedback loop that normally brings about rapid activation of cdc2. JF - Proceedings of the National Academy of Sciences of the United States of America AU - O'Connor, P M AU - Ferris, D K AU - Hoffmann, I AU - Jackman, J AU - Draetta, G AU - Kohn, K W AD - Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/09/27/ PY - 1994 DA - 1994 Sep 27 SP - 9480 EP - 9484 VL - 91 IS - 20 SN - 0027-8424, 0027-8424 KW - Cell Cycle Proteins KW - 0 KW - Proteins KW - Aphidicolin KW - 38966-21-1 KW - Mechlorethamine KW - 50D9XSG0VR KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - CDC25C protein, human KW - EC 3.1.3.48 KW - cdc25 Phosphatases KW - Nocodazole KW - SH1WY3R615 KW - Index Medicus KW - Aphidicolin -- pharmacology KW - Tumor Cells, Cultured KW - HeLa Cells KW - CDC2 Protein Kinase -- metabolism KW - Kinetics KW - Humans KW - Burkitt Lymphoma KW - Interphase KW - Time Factors KW - Proteins -- metabolism KW - Nocodazole -- pharmacology KW - Cell Line KW - G2 Phase -- physiology KW - G2 Phase -- drug effects KW - Mechlorethamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76778536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+the+cdc25C+phosphatase+in+G2+arrest+induced+by+nitrogen+mustard.&rft.au=O%27Connor%2C+P+M%3BFerris%2C+D+K%3BHoffmann%2C+I%3BJackman%2C+J%3BDraetta%2C+G%3BKohn%2C+K+W&rft.aulast=O%27Connor&rft.aufirst=P&rft.date=1994-09-27&rft.volume=91&rft.issue=20&rft.spage=9480&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 - 1994-10-27 N1 - Date created - 1994-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1993 Aug;12(8):3133-42 [8344252] Mol Biol Cell. 1993 Apr;4(4):397-411 [8389619] Genes Dev. 1994 Mar 15;8(6):652-65 [7926756] Science. 1989 Nov 3;246(4930):629-34 [2683079] Proc Natl Acad Sci U S A. 1990 Jul;87(13):5139-43 [2195549] Cell. 1990 Nov 30;63(5):1013-24 [2147872] EMBO J. 1990 Dec;9(13):4331-8 [2176149] Cell. 1991 Mar 22;64(6):1111-22 [1706223] EMBO J. 1991 Nov;10(11):3311-9 [1833185] EMBO J. 1991 Nov;10(11):3321-9 [1655417] Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10500-4 [1961714] Cell. 1992 Feb 7;68(3):407-10 [1310893] EMBO J. 1992 Mar;11(3):961-71 [1312467] EMBO J. 1992 Apr;11(4):1335-42 [1563349] Cell Growth Differ. 1992 Jan;3(1):43-52 [1534688] Cold Spring Harb Symp Quant Biol. 1991;56:417-25 [1819503] Cold Spring Harb Symp Quant Biol. 1991;56:449-63 [1840258] Mol Biol Cell. 1992 Jun;3(6):687-98 [1323352] Nature. 1992 Oct 15;359(6396):599-604 [1406993] Genes Dev. 1992 Nov;6(11):2035-46 [1427071] Mol Biol Cell. 1992 Dec;3(12):1373-88 [1337289] EMBO J. 1993 Jan;12(1):53-63 [8428594] Semin Cancer Biol. 1992 Dec;3(6):409-16 [1286161] J Biol Chem. 1993 Apr 15;268(11):8298-308 [8463339] Nature. 1993 May 27;363(6427):368-71 [8497322] Cancer Res. 1993 Oct 15;53(20):4776-80 [8402660] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dual regulation of Ca2+/calmodulin-dependent kinase II activity by membrane voltage and by calcium influx. AN - 76769017; 7937825 AB - Calcium entry through voltage-gated Ca2+ channels is critical in cardiac excitation-contraction coupling and calcium metabolism. In this report, we demonstrate both spatially resolved and temporally distinct effects of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on L-type Ca2+ channel current (ICa) in rat cardiac myocytes. Either depolarization alone or calcium influx can increase the amplitude and slow the inactivation of ICa. The distinct voltage- and Ca(2+)-dependent effects persist with time constants of approximately 1.7 sec and 9 sec, respectively. Both effects are completely abolished by a specific peptide inhibitor of CaMKII. This CaMKII inhibitor also suppresses the prolongation of ICa induced by depolarizing holding potentials. Furthermore, using an antibody specific for the autophosphorylated (activated) CaMKII, we find that this kinase is localized close to sarcolemmal membranes and that the profile of CaMKII activation correlates qualitatively with the changes in ICa under various conditions. Therefore, we conclude that the action of CaMKII on ICa is dually regulated by membrane depolarization and by Ca2+ influx; the latter directly activates CaMKII, whereas the former likely promotes the interaction between constitutive CaMKII and the membrane-channel proteins. These regulatory mechanisms provide positive-feedback control of Ca2+ channels and are probably important in the regulation of cardiac contractility and other intracellular Ca(2+)-regulated processes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Xiao, R P AU - Cheng, H AU - Lederer, W J AU - Suzuki, T AU - Lakatta, E G AD - Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994/09/27/ PY - 1994 DA - 1994 Sep 27 SP - 9659 EP - 9663 VL - 91 IS - 20 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Isoenzymes KW - Isoquinolines KW - Piperazines KW - Protein Kinase Inhibitors KW - Sulfonamides KW - Adenylyl Imidodiphosphate KW - 25612-73-1 KW - Egtazic Acid KW - 526U7A2651 KW - W 7 KW - 65595-90-6 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Isoproterenol KW - L628TT009W KW - Thioridazine KW - N3D6TG58NI KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Egtazic Acid -- analogs & derivatives KW - Thioridazine -- pharmacology KW - Electric Conductivity KW - Norepinephrine -- pharmacology KW - Adenylyl Imidodiphosphate -- pharmacology KW - Piperazines -- pharmacology KW - Electric Stimulation KW - Isoenzymes -- metabolism KW - Isoproterenol -- pharmacology KW - Rats KW - Isoquinolines -- pharmacology KW - Sulfonamides -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Membrane Potentials -- drug effects KW - Time Factors KW - Egtazic Acid -- pharmacology KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Calcium Channels -- physiology KW - Myocardium -- enzymology KW - Heart -- physiology KW - Heart -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76769017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dual+regulation+of+Ca2%2B%2Fcalmodulin-dependent+kinase+II+activity+by+membrane+voltage+and+by+calcium+influx.&rft.au=Xiao%2C+R+P%3BCheng%2C+H%3BLederer%2C+W+J%3BSuzuki%2C+T%3BLakatta%2C+E+G&rft.aulast=Xiao&rft.aufirst=R&rft.date=1994-09-27&rft.volume=91&rft.issue=20&rft.spage=9659&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 - 1994-10-27 N1 - Date created - 1994-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1988 Nov 25;263(33):17209-12 [2846557] Science. 1993 Oct 29;262(5134):740-4 [8235594] J Biol Chem. 1988 Dec 5;263(34):18145-51 [2848027] J Biol Chem. 1989 Jul 5;264(19):11468-74 [2544595] Nature. 1989 Sep 7;341(6237):65-8 [2549428] J Biol Chem. 1989 Dec 25;264(36):21830-6 [2557342] Biochemistry. 1990 Jun 26;29(25):5899-905 [2166564] J Biol Chem. 1991 Jun 15;266(17):11144-52 [1645727] Neuron. 1991 Jun;6(6):907-14 [1647175] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):109-13 [1309602] Nature. 1992 May 7;357(6373):74-7 [1315424] Science. 1992 May 22;256(5060):1199-202 [1317063] Am J Physiol. 1992 Jun;262(6 Pt 2):H1941-9 [1621851] Biochemistry. 1980 May 27;19(11):2396-404 [6770893] J Physiol. 1982 Aug;329:589-614 [6292410] J Neurosci. 1985 Oct;5(10):2609-17 [4045548] Proc Natl Acad Sci U S A. 1987 Jun;84(11):3941-5 [2438689] J Physiol. 1987 Aug;389:205-22 [2445973] Science. 1992 Jul 10;257(5067):206-11 [1321493] Nature. 1992 Oct 22;359(6397):739-41 [1331805] Nature. 1993 Jul 15;364(6434):240-3 [8391648] Circ Res. 1993 Aug;73(2):286-300 [8101141] Nature. 1988 Oct 27;335(6193):820-4 [2847049] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific conjugation to interleukin 4 containing mutated cysteine residues produces interleukin 4-toxin conjugates with improved binding and activity. AN - 76731541; 7918378 AB - Fusion of a ligand to another protein frequently impairs the binding of the ligand. Recombinant toxins composed of mutants of Pseudomonas exotoxin (PE) fused to the C-terminus of human interleukin 4 (IL4) are cytotoxic to IL4 receptor- (IL4R-) bearing tumor cells but bind to the IL4R with only 1% the affinity of IL4. We have developed a method to connect a toxin to a ligand which allows the junction to be moved to a location on the ligand which would minimize the binding impairment. We designed mutants of IL4 in which residue 28, 38, 68, 70, 97, or 105 was substituted with cysteine. All purified mutants bound to the IL4R with 60-100% the affinity of IL4, indicating that the IL4 structure was essentially unchanged. The IL4 mutants were then each conjugated through a disulfide bond to PE35, a truncated form of PE which contains a single cysteine. IL4 conjugated to PE35 at residue 28, 38, or 105 of IL4 bound with 10-fold improved affinity and was 10-fold more cytotoxic than the recombinant IL4-toxin in which PE is fused to position 129 at the C-terminus of IL4. IL4 containing PE35 conjugated at position 68, 70, or 97 had lower binding affinity and cytotoxic activity. These results indicate that the location of the ligand-protein junction can be selectively moved to enhance conjugate effectiveness, and implications could be made regarding which regions of IL4 are important for binding. JF - Biochemistry AU - Kreitman, R J AU - Puri, R K AU - Leland, P AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09/27/ PY - 1994 DA - 1994 Sep 27 SP - 11637 EP - 11644 VL - 33 IS - 38 SN - 0006-2960, 0006-2960 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin KW - Receptors, Interleukin-4 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Interleukin-4 KW - 207137-56-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Receptors, Interleukin -- metabolism KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - Cysteine -- genetics KW - Humans KW - Amino Acid Sequence KW - Protein Binding KW - Structure-Activity Relationship KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Protein Engineering KW - Binding, Competitive KW - Molecular Sequence Data KW - Interleukin-4 -- genetics KW - Exotoxins -- genetics KW - Exotoxins -- pharmacology KW - Immunotoxins -- toxicity KW - Interleukin-4 -- pharmacology KW - Lymphocytes -- metabolism KW - Immunotoxins -- metabolism KW - Interleukin-4 -- metabolism KW - Exotoxins -- metabolism KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology KW - Lymphocytes -- drug effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76731541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-specific+conjugation+to+interleukin+4+containing+mutated+cysteine+residues+produces+interleukin+4-toxin+conjugates+with+improved+binding+and+activity.&rft.au=Kreitman%2C+R+J%3BPuri%2C+R+K%3BLeland%2C+P%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1994-09-27&rft.volume=33&rft.issue=38&rft.spage=11637&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of tyrosine hydroxylase in olfactory bulb cultures: selective inhibition of depolarization-induced increase by endogenous opioids. AN - 77693871; 7834330 AB - Regulation of tyrosine hydroxylase (TH) by second messenger pathway activators was examined in rat olfactory bulb cell cultures. The number of TH-immunoreactive neurons was increased 2-3-fold by 36 h treatments with forskolin (Fsk, 10(-6) M) or phorbol myristate acetate (PMA, 10(-7) M), but was not significantly increased by a depolarizing concentration of KCl (45 mM). In contrast, KCl increased media [Met5]enkephalin (ME) immunoreactivity 2-fold in these cultures, equivalent to stimulation with Fsk or PMA. The possibility was examined that ME or another opioid produced by the cultures selectively inhibited the TH response to KCl. Pretreatment with the opioid receptor antagonist naloxone (10(-6) M) greatly increased the number of TH-immunoreactive neurons observed in response to KCl treatment, but had no effect on basal or Fsk-stimulated TH immunostaining, nor on basal or stimulated ME release. The increase in TH-immunoreactivity observed with combined KCl plus naloxone treatment was prevented by pretreating the cultures with the calcium channel blocker nimodipine (10(-6) M), which had no effect on Fsk stimulation or basal TH immunostaining. These data suggest that endogenous opioids selectively inhibit KCl-stimulated Ca2+ entry and thus TH induction in olfactory bulb cell cultures. These cultures offer a simple model system for further study of TH regulation in dopaminergic neurons. JF - Brain research AU - McMillian, M K AU - Mullis, S B AU - Wu, G C AU - Hudson, P M AU - Pennypacker, K R AU - Hong, J S AD - Laboratory of Molecular and Integrative Neurosciences, NIEHS, NIH, Research Triangle Park, NC 27709. Y1 - 1994/09/26/ PY - 1994 DA - 1994 Sep 26 SP - 105 EP - 111 VL - 658 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Opioid Peptides KW - 0 KW - Colforsin KW - 1F7A44V6OU KW - Potassium Chloride KW - 660YQ98I10 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cyclic AMP KW - E0399OZS9N KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Protein Kinase C -- drug effects KW - Animals KW - Colforsin -- pharmacology KW - Enzyme Activation KW - Cells, Cultured KW - Dexamethasone -- pharmacology KW - Potassium Chloride -- pharmacology KW - Membrane Potentials -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tyrosine 3-Monooxygenase -- metabolism KW - Opioid Peptides -- physiology KW - Olfactory Bulb -- enzymology KW - Calcium -- physiology KW - Neurons -- enzymology KW - Cyclic AMP -- physiology KW - Olfactory Bulb -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77693871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+tyrosine+hydroxylase+in+olfactory+bulb+cultures%3A+selective+inhibition+of+depolarization-induced+increase+by+endogenous+opioids.&rft.au=McMillian%2C+M+K%3BMullis%2C+S+B%3BWu%2C+G+C%3BHudson%2C+P+M%3BPennypacker%2C+K+R%3BHong%2C+J+S&rft.aulast=McMillian&rft.aufirst=M&rft.date=1994-09-26&rft.volume=658&rft.issue=1-2&rft.spage=105&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 - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning and expression of the acidic fibroblast growth factor receptors in a rat parathyroid cell line (PT-r). Parathyroid cell-specific calcium-dependent change of ligand accessibility and covalent attachment of heparan sulfate glycosaminoglycan to the receptors. AN - 76712031; 8089146 AB - We have previously identified two fibroblast growth factor (FGF) receptors with higher affinity for acidic FGF rather than basic FGF in a rat parathyroid cell line (PT-r). Carbohydrate analyses of the receptors suggested the presence of three different types of FGF receptors, a 150-kDa glycoprotein receptor, a approximately 150-kDa heparan sulfate-proteoglycan receptor, and a 130-kDa glycoprotein receptor (Sakaguchi, K., Yanagishita, M., Takeuchi, Y., and Aurbach, G.D. (1991) J. Biol. Chem. 266, 7270-7278). Here, we have cloned two isoforms of the FGF receptors from PT-r cells; one with two immunoglobulin (Ig)-like domains (clone a), and the other with an additional Ig-like domain and an acidic box (clone b). They showed highest homology to the mouse and human keratinocyte growth factor receptors among the FGF receptors reported. Clones a and b had one and three possible glycosaminoglycan attachment sites, respectively. Heparitinase treatment of PT-r cells transfected with clone a suggested that the protein for the 130-kDa glycoprotein receptor was encoded by clone a, and that the same protein also served as a core protein for the approximately 150-kDa heparan sulfate-proteoglycan receptor. Heparan sulfate glycosaminoglycan attachment to the 150-kDa receptor encoded by clone b was not detectable by the same enzyme treatment. Site-directed mutagenesis (from Ser to Ala) studies of the consensus sequence for the attachment of glycosaminoglycans further supported the presence of covalently attached heparan sulfate glycosaminoglycan in the approximately 150-kDa heparan sulfate-proteoglycan receptor. These receptors overexpressed in PT-r cells changed ligand accessibility or apparently translocated after changing extracellular calcium concentrations in a manner similar to the native receptors in PT-r cells (Sakaguchi, K. (1992) J. Biol. Chem. 267, 24554-24562), whereas those expressed in CHO-K1 or NIH/3T3 cells did not. These findings strongly suggest that the two FGF receptor isoforms cloned here represent the acidic FGF receptors that we reported earlier. A subpopulation of the receptors carries heparan sulfate glycosaminoglycan covalently attached to the core protein, and the change in ligand accessibility in response to the shift in ambient calcium concentration is specific to the parathyroid cells. JF - The Journal of biological chemistry AU - Takagi, Y AU - Shrivastav, S AU - Miki, T AU - Sakaguchi, K AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09/23/ PY - 1994 DA - 1994 Sep 23 SP - 23743 EP - 23749 VL - 269 IS - 38 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Ligands KW - Receptors, Fibroblast Growth Factor KW - Heparitin Sulfate KW - 9050-30-0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Cloning, Molecular KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Rats KW - Base Sequence KW - Sequence Alignment KW - Cell Compartmentation KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Sequence Homology, Amino Acid KW - DNA Primers -- chemistry KW - Heparitin Sulfate -- metabolism KW - Receptors, Fibroblast Growth Factor -- chemistry KW - Receptors, Fibroblast Growth Factor -- metabolism KW - Parathyroid Glands -- chemistry KW - Receptors, Fibroblast Growth Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76712031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+cloning+and+expression+of+the+acidic+fibroblast+growth+factor+receptors+in+a+rat+parathyroid+cell+line+%28PT-r%29.+Parathyroid+cell-specific+calcium-dependent+change+of+ligand+accessibility+and+covalent+attachment+of+heparan+sulfate+glycosaminoglycan+to+the+receptors.&rft.au=Takagi%2C+Y%3BShrivastav%2C+S%3BMiki%2C+T%3BSakaguchi%2C+K&rft.aulast=Takagi&rft.aufirst=Y&rft.date=1994-09-23&rft.volume=269&rft.issue=38&rft.spage=23743&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 - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pervanadate simulates the effects of interleukin-2 (IL-2) in human T cells and provides evidence for the activation of two distinct tyrosine kinase pathways by IL-2. AN - 76708042; 8089104 AB - Pervanadate has been shown to rapidly increase the level of tyrosine phosphorylation in intact cells. Because one of the most rapidly detectable events following treatment of human T cells with interleukin-2 (IL-2) is tyrosine kinase activation, we were interested to determine whether pervanadate could act to induce IL-2-associated events. We show here that pervanadate does act to induce IL-2 signal transduction pathways as determined by induction of mitogenesis and interferon gamma production in normal human T cells and the factor independent T cell line YT. Analysis of signal transduction events shows that pervanadate induces the activity of the src family of tyrosine kinases lck and fyn and the tyrosine phosphorylation of a major IL-2 responsive protein of 97 kDa. Pervanadate does not, however, induce the activity of tyrosine kinases associated with the IL-2 receptor or the phosphorylation of a major IL-2 responsive protein of 116 kDa (Jak-3). Together these data suggest that src family kinase activation is a down stream event following IL-2 stimulation and is not directly associated with the activation of the IL-2 receptor-associated tyrosine kinase. The data also imply that tyrosine phosphorylation of p116/Jak-3 is strictly associated with activation of tyrosine kinases associated with the IL-2 receptor. With the use of pervanadate as a tool, we have established a dissociation of src family kinases with IL-2 receptor activation and imply the involvement of two distinct tyrosine kinase pathways, a receptor-associated pathway closely coupled with Jak-3 phosphorylation and a downstream pathway involving src family kinase activation. JF - The Journal of biological chemistry AU - Evans, G A AU - Garcia, G G AU - Erwin, R AU - Howard, O M AU - Farrar, W L AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/09/23/ PY - 1994 DA - 1994 Sep 23 SP - 23407 EP - 23412 VL - 269 IS - 38 SN - 0021-9258, 0021-9258 KW - fyn KW - lck KW - Interleukin-2 KW - 0 KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - pervanadate KW - Vanadates KW - 3WHH0066W5 KW - Interferon-gamma KW - 82115-62-6 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - FYN protein, human KW - EC 2.7.10.2 KW - JAK3 protein, human KW - Janus Kinase 3 KW - Lymphocyte Specific Protein Tyrosine Kinase p56(lck) KW - Proto-Oncogene Proteins c-fyn KW - Index Medicus KW - Humans KW - Cell Division -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Interferon-gamma -- biosynthesis KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Molecular Weight KW - Lymphocyte Activation -- drug effects KW - Cells, Cultured KW - In Vitro Techniques KW - Signal Transduction KW - Phosphoproteins -- metabolism KW - Interleukin-2 -- administration & dosage KW - Vanadates -- administration & dosage KW - T-Lymphocytes -- drug effects KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76708042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pervanadate+simulates+the+effects+of+interleukin-2+%28IL-2%29+in+human+T+cells+and+provides+evidence+for+the+activation+of+two+distinct+tyrosine+kinase+pathways+by+IL-2.&rft.au=Evans%2C+G+A%3BGarcia%2C+G+G%3BErwin%2C+R%3BHoward%2C+O+M%3BFarrar%2C+W+L&rft.aulast=Evans&rft.aufirst=G&rft.date=1994-09-23&rft.volume=269&rft.issue=38&rft.spage=23407&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 - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - fyn; lck N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria. AN - 76702447; 8083224 AB - The pig and human dihydropyrimidine dehydrogenase (DPD) cDNAs were cloned and sequenced. The pig enzyme, expressed in Escherichia coli, catalyzed the reduction of uracil, thymine, and 5-fluorouracil with kinetics approximating those published for the enzyme purified from mammalian liver. DPD could be expressed in significant quantities only when uracil was added to the bacterial growth medium. The pig and human enzymes contained 1025 amino acids and calculated M(r) = 111,416 and 111,398, respectively. Conserved domains corresponding to a possible NADPH binding site and FAD binding site were found in the NH2-terminal half of the proteins and two motifs of putative [4Fe-4S] binding sites were found near to the carboxyl terminus of the enzyme. The latter corresponds to the labile COOH-terminal fragment previously shown to contain the iron sulfur centers. A sequence encompassing a peptide corresponding to the uracil binding site was found between the NADPH/FAD-containing NH2-terminal portion of the protein and the iron-sulfur binding sites near to the COOH terminus. Thus, the DPD appears to be derived from at least three distinct domains. The DPYD gene was localized to the centromeric region of human chromosome 1 between 1p22 and q21. JF - The Journal of biological chemistry AU - Yokota, H AU - Fernandez-Salguero, P AU - Furuya, H AU - Lin, K AU - McBride, O W AU - Podschun, B AU - Schnackerz, K D AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/09/16/ PY - 1994 DA - 1994 Sep 16 SP - 23192 EP - 23196 VL - 269 IS - 37 SN - 0021-9258, 0021-9258 KW - DPD KW - DPYD KW - DNA, Complementary KW - 0 KW - Recombinant Proteins KW - Uracil KW - 56HH86ZVCT KW - Oxidoreductases KW - EC 1.- KW - Dihydrouracil Dehydrogenase (NADP) KW - EC 1.3.1.2 KW - Thymine KW - QR26YLT7LT KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Swine KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Hybrid Cells KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Chromosome Mapping KW - Cricetinae KW - Chromosomes, Human, Pair 1 KW - Fluorouracil -- adverse effects KW - Thymine -- urine KW - Oxidoreductases -- genetics KW - Metabolism, Inborn Errors -- genetics KW - Oxidoreductases -- deficiency KW - Uracil -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76702447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=cDNA+cloning+and+chromosome+mapping+of+human+dihydropyrimidine+dehydrogenase%2C+an+enzyme+associated+with+5-fluorouracil+toxicity+and+congenital+thymine+uraciluria.&rft.au=Yokota%2C+H%3BFernandez-Salguero%2C+P%3BFuruya%2C+H%3BLin%2C+K%3BMcBride%2C+O+W%3BPodschun%2C+B%3BSchnackerz%2C+K+D%3BGonzalez%2C+F+J&rft.aulast=Yokota&rft.aufirst=H&rft.date=1994-09-16&rft.volume=269&rft.issue=37&rft.spage=23192&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 - 1994-10-11 N1 - Date created - 1994-10-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DPD; DPYD N1 - Genetic sequence - U09179; GENBANK; U09178 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of the gamma chain of the high affinity receptor for immunoglobulin E by receptor-associated protein kinase C-delta. AN - 76702327; 8083212 AB - The gamma chain of the high affinity receptor for immunoglobulin E is a member of the T-cell antigen receptor zeta chain family and a functional subunit common to both T-cell and Fc receptors. Here we report that the gamma chain is phosphorylated on threonine in response to protein kinase C activation. Furthermore, the threonine phosphorylation of the gamma chain correlates with the endocytosis of this receptor. We identified a receptor-associated kinase as the calcium-independent protein kinase C-delta and found that it associates with the carboxyl-terminal cytoplasmic domain of the beta chain. In addition, protein kinase C-delta was the only isozyme capable of phosphorylating the gamma chain in vitro. These findings provide evidence for the functional role of protein kinase C-delta in early signal transduction events in the mast cell and suggest a more general mechanism of activation for receptors that share subunits of the zeta chain family. JF - The Journal of biological chemistry AU - Germano, P AU - Gomez, J AU - Kazanietz, M G AU - Blumberg, P M AU - Rivera, J AD - Section on Chemical Immunology, NIAMSD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09/16/ PY - 1994 DA - 1994 Sep 16 SP - 23102 EP - 23107 VL - 269 IS - 37 SN - 0021-9258, 0021-9258 KW - Indoles KW - 0 KW - Isoenzymes KW - Maleimides KW - Receptors, IgE KW - Ro 31-7549 KW - 125313-65-7 KW - Threonine KW - 2ZD004190S KW - Prkcd protein, rat KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Endocytosis KW - Animals KW - Tumor Cells, Cultured KW - Threonine -- metabolism KW - Phosphorylation KW - Enzyme Activation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Isoenzymes -- antagonists & inhibitors KW - Receptors, IgE -- metabolism KW - Receptors, IgE -- chemistry KW - Protein Kinase C -- antagonists & inhibitors KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76702327?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+the+gamma+chain+of+the+high+affinity+receptor+for+immunoglobulin+E+by+receptor-associated+protein+kinase+C-delta.&rft.au=Germano%2C+P%3BGomez%2C+J%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M%3BRivera%2C+J&rft.aulast=Germano&rft.aufirst=P&rft.date=1994-09-16&rft.volume=269&rft.issue=37&rft.spage=23102&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 - 1994-10-11 N1 - Date created - 1994-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylation- and mutation-dependent stimulation of Alu transcription in vitro. AN - 76722260; 8093066 AB - Alu genes are GC-rich, highly repetitive genetic elements whose functions remain unknown. Members of this family are readily transcribed in vitro by RNA polymerase III, but RNA corresponding to only a small sub-set of Alu elements has been found in vivo. Based on the hypothesis that methylation of Alu elements affects their transcription, the transcriptional activity of unmethylated and methylated template DNA was assessed in vitro. It was found that methylation of a single CG site just 5' to Alu functions to stimulate transcription; the base composition in this region also affects transcriptional activity. These results indicate that the methylation state and sequence of DNA flanking Alu elements influence its transcription rate. JF - Biochemical and biophysical research communications AU - Vorce, R L AU - Lee, B AU - Howard, B H AD - Laboratory of Molecular Growth Regulation, NICHD, NIH, Bethesda, MD. Y1 - 1994/09/15/ PY - 1994 DA - 1994 Sep 15 SP - 845 EP - 851 VL - 203 IS - 2 SN - 0006-291X, 0006-291X KW - DNA KW - 9007-49-2 KW - DNA modification methylase HhaI KW - EC 2.1.1.- KW - DNA modification methylase HpaII KW - DNA-Cytosine Methylases KW - RNA Polymerase III KW - EC 2.7.7.6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - DNA-Cytosine Methylases -- metabolism KW - DNA -- metabolism KW - Molecular Sequence Data KW - RNA Polymerase III -- metabolism KW - Templates, Genetic KW - Methylation KW - Binding Sites KW - Transcription, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76722260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methylation-+and+mutation-dependent+stimulation+of+Alu+transcription+in+vitro.&rft.au=Vorce%2C+R+L%3BLee%2C+B%3BHoward%2C+B+H&rft.aulast=Vorce&rft.aufirst=R&rft.date=1994-09-15&rft.volume=203&rft.issue=2&rft.spage=845&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 - 1994-10-18 N1 - Date created - 1994-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. AN - 76667174; 8069852 JF - Cancer research AU - Greenblatt, M S AU - Bennett, W P AU - Hollstein, M AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/09/15/ PY - 1994 DA - 1994 Sep 15 SP - 4855 EP - 4878 VL - 54 IS - 18 SN - 0008-5472, 0008-5472 KW - p53 KW - Aflatoxins KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Chromosome Deletion KW - DNA Repair KW - DNA Damage KW - DNA Mutational Analysis KW - Humans KW - Smoking -- adverse effects KW - Disease Models, Animal KW - Neoplasms, Radiation-Induced -- genetics KW - Sequence Analysis, DNA KW - Structure-Activity Relationship KW - Phenotype KW - Hepatitis B -- complications KW - Conserved Sequence KW - Tumor Suppressor Protein p53 -- chemistry KW - Aflatoxins -- toxicity KW - Cell Transformation, Neoplastic -- genetics KW - DNA Replication KW - Genes, p53 -- physiology KW - Genes, p53 -- genetics KW - Mutation -- genetics KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76667174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+p53+tumor+suppressor+gene%3A+clues+to+cancer+etiology+and+molecular+pathogenesis.&rft.au=Greenblatt%2C+M+S%3BBennett%2C+W+P%3BHollstein%2C+M%3BHarris%2C+C+C&rft.aulast=Greenblatt&rft.aufirst=M&rft.date=1994-09-15&rft.volume=54&rft.issue=18&rft.spage=4855&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 - 1994-09-27 N1 - Date created - 1994-09-27 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. AN - 76713581; 8090721 AB - We have found several genetic changes in the TGF-beta-type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Park, K AU - Kim, S J AU - Bang, Y J AU - Park, J G AU - Kim, N K AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/09/13/ PY - 1994 DA - 1994 Sep 13 SP - 8772 EP - 8776 VL - 91 IS - 19 SN - 0027-8424, 0027-8424 KW - DNA, Neoplasm KW - 0 KW - Plasminogen Activator Inhibitor 1 KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Plasminogen Activator Inhibitor 1 -- genetics KW - Genes KW - Tumor Cells, Cultured KW - Humans KW - In Vitro Techniques KW - Gene Expression KW - DNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - DNA, Neoplasm -- biosynthesis KW - Gene Deletion KW - Gene Amplification KW - Receptors, Transforming Growth Factor beta -- genetics KW - Stomach Neoplasms -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76713581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+changes+in+the+transforming+growth+factor+beta+%28TGF-beta%29+type+II+receptor+gene+in+human+gastric+cancer+cells%3A+correlation+with+sensitivity+to+growth+inhibition+by+TGF-beta.&rft.au=Park%2C+K%3BKim%2C+S+J%3BBang%2C+Y+J%3BPark%2C+J+G%3BKim%2C+N+K%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Park&rft.aufirst=K&rft.date=1994-09-13&rft.volume=91&rft.issue=19&rft.spage=8772&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 - 1994-10-14 N1 - Date created - 1994-10-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Nature. 1985 Feb 28-Mar 6;313(6005):745-7 [3883191] J Biol Chem. 1989 Feb 5;264(4):2272-8 [2536702] J Cancer Res Clin Oncol. 1990;116(2):121-31 [2157713] Cancer Res. 1990 May 1;50(9):2773-80 [2158397] Cell. 1990 Jun 1;61(5):759-67 [2188735] Nucleic Acids Res. 1990 May 25;18(10):3059 [2349108] J Biol Chem. 1990 Oct 25;265(30):18518-24 [2170414] J Natl Cancer Inst. 1991 Jul 3;83(13):938-43 [1676761] Nature. 1991 Sep 5;353(6339):83-6 [1881452] Cell. 1991 Nov 15;67(4):785-95 [1657406] Cell. 1991 Nov 15;67(4):797-805 [1657407] Cancer Res. 1992 Jan 15;52(2):295-300 [1309437] J Biol Chem. 1992 Feb 5;267(4):2588-93 [1370826] Cell. 1992 Feb 21;68(4):775-85 [1310899] Jpn J Cancer Res. 1992 Jan;83(1):86-92 [1312080] Cell. 1992 Jun 26;69(7):1067-70 [1319842] Cancer Surv. 1992;12:81-103 [1638549] Cancer Res. 1992 Dec 15;52(24):6735-40 [1458460] Cell. 1992 Dec 11;71(6):1003-14 [1333888] Science. 1993 May 28;260(5112):1344-8 [8388127] Science. 1993 May 28;260(5112):1335-8 [8388126] J Cancer Res Clin Oncol. 1993;119(5):265-72 [8440743] Cancer Res. 1993 Jun 15;53(12):2704-7 [8389240] Cell. 1993 Jul 2;73(7):1435-44 [8391934] Cell. 1993 Nov 19;75(4):681-92 [8242743] Science. 1994 Jan 7;263(5143):87-9 [8272871] Science. 1988 Apr 8;240(4849):196-9 [2895499] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 6-Chloro-D,L-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation. AN - 76949243; 7824198 AB - Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of L-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-D,L-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-D,L-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma L-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism. JF - Neuroscience letters AU - Saito, K AU - Markey, S P AU - Heyes, M P AD - Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/09/12/ PY - 1994 DA - 1994 Sep 12 SP - 211 EP - 215 VL - 178 IS - 2 SN - 0304-3940, 0304-3940 KW - Pokeweed Mitogens KW - 0 KW - 6-chlorotryptophan KW - 17808-35-4 KW - 3-Hydroxyanthranilic Acid KW - 1UQB1BT4OT KW - 4-chloro-3-hydroxyanthranilic acid KW - 23219-33-2 KW - Kynurenine KW - 343-65-7 KW - Dexamethasone KW - 7S5I7G3JQL KW - Tryptophan KW - 8DUH1N11BX KW - Tryptophan Oxygenase KW - EC 1.13.11.11 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Kynurenine -- blood KW - Animals KW - Pokeweed Mitogens -- pharmacology KW - Mice, Inbred C57BL KW - Kynurenine -- metabolism KW - Mice KW - Lung -- enzymology KW - Male KW - Tryptophan Oxygenase -- metabolism KW - Tryptophan -- pharmacology KW - Tryptophan -- analogs & derivatives KW - Immune System -- drug effects KW - 3-Hydroxyanthranilic Acid -- pharmacology KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Dexamethasone -- pharmacology KW - Brain -- metabolism KW - Immune System -- physiology KW - 3-Hydroxyanthranilic Acid -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76949243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=6-Chloro-D%2CL-tryptophan%2C+4-chloro-3-hydroxyanthranilate+and+dexamethasone+attenuate+quinolinic+acid+accumulation+in+brain+and+blood+following+systemic+immune+activation.&rft.au=Saito%2C+K%3BMarkey%2C+S+P%3BHeyes%2C+M+P&rft.aulast=Saito&rft.aufirst=K&rft.date=1994-09-12&rft.volume=178&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-13 N1 - Date created - 1995-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of leukemia risk to radiation dose following cancer of the uterine corpus. AN - 76664286; 8064889 AB - Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients. We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy. A cohort of 110,000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects. Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] = 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5). The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases were due to radiation per 10,000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors. JF - Journal of the National Cancer Institute AU - Curtis, R E AU - Boice, J D AU - Stovall, M AU - Bernstein, L AU - Holowaty, E AU - Karjalainen, S AU - Langmark, F AU - Nasca, P C AU - Schwartz, A G AU - Schymura, M J AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Md. Y1 - 1994/09/07/ PY - 1994 DA - 1994 Sep 07 SP - 1315 EP - 1324 VL - 86 IS - 17 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Registries KW - Brachytherapy KW - Radiotherapy Dosage KW - Humans KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Female KW - Neoplasms, Second Primary -- etiology KW - Uterine Neoplasms -- radiotherapy KW - Leukemia, Radiation-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76664286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+of+leukemia+risk+to+radiation+dose+following+cancer+of+the+uterine+corpus.&rft.au=Curtis%2C+R+E%3BBoice%2C+J+D%3BStovall%2C+M%3BBernstein%2C+L%3BHolowaty%2C+E%3BKarjalainen%2C+S%3BLangmark%2C+F%3BNasca%2C+P+C%3BSchwartz%2C+A+G%3BSchymura%2C+M+J&rft.aulast=Curtis&rft.aufirst=R&rft.date=1994-09-07&rft.volume=86&rft.issue=17&rft.spage=1315&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 - 1994-09-19 N1 - Date created - 1994-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are racial differences in squamous cell esophageal cancer explained by alcohol and tobacco use? AN - 76658312; 8064893 AB - In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought. We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks. We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included. Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 94% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis was statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates. Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100,000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors. JF - Journal of the National Cancer Institute AU - Brown, L M AU - Hoover, R N AU - Greenberg, R S AU - Schoenberg, J B AU - Schwartz, A G AU - Swanson, G M AU - Liff, J M AU - Silverman, D T AU - Hayes, R B AU - Pottern, L M AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md. Y1 - 1994/09/07/ PY - 1994 DA - 1994 Sep 07 SP - 1340 EP - 1345 VL - 86 IS - 17 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Odds Ratio KW - Logistic Models KW - Humans KW - Adult KW - Case-Control Studies KW - Incidence KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Carcinoma, Squamous Cell -- ethnology KW - Carcinoma, Squamous Cell -- etiology KW - Esophageal Neoplasms -- ethnology KW - African Americans -- statistics & numerical data KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - European Continental Ancestry Group -- statistics & numerical data KW - Esophageal Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76658312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Are+racial+differences+in+squamous+cell+esophageal+cancer+explained+by+alcohol+and+tobacco+use%3F&rft.au=Brown%2C+L+M%3BHoover%2C+R+N%3BGreenberg%2C+R+S%3BSchoenberg%2C+J+B%3BSchwartz%2C+A+G%3BSwanson%2C+G+M%3BLiff%2C+J+M%3BSilverman%2C+D+T%3BHayes%2C+R+B%3BPottern%2C+L+M&rft.aulast=Brown&rft.aufirst=L&rft.date=1994-09-07&rft.volume=86&rft.issue=17&rft.spage=1340&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 - 1994-09-19 N1 - Date created - 1994-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of animal studies in risk assessment for immunotoxicology. AN - 76787280; 7940563 AB - We have previously reported on the design and content of a screening battery involving a 'tier' approach for detecting potential immunosuppressive compounds in mice. This battery has been used to examine a variety of compounds, and the database generated from these studies, which consists of over 50 compounds, has been collected and analyzed in an attempt to improve the accuracy and efficiency of screening chemicals for immunosuppression and to identify better those tests that predict experimentally-induced, immune-mediated diseases. Specifically, these analyses attempted to develop an improved testing configuration for the accurate prediction of immunotoxic agents and to provide insight into the qualitative and quantitative relationships between a number of immune and host resistance assays commonly employed to examine potential immunotoxic chemicals in experimental animals. While a number of limitations existed in the analyses, several conclusions were drawn from the results which will be discussed. JF - Toxicology AU - Luster, M I AU - Portier, C AU - Pait, D G AU - Germolec, D R AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709. Y1 - 1994/09/06/ PY - 1994 DA - 1994 Sep 06 SP - 229 EP - 243 VL - 92 IS - 1-3 SN - 0300-483X, 0300-483X KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Animals KW - Cyclophosphamide -- toxicity KW - Risk Assessment KW - Immune System -- drug effects KW - Toxicology -- methods KW - Immune System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76787280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Use+of+animal+studies+in+risk+assessment+for+immunotoxicology.&rft.au=Luster%2C+M+I%3BPortier%2C+C%3BPait%2C+D+G%3BGermolec%2C+D+R&rft.aulast=Luster&rft.aufirst=M&rft.date=1994-09-06&rft.volume=92&rft.issue=1-3&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-01 N1 - Date created - 1994-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depolarization or glutamate receptor activation blocks apoptotic cell death of cultured cerebellar granule neurons. AN - 76911054; 7804844 AB - Cerebellar granule neurons can be readily maintained in culture if depolarized with high concentrations of K+ or subtoxic concentrations of various excitatory amino acids. We now report that these depolarizing stimuli promote cerebellar granule neuron survival by blocking their programmed death via apoptosis. Cerebellar granule neurons maintained in depolarizing conditions and then changed to non-depolarizing conditions, exhibit the morphological and biochemical features of apoptosis, including cytoplasmic blebbing, condensation and aggregation of nuclear chromatin and internucleosomal DNA fragmentation. Inhibitors of RNA or protein synthesis greatly attenuate cell death induced by non-depolarizing culture conditions. In contrast, cerebellar granule neurons, when exposed to fresh serum-containing medium or to high concentrations of glutamate, exhibit a delayed-type of neurotoxicity which is non-apoptotic in nature. Given the actions of excitatory amino acid receptor agonists in preventing apoptosis of cultured cerebellar granule neurons, we hypothesize that the functional innervation of postmigratory granule neurons during cerebellar development may prevent further elimination of these neurons by blocking their programmed death. JF - Brain research AU - Yan, G M AU - Ni, B AU - Weller, M AU - Wood, K A AU - Paul, S M AD - Section on Molecular Pharmacology, NIMH, NIH, Bethesda, MD 20892. Y1 - 1994/09/05/ PY - 1994 DA - 1994 Sep 05 SP - 43 EP - 51 VL - 656 IS - 1 SN - 0006-8993, 0006-8993 KW - Antimetabolites KW - 0 KW - Culture Media KW - Excitatory Amino Acid Agonists KW - Receptors, Glutamate KW - Glutamic Acid KW - 3KX376GY7L KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - DNA KW - 9007-49-2 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Rats KW - Antimetabolites -- pharmacology KW - Potassium -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - N-Methylaspartate -- pharmacology KW - Cells, Cultured KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - DNA -- analysis KW - Glutamic Acid -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Cerebellum -- cytology KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Receptors, Glutamate -- physiology KW - Apoptosis -- drug effects KW - Excitatory Amino Acid Agonists -- pharmacology KW - Neurons -- ultrastructure KW - Cerebellum -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Depolarization+or+glutamate+receptor+activation+blocks+apoptotic+cell+death+of+cultured+cerebellar+granule+neurons.&rft.au=Yan%2C+G+M%3BNi%2C+B%3BWeller%2C+M%3BWood%2C+K+A%3BPaul%2C+S+M&rft.aulast=Yan&rft.aufirst=G&rft.date=1994-09-05&rft.volume=656&rft.issue=1&rft.spage=43&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 - 1995-01-31 N1 - Date created - 1995-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Utility of Multiple-Section Sampling in the Histopathological Evaluation of the Kidney for Carcinogenicity Studies AN - 856755624; 13645569 AB - In a recent review of 379 carcinogenicity studies in rodents conducted under the auspices of the National Cancer Institute and, later, the National Toxicology Program (NTP), the kidneys were the third most frequent site for chemical-related neoplasia. While some potent carcinogens induced high incidences of renal neoplasms with shortened latency in Fischer-344 (F-344) rats or B6C3F sub(1) mice, other usually nonmutagenic compounds produced marginally increased incidences of renal neoplasms that were difficult to interpret. As an aid to the interpretation of 16 recent studies, additional kidney sections from rats or mice were prepared and examined microscopically. The remaining pieces of formalin-fixed kidney were embedded and sectioned at intervals of 1 mm (rats) or 0.5 mm (mice) to produce an additional 6-8 (rats) or 4-6 (mice) H&E-stained sections per kidney per animal for microscopic examination. The average number of additional sections per animal was similar between dosed and control groups to avoid sampling bias. The supplemental evaluation of these additional kidney sections was clearly useful in determining potential renal carcinogenicity in male F-344 rats in these NTP studies. Of the 13 studies in male rats in which step-sections of kidney were evaluated, the supplemental data demonstrated conclusively an association between chemical administration and renal tubule hyperplasia, adenoma, or both in 9 studies. For 3 chemicals, the evidence of an association with renal proliferative lesions in male rats remained uncertain. In contrast, the supplemental evaluation of step-sections was less useful for female rats, male mice, and female mice, largely because such evaluations generally revealed few if any additional neoplasms. For these sex-species groups, there were only two instances, both involving male mice, in which the additional data confirmed an association with kidney neoplasia. JF - Toxicologic Pathology AU - Eustis, Scot L AU - Hailey, James R AU - Boorman, Gary A AU - Haseman, Joseph K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1994/09// PY - 1994 DA - Sep 1994 SP - 457 EP - 472 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 22 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Hyperplasia KW - Data processing KW - Carcinogenicity KW - renal tubules KW - Reviews KW - Kidney KW - Sampling KW - Carcinogens KW - Adenoma KW - Neoplasia KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856755624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=The+Utility+of+Multiple-Section+Sampling+in+the+Histopathological+Evaluation+of+the+Kidney+for+Carcinogenicity+Studies&rft.au=Eustis%2C+Scot+L%3BHailey%2C+James+R%3BBoorman%2C+Gary+A%3BHaseman%2C+Joseph+K&rft.aulast=Eustis&rft.aufirst=Scot&rft.date=1994-09-01&rft.volume=22&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339402200501 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Hyperplasia; Data processing; renal tubules; Carcinogenicity; Reviews; Kidney; Carcinogens; Sampling; Adenoma; Neoplasia DO - http://dx.doi.org/10.1177/019262339402200501 ER - TY - JOUR T1 - Potentiation of antitumor activities of carboplatin and camptothecin by interleukin-1 alpha against human ovarian carcinoma in vivo. AN - 85265695; pmid-7847805 AB - Interleukin-1 alpha significantly potentiated the cytotoxicity of carboplatin (8-fold) and camptothecin (4-fold) during simultaneous drug exposure in human ovarian NIH: OVCAR-3 cancer cells in vitro. Treatment of human ovarian tumor cells grown as xenografts in nude mice with IL-1 alpha followed by either carboplatin or CTP-11 at minimally toxic doses significantly (2-3-fold and 7-fold for carboplatin and CTP-11, respectively) enhanced antitumor activity of either agent alone, indicating that IL-1-alpha-drug combinations may be potentially more effective for the treatment of ovarian tumors, including those difficult to cure in the clinic. JF - Anticancer Research AU - Wang, Z AU - Benchekroun, M N AU - Sinha, B K AD - Biochemical and Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 1723 EP - 1726 VL - 14 IS - 5A SN - 0250-7005, 0250-7005 KW - Ovarian Neoplasms KW - Human KW - Animal KW - Mice KW - Mice, Nude KW - Carboplatin KW - Mice, Inbred BALB C KW - Camptothecin KW - Neoplasm Transplantation KW - Tumor Cells, Cultured KW - Interleukin-1 KW - Antineoplastic Combined Chemotherapy Protocols KW - Drug Synergism KW - Female KW - Cell Division UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265695?accountid=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=Anticancer+Research&rft.atitle=Potentiation+of+antitumor+activities+of+carboplatin+and+camptothecin+by+interleukin-1+alpha+against+human+ovarian+carcinoma+in+vivo.&rft.au=Wang%2C+Z%3BBenchekroun%2C+M+N%3BSinha%2C+B+K&rft.aulast=Wang&rft.aufirst=Z&rft.date=1994-09-01&rft.volume=14&rft.issue=5A&rft.spage=1723&rft.isbn=&rft.btitle=&rft.title=Anticancer+Research&rft.issn=02507005&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Synchronization properties of spindle oscillations in a thalamic reticular nucleus model. AN - 85240825; pmid-7807198 AB - 1. We address the hypothesis of Steriade and colleagues that the thalamic reticular nucleus (RE) is a pacemaker for thalamocortical spindle oscillations by developing and analyzing a model of a large population of all-to-all coupled inhibitory RE neurons. 2. Each RE neuron has three ionic currents: a low-threshold T-type Ca2+ current (ICa-T), a calcium-activated potassium current (IAHP) and a leakage current (IL). ICa-T underlies a cell's postinhibitory rebound properties, whereas IAHP hyperpolarizes the neuron after a burst. Each neuron, which is a conditional oscillator, is coupled to all other RE neurons via fast gamma-aminobutyric acid-A (GABAA) and slow GABAB synapses. 3. For generating network oscillations IAHP may not be necessary. Synaptic inhibition can provide the hyperpolarization for deinactivating ICa-T that causes bursting if the reversal potentials for GABAA and GABAB synapses are sufficiently negative. 4. If model neurons display sufficiently powerful rebound excitability, an isolated RE network of such neurons oscillates with partial but typically not full synchrony. The neurons spontaneously segregate themselves into several macroscopic clusters. The neurons within a cluster follow the same time course, but the clusters oscillate differently from one another. In addition to activity patterns in which clusters burst sequentially (e.g., 2 or 3 clusters bursting alternately), a two-cluster state may occur with one cluster active and one quiescent. Because the neurons are all-to-all coupled, the cluster states do not have any spatial structure. 5. We have explored the sensitivity of such partially synchronized patterns to heterogeneity in cells' intrinsic properties and to simulated neuroelectric noise. Although either precludes precise clustering, modest levels of heterogeneity or noise lead to approximate clustering of active cells. The population-averaged voltage may oscillate almost regularly but individual cells burst at nearly every second cycle or less frequently. The active-quiescent state is not robust at all to heterogeneity or noise. Total asynchrony is observed when heterogeneity or noise is too large, e.g., even at 25% heterogeneity for our reference set of parameter values. 6. The fast GABAA inhibition (with a reversal potential more negative than, say, -65 mV) favors the cluster states and prevents full synchrony. Our simulation results suggest two mechanisms that can fully synchronize the isolated RE network model. With GABAA removed or almost totally blocked, GABAB inhibition (because it is slow) can lead to full synchrony, which is partially robust to heterogeneity and noise.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Journal of Neurophysiology AU - Golomb, D AU - Wang, X J AU - Rinzel, J AD - Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20814. PY - 1994 SP - 1109 EP - 1126 VL - 72 IS - 3 SN - 0022-3077, 0022-3077 KW - Receptors, GABA-B KW - Receptors, GABA-A KW - Cortical Synchronization KW - Human KW - Animal KW - Neural Inhibition KW - Nerve Net KW - Potassium Channels KW - Calcium Channels KW - Cerebral Cortex KW - gamma-Aminobutyric Acid KW - Sleep KW - Neural Pathways KW - Membrane Potentials KW - Receptors, AMPA KW - Thalamic Nuclei KW - Synaptic Transmission KW - Neural Networks (Computer) KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85240825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Synchronization+properties+of+spindle+oscillations+in+a+thalamic+reticular+nucleus+model.&rft.au=Golomb%2C+D%3BWang%2C+X+J%3BRinzel%2C+J&rft.aulast=Golomb&rft.aufirst=D&rft.date=1994-09-01&rft.volume=72&rft.issue=3&rft.spage=1109&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - ADP-ribosylation factors: a family of approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin. AN - 77781831; 7898460 AB - ADP-ribosylation factors (ARFs) comprise a family of approximately 20 kDa guanine nucleotide-binding proteins that were discovered as one of several cofactors required in cholera toxin-catalyzed ADP-ribosylation of Gs alpha, the guanine nucleotide-binding protein responsible for stimulation of adenylyl cyclase, and was subsequently found to enhance all cholera toxin-catalyzed reactions and to directly interact with, and activate the toxin. ARF is dependent on GTP or its analogues for activity, binds GTP with high affinity in the presence of dimyristoylphosphatidylcholine/cholate and contains consensus sequences for GTP-binding and hydrolysis. Six mammalian family members have been identified which have been classified into three groups (Class I, II, and III) based on size, deduced amino acid sequence identity, phylogenetic analysis and gene structure. ARFs are ubiquitous among eukaryotes, with a deduced amino acid sequence that is highly conserved across diverse species. They have recently been shown to associate with phospholipid and Golgi membranes in a GTP-dependent manner and are involved in regulating vesicular transport. JF - Molecular and cellular biochemistry AU - Welsh, C F AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 157 EP - 166 VL - 138 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Animals KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Biological Transport -- physiology KW - Protein Structure, Tertiary KW - Molecular Weight KW - Multigene Family KW - GTP-Binding Proteins -- genetics KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77781831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=ADP-ribosylation+factors%3A+a+family+of+approximately+20-kDa+guanine+nucleotide-binding+proteins+that+activate+cholera+toxin.&rft.au=Welsh%2C+C+F%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Welsh&rft.aufirst=C&rft.date=1994-09-01&rft.volume=138&rft.issue=1-2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=03008177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Demonstration of a temporal relationship between ethyl acrylate-induced forestomach cell proliferation and carcinogenicity. AN - 77773648; 7899778 AB - Ethyl acrylate (EA) is a known forestomach carcinogen in both rats and mice. Recent work in this laboratory indicated that carcinogenic doses of EA administered by gavage for 13 wk resulted in a sustained increase in forestomach epithelial hyperplasia as long as exposure to EA continued. However, hyperplasia regressed and no forestomach neoplasms were seen after a 19-mo recovery period. Current studies were designed to further investigate the time required for sustained hyperplasia to lead to neoplasia as well as the organ specificity of EA-induced cell proliferation/hyperplasia vs carcinogenicity. EA was administered at 200 mg/kg (po) to male Fischer-344 rats, 5 days/wk. Squamous cell proliferation/hyperplasia was observed in the forestomach of all rats that received EA for 6 or 12 mo. Treatment of rats with EA for 12 mo followed by 2 mo of recovery resulted in the development of forestomach papillomas in 2 of 5 treated rats. Furthermore, animals treated for 12 mo and allowed 9 mo of recovery exhibited an increase in forestomach squamous cell carcinomas and papillomas at a combined incidence of 4 in 13. In contrast, animals treated with EA for 6 mo and allowed 2 or 15 mo of recovery exhibited a time-dependent regression of cell proliferation and did not develop forestomach neoplasms. No significant elevation in liver cell proliferation or neoplasia was seen at any time in any of the rats included in the present study, further confirming the organ specificity in the relationship between EA-induced cell proliferation and carcinogenicity. In conclusion, EA resulted in increased cell proliferation in the target organ of carcinogenicity (forestomach) but not in nontarget organs such as the liver. This work indicates that cell proliferation, sustained for a sufficient period of time, results in the development of neoplasia despite cessation of chemical administration. Furthermore, a temporal relationship exists between EA-induced epithelial cell proliferation and forestomach carcinogenicity. JF - Toxicologic pathology AU - Ghanayem, B I AU - Sanchez, I M AU - Matthews, H B AU - Elwell, M R AD - National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 497 EP - 509 VL - 22 IS - 5 SN - 0192-6233, 0192-6233 KW - Acrylates KW - 0 KW - Carcinogens KW - ethyl acrylate KW - 71E6178C9T KW - Index Medicus KW - Animals KW - Papilloma -- pathology KW - Cell Division -- drug effects KW - Carcinoma, Squamous Cell -- chemically induced KW - Organ Specificity KW - Rats KW - Hyperplasia -- chemically induced KW - Rats, Inbred F344 KW - Carcinoma, Squamous Cell -- pathology KW - Liver -- drug effects KW - Time Factors KW - Papilloma -- chemically induced KW - Male KW - Stomach Neoplasms -- pathology KW - Stomach Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Acrylates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77773648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Demonstration+of+a+temporal+relationship+between+ethyl+acrylate-induced+forestomach+cell+proliferation+and+carcinogenicity.&rft.au=Ghanayem%2C+B+I%3BSanchez%2C+I+M%3BMatthews%2C+H+B%3BElwell%2C+M+R&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1994-09-01&rft.volume=22&rft.issue=5&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-21 N1 - Date created - 1995-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apparent quiescence of the metallothionein gene in the rat ventral prostate: association with cadmium-induced prostate tumors in rats. AN - 77723420; 7843088 AB - Several chronic studies in rats indicating that cadmium exposure can induce tumors of the ventral prostate have recently been completed in our laboratory. In one such study, a single dose of cadmium, s.c., increased prostatic tumor incidence only at doses below 5.0 mumol/kg, the approximate threshold for cadmium-induced testicular damage. In a further study, prostatic tumors were elevated with higher doses of cadmium (30 mumol/kg, s.c.) if testicular damage was prevented by zinc pretreatment. Most recently, we found that dietary cadmium (25 to 200 micrograms/g) also can increase prostatic neoplastic lesions, but these were reduced by zinc-deficient diets. Thus it appears that cadmium produces prostatic tumors only if testicular function is maintained. Furthermore, we find that metallothionein (MT), a protein associated with cadmium tolerance, may be deficient in the rat prostate, and the prostatic MT gene, at least in the ventral lobe, is unresponsive to metal stimuli. In liver, MT gene expression, as assessed by MT-1 mRNA, was quite apparent in control tissue and was induced in a dose-dependent manner 24 hr following cadmium exposure (1 to 10 mumol/kg, s.c.). However, in the ventral prostate very low constitutive levels of MT-1 mRNA were detected and increases did not occur with cadmium exposure. Cadmium concentrations in the ventral prostate were in excess of those that cause significant induction in the liver. In sharp contrast to the gene in the ventral prostate, in the dorsal prostate the MT gene was quite active. The dorsal prostate is not susceptible to cadmium carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Coogan, T P AU - Shiraishi, N AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 137 EP - 139 VL - 102 Suppl 3 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Wistar KW - Male KW - Prostatic Neoplasms -- metabolism KW - Prostate -- drug effects KW - Gene Expression Regulation -- physiology KW - Prostatic Neoplasms -- chemically induced KW - Prostate -- metabolism KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Metallothionein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77723420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Apparent+quiescence+of+the+metallothionein+gene+in+the+rat+ventral+prostate%3A+association+with+cadmium-induced+prostate+tumors+in+rats.&rft.au=Coogan%2C+T+P%3BShiraishi%2C+N%3BWaalkes%2C+M+P&rft.aulast=Coogan&rft.aufirst=T&rft.date=1994-09-01&rft.volume=102+Suppl+3&rft.issue=&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1983 Feb;70(2):367-73 [6571943] Toxicol Appl Pharmacol. 1982 Oct;66(1):134-42 [7157381] DNA. 1983;2(1):15-22 [6687866] Cancer Res. 1988 Aug 15;48(16):4656-63 [3396014] Fundam Appl Toxicol. 1992 Nov;19(4):512-20 [1426709] Cancer Res. 1989 Aug 1;49(15):4282-8 [2743314] Epidemiology. 1990 Mar;1(2):107-15 [2073496] Chem Res Toxicol. 1990 Jul-Aug;3(4):281-8 [2133072] Toxicol Appl Pharmacol. 1992 Apr;113(2):227-33 [1561631] Biochemistry. 1988 Nov 15;27(23):8509-15 [3064814] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. AN - 77718876; 7854123 AB - Comparison of the anthrax toxin lethal factor (LF) amino acid sequence with sequences in the Swiss protein database revealed short regions of similarity with the consensus zinc-binding site, HEXXH, that is characteristic of metalloproteases. Several protease inhibitors, including bestatin and captopril, prevented intoxication of macrophages by lethal toxin. LF was fully inactivated by site-directed mutagenesis that substituted Ala for either of the residues (H-686 and H-690) implicated in zinc binding. Similarly, LF was inactivated by substitution of Cys for E-687, which is thought to be an essential part of the catalytic site. In contrast, replacement of E-720 and E-721 with Ala had no effect on LF activity. LF bound 65Zn both in solution and on protein blots. The 65Zn binding was reduced for several of the LF mutants. These data suggest that anthrax toxin LF is a zinc metallopeptidase, the catalytic function of which is responsible for the lethal activity observed in cultured cells and in animals. JF - Molecular microbiology AU - Klimpel, K R AU - Arora, N AU - Leppla, S H AD - Laboratory of Microbial Ecology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1093 EP - 1100 VL - 13 IS - 6 SN - 0950-382X, 0950-382X KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Cations, Divalent KW - Protease Inhibitors KW - Recombinant Fusion Proteins KW - anthrax toxin KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Protease Inhibitors -- pharmacology KW - Cations, Divalent -- metabolism KW - Amino Acid Sequence KW - Mice KW - Recombinant Fusion Proteins -- toxicity KW - Macrophages -- drug effects KW - Structure-Activity Relationship KW - Virulence KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Bacterial Toxins -- genetics KW - Bacterial Toxins -- antagonists & inhibitors KW - Bacillus anthracis -- genetics KW - Bacillus anthracis -- pathogenicity KW - Zinc -- metabolism KW - Bacterial Toxins -- chemistry KW - Bacterial Toxins -- toxicity KW - Bacillus anthracis -- enzymology KW - Metalloendopeptidases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77718876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology&rft.atitle=Anthrax+toxin+lethal+factor+contains+a+zinc+metalloprotease+consensus+sequence+which+is+required+for+lethal+toxin+activity.&rft.au=Klimpel%2C+K+R%3BArora%2C+N%3BLeppla%2C+S+H&rft.aulast=Klimpel&rft.aufirst=K&rft.date=1994-09-01&rft.volume=13&rft.issue=6&rft.spage=1093&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-14 N1 - Date created - 1995-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA sequence changes induced by two nitric oxide donor drugs in the supF assay. AN - 77716361; 7841341 AB - To refine our understanding of the mutational spectra one might expect on exposure of human cells to nitric oxide (NO), we have treated the plasmid pSP189 at pH 7.4 with two compounds that generate NO spontaneously in solution, and then sequenced the mutations found when the treated plasmid was transfected into human Ad293 cells and allowed to replicate. G.C-->A.T transitions were the most abundant mutation observed with these NO donor drugs, whereas in previous work, A.T-->G.C transitions predominated when nitric oxide gas was bubbled through the plasmid solution under otherwise identical conditions. A difference in reactive intermediates formed in solution- versus gas-phase NO exposure was demonstrated by treating buffered 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) or ferrocyanide, in the presence or absence of azide, aerobically with preformed solutions of NO, with solutions of the two NO-releasing compounds, or with gaseous mixtures of equimolar NO/O2 in air; oxidation of these substrates was extensive with the gas-phase NO source whether azide was present or not, while azide almost completely quenched the oxidation pathway in the solution-phase reactions. JF - Chemical research in toxicology AU - Routledge, M N AU - Wink, D A AU - Keefer, L K AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-FCRDC, Maryland 21702. PY - 1994 SP - 628 EP - 632 VL - 7 IS - 5 SN - 0893-228X, 0893-228X KW - Azides KW - 0 KW - Hydrazines KW - Mutagens KW - Nitrogen Oxides KW - spermine nitric oxide complex KW - 136587-13-8 KW - Spermine KW - 2FZ7Y3VOQX KW - Nitric Oxide KW - 31C4KY9ESH KW - 1,1-diethyl-2-hydroxy-2-nitrosohydrazine KW - 86831-65-4 KW - Index Medicus KW - Mutagenicity Tests KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Escherichia coli -- drug effects KW - Escherichia coli -- genetics KW - Plasmids -- drug effects KW - Azides -- chemistry KW - Hydrazines -- toxicity KW - Base Sequence -- drug effects KW - Spermine -- chemistry KW - Spermine -- analogs & derivatives KW - Spermine -- toxicity KW - Nitric Oxide -- pharmacology KW - Mutagens -- toxicity KW - Nitric Oxide -- chemistry KW - Hydrazines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77716361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=DNA+sequence+changes+induced+by+two+nitric+oxide+donor+drugs+in+the+supF+assay.&rft.au=Routledge%2C+M+N%3BWink%2C+D+A%3BKeefer%2C+L+K%3BDipple%2C+A&rft.aulast=Routledge&rft.aufirst=M&rft.date=1994-09-01&rft.volume=7&rft.issue=5&rft.spage=628&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-07 N1 - Date created - 1995-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amelioration of diabetes-like retinal changes in galactose-fed dogs. AN - 77715566; 7845946 AB - Diabetic retinopathy, the leading cause of blindness among young adults in the developed world, is characterized by vascular changes of the retinal capillary bed. Beagles fed a diet containing 30% galactose develop retinal vascular lesions that are similar to those observed in diabetics. These progress from initial retinal changes which include aldose-reductase-linked formation of pericyte ghosts and the subsequent development of acellular capillaries, microaneurysms, and intraretinal hemorrhages to the appearance of occluded vessels, areas of nonperfusion, and intraretinal microvascular abnormalities (IRMA) and in the final stages, the formation of fibrovascular membranes on both the retinal surface and the posterior hyaloid membrane. In prevention studies utilizing 0.5, 5.0, 10, and 16 mg/kg/day of the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spirochroman-4-5'-imidazolidine-2',4'-dione), pericyte ghost formation, and the subsequent appearance of microaneurysms, intraretinal hemorrhages, acellular capillaries associated with background retinopathy were arrested in a dose-dependent manner. Similar dose-dependent changes in the appearance of cataracts were also observed. The dog represents the first animal model to demonstrate all of the clinical and histological retinal vessel changes observed in human diabetics. JF - Preventive medicine AU - Kador, P F AU - Takahashi, Y AU - Sato, S AU - Wyman, M AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 717 EP - 721 VL - 23 IS - 5 SN - 0091-7435, 0091-7435 KW - Imidazoles KW - 0 KW - Imidazolidines KW - M 79175 KW - 82319-87-7 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - sorbinil KW - G4186B906P KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Cataract -- pathology KW - Animals KW - Imidazoles -- pharmacology KW - Dose-Response Relationship, Drug KW - Cataract -- chemically induced KW - Dogs KW - Retinal Vessels -- drug effects KW - Aldehyde Reductase -- antagonists & inhibitors KW - Male KW - Retinal Vessels -- pathology KW - Diabetic Retinopathy -- pathology KW - Diabetic Retinopathy -- chemically induced KW - Retina -- drug effects KW - Retina -- pathology KW - Galactose -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77715566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Preventive+medicine&rft.atitle=Amelioration+of+diabetes-like+retinal+changes+in+galactose-fed+dogs.&rft.au=Kador%2C+P+F%3BTakahashi%2C+Y%3BSato%2C+S%3BWyman%2C+M&rft.aulast=Kador&rft.aufirst=P&rft.date=1994-09-01&rft.volume=23&rft.issue=5&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=Preventive+medicine&rft.issn=00917435&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-09 N1 - Date created - 1995-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of recombinant interferon-alpha and 5-fluorouracil against colon cancer cells or against peripheral blood mononuclear cells. AN - 77714802; 7847809 AB - Comparative studies on the suppressive effects of recombinant interferon-alpha (IFN-alpha), 5-fluorouracil (5-FU), or IFN-alpha + 5-FU have been performed in vitro on colon carcinoma cells (HT-29 cell line) and PHA-stimulated mononuclear cells (MNC) of peripheral blood obtained from healthy donors. IFN-alpha was used at 500 U/ml against HT-29 cells and at 1000 U/ml against MNC on day 1 of culture; 5-FU was used at 250 microM against HT-29 and at 1400 microM against MNC on day 2 of culture. The results show that: (a) IFN-alpha inhibited MNC and HT-29 cells by 13.4% and 32.9%, respectively; (b) 5-FU inhibited MNC and HT-29 cells by 54.7% and 87.0%, respectively; (c) IFN-alpha + 5-FU resulted in a stronger inhibition of HT-29 cells (i.e., 96.1%). In contrast, that combination was significantly less suppressive than 5-FU alone when MNC were used as targets (i.e., 35.9% inhibition). Natural cell-mediated cytotoxic activity relative to 10(6) MNC was not markedly altered by all agents alone or in combination. Moreover, treatment with IFN-alpha, 5-FU or IFN-alpha + 5-FU resulted in a marked increase in the number of HT-29 cells positive for the CEA surface antigen. These data seem to provide further rational support of the clinical use of IFN-alpha + 5-FU in colorectal cancer, based on the differential toxicity of this drug combination on tumor versus normal immunocompetent cells. JF - Anticancer research AU - De Filippi, R AU - Prete, S P AU - Giuliani, A AU - Silvi, E AU - Yamaue, H AU - Nieroda, C A AU - Greiner, J W AU - De Vecchis, L AU - Bonmassar, E AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. PY - 1994 SP - 1767 EP - 1773 VL - 14 IS - 5A SN - 0250-7005, 0250-7005 KW - Interferon Type I KW - 0 KW - Phytohemagglutinins KW - Recombinant Proteins KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Stimulation, Chemical KW - Lymphocyte Activation -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Immunity, Cellular -- drug effects KW - Cell Division -- drug effects KW - Cytotoxicity, Immunologic -- drug effects KW - Drug Synergism KW - Phytohemagglutinins -- pharmacology KW - Fluorouracil -- administration & dosage KW - Interferon Type I -- administration & dosage KW - Colonic Neoplasms -- therapy KW - Interferon Type I -- pharmacology KW - Colonic Neoplasms -- drug therapy KW - Fluorouracil -- pharmacology KW - Leukocytes, Mononuclear -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Leukocytes, Mononuclear -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77714802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Differential+effects+of+recombinant+interferon-alpha+and+5-fluorouracil+against+colon+cancer+cells+or+against+peripheral+blood+mononuclear+cells.&rft.au=De+Filippi%2C+R%3BPrete%2C+S+P%3BGiuliani%2C+A%3BSilvi%2C+E%3BYamaue%2C+H%3BNieroda%2C+C+A%3BGreiner%2C+J+W%3BDe+Vecchis%2C+L%3BBonmassar%2C+E&rft.aulast=De+Filippi&rft.aufirst=R&rft.date=1994-09-01&rft.volume=14&rft.issue=5A&rft.spage=1767&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-09 N1 - Date created - 1995-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobehavioral test strategies for environmental exposures in pediatric populations. AN - 77712053; 7845333 AB - The Agency for Toxic Substances and Disease Registry convened a workshop in Atlanta, GA, that evaluated approaches and methods to ascertain whether there are neurobehavioral sequelae to children and adults exposed to hazardous substances in the environment. This article, developed from that workshop, addresses the feasibility of employing extant neurobehavioral tests to screen pediatric populations. A matrix lists basic functions to be assessed during eight developmental periods ranging from birth to high school. The best of these neurobehavioral tests for pediatric populations and the types of assessment tools that are still needed are discussed. We make 10 specific recommendations to establish a hazardous substances neurobehavioral screen for pediatric populations, including appointing a review panel, developing a structured questionnaire, convening a conference on design and analysis, addressing minority and socially disadvantaged populations, coordinating adult and child assessment methods, information sharing among Federal agencies, baseline data, methodology research, research associated with hazardous worksites, and establishment of a pediatric databank. JF - Neurotoxicology and teratology AU - Krasnegor, N A AU - Otto, D A AU - Bernstein, J H AU - Burke, R AU - Chappell, W AU - Eckerman, D A AU - Needleman, H L AU - Oakley, G AU - Rogan, W AU - Terracciano, G AD - National Institute of Child Health and Human Development, Bethesda, MD 20852. PY - 1994 SP - 499 EP - 509 VL - 16 IS - 5 SN - 0892-0362, 0892-0362 KW - Hazardous Substances KW - 0 KW - Index Medicus KW - Infant KW - Humans KW - Infant, Newborn KW - Child KW - Adolescent KW - Research Design KW - Child, Preschool KW - Behavior -- drug effects KW - Hazardous Substances -- adverse effects KW - Environmental Exposure KW - Neuropsychological Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77712053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology+and+teratology&rft.atitle=Neurobehavioral+test+strategies+for+environmental+exposures+in+pediatric+populations.&rft.au=Krasnegor%2C+N+A%3BOtto%2C+D+A%3BBernstein%2C+J+H%3BBurke%2C+R%3BChappell%2C+W%3BEckerman%2C+D+A%3BNeedleman%2C+H+L%3BOakley%2C+G%3BRogan%2C+W%3BTerracciano%2C+G&rft.aulast=Krasnegor&rft.aufirst=N&rft.date=1994-09-01&rft.volume=16&rft.issue=5&rft.spage=499&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology+and+teratology&rft.issn=08920362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-07 N1 - Date created - 1995-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) and Wistar (WF/NCr) rats. AN - 77709039; 7843114 AB - A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mumole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr) and then given cadmium (20 mumole CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing 53% mortality. Progesterone pretreatment had no effect on cadmium-induced lethality in WF rats or on testicular lesions in either strain. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated F344 rats given cadmium as compared to rats given Cd alone. Progesterone did not induce increases in hepatic or renal metallothionein (MT) and hepatic or testicular MT-I mRNA levels in F344 rats. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated F344 rats were doubled. This increase in TCBP provided no protection against cadmium toxicity in the testes. These results indicate that, in contrast to previously reported data for mice, progesterone pretreatment increased the lethality of cadmium in male F344 rats and had no effect on cadmium-induced testicular toxicity in F344 and WF rats. JF - Environmental health perspectives AU - Shiraishi, N AU - Barter, R A AU - Uno, H AU - Waalkes, M P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 277 EP - 280 VL - 102 Suppl 3 SN - 0091-6765, 0091-6765 KW - Carrier Proteins KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Progesterone KW - 4G7DS2Q64Y KW - Index Medicus KW - Rats KW - Animals KW - Species Specificity KW - Protein Binding KW - Male KW - Carrier Proteins -- biosynthesis KW - Rats, Inbred F344 KW - Rats, Inbred WF KW - Progesterone -- pharmacology KW - Cadmium -- toxicity KW - Cadmium -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77709039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+progesterone+pretreatment+on+cadmium+toxicity+in+male+Fischer+%28F344%2FNCr%29+and+Wistar+%28WF%2FNCr%29+rats.&rft.au=Shiraishi%2C+N%3BBarter%2C+R+A%3BUno%2C+H%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1994-09-01&rft.volume=102+Suppl+3&rft.issue=&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Appl Toxicol. 1981 Oct;1(5):264-9 [7185887] Biochem J. 1984 Jun 15;220(3):811-8 [6466305] J Biol Chem. 1986 Oct 5;261(28):13097-103 [3759948] Toxicol Appl Pharmacol. 1987 Mar 15;87(3):381-8 [2882620] Toxicol Appl Pharmacol. 1988 Mar 30;93(1):47-61 [3354001] Toxicol Appl Pharmacol. 1982 Oct;66(1):134-42 [7157381] J Reprod Fertil. 1965 Feb;9:111-2 [14257711] Proc Soc Exp Biol Med. 1965 Jul;119:901-5 [14329029] J Reprod Fertil. 1968 Aug;16(3):507-9 [5673747] Teratology. 1979 Dec;20(3):341-52 [232313] Toxicol Appl Pharmacol. 1982 Sep 15;65(2):302-13 [7179286] Toxicol Appl Pharmacol. 1992 Apr;113(2):227-33 [1561631] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The heparin-binding domain of heparin-binding EGF-like growth factor can target Pseudomonas exotoxin to kill cells exclusively through heparan sulfate proteoglycans. AN - 77708660; 7844173 AB - Heparin-binding EGF-like growth factor (HB-EGF) is a smooth muscle cell mitogen composed of both EGF receptor and heparin-binding domains. To better understand the function of its domains, intact HB-EGF or its heparin-binding (HB) domain (amino acids 1-45) were fused to a mutant Pseudomonas exotoxin with an inactivated cell-binding domain. The resulting chimeric toxins, HB-EGF-PE* and HB-PE*, were tested on tumor cells, proliferating smooth muscle cells and a mutant Chinese hamster ovary cell line deficient in heparan sulfate proteoglycans (HSPGs). Two targets were found for HB-EGF-PE*. Cells were killed mainly through EGF receptors, but the HB domain was responsible for killing via HSPGs. HB-PE* did not bind to the EGF receptor and thus was cytotoxic by interacting exclusively with HSPGs. We conclude that the HB domain of HB-EGF is able to mediate internalization through HSPGs, without requiring the EGF receptor. JF - Journal of cell science AU - Mesri, E A AU - Ono, M AU - Kreitman, R J AU - Klagsbrun, M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 2599 EP - 2608 VL - 107 ( Pt 9) SN - 0021-9533, 0021-9533 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - HBEGF protein, human KW - Heparan Sulfate Proteoglycans KW - Heparin-binding EGF-like Growth Factor KW - Intercellular Signaling Peptides and Proteins KW - Ligands KW - Mitogens KW - Peptide Fragments KW - Proteoglycans KW - Recombinant Fusion Proteins KW - Transforming Growth Factor alpha KW - Virulence Factors KW - Epidermal Growth Factor KW - 62229-50-9 KW - Heparin KW - 9005-49-6 KW - Heparitin Sulfate KW - 9050-30-0 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Cricetulus KW - Humans KW - Genes, Synthetic KW - Mitogens -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Protein Binding KW - Binding Sites KW - Base Sequence KW - Cattle KW - Tumor Cells, Cultured KW - Transforming Growth Factor alpha -- genetics KW - Molecular Sequence Data KW - Muscle, Smooth, Vascular -- cytology KW - CHO Cells KW - Protein Structure, Tertiary KW - Cricetinae KW - Peptide Fragments -- metabolism KW - Exotoxins -- genetics KW - Peptide Fragments -- genetics KW - Epidermal Growth Factor -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Heparitin Sulfate -- metabolism KW - Proteoglycans -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity KW - Heparin -- metabolism KW - Epidermal Growth Factor -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77708660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+heparin-binding+domain+of+heparin-binding+EGF-like+growth+factor+can+target+Pseudomonas+exotoxin+to+kill+cells+exclusively+through+heparan+sulfate+proteoglycans.&rft.au=Mesri%2C+E+A%3BOno%2C+M%3BKreitman%2C+R+J%3BKlagsbrun%2C+M%3BPastan%2C+I&rft.aulast=Mesri&rft.aufirst=E&rft.date=1994-09-01&rft.volume=107+%28+Pt+9%29&rft.issue=&rft.spage=2599&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 - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced generation of hydroxyl radical and sulfur trioxide anion radical from oxidation of sodium sulfite, nickel(II) sulfite, and nickel subsulfide in the presence of nickel(II) complexes. AN - 77707084; 7843142 AB - Electron spin resonance (ESR) spin trapping was utilized to investigate the generation of free radicals from oxidation of sodium sulfite, nickel(II) sulfite, and nickel subsulfide (Ni3S2) by ambient oxygen or H2O2 at pH 7.4. The spin trap used was 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Under ambient oxygen, a solution of sodium sulfite alone generated predominantly sulfur trioxide anion radical (.SO3-) due to the autoxidation of sulfite. Addition of nickel(II) chloride [Ni(II)] enhanced the .SO3- yield about 4-fold. Incubation of sulfite with Ni(II) in the presence of chelators such as tetraglycine, histidine, beta-alanyl-3-methyl-L-histidine (anserine), beta--L-histidine (carnosine), gamma-aminobutyryl-L-histidine (homocarnosine), glutathione, and penicillamine did not have any significant effect on that enhancement. In contrast, albumin, and especially glycylglycylhistidine (GlyGlyHis), augmented the enhancing effect of Ni(II) by factors of 1.4 and 4, respectively. Computer simulation analysis of the spin-adduct spectrum and formate scavenging experiment showed that the mixture of sodium sulfite, Ni(II), and GlyGlyHis generated both hydroxyl (.OH) radical and .SO3- radical, in the ratio of approximately 1:2. The free-radical spin adduct intensity reached its saturation level in about 5 min. The yield of the radical adducts could be slightly reduced by deferoxamine and very strongly reduced by diethylenetriaminepentaacetic acid (DTPA). Aqueous suspensions of sparingly soluble nickel(II) sulfite in the presence of air and GlyGlyHis generated surface-located .SO3- and .OH radicals. The same radicals were generated in Ni3S2 suspension in the presence of GlyGlyHis and H2O2, indicating sulfite production by oxidation of the sulfide moiety of this compound.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Environmental health perspectives AU - Shi, X AU - Dalal, N AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 91 EP - 96 VL - 102 Suppl 3 SN - 0091-6765, 0091-6765 KW - Anions KW - 0 KW - Chelating Agents KW - Free Radicals KW - Oligopeptides KW - Solutions KW - Sulfites KW - Sulfur Oxides KW - nickel subsulfide KW - 12035-72-2 KW - Hydroxyl Radical KW - 3352-57-6 KW - nickel sulfite KW - 7757-95-1 KW - Nickel KW - 7OV03QG267 KW - Hydrogen Peroxide KW - BBX060AN9V KW - sulfur trioxide KW - HH2O7V4LYD KW - sodium sulfite KW - VTK01UQK3G KW - Index Medicus KW - Oxidation-Reduction KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sulfur Oxides -- metabolism KW - Sulfites -- chemistry KW - Hydroxyl Radical -- metabolism KW - Nickel -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77707084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhanced+generation+of+hydroxyl+radical+and+sulfur+trioxide+anion+radical+from+oxidation+of+sodium+sulfite%2C+nickel%28II%29+sulfite%2C+and+nickel+subsulfide+in+the+presence+of+nickel%28II%29+complexes.&rft.au=Shi%2C+X%3BDalal%2C+N%3BKasprzak%2C+K+S&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-09-01&rft.volume=102+Suppl+3&rft.issue=&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Zh Vyssh Nerv Deiat Im I P Pavlova. 1967 Nov-Dec;17(6):1034-42 [5622910] Cancer Res. 1989 Nov 1;49(21):5964-8 [2790811] Carcinogenesis. 1990 Sep;11(9):1447-50 [2205403] Cancer Res. 1990 Dec 1;50(23):7564-70 [2253206] Food Chem Toxicol. 1991 Jan;29(1):1-6 [1847890] FEBS Lett. 1991 Apr 9;281(1-2):9-19 [1849843] Chem Res Toxicol. 1991 Nov-Dec;4(6):592-604 [1807442] Chem Res Toxicol. 1991 Nov-Dec;4(6):604-15 [1807443] Arch Biochem Biophys. 1992 Nov 15;299(1):154-62 [1332613] J Inorg Biochem. 1993 May 15;50(3):211-25 [8388916] Biochim Biophys Acta. 1961 Mar 18;48:93-103 [13756587] Biochemistry. 1970 Dec 8;9(25):5008-14 [5480164] Biochem Biophys Res Commun. 1972 Jan 14;46(1):120-4 [4621352] Prog Nucleic Acid Res Mol Biol. 1976;16:75-124 [2948] Res Commun Chem Pathol Pharmacol. 1977 Jan;16(1):95-108 [841185] Mutat Res. 1977;39(2):149-75 [405577] Fed Proc. 1978 Jan;37(1):40-6 [338365] Toxicol Appl Pharmacol. 1978 Oct;46(1):29-38 [214901] Food Cosmet Toxicol. 1981 Oct;19(5):667-82 [6171492] Biochemistry. 1982 Feb 16;21(4):771-8 [7074040] J Toxicol Environ Health. 1982 Sep;10(3):479-91 [7175975] Basic Life Sci. 1983;23:35-60 [6340660] Nucleic Acids Res. 1984 Feb 24;12(4):2137-45 [6701097] IARC Sci Publ. 1984;(53):127-42 [6532978] Exp Pathol. 1985;28(1):31 [4029362] Environ Health Perspect. 1985 Dec;64:209-17 [3830699] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7499-502 [3463979] J Free Radic Biol Med. 1986;2(3):219-25 [3033049] Free Radic Biol Med. 1987;3(4):259-303 [2826304] Carcinogenesis. 1989 Mar;10(3):621-4 [2924407] Biochem Biophys Res Commun. 1989 Mar 15;159(2):445-51 [2539111] Crit Rev Toxicol. 1989;19(4):341-84 [2663022] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic studies of sodium fluoride in mice. AN - 77702027; 7837981 AB - The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks. Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined. JF - Mutagenesis AU - Zeiger, E AU - Gulati, D K AU - Kaur, P AU - Mohamed, A H AU - Revazova, J AU - Deaton, T G AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 467 EP - 471 VL - 9 IS - 5 SN - 0267-8357, 0267-8357 KW - Mutagens KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Sodium Fluoride KW - 8ZYQ1474W7 KW - Index Medicus KW - Animals KW - Erythrocytes -- drug effects KW - Anaphase KW - Mice KW - Mutagens -- pharmacology KW - Mutagens -- administration & dosage KW - Metaphase KW - Erythrocytes -- ultrastructure KW - Micronucleus Tests KW - Chromosome Aberrations KW - Bone Marrow -- ultrastructure KW - Time Factors KW - Bone Marrow -- drug effects KW - Male KW - Cyclophosphamide -- pharmacology KW - Sodium Fluoride -- administration & dosage KW - Sodium Fluoride -- pharmacology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77702027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Cytogenetic+studies+of+sodium+fluoride+in+mice.&rft.au=Zeiger%2C+E%3BGulati%2C+D+K%3BKaur%2C+P%3BMohamed%2C+A+H%3BRevazova%2C+J%3BDeaton%2C+T+G&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1994-09-01&rft.volume=9&rft.issue=5&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-24 N1 - Date created - 1995-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of gamma interferon on inflammatory mediators that induce interleukin-6 gene expression and secretion by human retinal pigment epithelial cells. AN - 77114662; 8556503 AB - The retinal pigment epithelial (RPE) cell is a potent regulatory cell within the retina. It helps to maintain normal retinal activity, and following gamma interferon (IFN-gamma) exposure, it may express major histocompatibility complex class II molecules and function as an antigen-presenting cell. Since interleukin-1 (IL-1) and IL-6 are potent cytokines observed in ocular inflammatory processes, we initiated studies to evaluate conditions which enable RPE cells to produce these cytokines. Cultures of human RPE cells from two eye donors were established and characterized, and enzyme immunoassays were employed to screen for IL-1 and IL-6 production. Treatment of RPE cells with lipopolysaccharide (LPS) or recombinant tumor necrosis factor alpha, IL-1, or IFN-gamma resulted in a significant level of secretion of IL-6. In contrast, treatment with recombinant epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, or transforming growth factor alpha, or LPS can dramatically augment the secretion of IL-6 by RPE cells. Thus, these inflammatory mediators can act alone or synergistically with IFN-gamma to activate RPE cells and dramatically increase the expression and secretion of IL-6. In contrast, IL-1 was not detected following stimulation with any of the above-mentioned cytokines or LPS. Characterization of IL-6 protein production by RPE cells revealed that 98% of the protein is promptly secreted by the cell, its induction is dependent upon the time and concentration of the stimulant, and the continuous presence of the stimulant is required for IL-6 production. Moreover, Western blot (immunoblot) analysis of secreted proteins revealed that IL-6 was produced in multiple molecular forms.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Clinical and diagnostic laboratory immunology AU - Nagineni, C N AU - Detrick, B AU - Hooks, J J AD - Immunology and Virology Section, Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892, USA. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 569 EP - 577 VL - 1 IS - 5 SN - 1071-412X, 1071-412X KW - Interleukin-1 KW - 0 KW - Interleukin-6 KW - Lipopolysaccharides KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Gene Expression -- immunology KW - Interleukin-1 -- metabolism KW - Dose-Response Relationship, Drug KW - Lipopolysaccharides -- pharmacology KW - Kinetics KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - RNA, Messenger -- analysis KW - Cells, Cultured -- immunology KW - Drug Synergism KW - Interleukin-6 -- secretion KW - Pigment Epithelium of Eye -- metabolism KW - Interleukin-6 -- genetics KW - Pigment Epithelium of Eye -- cytology KW - Interleukin-6 -- immunology KW - Interferon-gamma -- pharmacology KW - Interferon-gamma -- immunology KW - Pigment Epithelium of Eye -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77114662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+diagnostic+laboratory+immunology&rft.atitle=Synergistic+effects+of+gamma+interferon+on+inflammatory+mediators+that+induce+interleukin-6+gene+expression+and+secretion+by+human+retinal+pigment+epithelial+cells.&rft.au=Nagineni%2C+C+N%3BDetrick%2C+B%3BHooks%2C+J+J&rft.aulast=Nagineni&rft.aufirst=C&rft.date=1994-09-01&rft.volume=1&rft.issue=5&rft.spage=569&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 completed - 1996-02-23 N1 - Date created - 1996-02-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Invest Ophthalmol Vis Sci. 1992 Jan;33(1):78-82 [1370441] Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S60-5 [1728989] Invest Ophthalmol Vis Sci. 1992 Mar;33(3):532-9 [1544781] Eye (Lond). 1991;5 ( Pt 6):686-93 [1800167] Arch Ophthalmol. 1992 May;110(5):662-6 [1374609] Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2120-7 [1318867] Cytokine. 1992 Jan;4(1):1-5 [1617154] Curr Eye Res. 1992 Jun;11(6):581-97 [1505201] Exp Eye Res. 1992 Mar;54(3):361-8 [1381679] Curr Eye Res. 1992;11 Suppl:181-6 [1424743] Curr Eye Res. 1992;11 Suppl:187-91 [1424744] J Neurosci Res. 1993 Mar 1;34(4):414-25 [8474143] Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2613-21 [7688356] Cell. 1982 Nov;31(1):11-24 [6186379] J Cell Biol. 1969 Aug;42(2):392-403 [5792328] Am J Ophthalmol. 1975 Jul;80(1):1-23 [808131] Clin Immunol Immunopathol. 1985 Aug;36(2):201-11 [3924457] Invest Ophthalmol Vis Sci. 1985 Dec;26(12):1659-94 [2933359] Am J Ophthalmol. 1986 May 15;101(5):584-90 [3518466] Arch Ophthalmol. 1986 May;104(5):725-9 [3518683] Surv Ophthalmol. 1987 Mar-Apr;31(5):291-306 [3299827] Arch Ophthalmol. 1987 Aug;105(8):1117-20 [3498471] Br J Ophthalmol. 1988 Feb;72(2):83-7 [2964862] J Biol Chem. 1988 Jun 5;263(16):7760-6 [3131326] Arthritis Rheum. 1988 Jun;31(6):784-8 [3260102] Invest Ophthalmol Vis Sci. 1988 Sep;29(9):1444-51 [3138201] Am J Pathol. 1988 Oct;133(1):47-53 [3263050] J Immunol. 1989 Jan 1;142(1):144-7 [2783321] J Clin Invest. 1989 Feb;83(2):585-92 [2464001] Ann N Y Acad Sci. 1989;557:114-9; discussion 119-21 [2660692] Ann N Y Acad Sci. 1989;557:130-41, discussion 141-3 [2500051] Blood. 1989 Jul;74(1):1-10 [2473791] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6367-71 [2474833] Invest Ophthalmol Vis Sci. 1989 Oct;30(10):2106-13 [2477341] Immunol Today. 1990 Jan;11(1):13-20 [2405873] Ophthalmologica. 1990;200(1):39-44 [2181360] Am J Pathol. 1990 Apr;136(4):745-50 [2183623] Invest Ophthalmol Vis Sci. 1990 May;31(5):917-20 [2335453] Annu Rev Immunol. 1990;8:253-78 [2188664] J Immunol. 1990 Jul 1;145(1):161-6 [2358670] Immunol Lett. 1990 Mar-Apr;24(1):1-9 [2197219] J Immunol. 1990 Dec 15;145(12):4101-7 [2147935] Invest Ophthalmol Vis Sci. 1991 Jan;32(1):88-95 [1987109] Invest Ophthalmol Vis Sci. 1991 May;32(6):1714-22 [1903363] Lab Invest. 1991 Jun;64(6):819-25 [2046333] Lab Invest. 1992 Feb;66(2):200-11 [1346541] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Downstream in America. AN - 77113455; 9657703 JF - Environmental health perspectives AU - Fisher, B E AD - NIEHS Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 740 EP - 745 VL - 102 IS - 9 SN - 0091-6765, 0091-6765 KW - Water Pollutants KW - 0 KW - Index Medicus KW - United States KW - United States Environmental Protection Agency KW - Fresh Water KW - Quality Control KW - Water Pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77113455?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Downstream+in+America.&rft.au=Fisher%2C+B+E&rft.aulast=Fisher&rft.aufirst=B&rft.date=1994-09-01&rft.volume=102&rft.issue=9&rft.spage=740&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1998-10-05 N1 - Date created - 1998-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide inhibits 3H-glutamate transport in synaptosomes. AN - 76953763; 7825120 AB - 3H-glutamate (GLU) uptake was measured in hippocampal synaptosomes from rat brain. Addition of sodium nitroprusside (SNP) (Sodium nitroferricyanide), a generator of nitric oxide (NO), produced a time-, temperature-, and dose-dependent inhibition of 3H-GLU uptake. The inhibition was due to changes in both Kd and Vmax of GLU uptake, and it was at least partially reversible upon washing. Addition of reduced hemoglobin (Hb), a substance that binds NO, prevented the SNP-induced depression of uptake. Potassium ferricyanide, a compound similar to SNP, did not cause a reduction in 3H-GLU uptake. Utilization of another generator of NO, S-nitroso-N-acetylpenicillamine (SNAP), produced similar results as did NO itself. Decreases in uptake were also observed in the striatum and cerebellum. Similar treatments did not consistently affect 3H-norepinephrine (NE) uptake, suggesting some selectivity in the NO effect. Thus, the observed inhibition of 3H-GLU uptake appears to be produced by NO, and it may represent a novel type of transynaptic retrograde regulation of transport. If found in vivo, inhibition of uptake activity could also be involved in the toxic effects of NO, the neurotoxicity of glutamate, and other potential neuronal changes associated with NO such as hippocampal long-term potentiation. JF - Synapse (New York, N.Y.) AU - Pogun, S AU - Dawson, V AU - Kuhar, M J AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland 21224. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 21 EP - 26 VL - 18 IS - 1 SN - 0887-4476, 0887-4476 KW - Hemoglobins KW - 0 KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - Glutamic Acid KW - 3KX376GY7L KW - S-Nitroso-N-Acetylpenicillamine KW - 79032-48-7 KW - Penicillamine KW - GNN1DV99GX KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Penicillamine -- analogs & derivatives KW - Penicillamine -- pharmacology KW - Brain Chemistry -- drug effects KW - Biological Transport, Active KW - Depression, Chemical KW - Rats KW - Rats, Sprague-Dawley KW - Hemoglobins -- metabolism KW - Kinetics KW - Norepinephrine -- metabolism KW - In Vitro Techniques KW - Nitroprusside -- pharmacology KW - Male KW - Synaptosomes -- drug effects KW - Glutamic Acid -- metabolism KW - Hippocampus -- metabolism KW - Nitric Oxide -- pharmacology KW - Synaptosomes -- metabolism KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76953763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Nitric+oxide+inhibits+3H-glutamate+transport+in+synaptosomes.&rft.au=Pogun%2C+S%3BDawson%2C+V%3BKuhar%2C+M+J&rft.aulast=Pogun&rft.aufirst=S&rft.date=1994-09-01&rft.volume=18&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-16 N1 - Date created - 1995-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellularly recorded response of rat striatal neurons in vitro to fenoldopam and SKF 38393 following lesions of midbrain dopamine cells. AN - 76951999; 7825125 AB - The effect of long-term (6-19 weeks) 6-hydroxydopamine-induced (6-OHDA) lesions of midbrain dopamine cells on dopamine D1-like agonist-induced changes in the excitability of rat striatal neurons was investigated in vitro using tissue slices and intracellular recording techniques. Fenoldopam and (+/-)-SKF 38393 predominantly decreased excitability in control preparations including striatal neurons located contralateral to 6-OHDA injection sites and neurons obtained from rats receiving sham injections or no treatment. Fenoldopam also inhibited neurons ipsilateral to lesions of midbrain dopamine cells. (+/-)-SKF 38393, unlike fenoldopam, produced predominantly increases in the excitability of ipsilateral striatal neurons. Superfusion of the D1 receptor antagonist, SCH 23390, blocked fenoldopam-induced decreases in excitability but not the (+/-)-SKF 38393-induced excitation of neurons ipsilateral to the lesion. Sequential application of fenoldopam and quinpirole, a D2/D3 receptor agonist, produced responses to both drugs in a majority of neurons. The results demonstrate that inhibitory responses to fenoldopam are mediated by D1 receptors, while excitatory effects of (+/-)-SKF 38393 in the striatum ipsilateral to the lesion are apparently not dependent on D1 receptor activation. These findings also suggest that dopamine D1 and D2/D3 receptors are able to concurrently influence the excitability of striatal neurons in the dopamine deafferentated striatum. Similar regulation of striatal neurons in vivo may contribute to dopaminergic regulation of basal ganglia output and the ability of dopaminomimetic agents to ameliorate symptoms of dopaminergic deficiency in Parkinson's disease. JF - Synapse (New York, N.Y.) AU - Twery, M J AU - Thompson, L A AU - Walters, J R AD - Cellular Physiology and Neurotransmission Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 67 EP - 78 VL - 18 IS - 1 SN - 0887-4476, 0887-4476 KW - Dopamine Agonists KW - 0 KW - Ergolines KW - Quinpirole KW - 20OP60125T KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Oxidopamine KW - 8HW4YBZ748 KW - Fenoldopam KW - INU8H2KAWG KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Drug Interactions KW - Ergolines -- pharmacology KW - Electric Stimulation KW - Oxidopamine -- pharmacology KW - Rats KW - Evoked Potentials -- drug effects KW - Rats, Sprague-Dawley KW - Dopamine Agonists -- pharmacology KW - In Vitro Techniques KW - Male KW - Microelectrodes KW - Mesencephalon -- drug effects KW - Fenoldopam -- pharmacology KW - Neostriatum -- physiology KW - Neostriatum -- drug effects KW - Neurons -- physiology KW - Dopamine -- physiology KW - Neostriatum -- cytology KW - Mesencephalon -- cytology KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Mesencephalon -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76951999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Intracellularly+recorded+response+of+rat+striatal+neurons+in+vitro+to+fenoldopam+and+SKF+38393+following+lesions+of+midbrain+dopamine+cells.&rft.au=Twery%2C+M+J%3BThompson%2C+L+A%3BWalters%2C+J+R&rft.aulast=Twery&rft.aufirst=M&rft.date=1994-09-01&rft.volume=18&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-16 N1 - Date created - 1995-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Viral variability and serum antibody response in a laboratory worker infected with HIV type 1 (HTLV type IIIB). AN - 76949461; 7826699 AB - Molecular clones of HIV-1 were obtained from isolates cultured from peripheral blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a laboratory worker accidentally infected with the HIV-1 laboratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtained from clones of cultured virus and sequenced. Three env clones obtained shortly after infection differed among themselves at only seven nucleotide positions, resulting in one amino acid substitution and one frameshift mutation. These envelope sequences were as similar to the envelope sequences of various IIIB clones as the latter were to each other. env divergence increased over the course of infection. However, the overall diversity in env clones obtained two or more years after infection was still comparable to that among IIIB env clones from the original IIIB culture. Multiple clones of partial env gene sequences containing the V3 loop were also obtained directly from uncultured PBMCs by polymerase chain reaction amplification. The env sequences of these clones were generally similar to those of the cultured viruses. Within the V3 region, the earliest isolates retained the sequence of the HXB2 clone from IIIB. Clones obtained later showed a progressive divergence in V3. An A-to-T substitution within the GPGRAF sequence at the tip of the V3 loop was observed within 1 year after infection, and this mutation predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared simultaneously in laboratory worker serum and persisted with no significant differences in titer. Furthermore, neutralization studies with autologous sequential sera suggested selection for the A-to-T change in V3 was not due to V3-directed antibodies. These results demonstrate a surprising homogeneity among env sequences of HIV-1 from an infected laboratory worker, perhaps because the initial infection originated from a relatively homogeneous population of tissue culture-adapted virus. JF - AIDS research and human retroviruses AU - Reitz, M S AU - Hall, L AU - Robert-Guroff, M AU - Lautenberger, J AU - Hahn, B M AU - Shaw, G M AU - Kong, L I AU - Weiss, S H AU - Waters, D AU - Gallo, R C AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1143 EP - 1155 VL - 10 IS - 9 SN - 0889-2229, 0889-2229 KW - env KW - DNA Primers KW - 0 KW - Gene Products, env KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Gene Products, env -- chemistry KW - Phylogeny KW - Genetic Variation KW - Humans KW - Antibody Formation KW - Amino Acid Sequence KW - Gene Products, env -- genetics KW - Frameshift Mutation KW - Polymerase Chain Reaction KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Time Factors KW - HIV-1 -- genetics KW - Acquired Immunodeficiency Syndrome -- virology KW - Occupational Diseases -- blood KW - Occupational Diseases -- immunology KW - HIV-1 -- isolation & purification KW - Medical Laboratory Personnel KW - HIV-1 -- physiology KW - Lymphocytes -- immunology KW - Acquired Immunodeficiency Syndrome -- blood KW - Occupational Diseases -- virology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Genes, env KW - Lymphocytes -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76949461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+research+and+human+retroviruses&rft.atitle=Viral+variability+and+serum+antibody+response+in+a+laboratory+worker+infected+with+HIV+type+1+%28HTLV+type+IIIB%29.&rft.au=Reitz%2C+M+S%3BHall%2C+L%3BRobert-Guroff%2C+M%3BLautenberger%2C+J%3BHahn%2C+B+M%3BShaw%2C+G+M%3BKong%2C+L+I%3BWeiss%2C+S+H%3BWaters%2C+D%3BGallo%2C+R+C&rft.aulast=Reitz&rft.aufirst=M&rft.date=1994-09-01&rft.volume=10&rft.issue=9&rft.spage=1143&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 completed - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Gene symbol - env N1 - Genetic sequence - U12030; GENBANK; U12052; U12051; U12050; U12038; U12055; U12037; U12036; U12054; U12035; U12053; U12034; U12033; U12032; U12031; U12041; U12040; U12047; U12046; U12049; U12048; U12043; U12042; U12045; U12044; U12039 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photolytic destruction and polymeric resin decontamination of aqueous solutions of pharmaceuticals. AN - 76948614; 7830245 AB - Amoxicillin, ampicillin, bleomycin, carmustine, cephalothin, dacarbazine, lomustine, metronidazole, norethindrone, streptozocin, sulfamethoxazole, and verapamil were completely degraded in solution, without the production of mutagenic residues, by photolysis using a medium-pressure mercury lamp in an all-quartz apparatus. A stream of air was passed through the solution and for amoxicillin, ampicillin, bleomycin, lomustine, metronidazole, and norethindrone it was necessary to add hydrogen peroxide. Dilute aqueous solutions of ampicillin, bleomycin, carmustine, cephalothin, lomustine, norethindrone, streptozocin, trimethoprim, and verapamil can be decontaminated using polymeric Amberlite resins. JF - Journal of pharmaceutical sciences AU - Lunn, G AU - Rhodes, S W AU - Sansone, E B AU - Schmuff, N R AD - Program Resources, Inc./DynCorp, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1289 EP - 1293 VL - 83 IS - 9 SN - 0022-3549, 0022-3549 KW - Hazardous Waste KW - 0 KW - Medical Waste Disposal KW - Mutagens KW - Pharmaceutical Preparations KW - Resins, Plant KW - Solutions KW - Water KW - 059QF0KO0R KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Spectrophotometry, Ultraviolet KW - Mutagens -- toxicity KW - Salmonella typhimurium -- drug effects KW - Chromatography, High Pressure Liquid KW - Rats KW - In Vitro Techniques KW - Salmonella typhimurium -- genetics KW - Mutagens -- chemistry KW - Photolysis KW - Pharmaceutical Preparations -- radiation effects KW - Resins, Plant -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76948614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pharmaceutical+sciences&rft.atitle=Photolytic+destruction+and+polymeric+resin+decontamination+of+aqueous+solutions+of+pharmaceuticals.&rft.au=Lunn%2C+G%3BRhodes%2C+S+W%3BSansone%2C+E+B%3BSchmuff%2C+N+R&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-09-01&rft.volume=83&rft.issue=9&rft.spage=1289&rft.isbn=&rft.btitle=&rft.title=Journal+of+pharmaceutical+sciences&rft.issn=00223549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-17 N1 - Date created - 1995-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive over-expression of transforming growth factor-alpha in rat liver epithelial cells leads to increased cell cycling without transformation. AN - 76936337; 7820313 AB - Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi 13) and has been implicated in the transformation of other cultured cells. We have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known to express epidermal growth factor receptors, to determine if TGF-alpha over-expression plays a role in transformation or differentiation, or both, of these cells. Early passage RLE phi 13 cells were infected with a replication-defective murine retrovirus that expresses both the full length coding sequence for human TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally active provirus and expression of TGF-alpha mRNA were confirmed. Neither morphologic transformation nor molecular evidence for differentiation was noted in TGF-alpha-producing clones. However, these clones did exhibit an accelerated growth rate, increased expression of several cell cycle related genes including mitotic cyclic B1, proliferating cell nuclear antigen, c-myc, and p53 as well as increased expression of the preneoplastic marker enzyme, glutathione-S-transferase. This suggests that over-expression of TGF-alpha results in increased cell cycling, and that subsequent events must be necessary for cellular transformation or differentiation or both. JF - In vitro cellular & developmental biology. Animal AU - Tan, T B AU - Marino, P A AU - Padmanabhan, R AU - Hampton, L L AU - Hanley-Hyde, J M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 615 EP - 621 VL - 30A IS - 9 SN - 1071-2690, 1071-2690 KW - RNA, Messenger KW - 0 KW - Transforming Growth Factor alpha KW - Neomycin KW - 1404-04-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Drug Resistance -- genetics KW - Mice KW - Mice, Nude KW - Rats KW - RNA, Messenger -- metabolism KW - Receptor, Epidermal Growth Factor -- genetics KW - Transfection KW - Blotting, Southern KW - Epithelium -- metabolism KW - Retroviridae -- genetics KW - Cell Line KW - Liver -- cytology KW - Transforming Growth Factor alpha -- genetics KW - Gene Expression KW - Liver -- metabolism KW - Cell Cycle KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76936337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vitro+cellular+%26+developmental+biology.+Animal&rft.atitle=Constitutive+over-expression+of+transforming+growth+factor-alpha+in+rat+liver+epithelial+cells+leads+to+increased+cell+cycling+without+transformation.&rft.au=Tan%2C+T+B%3BMarino%2C+P+A%3BPadmanabhan%2C+R%3BHampton%2C+L+L%3BHanley-Hyde%2C+J+M%3BThorgeirsson%2C+S+S&rft.aulast=Tan&rft.aufirst=T&rft.date=1994-09-01&rft.volume=30A&rft.issue=9&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=In+vitro+cellular+%26+developmental+biology.+Animal&rft.issn=10712690&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-13 N1 - Date created - 1995-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factors beta 1, beta 2, and beta 3 messenger RNA and protein expression in mouse uterus and vagina during estrogen-induced growth: a comparison to other estrogen-regulated genes. AN - 76934458; 7819129 AB - Increasing evidence suggests that the differential regulation of multiple peptide growth factors by steroid hormones contributes significantly to the pleiotropic effects elicited in target tissues. We report here an evaluation of the effects of the potent estrogen, diethylstilbestrol, on the expression of the three mammalian transforming growth factor beta (TGF beta) isoforms, TGF beta 1, TGF beta 2, and TGF beta 3, in both the uterus and the vagina of the prepubescent mouse. Immunohistochemical protein detection, in situ hybridization, and Northern RNA analyses demonstrate overlapping but distinct time-dependent and site-specific induction of all three TGF beta genes in the reproductive tract in response to estrogen. Temporal analysis of steady-state levels of the TGF beta mRNAs in the uterus by Northern blotting clearly demonstrates that diethylstilbestrol significantly but transiently up-regulates TGF beta 3 mRNA within 30 min and TGF beta 1 and TGF beta 2 mRNAs by 3 h with decreases to/or below control levels by 6 h. The vagina also responds to diethylstilbestrol with similar kinetics of induction for TGF beta 2 and TGF beta 3 mRNAs as that observed in the uterus; however, TGF beta 1 mRNA levels increase gradually and peak around 16 h after treatment. Investigation of the steroid specificity demonstrates predominant estrogen specificity in the control of TGF beta expression in the immature mouse reproductive tract. In situ hybridization localizes the mRNAs for all three TGF beta isoforms, primarily to the uterine and vaginal epithelium. Unlike the transient nature of TGF beta mRNA induction elicited by estrogen, immunohistochemistry demonstrates that estrogen treatment results in a more prolonged elevation of the proteins for TGF beta 1, TGF beta 2, and TGF beta 3 in the epithelium of both tissues. Investigation of specific binding of 125I-TGF beta 1 by affinity labeling reveals the existence of the receptor/binding proteins (types I, II, and III) in the uterus. Estrogen treatment significantly reduces binding to each of these components in the uterus, which suggests that estrogen may modulate TGF beta responsiveness at the receptor level. A comparison of TGF beta mRNA expression to the induction of other estrogen-regulated genes, TGF alpha, insulin-like growth factor-1, c-myc, progesterone receptor and lactotransferrin reveals that, in general, the TGF beta transcript levels are regulated in a more transient manner by estrogen.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Takahashi, T AU - Eitzman, B AU - Bossert, N L AU - Walmer, D AU - Sparrow, K AU - Flanders, K C AU - McLachlan, J AU - Nelson, K G AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 919 EP - 935 VL - 5 IS - 9 SN - 1044-9523, 1044-9523 KW - RNA, Messenger KW - 0 KW - Steroids KW - Transforming Growth Factor beta KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - In Situ Hybridization KW - Genitalia, Female -- drug effects KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Steroids -- pharmacology KW - Mice KW - Cell Differentiation -- drug effects KW - Immunohistochemistry KW - Female KW - Binding Sites KW - Uterus -- metabolism KW - Transforming Growth Factor beta -- biosynthesis KW - Diethylstilbestrol -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Transforming Growth Factor beta -- genetics KW - Vagina -- metabolism KW - RNA, Messenger -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76934458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Transforming+growth+factors+beta+1%2C+beta+2%2C+and+beta+3+messenger+RNA+and+protein+expression+in+mouse+uterus+and+vagina+during+estrogen-induced+growth%3A+a+comparison+to+other+estrogen-regulated+genes.&rft.au=Takahashi%2C+T%3BEitzman%2C+B%3BBossert%2C+N+L%3BWalmer%2C+D%3BSparrow%2C+K%3BFlanders%2C+K+C%3BMcLachlan%2C+J%3BNelson%2C+K+G&rft.aulast=Takahashi&rft.aufirst=T&rft.date=1994-09-01&rft.volume=5&rft.issue=9&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-14 N1 - Date created - 1995-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The consistent use of organic solvents for purification of phospholipids from brain tissue effectively removes scrapie infectivity. AN - 76923460; 7811455 AB - A procedure for the purification of phospholipids from brain tissue was evaluated for its efficacy in eliminating scrapie agent infectivity. The key feature of the process was that phospholipids were extracted and purified by exclusive use of organic solvents. Experiments were done by in vivo animal bioassay on a scaled-down version of the original procedure using 263 K-infected hamster brains as source material. The absence of any detectable infectivity in the final preparations indicated that organic solvent extraction is acceptable for purification and decontamination of biological products from scrapie-like agents provided that only the organic phase is used. JF - Biologicals : journal of the International Association of Biological Standardization AU - Di Martino, A AU - Safar, J AU - Gibbs, C J AD - Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 221 EP - 225 VL - 22 IS - 3 SN - 1045-1056, 1045-1056 KW - Phospholipids KW - 0 KW - PrPSc Proteins KW - Solvents KW - Index Medicus KW - Immunoblotting KW - Animals KW - Lethal Dose 50 KW - Biological Assay KW - Mesocricetus KW - Chromatography, Thin Layer KW - Cricetinae KW - Phospholipids -- isolation & purification KW - Scrapie -- pathology KW - Brain Chemistry KW - PrPSc Proteins -- toxicity KW - PrPSc Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76923460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Social+Service+Research&rft.atitle=Understanding+of+and+attitudes+towards+self-help%3A+Views+from+Palestinian+and+Israeli+members+of+self-help+groups&rft.au=Ben-Ari%2C+Adital+Tirosh&rft.aulast=Ben-Ari&rft.aufirst=Adital&rft.date=1998-01-01&rft.volume=24&rft.issue=1-2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+Social+Service+Research&rft.issn=01488376&rft_id=info:doi/10.1300%2FJ079v24n01_06 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-03 N1 - Date created - 1995-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subunit specificity of mutations that confer resistance to nonnucleoside inhibitors in human immunodeficiency virus type 1 reverse transcriptase. AN - 76922559; 7529011 AB - We constructed plasmid vectors that simultaneously express both the p66 and p51 subunits of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in Escherichia coli. These vectors allow us to generate HIV-1 RT heterodimers in which either the p66 or the p51 subunit has the wild-type sequence and the other subunit has a specific amino acid substitution. We used these vectors to express HIV-1 RT heterodimers containing several different amino acid substitutions reported to confer resistance to nonnucleoside inhibitors. Most of the amino acid substitutions conferred resistance to nonnucleoside inhibitors R86183 (TIBO) and TSAO-m3T only when present in the p66 subunit of the p66-p51 heterodimer; heterodimers that contained a wild-type p66 subunit and a mutant p51 subunit remained sensitive to the inhibitors. However, there was one mutation, E138K, that conferred drug resistance when the mutation was present in the p51 subunit. The corresponding heterodimer with the E138K mutation in the p66 subunit and a wild-type p51 subunit remained sensitive to the inhibitors. Analysis of the three-dimensional structure of HIV-1 RT indicated that residue 138 of the p51 subunit is in the nonnucleoside inhibitor-binding pocket while residue 138 of the p66 subunit is not. The mutagenesis results, combined with structural data, support the idea that the nonnucleoside inhibitors exert their effects by binding to a hydrophobic pocket in the RT heterodimer and that mutations which give rise to drug resistance directly interfere with the interactions between the nonnucleoside inhibitors and HIV-1 RT. JF - Antimicrobial agents and chemotherapy AU - Boyer, P L AU - Ding, J AU - Arnold, E AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1909 EP - 1914 VL - 38 IS - 9 SN - 0066-4804, 0066-4804 KW - Antiviral Agents KW - 0 KW - Imidazoles KW - Macromolecular Substances KW - R 86183 KW - Reverse Transcriptase Inhibitors KW - Spiro Compounds KW - R 82913 KW - 126347-69-1 KW - Benzodiazepines KW - 12794-10-4 KW - 1-(2',5'-bis-O-(tert-butyldimethylsilylribofuranosyl)-3-N-methylthymine)-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) KW - 142102-79-2 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - AIDS/HIV KW - Plasmids -- genetics KW - Drug Resistance, Microbial KW - Substrate Specificity KW - Protein Conformation KW - Spiro Compounds -- pharmacology KW - Imidazoles -- pharmacology KW - Antiviral Agents -- pharmacology KW - Benzodiazepines -- pharmacology KW - Mutation KW - Thymidine -- pharmacology KW - Thymidine -- analogs & derivatives KW - RNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76922559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Subunit+specificity+of+mutations+that+confer+resistance+to+nonnucleoside+inhibitors+in+human+immunodeficiency+virus+type+1+reverse+transcriptase.&rft.au=Boyer%2C+P+L%3BDing%2C+J%3BArnold%2C+E%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1994-09-01&rft.volume=38&rft.issue=9&rft.spage=1909&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-27 N1 - Date created - 1995-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1989 May;86(9):3104-8 [2470090] Science. 1986 Mar 14;231(4743):1289-91 [2418504] J Biol Chem. 1991 Aug 5;266(22):14670-4 [1713587] J Virol. 1991 Sep;65(9):4887-92 [1714522] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11241-5 [1722324] J Virol. 1992 Feb;66(2):1031-9 [1370546] AIDS Res Hum Retroviruses. 1992 Feb;8(2):119-34 [1371690] AIDS Res Hum Retroviruses. 1992 Feb;8(2):145-52 [1371691] Mol Pharmacol. 1992 Mar;41(3):446-51 [1372083] Nature. 1992 May 7;357(6373):85-9 [1374166] Science. 1992 Jun 26;256(5065):1783-90 [1377403] Antimicrob Agents Chemother. 1992 Jul;36(7):1441-6 [1380789] J Biol Chem. 1992 Sep 5;267(25):17526-30 [1381350] J Virol. 1992 Dec;66(12):7533-7 [1279205] Mol Pharmacol. 1993 Jan;43(1):109-14 [7678689] Mol Pharmacol. 1993 Jan;43(1):11-6 [7678690] J Virol. 1993 Apr;67(4):2412-20 [7680393] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4713-7 [7685109] Virology. 1993 Jan;192(1):246-53 [7685964] Antimicrob Agents Chemother. 1993 May;37(5):947-9 [7685996] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] Antimicrob Agents Chemother. 1993 Jun;37(6):1207-13 [8328771] J Biol Chem. 1993 Aug 5;268(22):16571-7 [7688367] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6952-6 [7688467] J Virol. 1993 Sep;67(9):5353-9 [7688822] Virology. 1993 Oct;196(2):576-85 [7690501] EMBO J. 1987 Oct;6(10):3133-7 [2446866] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] EMBO J. 1988 Jan;7(1):239-43 [2452083] Science. 1988 Jun 10;240(4858):1427-35 [3287617] Antimicrob Agents Chemother. 1993 Aug;37(8):1576-9 [7692811] Mol Pharmacol. 1993 Oct;44(4):694-701 [7694068] Biochem Pharmacol. 1994 Jan 20;47(2):155-69 [7508227] AIDS Res Hum Retroviruses. 1993 Nov;9(11):1097-106 [7508723] Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3911-5 [7513427] AIDS Res Hum Retroviruses. 1994 Jan;10(1):39-46 [7514016] Gene. 1982 Oct;19(3):259-68 [6295879] J Biol Chem. 1989 Aug 25;264(24):13975-8 [2474539] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ouabain on lymphokine-activated killer cells. AN - 76911365; 7806435 AB - A large amount of evidence points towards the potential role of lymphokine activated killer (LAK) cells as tools in the treatment of chronically stressed conditions, such as cancer. The modulation of this activity by biologically active endogenous compounds of the HPA (hypothalamic-pituitary-adrenal) axis, however, is not completely understood. Ouabain, a specific inhibitor of Na(+)-K(+)-ATPase, and now recognized as an endogenous component present in human plasma, was tested on IL-2 and TPA-activated killer cells. Ouabain was able to inhibit the generation of LAK activity, as well as to suppress either PHA or TPA-induced lymphocyte proliferation. Once the cells were triggered for cytotoxicity, however, ouabain was not able to interfere with their effector phase, as it did not show any effect when present only during the assay. TPA-induced "LAK-simile" cells displayed the same sensitivity towards ouabain as LAK cells did. Although the physiological relevance of endogenous ouabain secretion remains elusive, these effects of ouabain on LAK cytotoxicity should be considered in patients undergoing this kind of immunotherapy. JF - International journal of immunopharmacology AU - Olej, B AU - de La Rocque, L AU - Castilho, F P AU - Mediano, I F AU - Campos, M M AU - Rumjanek, V M AD - Basic Research Centre, National Cancer Institute, Rio de Janeiro, Brazil. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 769 EP - 774 VL - 16 IS - 9 SN - 0192-0561, 0192-0561 KW - Interleukin-2 KW - 0 KW - Phytohemagglutinins KW - Receptors, Interleukin-2 KW - Ouabain KW - 5ACL011P69 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Interleukin-2 -- pharmacology KW - Tumor Cells, Cultured KW - Receptors, Interleukin-2 -- analysis KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytotoxicity, Immunologic -- drug effects KW - Phytohemagglutinins -- pharmacology KW - Killer Cells, Lymphokine-Activated -- drug effects KW - Ouabain -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunopharmacology&rft.atitle=Effect+of+ouabain+on+lymphokine-activated+killer+cells.&rft.au=Olej%2C+B%3Bde+La+Rocque%2C+L%3BCastilho%2C+F+P%3BMediano%2C+I+F%3BCampos%2C+M+M%3BRumjanek%2C+V+M&rft.aulast=Olej&rft.aufirst=B&rft.date=1994-09-01&rft.volume=16&rft.issue=9&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=International+journal+of+immunopharmacology&rft.issn=01920561&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Squamous metaplasia of bronchiolar cell-derived adenocarcinoma induced by N-nitrosomethyl-n-heptylamine in Syrian hamsters. AN - 76903117; 7801434 AB - Morphology and development of experimental bronchiolar lung tumors were studied in Syrian hamsters, using light and electron microscopic techniques. At the age of 9 weeks, 46 hamsters were each given one weekly gavage of 6.8 mg N-nitrosomethyl-n-heptylamine for 35 weeks, and hamsters were examined at intervals from 2 to 46 weeks. The present report describes the progression of adenocarcinomas of bronchiolar cell origin to adenosquamous and squamous cell carcinomas. Squamous metaplasia was commonly noted at the tumor periphery, i.e., zone of growth. In 20 hamsters, 22 adenosquamous and two squamous cell carcinomas (one a large cell carcinoma) were diagnosed by light microscopy. Overt keratinization was infrequent. Squamous cell metaplasia was not a feature of papillary neoplasms but was seen mainly with acinar structures. Ultrastructurally, squamous differentiation (metaplasia) appeared to develop along two different pathways. First, secretory cells were observed with large numbers of intermediate filaments and tonofilaments, with concurrent loss of organelles such as secretory granules and microvilli. Second, squamous metaplasia also appeared to develop from a progeny of tumor cells that failed to mature into secretory cells. Such cells were often present within the basal layer of secretory acini and resembled basal cells of the tracheobronchial tree. These observations were supported by increased expression of cytokeratins, as revealed by immunohistochemical procedures. Immunoelectron microscopic examination localized hamster Clara cell antigen in secretory granules of neoplastic Clara cells, in the cytoplasm between granules, and at the microvillous border. With the onset of squamous differentiation, Clara cell antigen was progressively lost from secretory cells and was only rarely seen in cells with tonofilaments. No labeling was present in squamous cells arising at the base of tumor acini. These results suggest that pulmonary squamous cell carcinomas may develop by direct squamous differentiation of secretory cells or may proceed from undifferentiated tumor cells. JF - Veterinary pathology AU - Rehm, S AU - Lijinsky, W AD - Tumor Pathology and Pathogenesis Section, National Cancer Institute, Bethesda, MD. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 561 EP - 571 VL - 31 IS - 5 SN - 0300-9858, 0300-9858 KW - Carcinogens KW - 0 KW - Clara cell antigen KW - Neoplasm Proteins KW - Nitrosamines KW - nitrosomethyl-N-heptylamine KW - 16338-99-1 KW - Index Medicus KW - Animals KW - Mesocricetus KW - Neoplasm Proteins -- analysis KW - Microscopy, Immunoelectron KW - Male KW - Cricetinae KW - Carcinoma, Squamous Cell -- immunology KW - Cell Transformation, Neoplastic -- pathology KW - Carcinoma, Adenosquamous -- immunology KW - Cell Transformation, Neoplastic -- chemistry KW - Carcinoma, Squamous Cell -- pathology KW - Lung Neoplasms -- immunology KW - Carcinoma, Squamous Cell -- chemically induced KW - Carcinoma, Adenosquamous -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Carcinoma, Adenosquamous -- pathology KW - Cell Transformation, Neoplastic -- immunology KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76903117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=Squamous+metaplasia+of+bronchiolar+cell-derived+adenocarcinoma+induced+by+N-nitrosomethyl-n-heptylamine+in+Syrian+hamsters.&rft.au=Rehm%2C+S%3BLijinsky%2C+W&rft.aulast=Rehm&rft.aufirst=S&rft.date=1994-09-01&rft.volume=31&rft.issue=5&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=03009858&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-24 N1 - Date created - 1995-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of cytochrome P450 2E1 genetic polymorphisms in relation to human lung cancer. AN - 76897712; 8000304 AB - Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [DraI restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (PstI, RsaI, and DraI) in African-Americans (n = 109), Caucasian Americans (n = 153), and octogenarian Japanese (n = 42), and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 DraI polymorphism to other CYP2E1 polymorphisms (PstI and RsaI RFLP) was examined. The allelic frequency of the DraI C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese. In the case-control study of lung cancer, no association of the CYP2E1 DraI genotype with lung cancer was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Comparison after discordant CYP2E1 genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2E1 DraI RFLP is probably not a cancer risk factor in United States Caucasian or African-Americans, although statistical power is limited given the low frequency of the CYP2E1 DraI C minor alleles. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Kato, S AU - Shields, P G AU - Caporaso, N E AU - Sugimura, H AU - Trivers, G E AU - Tucker, M A AU - Trump, B F AU - Weston, A AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 515 EP - 518 VL - 3 IS - 6 SN - 1055-9965, 1055-9965 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - United States KW - Gene Frequency KW - Humans KW - Transcription, Genetic -- genetics KW - Aged KW - Introns -- genetics KW - Gene Amplification KW - Asian Continental Ancestry Group KW - Genotype KW - Haplotypes -- genetics KW - Alleles KW - Polymorphism, Restriction Fragment Length KW - Aged, 80 and over KW - Risk Factors KW - European Continental Ancestry Group KW - Case-Control Studies KW - Middle Aged KW - African Continental Ancestry Group KW - Male KW - Japan KW - Female KW - Oxidoreductases, N-Demethylating -- genetics KW - Lung Neoplasms -- enzymology KW - Cytochrome P-450 Enzyme System -- genetics KW - Polymorphism, Genetic -- genetics KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76897712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+cytochrome+P450+2E1+genetic+polymorphisms+in+relation+to+human+lung+cancer.&rft.au=Kato%2C+S%3BShields%2C+P+G%3BCaporaso%2C+N+E%3BSugimura%2C+H%3BTrivers%2C+G+E%3BTucker%2C+M+A%3BTrump%2C+B+F%3BWeston%2C+A%3BHarris%2C+C+C&rft.aulast=Kato&rft.aufirst=S&rft.date=1994-09-01&rft.volume=3&rft.issue=6&rft.spage=515&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 - 1995-01-25 N1 - Date created - 1995-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (preclamol) in Parkinson's disease. AN - 76870511; 7990854 AB - The motor effects of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP, preclamol] were evaluated in nine patients with Parkinson's disease using a double-blind, placebo-controlled design. (-)-3-PPP monotherapy had an antiparkinsonian effect in five of nine patients at a mean dose of 37 +/- 10 mg intramuscularly. The co-administration of (-)-3-PPP and a mildly dyskinetic dose of levodopa, infused intravenously at steady-state, resulted in complete suppression of dyskinesias and reemergence of parkinsonian signs in two of seven patients. These dopamine antagonist effects of (-)-3-PPP occurred at relatively low (2.5 and 5 mg) doses. Our results suggest that partial dopamine agonists can exert agonist or antagonist activity in parkinsonian patients depending on concurrent dopaminergic tone. Although this dual action of (-)-3-PPP and other partial agonists could be therapeutically important on theoretical grounds, the small number of patients manifesting a clinically significant response and the frequently inconsistent effects could indicate that this class of agents may have relatively limited clinical utility. JF - Movement disorders : official journal of the Movement Disorder Society AU - Metman, L V AU - Sethy, V H AU - Roberts, J R AU - Bravi, D AU - Hoff, J I AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 577 EP - 581 VL - 9 IS - 5 SN - 0885-3185, 0885-3185 KW - Antiparkinson Agents KW - 0 KW - Piperidines KW - Levodopa KW - 46627O600J KW - preclamol KW - 9V2O6CRQ6Z KW - Index Medicus KW - Drug Therapy, Combination KW - Infusions, Intravenous KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Injections, Intramuscular KW - Neurologic Examination -- drug effects KW - Levodopa -- therapeutic use KW - Aged KW - Middle Aged KW - Levodopa -- adverse effects KW - Male KW - Female KW - Antiparkinson Agents -- adverse effects KW - Piperidines -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Parkinson Disease -- physiopathology KW - Piperidines -- adverse effects KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76870511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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=Motor+effects+of+the+partial+dopamine+agonist+%28-%29-3-%283-hydroxyphenyl%29-N-n-propylpiperidine+%28preclamol%29+in+Parkinson%27s+disease.&rft.au=Metman%2C+L+V%3BSethy%2C+V+H%3BRoberts%2C+J+R%3BBravi%2C+D%3BHoff%2C+J+I%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Metman&rft.aufirst=L&rft.date=1994-09-01&rft.volume=9&rft.issue=5&rft.spage=577&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 - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-09 N1 - Date created - 1995-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of water loading in schizophrenic patients with polydipsia-hyponatremia: an MRI pilot study. AN - 76864605; 7986774 AB - We conducted an MRI pilot study of three schizophrenic patients with the syndrome of polydipsia-hyponatremia. Paired MRI scans were obtained at baseline and in the water-loaded state to study the acute effects of water loading and accompanying changes in serum sodium and osmolality on brain structures. We report the pilot data on the observed individual MRI changes of reduced volume of the lateral ventricles in all three patients, and the third ventricles in two patients, in the water-loaded state. These changes were not statistically significant possibly because of small sample size. JF - Schizophrenia research AU - Elkashef, A M AU - Issa, F AU - Gindraw, A AU - Wyatt, R J AU - Kirch, D G AD - Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeths, Washington, DC 20032. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 169 EP - 172 VL - 13 IS - 2 SN - 0920-9964, 0920-9964 KW - Sodium KW - 9NEZ333N27 KW - Index Medicus KW - Humans KW - Adult KW - Cerebral Ventricles -- pathology KW - Body Weight -- physiology KW - Pilot Projects KW - Sodium -- blood KW - Male KW - Female KW - Water-Electrolyte Balance -- physiology KW - Magnetic Resonance Imaging KW - Brain -- pathology KW - Water Intoxication -- diagnosis KW - Hyponatremia -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76864605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Effects+of+water+loading+in+schizophrenic+patients+with+polydipsia-hyponatremia%3A+an+MRI+pilot+study.&rft.au=Elkashef%2C+A+M%3BIssa%2C+F%3BGindraw%2C+A%3BWyatt%2C+R+J%3BKirch%2C+D+G&rft.aulast=Elkashef&rft.aufirst=A&rft.date=1994-09-01&rft.volume=13&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-09 N1 - Date created - 1995-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of clozapine, fluphenazine, and placebo on reaction time measures of attention and sensory dominance in schizophrenia. AN - 76863057; 7986770 AB - Two reaction time (RT) paradigms were used to study clozapine's effects on sustained and selective attention compared to fluphenazine and placebo in 25 chronic schizophrenic patients. Sensory dominance was studied via simple and choice RTs to lights and tones, and on double-stimulus trials in which the two stimuli were presented simultaneously. Although 8 of the 25 patients could not perform the RT tasks when taking placebo, there were no effects of clozapine on simple or choice RT compared to placebo or fluphenazine. Subjects on all 3 treatments showed visual dominance: faster RT to lights than to tones on choice and double-stimulus trials. However, clozapine reduced this by means of a selective increase in RT to lights. Clozapine reduced failures to respond to the tone on double-stimulus trials. This was shown to be due to reductions in hallucinations. Clozapine does not generally improve attention, but it may increase the ability of schizophrenic persons to process nondominant or unattended stimuli possibly by increasing the efficiency of resource allocation. This may be partially mediated by a reduction in hallucinations. JF - Schizophrenia research AU - Zahn, T P AU - Pickar, D AU - Haier, R J AD - Laboratory of Psychology and Psychopathology, National Institute of Mental Health, NIH, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 133 EP - 144 VL - 13 IS - 2 SN - 0920-9964, 0920-9964 KW - Clozapine KW - J60AR2IKIC KW - Fluphenazine KW - S79426A41Z KW - Index Medicus KW - Hallucinations -- psychology KW - Psychiatric Status Rating Scales KW - Hallucinations -- drug therapy KW - Humans KW - Adult KW - Middle Aged KW - Dyskinesia, Drug-Induced -- etiology KW - Male KW - Female KW - Reaction Time -- drug effects KW - Clozapine -- administration & dosage KW - Dominance, Cerebral -- drug effects KW - Fluphenazine -- adverse effects KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Fluphenazine -- administration & dosage KW - Attention -- drug effects KW - Clozapine -- adverse effects KW - Visual Perception -- drug effects KW - Auditory Perception -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76863057?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Effects+of+clozapine%2C+fluphenazine%2C+and+placebo+on+reaction+time+measures+of+attention+and+sensory+dominance+in+schizophrenia.&rft.au=Zahn%2C+T+P%3BPickar%2C+D%3BHaier%2C+R+J&rft.aulast=Zahn&rft.aufirst=T&rft.date=1994-09-01&rft.volume=13&rft.issue=2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-09 N1 - Date created - 1995-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational case-control studies: II. Recommendations for exposure assessment. AN - 76851582; 7977405 AB - Obtaining valid and reliable quantitative exposure estimates is a significant challenge in community-based case-control studies in part, because industrial hygiene monitoring data are usually not available and detailed information on the job and work environment is usually not systematically obtained or assessed. To improve the quality and credibility of disease risk information obtained from occupational case-control studies, we recommend that standardized exposure assessment methods be used to derive quantitative exposure estimates. We identify sources of variation inherent to the assessment process, including: the quality of the information reported on the job, industry, activities, and materials; the industrial hygienist's familiarity with the reported job/industry; the probability that the job/industry was exposed, which depends on plant preferences for particular substances, on process technology, and on customer specifications; and variability in workplace characteristics. To improve the reliability of estimating job-related exposures both within and between studies, we recommend that the epidemiologic analyses be conducted with and without data rated to be of poor quality; that contact be made with experts when the study industrial hygienist is unfamiliar with the manufacturing process in question; that existing data bases be used to estimate the probability of exposure; that a data base be developed that describes manufacturing processes; and that explicit criteria based on industrial hygiene principles be used to evaluate workplace characteristics. In addition, a procedure is described for deriving quantitative exposure estimates by using a reference scale of frequently monitored jobs with their associated mean exposure levels. Areas of research are identified to improve exposure assessment in community-based case-control studies. JF - American journal of industrial medicine AU - Stewart, P A AU - Stewart, W F AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 313 EP - 326 VL - 26 IS - 3 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Probability KW - Occupational Health KW - Humans KW - Case-Control Studies KW - Quality Control KW - Occupational Exposure KW - Data Collection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76851582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+case-control+studies%3A+II.+Recommendations+for+exposure+assessment.&rft.au=Stewart%2C+P+A%3BStewart%2C+W+F&rft.aulast=Stewart&rft.aufirst=P&rft.date=1994-09-01&rft.volume=26&rft.issue=3&rft.spage=313&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 - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cohort study among workers exposed to benzene in China: II. Exposure assessment. AN - 76850260; 7977413 AB - This report describes a retrospective exposure assessment method used in a follow-up mortality study of workers exposed to benzene. The approach quantified historical exposure to benzene in a multi-industry, multicenter cohort, involving 672 factories in 12 cities in China. Historical exposure data were collected to obtain exposure information related to 1,427 work units (departments) and 3,179 unique job titles from benzene-producing or -using factories in which written records and other data sources were evaluated. The basic unit for exposure assessment was a factory/work unit/job title combination which was considered separately during each of seven calendar-year time periods between 1949 and 1987 for a total of 18,435 exposure assignments. Historical information collected to estimate exposure included benzene monitoring data; lists of raw materials and factory products, and the percentage of benzene in each; the total amount and dates of use of benzene or benzene-containing materials; use of engineering controls and personal protective equipment; and other available exposure information. Overall, 38% (ranging from 3% for the earliest periods to 67% for the last period) of the estimates were based primarily on benzene monitoring data. In the absence of job-specific benzene monitoring data for a given calendar period, measurement results or exposure estimates for similar jobs and/or other calendar periods were used in conjunction with other exposure information to derive estimates. Estimated exposure levels are presented by industries and occupations. The highest average exposures during 1949-1987 were observed for the rubber and plastic industry (30.7 ppm), and for rubber glue applicators (52.6 ppm). JF - American journal of industrial medicine AU - Dosemeci, M AU - Li, G L AU - Hayes, R B AU - Yin, S N AU - Linet, M AU - Chow, W H AU - Wang, Y Z AU - Jiang, Z L AU - Dai, T R AU - Zhang, W U AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 401 EP - 411 VL - 26 IS - 3 SN - 0271-3586, 0271-3586 KW - Benzene KW - J64922108F KW - Index Medicus KW - Environmental Monitoring KW - Mortality KW - Data Collection -- methods KW - Humans KW - China -- epidemiology KW - Cohort Studies KW - Retrospective Studies KW - Epidemiological Monitoring KW - Occupations KW - Occupational Exposure KW - Benzene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76850260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3A&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PPmP%3A+Psychotherapie+Psychosomatik+Medizinische+Psychologie&rft.atitle=Wissen+Mitglieder+von+Selbsthilfegruppen+mehr+%C3%BCber+Brustkrebs%3F+Wissen+zur+Erkrankung%2C+Behandlung+und+Pr%C3%A4vention+bei+Patientinnen+im+Vergleich&rft.au=K%C3%BChner%2C+Sophie%3BFietkau%2C+Rainer%3BBruns%2C+Sonja%3BGonzalez%2C+Dagmar+Villarroel%3BGeyer%2C+Siegfried&rft.aulast=K%C3%BChner&rft.aufirst=Sophie&rft.date=2006-11-01&rft.volume=56&rft.issue=11&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=PPmP%3A+Psychotherapie+Psychosomatik+Medizinische+Psychologie&rft.issn=09372032&rft_id=info:doi/10.1055%2Fs-2006-951810 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictors of clozapine response in schizophrenia. AN - 76815850; 7525541 AB - The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neurotransmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action. JF - The Journal of clinical psychiatry AU - Pickar, D AU - Owen, R R AU - Litman, R E AU - Hsiao, J K AU - Su, T P AD - National Institute of Mental Health, Experimental Therapeutics Branch, National Institutes of Health, Bethesda, Md 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 129 EP - 132 VL - 55 Suppl B SN - 0160-6689, 0160-6689 KW - Antipsychotic Agents KW - 0 KW - Receptors, Neurotransmitter KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Clozapine KW - J60AR2IKIC KW - Fluphenazine KW - S79426A41Z KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Probability KW - Double-Blind Method KW - Humans KW - Fluphenazine -- therapeutic use KW - Receptors, Neurotransmitter -- drug effects KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Homovanillic Acid -- cerebrospinal fluid KW - Adult KW - Treatment Outcome KW - Antipsychotic Agents -- adverse effects KW - Basal Ganglia Diseases -- epidemiology KW - Female KW - Male KW - Basal Ganglia Diseases -- chemically induced KW - Clozapine -- therapeutic use KW - Clozapine -- pharmacology KW - Schizophrenia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76815850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Predictors+of+clozapine+response+in+schizophrenia.&rft.au=Pickar%2C+D%3BOwen%2C+R+R%3BLitman%2C+R+E%3BHsiao%2C+J+K%3BSu%2C+T+P&rft.aulast=Pickar&rft.aufirst=D&rft.date=1994-09-01&rft.volume=55+Suppl+B&rft.issue=&rft.spage=129&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 - 1994-11-28 N1 - Date created - 1994-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Misdiagnosed HIV infection in pregnant women: implications for clinical care. AN - 76770334; 7938392 AB - Out of nearly 900 women in a research study of human immunodeficiency virus infection in pregnancy, 8 were subsequently found not to be infected. Misdiagnoses could have resulted from (a) laboratory errors or specimen mixups; (b) failure to follow the testing algorithm recommended by the Centers for Disease Control and Prevention to confirm results; (c) women perceiving they were infected by high-risk behavior in the absence of testing, despite the receipt of negative test results, or based on screening results only; or (d) factitious disorder, HIV Munchausen syndrome, or malingering. Because of the potentially devastating impact of an HIV diagnosis and the toxicity of HIV therapies, health care providers should obtain independent confirmation of the diagnosis before initiating treatment or followup for HIV based on patient report or provider referral. Quality test interpretation and counseling must be ensured. Therapeutic interventions may be indicated for persons intentionally and falsely presenting themselves as HIV-infected. JF - Public health reports (Washington, D.C. : 1974) AU - Sheon, A R AU - Fox, H E AU - Alexander, G AU - Buck, A AU - Higgins, A AU - McDermott, S M AU - Moroso, G AU - Moye, J AU - Pacheco-Acosta, E AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892. PY - 1994 SP - 694 EP - 699 VL - 109 IS - 5 SN - 0033-3549, 0033-3549 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Munchausen Syndrome -- diagnosis KW - Sexual Behavior KW - Risk-Taking KW - Humans KW - HIV Seropositivity -- diagnosis KW - Factitious Disorders -- diagnosis KW - Adult KW - Malingering -- diagnosis KW - HIV Seronegativity KW - Diagnostic Errors KW - Female KW - Pregnancy KW - Pregnancy Complications, Infectious -- diagnosis KW - HIV Infections -- therapy KW - Pregnancy Complications, Infectious -- therapy KW - HIV-1 KW - HIV Infections -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76770334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Misdiagnosed+HIV+infection+in+pregnant+women%3A+implications+for+clinical+care.&rft.au=Sheon%2C+A+R%3BFox%2C+H+E%3BAlexander%2C+G%3BBuck%2C+A%3BHiggins%2C+A%3BMcDermott%2C+S+M%3BMoroso%2C+G%3BMoye%2C+J%3BPacheco-Acosta%2C+E&rft.aulast=Sheon&rft.aufirst=A&rft.date=1994-09-01&rft.volume=109&rft.issue=5&rft.spage=694&rft.isbn=&rft.btitle=&rft.title=Public+health+reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-08 N1 - Date created - 1994-11-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gen Hosp Psychiatry. 1987 Jan;9(1):75-6 [3817465] Arch Intern Med. 1994 May 23;154(10):1129-37 [7910452] N Engl J Med. 1987 Jul 23;317(4):238-41 [3474520] N Engl J Med. 1988 Oct 13;319(15):961-4 [3419477] Ann Intern Med. 1988 Oct 15;109(8):679-80 [3421581] Lancet. 1989 Apr 15;1(8642):852 [2564944] Psychosomatics. 1989 Summer;30(3):342-5 [2762493] Br J Psychiatry. 1989 Mar;154:420-1 [2597852] Eur J Haematol. 1991 Feb;46(2):125 [1995325] J Infect Dis. 1991 Oct;164(4):656-64 [1894929] Clin Infect Dis. 1992 Jan;14(1):211-6 [1571433] Med Sci Law. 1991 Jul;31(3):259-60 [1822589] Clin Infect Dis. 1992 Oct;15(4):707-9 [1420687] JAMA. 1993 Jun 9;269(22):2847 [8497085] JAMA. 1993 Jun 9;269(22):2876-9 [8497091] Womens Health Issues. 1993 Winter;3(4):216-22 [8111239] Sex Transm Dis. 1987 Jan-Mar;14(1):54-7 [3563832] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome. AN - 76760908; 7936305 AB - We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy. JF - Neurology AU - Higgins, J J AU - Kaneski, C R AU - Bernardini, I AU - Brady, R O AU - Barton, N W AD - Clinical Neurogenetics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1728 EP - 1732 VL - 44 IS - 9 SN - 0028-3878, 0028-3878 KW - beta-Alanine KW - 11P2JDE17B KW - 4-Aminobutyrate Transaminase KW - EC 2.6.1.19 KW - Pyridoxine KW - KV2JZ1BI6Z KW - Abridged Index Medicus KW - Index Medicus KW - Obesity -- drug therapy KW - Humans KW - Abnormalities, Multiple -- drug therapy KW - Child KW - Muscle Hypotonia -- drug therapy KW - 4-Aminobutyrate Transaminase -- metabolism KW - Obesity -- blood KW - Abnormalities, Multiple -- blood KW - Intellectual Disability -- drug therapy KW - Muscle Hypotonia -- blood KW - Syndrome KW - Female KW - Intellectual Disability -- blood KW - beta-Alanine -- blood KW - Pyridoxine -- therapeutic use KW - Metabolic Diseases -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76760908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Pyridoxine-responsive+hyper-beta-alaninemia+associated+with+Cohen%27s+syndrome.&rft.au=Higgins%2C+J+J%3BKaneski%2C+C+R%3BBernardini%2C+I%3BBrady%2C+R+O%3BBarton%2C+N+W&rft.aulast=Higgins&rft.aufirst=J&rft.date=1994-09-01&rft.volume=44&rft.issue=9&rft.spage=1728&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Internalization of the gastrin-releasing peptide receptor is mediated by both phospholipase C-dependent and -independent processes. AN - 76759666; 7935330 AB - Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-dependent (i.e., protein kinase A or C) and -independent (i.e., beta-adrenergic receptor kinase) kinases in mediating this process. Recent results for truncated and mutated gastrin-releasing peptide (GRP) receptors (GRP-R), as well as muscarinic cholinergic receptors, suggest that activation of protein kinase C may be needed for full receptor internalization. Nearly all G protein-coupled receptors studied to date, including the GRP-R, possess two highly conserved amino acids that are important in mediating receptor-G protein coupling to second messengers, i.e., arginine in the proximal second intracellular loop and alanine in the distal third intracellular loop. We selectively mutated each of these residues in the GRP-R to determine their importance for activation of PLC. Site-directed mutagenesis was performed to change arginine at position 139 to glycine (R139G mutant) and alanine at position 263 to glutamate (A263E mutant), with stable cell lines being created by transfection of the wild-type or mutated receptor cDNA into BALB/3T3 fibroblasts. Both R139G (Kd = 12.0 +/- 1.6 nM) and A263E (Kd = 12.2 +/- 1.7 nM) had a lower affinity for bombesin than did wild-type GRP-R (Kd = 1.4 +/- 0.4 nM); however, characteristic stoichiometries for the binding of agonists to this receptor were maintained equally in all three cell lines (bombesin > GRP >> neuromedin B). The wild-type GRP-R exposed to bombesin increased [3H]inositol phosphates (a measure of PLC activation) approximately 4-fold, with an EC50 of 5.1 +/- 2.2 nM. In contrast, [3H]inositol phosphates were not significantly increased in cells expressing R139G or A263E receptors, demonstrating that Arg139 and Ala263 are required for GRP-R activation of PLC. However, when receptor internalization at 37 degrees was assessed by ligand acid-stripping studies, 53 +/- 2% of A263E receptors were internalized at 90 min, compared with 85 +/- 5% of wild-type GRP-R, whereas only 10 +/- 3% of R139G receptors were internalized. Preincubation of either mutant cell line with 100 nM 12-O-tetradecanoylphorbol-13-acetate markedly increased internalization rates, such that at 90 min 62 +/- 2% of R139G receptors and 82 +/- 1% of A263E receptors were internalized.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Molecular pharmacology AU - Benya, R V AU - Akeson, M AU - Mrozinski, J AU - Jensen, R T AU - Battey, J F AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 495 EP - 501 VL - 46 IS - 3 SN - 0026-895X, 0026-895X KW - DNA, Complementary KW - 0 KW - Inositol Phosphates KW - Peptides KW - Receptors, Bombesin KW - Glutamic Acid KW - 3KX376GY7L KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Neurokinin B KW - 86933-75-7 KW - neuromedin B KW - 87096-84-2 KW - Arginine KW - 94ZLA3W45F KW - Type C Phospholipases KW - EC 3.1.4.- KW - Alanine KW - OF5P57N2ZX KW - Bombesin KW - PX9AZU7QPK KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Glycine -- chemistry KW - DNA, Complementary -- genetics KW - Inositol Phosphates -- metabolism KW - Bombesin -- metabolism KW - Humans KW - Glutamic Acid -- chemistry KW - Peptides -- metabolism KW - Mice KW - Amino Acid Sequence KW - Mice, Inbred BALB C KW - Neurokinin B -- metabolism KW - Fibroblasts -- metabolism KW - Enzyme Activation -- genetics KW - Glutamic Acid -- genetics KW - Rats KW - Mutagenesis, Site-Directed KW - Glycine -- genetics KW - Sequence Alignment KW - Transfection KW - Molecular Sequence Data KW - Mutation -- genetics KW - Neurokinin B -- analogs & derivatives KW - Cell Line KW - Cricetinae KW - Receptors, Bombesin -- genetics KW - Receptors, Bombesin -- agonists KW - Arginine -- genetics KW - Arginine -- chemistry KW - Arginine -- physiology KW - Alanine -- genetics KW - Alanine -- chemistry KW - Receptors, Bombesin -- metabolism KW - Alanine -- physiology KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76759666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Internalization+of+the+gastrin-releasing+peptide+receptor+is+mediated+by+both+phospholipase+C-dependent+and+-independent+processes.&rft.au=Benya%2C+R+V%3BAkeson%2C+M%3BMrozinski%2C+J%3BJensen%2C+R+T%3BBattey%2C+J+F&rft.aulast=Benya&rft.aufirst=R&rft.date=1994-09-01&rft.volume=46&rft.issue=3&rft.spage=495&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 - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phylogenetic reconstruction of South American felids defined by protein electrophoresis. AN - 76755085; 7932791 AB - Phylogenetic associations among six closely related South American felid species were defined by changes in protein-encoding gene loci. We analyzed proteins isolated from skin fibroblasts using two-dimensional electrophoresis and allozymes extracted from blood cells. Genotypes were determined for multiple individuals of ocelot, margay, tigrina, Geoffroy's cat, kodkod, and pampas cat at 548 loci resolved by two-dimensional electrophoresis and 44 allozyme loci. Phenograms were constructed using the methods of Fitch-Margoliash and neighbor-joining on a matrix of Nei's unbiased genetic distances for all pairs of species. Results of a relative-rate test indicate changes in two-dimensional electrophoresis data are constant among all South American felids with respect to a hyena outgroup. Allelic frequencies were transformed to discrete character states for maximum parsimony analysis. Phylogenetic reconstruction indicates a major split occurred approximately 5-6 million years ago, leading to three groups within the ocelot lineage. The earliest divergence led to Leopardus tigrina, followed by a split between an ancestor of an unresolved trichotomy of three species (Oncifelis guigna, O. geoffroyi, and Lynchailuris colocolo) and a recent common ancestor of Leopardus pardalis and L. wiedii. The results suggest that modern South American felids are monophyletic and evolved rapidly after the formation of the Panama land bridge between North and South America. JF - Journal of molecular evolution AU - Slattery, J P AU - Johnson, W E AU - Goldman, D AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 296 EP - 305 VL - 39 IS - 3 SN - 0022-2844, 0022-2844 KW - Isoenzymes KW - 0 KW - Index Medicus KW - Animals KW - South America KW - Alleles KW - Gene Frequency KW - Genetic Variation -- genetics KW - Isoenzymes -- genetics KW - Phylogeny KW - Cats -- genetics KW - Electrophoresis, Gel, Two-Dimensional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76755085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Phylogenetic+reconstruction+of+South+American+felids+defined+by+protein+electrophoresis.&rft.au=Slattery%2C+J+P%3BJohnson%2C+W+E%3BGoldman%2C+D%3BO%27Brien%2C+S+J&rft.aulast=Slattery&rft.aufirst=J&rft.date=1994-09-01&rft.volume=39&rft.issue=3&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-15 N1 - Date created - 1994-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. AN - 76749913; 7932175 AB - Certain neurosteroids rapidly alter the excitability of neurons, in part by potentiating gamma-aminobutyric acid (GABA)-evoked chloride currents, and, like other GABA potentiating drugs, may have anticonvulsant activity. We compared the abilities of a series of isomeric metabolites of progesterone and deoxycorticosterone (3-hydroxy pregnane-20-ones and 3-hydroxy pregnane-21-ol-20-ones) to enhance GABA-evoked chloride currents in cultured hippocampal neurons with their abilities to protect against pentylenetetrazol (PTZ)-induced seizures in mice. Metabolites with 3-hydroxy in the alpha-position and 5-H in the alpha- or beta-configuration were highly effective at potentiating GABA-evoked chloride current and also showed potent anticonvulsant activity in the PTZ seizure test. The corresponding metabolites with hydroxyl groups in the 3 beta-position were considerably less potent in enhancing GABA responses and were inactive in the PTZ test. All of the neurosteroids failed to protect against tonic hindlimb extension in the maximal electroshock seizure test. 5 alpha-Pregnane-3 alpha,11 beta,21-triol-20-one, a corticosterone metabolite reported to block voltage-dependent Ca++ channels, was inactive in either of the anticonvulsant tests. At higher doses, neurosteroids effective in the PTZ test also produced motor impairment. Relative motor toxicity was lower (higher protective index) for compounds with the 5 alpha-configuration than for their corresponding 5 beta-epimers. The anticonvulsant profile of the neurosteroids resembled that of the benzodiazepine clonazepam. Although the anticonvulsant steroids had greater in vitro potencies than clonazepam, they were less potent in vivo, and they had lower protective indices.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of pharmacology and experimental therapeutics AU - Kokate, T G AU - Svensson, B E AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1223 EP - 1229 VL - 270 IS - 3 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Chloride Channels KW - Receptors, N-Methyl-D-Aspartate KW - Desoxycorticosterone KW - 40GP35YQ49 KW - Progesterone KW - 4G7DS2Q64Y KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Clonazepam KW - 5PE9FDE8GB KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Rats KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Cells, Cultured KW - Neurons -- drug effects KW - Motor Activity -- drug effects KW - Mice KW - Male KW - Clonazepam -- pharmacology KW - Desoxycorticosterone -- metabolism KW - Anticonvulsants -- pharmacology KW - Progesterone -- metabolism KW - gamma-Aminobutyric Acid -- pharmacology KW - Progesterone -- pharmacology KW - Desoxycorticosterone -- pharmacology KW - Chloride Channels -- physiology KW - Chloride Channels -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76749913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Group+Analysis&rft.atitle=History%2C+concept+and+position+of+self-help+groups+in+Germany&rft.au=Moeller%2C+Michael+Lukas&rft.aulast=Moeller&rft.aufirst=Michael&rft.date=1999-06-01&rft.volume=32&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Group+Analysis&rft.issn=05333164&rft_id=info:doi/10.1177%2F05333169922076653 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-07 N1 - Date created - 1994-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. AN - 76728220; 7923571 AB - The carcinogenic and tumor-promoting effects of human transforming growth factor alpha (TGF-alpha) overexpression were examined in a two-stage chemical carcinogenesis protocol using TGF-alpha transgenic mouse line MT42. Male MT42 and CD-1 mice received a single i.p. injection of 5 mg N-nitrosodiethylamine (DEN)/kg body wt at 15 days of age, and were placed on a diet containing 0.05% of phenobarbital (PB) from 4 weeks of age for 35 weeks. DEN-, PB-treated and saline-injected animals in each strain were used as controls. A total of three sequential sacrifices (at 10, 23 and 37 experimental weeks) was performed. Hepatocellular carcinomas (HCCs) developed earlier at high incidence (100%) after 23 experimental weeks in MT42 mice receiving DEN/PB, while CD-1 mice had a 40% incidence of HCCs only after week 37. HCCs also developed in the DEN-initiated MT42 mice at 80% incidence after week 23, but no HCCs were observed in the DEN-initiated CD-1 mice. PB induced preneoplastic foci (67%), adenomas (33%) and HCCs (33%) after 37 weeks in MT42 mice, but no lesions were found in CD-1 mice. Thus, the carcinogenic response to DEN and/or PB was accelerated in the MT42 transgenic mice. Furthermore, PB promotion was observed from week 10 in MT42 mice and week 23 in CD-1 mice. Thus, the promoting effect of PB was also accelerated in the MT42 transgenic mice. Proliferating cell nuclear antigen (PCNA) labeling indices of hepatocellular foci and adenomas in DEN- or DEN/PB-treated MT42 mice were significantly higher than those of CD-1 mice. TGF-alpha expression determined by immunohistochemistry revealed higher levels in these lesions than in hepatocytes of surrounding parenchyma of MT42 transgenic mice. In conclusion, TGF-alpha transgenic mice clearly demonstrated enhanced sensitivity to the development of hepatocellular carcinoma in the DEN initiation and PB promotion regime, possibly through a mechanism of increased hepatocyte proliferation in precancerous lesions (foci and adenomas), driven by high expression of the mitogen TGF-alpha in these lesions. JF - Carcinogenesis AU - Tamano, S AU - Merlino, G T AU - Ward, J M AD - Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science, National Cancer Institute, Frederick, MD 21702-1201. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1791 EP - 1798 VL - 15 IS - 9 SN - 0143-3334, 0143-3334 KW - TGF-&agr; KW - Proliferating Cell Nuclear Antigen KW - 0 KW - Transforming Growth Factor alpha KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Body Weight -- drug effects KW - Cell Division -- drug effects KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Mice, Transgenic KW - Immunohistochemistry KW - Male KW - Diethylnitrosamine -- toxicity KW - Liver Neoplasms, Experimental -- genetics KW - Precancerous Conditions -- genetics KW - Cocarcinogenesis KW - Transforming Growth Factor alpha -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Transforming Growth Factor alpha -- physiology KW - Precancerous Conditions -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Transforming Growth Factor alpha -- analysis KW - Phenobarbital -- toxicity KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76728220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rapid+development+of+hepatic+tumors+in+transforming+growth+factor+alpha+transgenic+mice+associated+with+increased+cell+proliferation+in+precancerous+hepatocellular+lesions+initiated+by+N-nitrosodiethylamine+and+promoted+by+phenobarbital.&rft.au=Tamano%2C+S%3BMerlino%2C+G+T%3BWard%2C+J+M&rft.aulast=Tamano&rft.aufirst=S&rft.date=1994-09-01&rft.volume=15&rft.issue=9&rft.spage=1791&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-02 N1 - Date created - 1994-11-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TGF-&agr; N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clonal variation of tumorigenic potential in v-Ha-ras-transformed human bronchial epithelial cells: relationship to ras oncogene expression and CAD gene amplification. AN - 76721490; 7916988 AB - Infection of an SV40 large-T antigen-"immortalized" human bronchial epithelial cell line with a Zip-v-Ha-ras retroviral vector resulted in a mass culture that was tumorigenic in athymic nude mice. A tumor cell line derived from passage of the mass culture in vivo, however, exhibited increased tumorigenicity and v-Ha-ras expression. To examine and compare the molecular events involving the ras oncogene during cell transformation in vitro and subsequent tumor formation in vivo, clonal cell populations were isolated from the v-Ha-ras-transformed mass culture. While the clonal cell lines exhibited diverse tumorigenic profiles, these differences did not correlate with v-Ha-ras expression. However, the expression of the activated ras gene, while not necessary for growth in vitro, did appear to be associated with a selective growth advantage in vivo. In addition, the modulation of gene amplification ability in these cells was not associated with the induction of tumorigenicity or v-Ha-ras expression. JF - Molecular carcinogenesis AU - Forrester, K AU - Kispert, J AU - Sanchez, J H AU - Gerwin, B I AU - Tlsty, T D AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 34 EP - 41 VL - 11 IS - 1 SN - 0899-1987, 0899-1987 KW - CAD KW - v-Ha-ras KW - CAD trifunctional enzyme KW - 0 KW - DNA, Neoplasm KW - Multienzyme Complexes KW - RNA, Neoplasm KW - Aspartate Carbamoyltransferase KW - EC 2.1.3.2 KW - Dihydroorotase KW - EC 3.5.2.3 KW - Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) KW - EC 6.3.5.5 KW - Index Medicus KW - Neoplasm Transplantation KW - Gene Expression Regulation, Neoplastic KW - Clone Cells KW - Animals KW - Tumor Cells, Cultured KW - Bronchi -- cytology KW - Humans KW - DNA, Neoplasm -- genetics KW - Mice, Nude KW - Mice KW - RNA, Neoplasm -- genetics KW - Gene Amplification KW - Genes, ras KW - Bronchial Neoplasms -- genetics KW - Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) -- genetics KW - Multienzyme Complexes -- genetics KW - Dihydroorotase -- genetics KW - Cell Transformation, Viral KW - Aspartate Carbamoyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clonal+variation+of+tumorigenic+potential+in+v-Ha-ras-transformed+human+bronchial+epithelial+cells%3A+relationship+to+ras+oncogene+expression+and+CAD+gene+amplification.&rft.au=Forrester%2C+K%3BKispert%2C+J%3BSanchez%2C+J+H%3BGerwin%2C+B+I%3BTlsty%2C+T+D%3BHarris%2C+C+C&rft.aulast=Forrester&rft.aufirst=K&rft.date=1994-09-01&rft.volume=11&rft.issue=1&rft.spage=34&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 - 1994-11-02 N1 - Date created - 1994-11-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CAD; v-Ha-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of representational difference analysis for the identification of mdm2 oncogene amplification in diethylstilbestrol-induced murine uterine adenocarcinomas. AN - 76721010; 7916985 AB - Exposure in utero to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of reproductive-tract malignancies in female offspring. To search for the genetic targets of DES, representational difference analysis was used to compare genomic DNA from DES-associated mouse uterine adenocarcinoma cells with genomic DNA from normal CD-1 mouse tissue. Several difference clones were obtained, all of which recognized rearranged and amplified sequences in tumor compared with normal DNA. One of these difference fragments mapped to a region of mouse chromosome 10 that includes the mdm2 oncogene. Amplification and overexpression of mdm2 was found in all three early-passage cell lines established from independent DES-associated cancers. These findings demonstrate the potential power of representational difference analysis in cancer research and suggest a genetic mechanism for DES-induced carcinogenesis. JF - Molecular carcinogenesis AU - Risinger, J I AU - Terry, L A AU - Boyd, J AD - Gynecologic Pathobiology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 13 EP - 18 VL - 11 IS - 1 SN - 0899-1987, 0899-1987 KW - mdm2 KW - DNA, Neoplasm KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Gene Expression KW - Mice KW - Female KW - Chromosomes, Artificial, Yeast KW - Gene Amplification KW - Uterine Neoplasms -- genetics KW - Oncogenes KW - Polymerase Chain Reaction -- methods KW - Diethylstilbestrol -- pharmacology KW - DNA, Neoplasm -- genetics KW - Cloning, Molecular -- methods KW - Adenocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+representational+difference+analysis+for+the+identification+of+mdm2+oncogene+amplification+in+diethylstilbestrol-induced+murine+uterine+adenocarcinomas.&rft.au=Risinger%2C+J+I%3BTerry%2C+L+A%3BBoyd%2C+J&rft.aulast=Risinger&rft.aufirst=J&rft.date=1994-09-01&rft.volume=11&rft.issue=1&rft.spage=13&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 - 1994-11-02 N1 - Date created - 1994-11-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdm2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of in vivo tumorigenicity of human lung cancer cells by retrovirus-mediated transfer of the human tumor necrosis factor-alpha cDNA. AN - 76707330; 8086165 AB - The clinical use of tumor necrosis factor-alpha (TNF) is constrained by tumor cell resistance and systemic toxicity. Based on observations with murine tumors, we hypothesized that induction of local TNF production by the tumor may suppress growth of human cancer cells. To evaluate this, a human TNF cDNA was transferred to human lung cancer cell lines in vitro using a retrovirus vector to produce TNF cDNA-modified cell lines secreting TNF. In vitro cell growth was similar for parental and modified cells. All cells were resistant to TNF. The in vivo tumorigenicity of parental and modified cells was compared in nude mice. Animals injected subcutaneously with parental cells uniformly developed tumors. Tumor growth was markedly less for all modified cells, and this suppression of tumor development was reversed by anti-TNF antibody administration. Animals injected with a mixture of 50% modified and 50% parental cells or parental cell tumors injected with modified cells had decreased tumor growth, demonstrating that modified cells could suppress tumorigenicity. These data suggest that TNF can induce antitumor defenses to suppress in vivo human tumor cell growth and provide a rationale for transferring the human TNF cDNA directly to malignant cells for the therapy of human lung cancer. JF - American journal of respiratory cell and molecular biology AU - Han, S K AU - Brody, S L AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 270 EP - 278 VL - 11 IS - 3 SN - 1044-1549, 1044-1549 KW - DNA, Complementary KW - 0 KW - DNA, Neoplasm KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Humans KW - Mice, Nude KW - Genetic Therapy KW - Mice KW - Gene Expression Regulation, Neoplastic KW - Base Sequence KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Moloney murine leukemia virus -- genetics KW - Genetic Vectors -- genetics KW - Female KW - Male KW - Cell Division KW - Gene Transfer Techniques KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Lung Neoplasms -- therapy KW - Tumor Necrosis Factor-alpha -- physiology KW - Tumor Necrosis Factor-alpha -- genetics KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76707330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurological+Sciences&rft.atitle=Self-help+group+and+medication+overuse+headache%3A+Preliminary+data&rft.au=Sancisi%2C+Elisa%3BRausa%2C+Marialuisa%3BZanigni%2C+Stefano%3BCevoli%2C+Sabina%3BPala%2C+Andrea+Norcini%3BNicodemo%2C+Marianna%3BGrimaldi%2C+Daniela%3BMontagna%2C+Pasquale%3BCortelli%2C+Pietro%3BPierangeli%2C+Giulia&rft.aulast=Sancisi&rft.aufirst=Elisa&rft.date=2009-12-01&rft.volume=30&rft.issue=6&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Neurological+Sciences&rft.issn=15901874&rft_id=info:doi/10.1007%2Fs10072-009-0131-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spectrum of EEG abnormalities during clozapine treatment. AN - 76705892; 7522149 AB - Clozapine is a novel antipsychotic agent effective in treating refractory schizophrenia. Clozapine produces fewer extrapyramidal effects than other neuroleptics, although agranulocytosis and seizures are significant adverse effects. To characterize the spectrum of clozapine-related electroencephalographic abnormalities, we identified 10 patients who had electroencephalograms (EEGs) performed before and during clozapine treatment. These 10 patients represented a subset of individuals participating in an investigational trial. During clozapine treatment, five developed myoclonus and one experienced a generalized tonic-clonic seizure. Records were retrospectively reviewed by an electroencephalographer blinded to the patient's history and medications. All patients had normal EEGs before clozapine treatment. While receiving clozapine (250-900 mg daily), all patients developed background slowing in the theta and often delta ranges. Additionally, 7 patients exhibited bilateral spike, polyspike and slow wave discharges, one with a photoparoxysmal response. Follow-up EEGs performed in 4 of these 7 patients after a decrease in clozapine dosage and/or addition in valproic acid showed diminished epileptiform activity. JF - Electroencephalography and clinical neurophysiology AU - Malow, B A AU - Reese, K B AU - Sato, S AU - Bogard, P J AU - Malhotra, A K AU - Su, T P AU - Pickar, D AD - EEG Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 205 EP - 211 VL - 91 IS - 3 SN - 0013-4694, 0013-4694 KW - Clozapine KW - J60AR2IKIC KW - Index Medicus KW - Humans KW - Adult KW - Retrospective Studies KW - Male KW - Female KW - Myoclonus -- chemically induced KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - Clozapine -- therapeutic use KW - Myoclonus -- physiopathology KW - Electroencephalography -- drug effects KW - Schizophrenia -- drug therapy KW - Clozapine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76705892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electroencephalography+and+clinical+neurophysiology&rft.atitle=Spectrum+of+EEG+abnormalities+during+clozapine+treatment.&rft.au=Malow%2C+B+A%3BReese%2C+K+B%3BSato%2C+S%3BBogard%2C+P+J%3BMalhotra%2C+A+K%3BSu%2C+T+P%3BPickar%2C+D&rft.aulast=Malow&rft.aufirst=B&rft.date=1994-09-01&rft.volume=91&rft.issue=3&rft.spage=205&rft.isbn=&rft.btitle=&rft.title=Electroencephalography+and+clinical+neurophysiology&rft.issn=00134694&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repeated electroconvulsive shock produces long-lasting increases in messenger RNA expression of corticotropin-releasing hormone and tyrosine hydroxylase in rat brain. Therapeutic implications. AN - 76696814; 7916018 AB - Electroconvulsive shock (ECS) is a highly effective therapy for the treatment of major depression, but its mechanisms of action are not known. We report that repeated ECS in rats produces enduring changes in two clinically relevant stress-responsive brain systems: (a) the hypothalamic-pituitary-adrenal axis regulated by corticotropin-releasing hormone (CRH) in the paraventricular nucleus; and (b) the NE system in the locus coeruleus regulated by tyrosine hydroxylase (TH). CRH and TH mRNA levels in these brain regions were assessed by in situ hybridization histochemistry. A single interaural ECS elevated TH but not CRH mRNA measured 24 h later. Repeated daily treatments (3, 7, or 14) elevated both mRNAs, maximally with 7, correlating with the time course of clinical efficacy. The elevations persisted for 3 (CRH) or 8 wk (TH) after the ECS. No other therapeutic treatment is known to produce such long-lasting changes in central nervous system gene expression. The time course of events (delayed onset, long duration) implicate CRH as a principal mediator of the antidepressant effects of ECS. The locus coeruleus-NE system may be important in initiating the central nervous system response. JF - The Journal of clinical investigation AU - Brady, L S AU - Lynn, A B AU - Glowa, J R AU - Le, D Q AU - Herkenham, M AD - Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1263 EP - 1268 VL - 94 IS - 3 SN - 0021-9738, 0021-9738 KW - Oligonucleotide Probes KW - 0 KW - RNA, Messenger KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Pentylenetetrazole KW - WM5Z385K7T KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Analysis of Variance KW - Epilepsy, Tonic-Clonic -- therapy KW - Epilepsy, Tonic-Clonic -- chemically induced KW - Epilepsy, Tonic-Clonic -- metabolism KW - Male KW - Corticotropin-Releasing Hormone -- biosynthesis KW - Gene Expression KW - Tyrosine 3-Monooxygenase -- biosynthesis KW - Electroconvulsive Therapy KW - Brain -- metabolism KW - Electroshock KW - RNA, Messenger -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76696814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Repeated+electroconvulsive+shock+produces+long-lasting+increases+in+messenger+RNA+expression+of+corticotropin-releasing+hormone+and+tyrosine+hydroxylase+in+rat+brain.+Therapeutic+implications.&rft.au=Brady%2C+L+S%3BLynn%2C+A+B%3BGlowa%2C+J+R%3BLe%2C+D+Q%3BHerkenham%2C+M&rft.aulast=Brady&rft.aufirst=L&rft.date=1994-09-01&rft.volume=94&rft.issue=3&rft.spage=1263&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Psychiatry Res. 1980 Mar;2(1):49-61 [6106253] Cell. 1986 Aug 1;46(3):389-99 [3755378] Br J Psychiatry. 1981 Oct;139:265-83 [7034838] Br J Psychiatry. 1983 Dec;143:618-24 [6661605] Am J Psychiatry. 1984 May;141(5):619-27 [6324597] Biol Psychiatry. 1984 Mar;19(3):361-83 [6144329] Science. 1984 Dec 14;226(4680):1342-4 [6334362] EMBO J. 1986 Feb;5(2):287-91 [2872048] Tex Med. 1993 May;89(5):58-62 [8342162] Am J Psychiatry. 1987 May;144(5):641-5 [3495188] Psychopharmacology (Berl). 1987;93(1):122-6 [2957720] N Engl J Med. 1988 Aug 11;319(6):348-53 [3292920] Life Sci. 1989;44(15):985-1006 [2564616] Psychopharmacology (Berl). 1989;97(4):548-52 [2543014] Brain Res. 1989 Nov 6;501(2):235-46 [2819439] Psychopharmacology (Berl). 1990;100(1):60-5 [1688661] Neuron. 1988 Nov;1(9):887-900 [2856104] J Clin Endocrinol Metab. 1991 Feb;72(2):260-71 [1846869] J Clin Invest. 1991 Mar;87(3):831-7 [1671867] Biol Psychiatry. 1991 Feb 1;29(3):253-64 [1707686] Br J Psychiatry. 1991 Jan;158:59-63 [1673078] Gen Hosp Psychiatry. 1991 Mar;13(2):128-37 [2037243] Brain Res. 1991 Mar 22;544(1):26-32 [1677301] Can J Psychiatry. 1991 Jun;36(5):344-8 [1884335] Panminerva Med. 1977 Jul-Aug;19(4):237-43 [201900] Lancet. 1978 Feb 4;1(8058):254-7 [74675] Commun Psychopharmacol. 1977;1(4):393-405 [28203] Proc Natl Acad Sci U S A. 1985 Jan;82(2):617-21 [2857492] FEBS Lett. 1985 Oct 21;191(1):63-6 [3876950] FEBS Lett. 1985 Nov 25;193(1):54-8 [2998878] N Engl J Med. 1986 May 22;314(21):1329-35 [3010108] Psychiatr Clin North Am. 1991 Dec;14(4):947-60 [1771156] JAMA. 1992 Mar 4;267(9):1244-52 [1538563] J Neural Transm Suppl. 1991;34:3-9 [1687784] Brain Res. 1992 Feb 14;572(1-2):117-25 [1351783] Brain Res. 1992 Oct 2;592(1-2):228-38 [1333341] N Engl J Med. 1993 Mar 25;328(12):839-46 [8441428] Science. 1981 Nov 6;214(4521):662-5 [6117127] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditional regulatory elements of human immunodeficiency virus type 2 long terminal repeat. AN - 76688330; 8077923 AB - Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) long terminal repeat (LTR) revealed a novel cis-acting positive and a negative regulatory element in the U3 region, located upstream of the enhancer-promoter region. These elements acted in a cell type-specific manner, being most active in human lymphocytic CEM cells, more active in Jurkat cells than in human monocytic U937 cells and least active in epithelioid HeLa cells. The down-modulatory effect of the negative regulatory element was abolished by HIV-2 Tat, suggesting the involvement of upstream DNA elements in optimal Tat-mediated trans-activation. The sequence elements that respond to T cell activation signals were also located in the upstream U3 region. Notably, the magnitude of the effect of the upstream regulatory elements depended on the basal activity of the LTR, which was also cell type-dependent. This emphasizes the importance of the cell-specific transcriptional factors and other effectors in regulating HIV gene expression. These observations may be relevant to the cell type-specific restriction of virus replication in vivo. JF - The Journal of general virology AU - Arya, S K AU - Mohr, J R AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 2253 EP - 2260 VL - 75 ( Pt 9) SN - 0022-1317, 0022-1317 KW - DNA, Viral KW - 0 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - AIDS/HIV KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - HeLa Cells KW - DNA Mutational Analysis KW - Humans KW - Gene Expression KW - Lymphocytes KW - Mutagenesis KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Base Sequence KW - DNA, Viral -- chemistry KW - Transfection KW - Enhancer Elements, Genetic KW - Proviruses -- genetics KW - Molecular Sequence Data KW - DNA, Viral -- genetics KW - Cell Line KW - Regulatory Sequences, Nucleic Acid KW - HIV Long Terminal Repeat KW - HIV-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76688330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+virology&rft.atitle=Conditional+regulatory+elements+of+human+immunodeficiency+virus+type+2+long+terminal+repeat.&rft.au=Arya%2C+S+K%3BMohr%2C+J+R&rft.aulast=Arya&rft.aufirst=S&rft.date=1994-09-01&rft.volume=75+%28+Pt+9%29&rft.issue=&rft.spage=2253&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+virology&rft.issn=00221317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-03 N1 - Date created - 1994-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenylbutyrate. AN - 76682920; 8077698 AB - The increasing incidence of melanoma and the poor responsiveness of disseminated disease to conventional treatments call for the development of new therapeutic approaches. Phenylacetate, a nontoxic differentiation inducer, can suppress the growth of other neuroectodermal tumors, i.e., gliomas, in laboratory models and in humans. This finding led us to explore the efficacy of phenylacetate and related aromatic fatty acids in melanoma. Phenylacetate and phenylbutyrate were found to a) induce selective cytostasis and maturation of cultured human melanoma cells, b) modulate the expression of genes implicated in tumor metastasis (type IV collagenase and tissue inhibitor of metalloproteinases-2) and immunogenicity (HLA class I); and c) enhance the efficacy of other agents of clinical interest, including retinoids, interferon-alpha, suramin, and 5-aza-2'-deoxycytidine. Reflecting on the phenotypic heterogeneity of melanoma, the degree of biologic alterations induced by phenylacetate/phenylbutyrate varied significantly among the tumor cell lines tested. Although losing invasive capacity and tumorigenicity in athymic mice, poorly differentiated cells exhibited only a marginal change in morphology, remained amelanotic, and resumed growth after treatment was discontinued. By contrast, treatment of melanoma cells that were in a more advanced stage of maturation resulted in profound alterations in cell growth, morphology, and pigmentation consistent with terminal differentiation. The in vitro antitumor activity was observed with nontoxic, pharmacologic concentrations of phenylacetate and phenylbutyrate, suggesting potential clinical use of these drugs in the treatment of melanomas. JF - The Journal of investigative dermatology AU - Liu, L AU - Shack, S AU - Stetler-Stevenson, W G AU - Hudgins, W R AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 335 EP - 340 VL - 103 IS - 3 SN - 0022-202X, 0022-202X KW - Antineoplastic Agents KW - 0 KW - Fatty Acids KW - Phenylacetates KW - Phenylbutyrates KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Pigmentation -- drug effects KW - Gene Expression -- drug effects KW - Neoplasm Invasiveness KW - Tumor Cells, Cultured KW - Humans KW - Cell Division -- drug effects KW - Carcinogenicity Tests KW - Cell Differentiation KW - Drug Synergism KW - Antineoplastic Agents -- pharmacology KW - Fatty Acids -- pharmacology KW - Phenylacetates -- pharmacology KW - Melanoma -- pathology KW - Melanoma -- genetics KW - Phenylbutyrates -- pharmacology KW - Melanoma -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76682920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Differentiation+of+cultured+human+melanoma+cells+induced+by+the+aromatic+fatty+acids+phenylacetate+and+phenylbutyrate.&rft.au=Liu%2C+L%3BShack%2C+S%3BStetler-Stevenson%2C+W+G%3BHudgins%2C+W+R%3BSamid%2C+D&rft.aulast=Liu&rft.aufirst=L&rft.date=1994-09-01&rft.volume=103&rft.issue=3&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-05 N1 - Date created - 1994-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen. AN - 76678133; 8062253 AB - We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered. JF - Cancer research AU - Anzano, M A AU - Byers, S W AU - Smith, J M AU - Peer, C W AU - Mullen, L T AU - Brown, C C AU - Roberts, A B AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/09/01/ PY - 1994 DA - 1994 Sep 01 SP - 4614 EP - 4617 VL - 54 IS - 17 SN - 0008-5472, 0008-5472 KW - Tamoxifen KW - 094ZI81Y45 KW - Tretinoin KW - 5688UTC01R KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Rats KW - Breast Neoplasms -- drug therapy KW - Drug Screening Assays, Antitumor KW - Animals KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Humans KW - Mammary Neoplasms, Experimental -- chemically induced KW - Tretinoin -- analogs & derivatives KW - Tamoxifen -- therapeutic use KW - Mammary Neoplasms, Experimental -- prevention & control KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76678133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prevention+of+breast+cancer+in+the+rat+with+9-cis-retinoic+acid+as+a+single+agent+and+in+combination+with+tamoxifen.&rft.au=Anzano%2C+M+A%3BByers%2C+S+W%3BSmith%2C+J+M%3BPeer%2C+C+W%3BMullen%2C+L+T%3BBrown%2C+C+C%3BRoberts%2C+A+B%3BSporn%2C+M+B&rft.aulast=Anzano&rft.aufirst=M&rft.date=1994-09-01&rft.volume=54&rft.issue=17&rft.spage=4614&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 - 1994-09-20 N1 - Date created - 1994-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute pancreatitis after ifosfamide therapy. AN - 76674888; 8062195 AB - Acute pancreatitis is an uncommon but serious complication of cancer chemotherapy. A 16-year-old girl with metastatic osteosarcoma experienced recurrent bouts of symptomatic pancreatitis 24 hours after treatment with ifosfamide administered as a single agent. To the authors' knowledge, this is the first report of an association between ifosfamide and pancreatitis. Because serum amylase levels are not monitored routinely during treatment with most chemotherapeutic agents, subclinical cases of pancreatitis with ifosfamide and other agents may go undetected. JF - Cancer AU - Izraeli, S AU - Adamson, P C AU - Blaney, S M AU - Balis, F M AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/09/01/ PY - 1994 DA - 1994 Sep 01 SP - 1627 EP - 1628 VL - 74 IS - 5 SN - 0008-543X, 0008-543X KW - Ifosfamide KW - UM20QQM95Y KW - Abridged Index Medicus KW - Index Medicus KW - Acute Disease KW - Kidney Neoplasms -- drug therapy KW - Osteosarcoma -- drug therapy KW - Humans KW - Lung Neoplasms -- secondary KW - Lung Neoplasms -- drug therapy KW - Tibia KW - Osteosarcoma -- secondary KW - Bone Neoplasms -- drug therapy KW - Adolescent KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Kidney Neoplasms -- secondary KW - Ifosfamide -- adverse effects KW - Pancreatitis -- blood KW - Pancreatitis -- chemically induced KW - Ifosfamide -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76674888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+pancreatitis+after+ifosfamide+therapy.&rft.au=Izraeli%2C+S%3BAdamson%2C+P+C%3BBlaney%2C+S+M%3BBalis%2C+F+M&rft.aulast=Izraeli&rft.aufirst=S&rft.date=1994-09-01&rft.volume=74&rft.issue=5&rft.spage=1627&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute renal toxicity associated with suramin in the treatment of prostate cancer. AN - 76674848; 8062193 AB - The use of suramin, a polysulfonated naphthylurea, in the treatment of advanced prostate cancer currently is being investigated. A 52-year-old man developed acute renal dysfunction after receiving nine doses of suramin. His suramin therapy was discontinued, but his serum creatinine level continued to rise to 10.8 mg/dl during the next 6 days. The patient was not rechallenged with suramin, and his renal function returned to baseline within the next 3 weeks. Future investigators of this drug should be aware of the possibility of such a reaction with parenteral administration. JF - Cancer AU - Figg, W D AU - Cooper, M R AU - Thibault, A AU - Headlee, D AU - Humphrey, J AU - Bergan, R C AU - Reed, E AU - Sartor, O AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/09/01/ PY - 1994 DA - 1994 Sep 01 SP - 1612 EP - 1614 VL - 74 IS - 5 SN - 0008-543X, 0008-543X KW - Suramin KW - 6032D45BEM KW - Flutamide KW - 76W6J0943E KW - Creatinine KW - AYI8EX34EU KW - Leuprolide KW - EFY6W0M8TG KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Creatinine -- urine KW - Combined Modality Therapy KW - Humans KW - Hydrocortisone -- administration & dosage KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Leuprolide -- administration & dosage KW - Creatinine -- blood KW - Male KW - Flutamide -- administration & dosage KW - Suramin -- adverse effects KW - Carcinoma -- secondary KW - Carcinoma -- radiotherapy KW - Carcinoma -- drug therapy KW - Acute Kidney Injury -- chemically induced KW - Kidney -- drug effects KW - Suramin -- pharmacokinetics KW - Suramin -- administration & dosage KW - Prostatic Neoplasms -- drug therapy KW - Suramin -- blood KW - Prostatic Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76674848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+renal+toxicity+associated+with+suramin+in+the+treatment+of+prostate+cancer.&rft.au=Figg%2C+W+D%3BCooper%2C+M+R%3BThibault%2C+A%3BHeadlee%2C+D%3BHumphrey%2C+J%3BBergan%2C+R+C%3BReed%2C+E%3BSartor%2C+O&rft.aulast=Figg&rft.aufirst=W&rft.date=1994-09-01&rft.volume=74&rft.issue=5&rft.spage=1612&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Virus production and spontaneous cell proliferation in HTLV-I-infected lymphocytes. AN - 76672724; 8062446 AB - Cultured peripheral blood lymphocytes (PBL) from HTLV-I-infected individuals proliferate in the absence of added mitogens and/or cytokines. In an attempt to answer questions regarding the activating signals for cells and virus, antibodies that react with cell surface components that are known to regulate cell activation and antibodies reacting with viral proteins were added to cultures of PBL from HTLV-I-infected, disease-free individuals. Spontaneous proliferation and virus production increased in the presence of antibodies reacting with CD3 and alpha/beta T cell receptors (TCR) while antibodies to HLA class II and viral proteins had no effect. Addition of HLA class I antibodies shut down virus production and cell proliferation. These observations indicate that both virus and cell activation may occur through the alpha/beta TCR on the infected cell. Cyclosporin A, however, markedly decreased cell proliferation but had only a modest suppressive effect on virus production. Thus, the uncoupling of cell proliferation from virus production by cyclosporin A suggests the possibility that the signal transduction pathways for these two events are different. JF - Clinical immunology and immunopathology AU - Mann, D L AU - Martin, P AU - Hamlin-Green, G AU - Nalewaik, R AU - Blattner, W AD - Laboratory of Viral Carcinogenesis, Program Resources, Inc./DynCorp., National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 312 EP - 320 VL - 72 IS - 3 SN - 0090-1229, 0090-1229 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Surface KW - DNA, Viral KW - HTLV-I Antigens KW - RNA, Viral KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - AIDS/HIV KW - Polymerase Chain Reaction KW - HTLV-I Antigens -- immunology KW - Base Sequence KW - Cells, Cultured KW - RNA, Viral -- biosynthesis KW - Humans KW - Cyclosporine -- pharmacology KW - Molecular Sequence Data KW - RNA, Viral -- genetics KW - DNA, Viral -- genetics KW - Antigens, Surface -- immunology KW - T-Lymphocyte Subsets -- cytology KW - Lymphocyte Activation -- drug effects KW - Human T-lymphotropic virus 1 -- physiology KW - Virus Replication -- drug effects KW - Lymphocyte Activation -- immunology KW - HTLV-I Infections -- microbiology KW - T-Lymphocyte Subsets -- microbiology KW - T-Lymphocyte Subsets -- immunology KW - Human T-lymphotropic virus 1 -- drug effects KW - Human T-lymphotropic virus 1 -- immunology KW - HTLV-I Infections -- immunology KW - Virus Replication -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76672724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+immunology+and+immunopathology&rft.atitle=Virus+production+and+spontaneous+cell+proliferation+in+HTLV-I-infected+lymphocytes.&rft.au=Mann%2C+D+L%3BMartin%2C+P%3BHamlin-Green%2C+G%3BNalewaik%2C+R%3BBlattner%2C+W&rft.aulast=Mann&rft.aufirst=D&rft.date=1994-09-01&rft.volume=72&rft.issue=3&rft.spage=312&rft.isbn=&rft.btitle=&rft.title=Clinical+immunology+and+immunopathology&rft.issn=00901229&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-20 N1 - Date created - 1994-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of c-cbl proto-oncogene is modulated during differentiation but not during induction of proliferation. AN - 76662657; 8058312 AB - The proto-oncogene c-cbl is expressed as two mRNAs, ca. 10.5 and 3.1 kb, both of which appear to be functional inasmuch as both can be found on polyribosomes in tissues that express both mRNAs. The function of the 120 kDa c-cbl protein is not known, but its primary structure resembles that of a DNA-binding transcription factor with a basic region, a nuclear localization sequence, a zinc finger-like motif and a leucine zipper. To test whether expression of this protein resembles that of regulatory proteins, we studied expression of c-cbl mRNA and protein in differentiating cells and in proliferating cells, conditions in which expression of regulatory proteins commonly is modulated. Differentiation of both erythroleukemia cells and teratocarcinoma cells showed a decrease in c-cbl expression, with kinetics similar to those of transcription factors that are immediate early response genes. Unlike early response genes, however, c-cbl mRNA showed a very long half life in B lymphocytes. Further, in fibroblasts and spleen cells that were induced to proliferate, c-cbl mRNA expression did not change, and expression of c-cbl protein did not change during any stage of the cell cycle. These characteristics indicate that c-cbl does not belong to the immediate early response type of transcription factor. Yet when c-cbl is truncated, as in v-cbl, the protein does enter the nucleus and bind DNA, and it contributes to neoplastic transformation of B lymphocytes and fibroblasts. These findings indicate that the regulation of the c-cbl proto-oncogene is different from that of the proto-oncogenes identified to date and suggest that c-cbl belongs to a new class of proto-oncogenes. JF - Oncogene AU - Mushinski, J F AU - Goodnight, J AU - Rudikoff, E AU - Morse, H C AU - Langdon, W Y AD - Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 2489 EP - 2497 VL - 9 IS - 9 SN - 0950-9232, 0950-9232 KW - c-cbl KW - Proto-Oncogene Proteins KW - 0 KW - RNA, Messenger KW - Proto-Oncogene Proteins c-cbl KW - EC 2.3.2.27 KW - Ubiquitin-Protein Ligases KW - CBL protein, human KW - EC 6.3.2.- KW - Cbl protein, mouse KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Humans KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Mice KW - Cell Cycle KW - Cell Division KW - Proto-Oncogene Proteins -- biosynthesis KW - Gene Expression Regulation KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76662657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+c-cbl+proto-oncogene+is+modulated+during+differentiation+but+not+during+induction+of+proliferation.&rft.au=Mushinski%2C+J+F%3BGoodnight%2C+J%3BRudikoff%2C+E%3BMorse%2C+H+C%3BLangdon%2C+W+Y&rft.aulast=Mushinski&rft.aufirst=J&rft.date=1994-09-01&rft.volume=9&rft.issue=9&rft.spage=2489&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-cbl N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of the K-ras gene by insertion mutations in chemically induced rat renal mesenchymal tumors. AN - 76660035; 8058308 AB - Previously we reported the detection of transforming K-ras sequences in methyl(methoxymethyl)nitrosamine (DMN-OMe)-induced rat renal mesenchymal tumors by NIH3T3 transfection assays. Subsequent analysis by selective oligonucleotide hybridization revealed a variety of activating point mutations in codon 12 of K-ras in most of these tumors and in their NIH3T3 transformants, but in some, point mutations could not be detected by this technique. In the current study, insertion mutations were detected in two DMN-OMe-induced tumors from this group with previously undefined transforming K-ras alterations. These primary tumors and their NIH3T3 transformants contained K-ras sequences with either a 9 bp or a 12 bp repeat in exon one, both of which included codon 12. No other mutations in the entire coding region of the K-ras gene were observed. Site-directed mutagenesis studies by others have determined that deletions and insertions near codon 12 can activate the ras gene, but this is the first demonstration of insertional activation of K-ras in a chemically induced rat tumor. JF - Oncogene AU - Higinbotham, K G AU - Rice, J M AU - Buzard, G S AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701-1201. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 2455 EP - 2459 VL - 9 IS - 9 SN - 0950-9232, 0950-9232 KW - K-ras KW - Index Medicus KW - Rats KW - Animals KW - 3T3 Cells KW - Rats, Inbred F344 KW - Base Sequence KW - Molecular Sequence Data KW - Mice KW - Mutation KW - Kidney Neoplasms -- genetics KW - Genes, ras KW - Gene Expression Regulation, Neoplastic KW - Kidney Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76660035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Activation+of+the+K-ras+gene+by+insertion+mutations+in+chemically+induced+rat+renal+mesenchymal+tumors.&rft.au=Higinbotham%2C+K+G%3BRice%2C+J+M%3BBuzard%2C+G+S%3BPerantoni%2C+A+O&rft.aulast=Higinbotham&rft.aufirst=K&rft.date=1994-09-01&rft.volume=9&rft.issue=9&rft.spage=2455&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras N1 - Genetic sequence - U09793; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases. AN - 76637368; 8051562 AB - Nitric oxide has been proposed to mediate cytotoxic effects in inflammatory diseases. To investigate the possibility that overproduction of nitric oxide might play a role in the neuropathology of inflammatory and noninflammatory neurological diseases, we compared levels of the markers of nitric oxide, nitrite plus nitrate, in the CSF of controls with those in patients with various neurologic diseases, including Huntington's and Alzheimer's disease, amyotrophic lateral sclerosis, and HIV infection. We found that there were no significant increases in the CSF levels of these nitric oxide metabolites, even in patients infected with HIV or in monkeys infected with poliovirus, both of which have significantly elevated levels of the neurotoxin quinolinic acid and the marker of macrophage activation, neopterin. However, CSF quinolinic acid, neopterin, and nitrite/nitrate levels were significantly increased in a small group of patients with bacterial and viral meningitis. JF - Journal of neurochemistry AU - Milstien, S AU - Sakai, N AU - Brew, B J AU - Krieger, C AU - Vickers, J H AU - Saito, K AU - Heyes, M P AD - Laboratory of Neurochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 1178 EP - 1180 VL - 63 IS - 3 SN - 0022-3042, 0022-3042 KW - Nitrates KW - 0 KW - Nitrites KW - Biopterin KW - 22150-76-1 KW - Nitric Oxide KW - 31C4KY9ESH KW - Neopterin KW - 670-65-5 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Biopterin -- analogs & derivatives KW - Animals KW - Quinolinic Acid -- cerebrospinal fluid KW - Amyotrophic Lateral Sclerosis -- cerebrospinal fluid KW - Huntington Disease -- cerebrospinal fluid KW - Humans KW - Nitric Oxide -- metabolism KW - Biopterin -- cerebrospinal fluid KW - Macaca mulatta KW - Alzheimer Disease -- cerebrospinal fluid KW - HIV Infections -- cerebrospinal fluid KW - Nitrates -- cerebrospinal fluid KW - Nitrites -- cerebrospinal fluid KW - Nervous System Diseases -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76637368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Cerebrospinal+fluid+nitrite%2Fnitrate+levels+in+neurologic+diseases.&rft.au=Milstien%2C+S%3BSakai%2C+N%3BBrew%2C+B+J%3BKrieger%2C+C%3BVickers%2C+J+H%3BSaito%2C+K%3BHeyes%2C+M+P&rft.aulast=Milstien&rft.aufirst=S&rft.date=1994-09-01&rft.volume=63&rft.issue=3&rft.spage=1178&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-08 N1 - Date created - 1994-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine AIDS is an antigen-driven disease: requirements for major histocompatibility complex class II expression and CD4+ T cells. AN - 76630745; 7914549 AB - Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and immunodeficiency induced by a replication-defective murine leukemia virus (BM5def) that encodes Pr60gag as its only product. It has been suggested that the gag polyprotein is responsible for vigorous antigenic stimulation of CD4+ T cells and generalized secondary activation of the immune system. This model was tested first by infecting mice (C2K/O) that lack class II major histocompatibility complex molecules required for presentation of antigens to CD4+ T cells. C2K/O mice expressed BM5def at high levels but did not develop MAIDS either when unmanipulated or following transfer of CD4+ T cells. Second, B6 mice reconstituted with C2K/O bone marrow cells had normal frequencies of B cells (class II negative) and CD4+ cells and expressed high levels of BM5def transcripts but did not develop MAIDS; however, MAIDS developed in class II-competent nu/nu mice reconstituted with CD4+ T cells and in C2K/O mice reconstituted with B6 bone marrow to give class II-positive B cells and with purified CD4+ T cells. These results indicate that induction of MAIDS by BM5def is antigen driven and is dependent on expression of major histocompatibility complex class II molecules on antigen-presenting cells and the presence of CD4+ T cells. JF - Journal of virology AU - Giese, N A AU - Giese, T AU - Morse, H C AD - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/09// PY - 1994 DA - September 1994 SP - 5819 EP - 5824 VL - 68 IS - 9 SN - 0022-538X, 0022-538X KW - Antigens, Surface KW - 0 KW - Antigens, Thy-1 KW - DNA Primers KW - Histocompatibility Antigens Class II KW - Membrane Glycoproteins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Membrane Glycoproteins -- analysis KW - Mice KW - Mice, Nude KW - Structure-Activity Relationship KW - Lymphocyte Activation KW - Mutagenesis, Site-Directed KW - Base Sequence KW - T-Lymphocyte Subsets -- immunology KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Antigens, Surface -- analysis KW - DNA Primers -- chemistry KW - Murine Acquired Immunodeficiency Syndrome -- immunology KW - Leukemia Virus, Murine -- growth & development KW - CD4-Positive T-Lymphocytes -- immunology KW - Leukemia Virus, Murine -- pathogenicity KW - Histocompatibility Antigens Class II -- immunology KW - Leukemia Virus, Murine -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76630745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Murine+AIDS+is+an+antigen-driven+disease%3A+requirements+for+major+histocompatibility+complex+class+II+expression+and+CD4%2B+T+cells.&rft.au=Giese%2C+N+A%3BGiese%2C+T%3BMorse%2C+H+C&rft.aulast=Giese&rft.aufirst=N&rft.date=1994-09-01&rft.volume=68&rft.issue=9&rft.spage=5819&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 - 1994-09-09 N1 - Date created - 1994-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1970 Dec;42(4):1136-9 [4099080] J Immunol. 1993 Oct 1;151(7):3672-81 [7690809] J Exp Med. 1987 Jun 1;165(6):1737-42 [3035057] J Exp Med. 1988 Aug 1;168(2):623-35 [2842430] J Immunol. 1989 Feb 15;142(4):1144-9 [2464640] J Virol. 1989 Mar;63(3):1223-31 [2536830] Nature. 1989 Apr 6;338(6215):505-8 [2538760] J Exp Med. 1990 Jan 1;171(1):315-20 [1967300] Cytometry. 1990;11(2):231-8 [1690625] Eur J Immunol. 1990 Dec;20(12):2783-7 [1980114] Science. 1991 Mar 8;251(4998):1225-8 [1900951] Science. 1991 Apr 19;252(5004):424-7 [1850169] FASEB J. 1991 Jul;5(10):2398-405 [2065888] J Virol. 1991 Aug;65(8):4232-41 [1649328] Science. 1991 Sep 20;253(5026):1417-20 [1910207] J Immunol. 1991 Oct 1;147(7):2391-7 [1717559] J Virol. 1992 Apr;66(4):2398-406 [1312635] AIDS. 1992 Jul;6(7):607-21 [1503680] J Immunol. 1992 Nov 1;149(9):3097-106 [1383337] J Immunol. 1993 Jan 1;150(1):185-9 [8380187] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2779-83 [8464889] J Exp Med. 1985 May 1;161(5):1029-47 [3921649] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicology and Carcinogenesis Studies of Ozone and Ozone 4-(N-Nitrosomethylamino)-1-(3-Pyridyl)-1-Butanone in Fischer-344/N Rats AN - 755138367; 13645578 AB - The purpose of this study was to evaluate the toxicity and potential carcinogenicity or cocarcinogenicity of ozone exposure in rats. Fischer-344/N (F-344/N) rats were exposed 6 hr/day, 5 days/wk, to 0, 0.12, 0.5, or 1.0 ppm ozone by inhalation for 2-yr and lifetime exposures. The cocarcinogenicity study included subcutaneous administration of 0, 0.1, or 1.0 mg/kg body weight of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and inhalation of 0 or 0.5 ppm ozone to male rats. NNK was administered by subcutaneous injections 3 times per week for the first 20 wk with ozone inhalation exposure. The ozone inhalation exposure was for 2 yr (104 wk), including the first 20 wk of NNK treatment and continuing for 84 wk after the last NNK injection. Ozone exposure caused a concentration-related increase in inflammation of the centriacinar region of the lung. There was also increased fibrosis and an extension of the bronchiolar epithelium in these centriacinar regions to involve the proximal alveoli. There was no increased incidence of neoplasms at any site, including the lung, that was associated with ozone exposure. Rats administered 1.0 mg/kg body weight NNK alone had an increased incidence of bronchiolar/alveolar neoplasms, but this effect was not enhanced by ozone exposure. Ozone exposure for 2 yr and lifetime was associated with site-specific toxic alterations in the nasal passage and lung similar to those previously described for short-term exposures. While there was significant attenuation of the pulmonary lesions as compared to short-term exposures, lesions persisted in the lifetime study and there was evidence of a mild progressive fibrosis. We conclude that under the conditions of these studies: (a) ozone exposure is not carcinogenic to either male or female F-344/N rats, (b) ozone does not enhance the incidence of pulmonary neoplasms in F-344/N rats exposed to a known pulmonary carcinogen (NNK), and (c) mild site-specific toxic lesions characteristic of ozone exposure persist in the nasal passage and lung throughout the lifetime of the rat with continued ozone exposure. JF - Toxicologic Pathology AU - Boorman, Gary A AU - Hmley, Rick AU - Grumbein, Sondra AU - Chou, Billy J AU - Herbert, Ron A AU - Goehl, Thomas AU - Mellick, Paul W AU - Roycroft, Joseph H AU - Haseman, Joseph K AU - Sills, Robert AD - Pathology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1994/09// PY - 1994 DA - Sep 1994 SP - 545 EP - 554 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 22 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755138367?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Toxicology+and+Carcinogenesis+Studies+of+Ozone+and+Ozone+4-%28N-Nitrosomethylamino%29-1-%283-Pyridyl%29-1-Butanone+in+Fischer-344%2FN+Rats&rft.au=Boorman%2C+Gary+A%3BHmley%2C+Rick%3BGrumbein%2C+Sondra%3BChou%2C+Billy+J%3BHerbert%2C+Ron+A%3BGoehl%2C+Thomas%3BMellick%2C+Paul+W%3BRoycroft%2C+Joseph+H%3BHaseman%2C+Joseph+K%3BSills%2C+Robert&rft.aulast=Boorman&rft.aufirst=Gary&rft.date=1994-09-01&rft.volume=22&rft.issue=5&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339402200510 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339402200510 ER - TY - JOUR T1 - Macrophage Inflammatory Protein-1 alpha in Term and Preterm Parturtition: Effect of Microbial Invasion of the Amniotic Cavity AN - 1356933536; 18052076 AB - PROBLEM: This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein-1 alpha ; (2) amniotic fluid concentrations of macrophage inflammatory protein-1 alpha are correlated with the white blood cell count and the concentrations of interleukin-8 in amniotic fluid. METHOD: Amniotic fluid was retrieved by amniocentesis from 126 patients; 54 women with preterm labor and intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N = 16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor-no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma species. Determinations of amniotic fluid macrophage inflammatory protein-1 alpha and interleukin-8 were performed with immunoassays validated for amniotic fluid (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank correlation were performed for analysis. RESULTS: 1) Amniotic fluid macrophage inflammatory protein-1 alpha was present in only 31.0% (9/29) of patients not in labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher amniotic fluid concentrations of macrophage inflammatory protein-1 alpha than those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0-221.2; no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0-494.6; MIAC-preterm delivery: median 7171.0 pg/ml, range 402.5-37994.0; P<0.00001). 3) Among patients at term, MIAC was associated with higher concentrations of amniotic fluid macrophage inflammatory protein-1 alpha than patients without MIAC (no labor: median 0.0 pg/ml, range 0.0-25.6; labor-no MIAC: median 16.7 pg/ml, range 0.0-161.6; labor-MIAC: median 103.8 pg/ ml, range 0.0-4349.0, P<0.001). 4) Among patients in preterm labor, a strong correlation was found between amniotic fluid concentrations of macrophage inflammatory protein-1 alpha and interleukin-8 (r = 0.9, P<0.00001) and between amniotic fluid macrophage inflammatory protein-1 alpha concentrations and amniotic fluid white blood cell count (r = 0.6, P<0.0001). CONCLUSIONS: (1) Macrophage inflammatory protein-1 alpha is undetectable in most amniotic fluid samples from patients in the midtrimester of pregnancy and at term not in labor. (2) Microbial invasion of the amniotic cavity is associated with increased concentrations of immunoreactive amniotic fluid macrophage inflammatory protein-1 alpha in both term and preterm gestations. (3) Amniotic fluid macrophage inflammatory protein-1 alpha concentrations significantly correlate with interleukin-8 levels and white blood cell count in amniotic fluid. Our data strongly suggest a role for macrophage inflammatory protein-1 alpha in the mechanisms responsible for the recruitment of leukocytes into the amniotic cavity during the course of intrauterine infection. JF - American Journal of Reproductive Immunology AU - Romero, Roberto AU - Gomez, Ricardo AU - Galasso, Maurizio AU - Munoz, Hernan AU - Acosta, Leonardo AU - Yoon, Bo Hyun AU - Svinarich, David AU - Cotton, David B AD - Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hosptial, and Perinatology Research Branch, National Institute of Child Health and Human Development Y1 - 1994/09// PY - 1994 DA - Sep 1994 SP - 108 EP - 113 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 32 IS - 2 SN - 1046-7408, 1046-7408 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - Macrophages KW - Amniotic fluid KW - Cavities KW - Gestational age KW - Data processing KW - Leukocytes KW - Parturition KW - Infection KW - Interleukin 8 KW - Pregnancy KW - Inflammation KW - Leukocyte migration KW - Amniocentesis KW - Gestation KW - Immunoassays KW - Mycoplasma KW - F 06935:Development, Aging & Organ Systems KW - A 01300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1356933536?accountid=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=American+Journal+of+Reproductive+Immunology&rft.atitle=Macrophage+Inflammatory+Protein-1+alpha+in+Term+and+Preterm+Parturtition%3A+Effect+of+Microbial+Invasion+of+the+Amniotic+Cavity&rft.au=Romero%2C+Roberto%3BGomez%2C+Ricardo%3BGalasso%2C+Maurizio%3BMunoz%2C+Hernan%3BAcosta%2C+Leonardo%3BYoon%2C+Bo+Hyun%3BSvinarich%2C+David%3BCotton%2C+David+B&rft.aulast=Romero&rft.aufirst=Roberto&rft.date=1994-09-01&rft.volume=32&rft.issue=2&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Reproductive+Immunology&rft.issn=10467408&rft_id=info:doi/10.1111%2Fj.1600-0897.1994.tb01101.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-05-01 N1 - Last updated - 2015-09-03 N1 - SubjectsTermNotLitGenreText - Amniotic fluid; Macrophages; Cavities; Data processing; Gestational age; Leukocytes; Parturition; Infection; Interleukin 8; Inflammation; Pregnancy; Leukocyte migration; Amniocentesis; Gestation; Immunoassays; Mycoplasma DO - http://dx.doi.org/10.1111/j.1600-0897.1994.tb01101.x ER - TY - JOUR T1 - Hsp70RY: further characterization of a novel member of the hsp70 protein family. AN - 76683744; 8074706 AB - Hsp70RY was identified as a member of the hsp70 protein family on the basis of cDNA sequence homology (Fathallah, et. al. (1993) J. Immunol. 151, 810-813). We have shown that mRNA encoding hsp70RY is expressed in a variety of human cell lines and that mRNA expression remains unchanged in human promyelocytic HL-60 cells induced to differentiate with phorbol 12-myristate 13-acetate (PMA). We have also shown that the predicted amino acid sequence of hsp70RY diverges significantly from the other human hsp70 proteins and that it contains a unique glutamate-rich region near its carboxy-terminus. Finally, we have demonstrated the existence of a murine homolog of hsp70RY. JF - Biochemical and biophysical research communications AU - Dyer, K D AU - Lavigne, M C AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08/30/ PY - 1994 DA - 1994 Aug 30 SP - 577 EP - 581 VL - 203 IS - 1 SN - 0006-291X, 0006-291X KW - Glutamates KW - 0 KW - HSP110 Heat-Shock Proteins KW - HSP70 Heat-Shock Proteins KW - HSPA4 protein, human KW - Heat-Shock Proteins KW - RNA, Messenger KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Genetic Variation KW - Blotting, Northern KW - Glutamates -- analysis KW - Humans KW - Gene Expression KW - Mice KW - RNA, Messenger -- biosynthesis KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Leukemia, Promyelocytic, Acute KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line, Transformed KW - Sequence Homology, Amino Acid KW - Cell Differentiation -- drug effects KW - Cell Line KW - Heat-Shock Proteins -- biosynthesis KW - B-Lymphocytes -- metabolism KW - Heat-Shock Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76683744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hsp70RY%3A+further+characterization+of+a+novel+member+of+the+hsp70+protein+family.&rft.au=Dyer%2C+K+D%3BLavigne%2C+M+C%3BRosenberg%2C+H+F&rft.aulast=Dyer&rft.aufirst=K&rft.date=1994-08-30&rft.volume=203&rft.issue=1&rft.spage=577&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 - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Biochem Biophys Res Commun 1994 Nov 15;204(3):1383 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A simple and efficient method of protein delivery into cells using adenovirus. AN - 76683527; 8074707 AB - Human adenovirus type 2 has been previously shown to increase the delivery of a variety of proteins into cells when Ad is co-internalized with the protein ligands. To increase the efficiency of adenoviral-mediated delivery of proteins, I have linked adenovirus, separately with two proteins, epidermal growth factor and an antibody against human transferrin receptor through disulfide and thioether linkages. Competition experiments indicate that the conjugates are taken up into the cells through adenovirus receptor. During the internalization of adenovirus-protein conjugates into KB cells, the conjugates were equally effective as the native adenovirus in disrupting endocytic vesicles and releasing their protein content into the cytosol. This implies the possible use of adenovirus to deliver a large number of protein molecules into the cells. JF - Biochemical and biophysical research communications AU - Seth, P AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/30/ PY - 1994 DA - 1994 Aug 30 SP - 582 EP - 587 VL - 203 IS - 1 SN - 0006-291X, 0006-291X KW - Antibodies KW - 0 KW - Drug Carriers KW - Iodine Radioisotopes KW - Receptors, Transferrin KW - Receptors, Virus KW - Sulfur Radioisotopes KW - Epidermal Growth Factor KW - 62229-50-9 KW - Index Medicus KW - Protein Biosynthesis -- drug effects KW - KB Cells KW - Electrophoresis, Polyacrylamide Gel KW - Kinetics KW - Humans KW - Receptors, Virus -- physiology KW - Epidermal Growth Factor -- toxicity KW - Antibodies -- metabolism KW - Adenoviruses, Human -- physiology KW - Receptors, Transferrin -- immunology KW - Epidermal Growth Factor -- metabolism KW - Antibodies -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76683527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+simple+and+efficient+method+of+protein+delivery+into+cells+using+adenovirus.&rft.au=Seth%2C+P&rft.aulast=Seth&rft.aufirst=P&rft.date=1994-08-30&rft.volume=203&rft.issue=1&rft.spage=582&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 - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation of heterocyclic amine food mutagens in the mammary gland of lactating Fischer 344 rats. AN - 76685031; 7915639 AB - We investigated the ability of the mammary gland to metabolically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Although mammary gland microsomes had almost no capacity to metabolically activate the parent compounds, mammary gland cytosol was able to esterify the N-hydroxylamines. Acetyltransferase was the primary enzyme responsible for the phase II activation of the N-hydroxylamines. The level of acetyl CoA-stimulated binding when N-hydroxy PhIP served as the substrate was approximately 3- and 17-fold higher than when IQ and MeIQx served as substrates, respectively. N-Hydroxy-IQ and N-hydroxy PhIP can also be activated by tRNA synthetase and phosphatase, but not by sulfotransferase. However, the levels of proline- and ATP-enhanced DNA binding was approximately 30- and 60-fold lower than the acetyl CoA-enhanced DNA binding of IQ and PhIP, respectively. Differences observed in the phase II activation of the various heterocyclic amines in the mammary gland may explain why the mammary gland is a target organ for PhIP-induced carcinogenicity but not for IQ- or MeIQx-induced carcinogenicity in Fischer 344 rats. JF - Cancer letters AU - Davis, C D AU - Ghoshal, A AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-0037. Y1 - 1994/08/29/ PY - 1994 DA - 1994 Aug 29 SP - 67 EP - 73 VL - 84 IS - 1 SN - 0304-3835, 0304-3835 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Imidazoles KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Acetyl-CoA C-Acetyltransferase KW - EC 2.3.1.9 KW - Amino Acyl-tRNA Synthetases KW - EC 6.1.1.- KW - 2-amino-3,4-dimethylimidazo(4,5-f)quinoline KW - G2Q7M1P33X KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - DNA -- metabolism KW - Food KW - Liver -- metabolism KW - Autoradiography KW - Acetyl-CoA C-Acetyltransferase -- metabolism KW - Rats KW - Imidazoles -- pharmacokinetics KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Biotransformation KW - Microsomes -- metabolism KW - Amino Acyl-tRNA Synthetases -- metabolism KW - Quinolines -- pharmacokinetics KW - Female KW - Mammary Glands, Animal -- metabolism KW - Heterocyclic Compounds -- pharmacokinetics KW - Mammary Glands, Animal -- enzymology KW - Mutagens -- pharmacokinetics KW - Amines -- pharmacokinetics KW - Lactation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76685031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Metabolic+activation+of+heterocyclic+amine+food+mutagens+in+the+mammary+gland+of+lactating+Fischer+344+rats.&rft.au=Davis%2C+C+D%3BGhoshal%2C+A%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1994-08-29&rft.volume=84&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-03 N1 - Date created - 1994-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of class II and class III ADP-ribosylation factor genes and proteins in Drosophila melanogaster. AN - 76674962; 8063793 AB - ADP-ribosylation factors (ARFs) are ubiquitous approximately 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are involved in intracellular vesicular transport. Based on size, phylogenetic analysis, amino acid identity, and gene structure, mammalian ARFs fall into three classes (class I, ARF1, -2, and -3; class II, ARF4 and -5; class III, ARF6). A class I ARF had been identified in Drosophila melanogaster. To search for ARFs of other classes in Drosophila, polymerase chain reaction-based techniques were used, resulting in cloning of Drosophila ARF (dARF) II and dARF III with deduced amino acid sequences similar to those of class II and class III mammalian ARFs, respectively. The three Drosophila ARF genes map to different chromosomes and the coding regions have different splicing sites. dARF II mRNA, like ARF I mRNA, is fairly uniformly distributed throughout adult flies, whereas dARF III mRNA is significantly more abundant in heads than in legs or bodies. Recombinant dARF II and dARF III have biochemical and immunological properties similar to those of human ARF5 (hARF5) and hARF6, respectively. These observations are consistent with the conclusion that the three classes of ARFs are present in non-mammalian as well as mammalian species. JF - The Journal of biological chemistry AU - Lee, F J AU - Stevens, L A AU - Hall, L M AU - Murtagh, J J AU - Kao, Y L AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08/26/ PY - 1994 DA - 1994 Aug 26 SP - 21555 EP - 21560 VL - 269 IS - 34 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Recombinant Proteins KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Animals KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Tissue Distribution KW - Mammals -- genetics KW - Chromosome Mapping KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - In Situ Hybridization KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Cholera Toxin -- metabolism KW - GTP-Binding Proteins -- classification KW - Genes, Insect -- genetics KW - Drosophila melanogaster -- genetics KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76674962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Characterization+of+class+II+and+class+III+ADP-ribosylation+factor+genes+and+proteins+in+Drosophila+melanogaster.&rft.au=Lee%2C+F+J%3BStevens%2C+L+A%3BHall%2C+L+M%3BMurtagh%2C+J+J%3BKao%2C+Y+L%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Lee&rft.aufirst=F&rft.date=1994-08-26&rft.volume=269&rft.issue=34&rft.spage=21555&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 - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L25062; GENBANK; L25064 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of high affinity binding sites for LexA which define new DNA damage-inducible genes in Escherichia coli. AN - 76644425; 8057377 AB - A multi-step screening procedure was devised to identify new operators for the LexA repressor in the sequenced portions of the genomes of Escherichia coli and its plasmids and bacteriophages. Sequence analysis methods were employed initially to distinguish true LexA operators from "operator-like" sequences stored within the GenBank and EMBL databases. The affinity of purified LexA protein for cloned DNA fragments containing several of the prospective new sites was then assessed using quantitative electrophoretic mobility shift assays and site-directed mutagenesis. Calculated binding affinities were compared directly with values determined for known and mutant LexA operators in concurrent experiments. Three E. coli chromosomal segments (near pyrC, hsdS and ntrla) and two bacteriophage sequences (near the P1 cre and lambda oop genes) bound LexA protein specifically. These sites and most others identified in the screening are located immediately upstream of known genes and/or large open reading frames. These results and additional transcription data demonstrate that several of the sequences define new DNA damage-inducible (din) genes and include the previously uncharacterized dinD locus. Furthermore, the search identified an SOS gene within the genome of P1 which encodes a protein that is homologous to UmuD', the RecA-promoted cleavage product of the umuD gene. The success of the combinatorial approach described here suggests that analogous searches for new regulatory sequences within the E. coli genome and the genomes of other organisms will also yield favorable results. JF - Journal of molecular biology AU - Lewis, L K AU - Harlow, G R AU - Gregg-Jolly, L A AU - Mount, D W AD - Laboratory of Molecular Genetics, National Institutes of Health, NIEHS Research Triangle Park, NC 27709. Y1 - 1994/08/26/ PY - 1994 DA - 1994 Aug 26 SP - 507 EP - 523 VL - 241 IS - 4 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - DNA-Binding Proteins KW - LexA protein, Bacteria KW - Repressor Proteins KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Electrophoresis, Polyacrylamide Gel KW - Blotting, Southern KW - Models, Genetic KW - Chromosomes, Bacterial KW - Molecular Sequence Data KW - Coliphages -- genetics KW - Amino Acid Sequence KW - Binding Sites KW - Operator Regions, Genetic -- genetics KW - SOS Response (Genetics) -- genetics KW - Genes, Bacterial KW - Repressor Proteins -- metabolism KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76644425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Identification+of+high+affinity+binding+sites+for+LexA+which+define+new+DNA+damage-inducible+genes+in+Escherichia+coli.&rft.au=Lewis%2C+L+K%3BHarlow%2C+G+R%3BGregg-Jolly%2C+L+A%3BMount%2C+D+W&rft.aulast=Lewis&rft.aufirst=L&rft.date=1994-08-26&rft.volume=241&rft.issue=4&rft.spage=507&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - D38582; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aggregation of beta A3-crystallin is independent of the specific sequence of the domain connecting peptide. AN - 76658807; 8063735 AB - The beta- and gamma-crystallins are structural proteins whose high concentration and close packing are important in maintaining transparency of the eye lens. The beta gamma-crystallin superfamily includes proteins with similar core structures consisting of two compact domains linked by a short connecting peptide. In gamma-crystallins, the connecting peptide folds back on itself, allowing the amino and carboxyl domains to participate in close interactions. The beta-crystallin connecting peptide is extended so that dimerization of two beta-crystallin monomers is required for similar interdomain interactions. In order to examine the role of the sequence of the connecting peptide in determining the extended beta-crystallin conformation and hence their association into dimers, we have exchanged the 10 residues of the beta A3-crystallin connecting peptide with the 9-residue connecting peptide sequence of mouse gamma B-crystallin by site-directed mutagenesis. Unaltered and modified recombinant beta A3-crystallins were expressed in a baculovirus system and purified by sequential anion exchange chromatography and gel filtration. Integrity of the recombinant crystallins was confirmed by NH2-terminal sequence analysis, immunoblots, and CD spectrometry. Reconstitution of the mutant recombinant protein with crystallins from mouse lens soluble extract resulted in aggregates of identical size distribution as normal beta A3-crystallin. We conclude that the sequence of the connecting peptide is not critical for the association of beta A3-crystallin into dimers and higher order aggregates as had been postulated. JF - The Journal of biological chemistry AU - Hope, J N AU - Chen, H C AU - Hejtmancik, J F AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, NICHD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08/19/ PY - 1994 DA - 1994 Aug 19 SP - 21141 EP - 21145 VL - 269 IS - 33 SN - 0021-9258, 0021-9258 KW - CRYBA1 protein, human KW - 0 KW - Cryba1 protein, mouse KW - Crystallins KW - DNA Primers KW - Recombinant Proteins KW - beta-Crystallin A Chain KW - Index Medicus KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Spectrophotometry, Ultraviolet KW - Circular Dichroism KW - Amino Acid Sequence KW - Mice KW - Recombinant Proteins -- genetics KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Blotting, Western KW - Chromatography, Gel KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Crystallins -- chemistry KW - Crystallins -- genetics KW - Crystallins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76658807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aggregation+of+beta+A3-crystallin+is+independent+of+the+specific+sequence+of+the+domain+connecting+peptide.&rft.au=Hope%2C+J+N%3BChen%2C+H+C%3BHejtmancik%2C+J+F&rft.aulast=Hope&rft.aufirst=J&rft.date=1994-08-19&rft.volume=269&rft.issue=33&rft.spage=21141&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 - 1994-09-21 N1 - Date created - 1994-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topoisomerase II inhibition and cytotoxicity of the anthrapyrazoles DuP 937 and DuP 941 (Losoxantrone) in the National Cancer Institute preclinical antitumor drug discovery screen. AN - 76620052; 8040892 AB - The cumulative cardiotoxicity of anthracyclines is thought to result from the generation of free radicals. New DNA topoisomerase II inhibitors less prone to redox reactions, such as mitoxantrone and more recently the anthrapyrazoles, were developed to circumvent this toxicity. Two anthrapyrazoles currently in clinical evaluation, DuP 941 (Losoxantrone) and DuP 937, were compared to other topoisomerase II inhibitors with respect to their cytotoxic potency and selectivity and with respect to topoisomerase II inhibition. Cytotoxicity was tested in the 60 cell lines of the National Cancer Institute preclinical antitumor drug discovery screen (NCI screen). The potency of anthrapyrazoles to inhibit purified topoisomerase II was determined. The specificity of drug-induced topoisomerase II pattern of cleavage, one of the cellular determinants of cytotoxicity, was investigated in human c-myc DNA. Using the COMPARE analysis, we found that the most closely related cytotoxic profiles in the NCI screen were between the anthrapyrazoles and mitoxantrone. Among topoisomerase II inhibitors, the cytostatic potency was by decreasing order: mitoxantrone; doxorubicin, which was slightly greater than DuP 941, azatoxin; DuP 937; and amsacrine, which was much greater than VP-16. The potency of mitoxantrone and anthrapyrazoles to generate DNA double-strand breaks, by induction of the topoisomerase II cleavable complexes in nuclear extracts, was in agreement with cytotoxicity. Sequencing of drug-induced topoisomerase II cleavages in c-myc DNA showed a common cleavage pattern for anthrapyrazoles and mitoxantrone. This pattern was different from the patterns obtained with other topoisomerase II inhibitors. At the molecular and cellular levels, anthrapyrazoles are potent topoisomerase II inhibitors closely related to mitoxantrone. These results validate the COMPARE analysis using the NCI screen to predict molecular mechanisms of drug action. Anthrapyrazoles, which are unlikely to produce free radicals, might be useful in the same indications as mitoxantrone, especially for patients with cardiac risks, for pediatric patients, and for patients treated with intensified protocols. JF - Journal of the National Cancer Institute AU - Leteurtre, F AU - Kohlhagen, G AU - Paull, K D AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/17/ PY - 1994 DA - 1994 Aug 17 SP - 1239 EP - 1244 VL - 86 IS - 16 SN - 0027-8874, 0027-8874 KW - Anthraquinones KW - 0 KW - Antineoplastic Agents KW - Pyrazoles KW - Pyrazolones KW - Topoisomerase II Inhibitors KW - losoxantrone KW - 47KPH00809 KW - teloxantrone KW - 96521WL61B KW - Index Medicus KW - United States KW - Drug Screening Assays, Antitumor KW - Base Sequence KW - Tumor Cells, Cultured KW - Humans KW - National Institutes of Health (U.S.) KW - Molecular Sequence Data KW - Pyrazoles -- pharmacology KW - Pyrazoles -- chemistry KW - Anthraquinones -- pharmacology KW - Anthraquinones -- chemistry KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76620052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topoisomerase+II+inhibition+and+cytotoxicity+of+the+anthrapyrazoles+DuP+937+and+DuP+941+%28Losoxantrone%29+in+the+National+Cancer+Institute+preclinical+antitumor+drug+discovery+screen.&rft.au=Leteurtre%2C+F%3BKohlhagen%2C+G%3BPaull%2C+K+D%3BPommier%2C+Y&rft.aulast=Leteurtre&rft.aufirst=F&rft.date=1994-08-17&rft.volume=86&rft.issue=16&rft.spage=1239&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 - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. AN - 76604484; 8040890 AB - In the autumn of 1992, a novel form of chronic, active hepatitis of unknown etiology was discovered in mice at the National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Md. A high incidence of hepatocellular tumors occurred in affected animals. The disease entity was originally identified in A/JCr mice that were untreated controls in a long-term toxicologic study. Our original purpose was to determine the origin and etiology of the chronic hepatitis and to quantify its association with hepatocellular tumors in mice of low liver tumor incidence strains. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. Hepatic histopathology of many strains of mice and rats, as well as guinea pigs and Syrian hamsters, in our research and animal production facilities was reviewed. Steiner's modification of the Warthin-Starry stain and transmission electron microscopy were used to identify bacteria in the liver. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. Bacteria were cultivated on blood agar plates maintained under anaerobic or microaerophilic conditions and characterized morphologically, biochemically, and by 16S rRNA sequence. We report here the isolation of a new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice (and possibly the intrahepatic biliary system and large bowel), causing a morphologically distinctive pattern of chronic, active hepatitis and associated with a high incidence of hepatocellular neoplasms in infected animals. The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter-associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria. Adenocarcinoma of the stomach, the second most prevalent of all human malignancies world-wide, is associated with infection at an early age with Helicobacter pylori. Infection leads to several distinctive forms of gastritis, including chronic atrophic gastritis, which is a precursor of adenocarcinoma. H. hepaticus infection in mice constitutes the only other parallel association between a persistent bacterial infection and tumor development known to exist naturally. Study of the H. hepaticus syndrome of chronic active hepatitis and liver tumors in mice may yield insights into the role of H. pylori in human stomach cancer and gastric lymphoma. JF - Journal of the National Cancer Institute AU - Ward, J M AU - Fox, J G AU - Anver, M R AU - Haines, D C AU - George, C V AU - Collins, M J AU - Gorelick, P L AU - Nagashima, K AU - Gonda, M A AU - Gilden, R V AD - Office of Laboratory Animal Science, NCI-FCRDC, MD 21702-1201. Y1 - 1994/08/17/ PY - 1994 DA - 1994 Aug 17 SP - 1222 EP - 1227 VL - 86 IS - 16 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Animals KW - Adenoma, Liver Cell -- veterinary KW - Mice KW - Adenoma, Liver Cell -- microbiology KW - Rats KW - Carcinoma, Hepatocellular -- microbiology KW - Carcinoma, Hepatocellular -- veterinary KW - Rats, Inbred Strains -- microbiology KW - Mesocricetus -- microbiology KW - Chronic Disease KW - Guinea Pigs -- microbiology KW - Female KW - Male KW - Cricetinae KW - Liver Neoplasms -- microbiology KW - Liver Neoplasms -- pathology KW - Hepatitis, Animal -- pathology KW - Liver Neoplasms -- veterinary KW - Helicobacter Infections -- veterinary KW - Hepatitis, Animal -- microbiology KW - Helicobacter Infections -- complications KW - Mice, Inbred Strains -- microbiology KW - Rodent Diseases -- pathology KW - Rodent Diseases -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76604484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+active+hepatitis+and+associated+liver+tumors+in+mice+caused+by+a+persistent+bacterial+infection+with+a+novel+Helicobacter+species.&rft.au=Ward%2C+J+M%3BFox%2C+J+G%3BAnver%2C+M+R%3BHaines%2C+D+C%3BGeorge%2C+C+V%3BCollins%2C+M+J%3BGorelick%2C+P+L%3BNagashima%2C+K%3BGonda%2C+M+A%3BGilden%2C+R+V&rft.aulast=Ward&rft.aufirst=J&rft.date=1994-08-17&rft.volume=86&rft.issue=16&rft.spage=1222&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 - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells. AN - 76650048; 8058738 AB - Gene-expression modulator 91 (GEM91) is a 25-nt antisense oligodeoxynucleotide phosphorothioate complementary to the Gag mRNA of human immunodeficiency virus type 1 (HIV-1). Cellular uptake and intracellular distribution of GEM91 within cells suggest that this oligomer is readily available for antisense activity. GEM91 inhibited HIV-1 replication in a dose-dependent and sequence-specific manner. In a comparative study, 2 microM GEM91 was as effective as 5 microM 3'-azido-3'-deoxythymidine in blocking virus replication during the 28-day treatment of an HIV-1-infected T-cell line. GEM91 also completely inhibited (> 99%) the growth of three different HIV-1 isolates in primary lymphocytes and prevented the cytopathic effect of the virus in primary CD4+ T cells. Similarly, treatment with GEM91 for 3 weeks of HIV-1/BaL-infected primary macrophages blocked virus replication. Based on GEM91 anti-HIV-activity, safety, and pharmacokinetic profile in animals, a clinical trial was started using this compound as an antisense oligonucleotide drug for the treatment of the acquired immunodeficiency syndrome. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lisziewicz, J AU - Sun, D AU - Weichold, F F AU - Thierry, A R AU - Lusso, P AU - Tang, J AU - Gallo, R C AU - Agrawal, S AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/16/ PY - 1994 DA - 1994 Aug 16 SP - 7942 EP - 7946 VL - 91 IS - 17 SN - 0027-8424, 0027-8424 KW - Antigens, CD KW - 0 KW - Antigens, CD4 KW - Antigens, CD8 KW - Antiviral Agents KW - GEM91 KW - Gene Products, gag KW - Oligodeoxyribonucleotides, Antisense KW - Oligonucleotides, Antisense KW - RNA, Messenger KW - Thionucleotides KW - Index Medicus KW - AIDS/HIV KW - Antigens, CD -- biosynthesis KW - Base Sequence KW - Cells, Cultured KW - Kinetics KW - Humans KW - Molecular Sequence Data KW - Biological Transport KW - Flow Cytometry KW - Antigens, CD4 -- biosynthesis KW - Genes, gag KW - Cell Line KW - Antigens, CD8 -- biosynthesis KW - Macrophages -- cytology KW - Thionucleotides -- pharmacokinetics KW - Macrophages -- microbiology KW - RNA, Messenger -- drug effects KW - Thionucleotides -- toxicity KW - HIV-1 -- physiology KW - Lymphocytes -- microbiology KW - Oligonucleotides, Antisense -- toxicity KW - Virus Replication -- drug effects KW - Oligonucleotides, Antisense -- pharmacokinetics KW - Gene Products, gag -- biosynthesis KW - Lymphocytes -- cytology KW - Antiviral Agents -- toxicity KW - HIV-1 -- drug effects KW - Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76650048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antisense+oligodeoxynucleotide+phosphorothioate+complementary+to+Gag+mRNA+blocks+replication+of+human+immunodeficiency+virus+type+1+in+human+peripheral+blood+cells.&rft.au=Lisziewicz%2C+J%3BSun%2C+D%3BWeichold%2C+F+F%3BThierry%2C+A+R%3BLusso%2C+P%3BTang%2C+J%3BGallo%2C+R+C%3BAgrawal%2C+S&rft.aulast=Lisziewicz&rft.aufirst=J&rft.date=1994-08-16&rft.volume=91&rft.issue=17&rft.spage=7942&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 - 1994-09-14 N1 - Date created - 1994-09-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11209-13 [1454800] Nucleic Acids Res. 1992 Nov 11;20(21):5691-8 [1454532] Antisense Res Dev. 1992 Fall;2(3):211-22 [1490072] J Mol Biol. 1993 Jan 20;229(2):382-97 [8429553] Antisense Res Dev. 1992 Winter;2(4):261-6 [1363378] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3860-4 [8483903] Science. 1993 Aug 20;261(5124):1004-12 [8351515] AIDS. 1993 Jun;7(6):769-80 [8363755] Proc Natl Acad Sci U S A. 1978 Jan;75(1):280-4 [75545] Science. 1984 May 4;224(4648):497-500 [6200935] Science. 1984 May 4;224(4648):500-3 [6200936] Proc Natl Acad Sci U S A. 1986 Jun;83(12):4143-6 [3012555] Science. 1986 Jul 11;233(4760):215-9 [3014648] Virology. 1988 Jun;164(2):531-6 [3369091] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7079-83 [3174622] J Virol Methods. 1988 Aug;20(4):309-21 [2460479] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4244-8 [2471199] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6553-6 [2771942] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7790-4 [2682627] J Clin Apher. 1991;6(1):48-53 [1646202] Nucleic Acids Res. 1991 Jun 25;19(12):3359-68 [2062653] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7595-9 [1881900] Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1934-8 [1371886] J Virol. 1992 Jul;66(7):4144-53 [1602537] Pharmacol Ther. 1991 Dec;52(3):365-84 [1668180] AIDS Res Hum Retroviruses. 1992 Sep;8(9):1539-41 [1457197] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fast presynaptic GABAA receptor-mediated Cl- conductance in cultured rat hippocampal neurones. AN - 76882436; 7990035 AB - 1. Hippocampal neurones cultured from the 18-day-old embryonic rat for 3 days to 3 weeks were recorded with Cl(-)-filled patch pipettes. Spontaneous synaptic currents, which reversed at the equilibrium potential for Cl- ions (ECl) and were blocked by the GABAA (gamma-aminobutyric acid) receptor antagonists bicuculline or picrotoxin, were recorded in every culture. At 25 degrees C and -80 mV they decayed with a time constant > or = 20 ms that invariably increased at positive potentials. After 2 weeks, 50-75% of all neurones were GABA immunoreactive. 2. In pairs-recordings, coincident synaptic currents in both cells were either spontaneous or evoked by stimulation of one cell. In the presence of tetrodotoxin and using pipettes containing lidocaine (lignocaine) N-ethyl bromide, coincident spontaneous Cl- transients still occurred in both neurones far more frequently than expected by chance. 3. Holding the potential of one neurone at a positive value reversed the synaptic transients in that cell and, in half of the cells, increased the frequency of coincident events in both cells. 4. In neurones where depolarization increased the frequency of coinciding events and all regenerative current apparent at the soma was abolished, short depolarizing pulses occasionally evoked all-or-none, pre- and postsynaptic currents with matching transmission failures and identical delays in transmission. 5. The results suggest that the same pulse of GABA simultaneously activates GABAA receptor-coupled Cl- channels on both sides of the same synaptic cleft, producing immediate auto-transmission in the absence of collaterals or interneurones. JF - The Journal of physiology AU - Vautrin, J AU - Schaffner, A E AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 53 EP - 63 VL - 479 ( Pt 1) SN - 0022-3751, 0022-3751 KW - Chloride Channels KW - 0 KW - Chlorides KW - Receptors, GABA-A KW - Receptors, Presynaptic KW - Picrotoxin KW - 124-87-8 KW - Tetrodotoxin KW - 4368-28-9 KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Lidocaine KW - 98PI200987 KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - gamma-Aminobutyric Acid -- physiology KW - Chlorides -- metabolism KW - Synaptic Transmission -- physiology KW - Chlorides -- pharmacokinetics KW - Pregnancy KW - Rats KW - Synapses -- physiology KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Picrotoxin -- pharmacology KW - Interneurons -- physiology KW - Lidocaine -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Female KW - Receptors, Presynaptic -- analysis KW - Receptors, GABA-A -- physiology KW - Hippocampus -- physiology KW - Neurons -- chemistry KW - Neurons -- cytology KW - Hippocampus -- cytology KW - Receptors, Presynaptic -- physiology KW - Neurons -- physiology KW - Chloride Channels -- physiology KW - Receptors, GABA-A -- analysis KW - Hippocampus -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76882436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=Fast+presynaptic+GABAA+receptor-mediated+Cl-+conductance+in+cultured+rat+hippocampal+neurones.&rft.au=Vautrin%2C+J%3BSchaffner%2C+A+E%3BBarker%2C+J+L&rft.aulast=Vautrin&rft.aufirst=J&rft.date=1994-08-15&rft.volume=479+%28+Pt+1%29&rft.issue=&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-11 N1 - Date created - 1995-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurosci. 1989 May;9(5):1516-22 [2542477] Synapse. 1988;2(6):606-13 [2905537] J Physiol. 1990 Sep;428:707-22 [2231430] J Physiol. 1990 Nov;430:213-49 [1707966] J Neurophysiol. 1991 Apr;65(4):761-70 [1646871] Neuroscience. 1991;41(1):71-88 [2057065] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7834-8 [1679238] Neurosci Lett. 1992 Apr 13;138(1):67-71 [1407669] Nature. 1992 Oct 22;359(6397):733-6 [1436036] Science. 1993 Jan 22;259(5094):531-4 [8380942] Brain Res Dev Brain Res. 1993 Apr 16;72(2):265-76 [8485849] Trends Neurosci. 1993 Jun;16(6):222-7 [7688163] Hippocampus. 1993 Jan;3(1):93-101 [8395950] J Neurophysiol. 1993 Sep;70(3):976-84 [7901347] J Physiol. 1993 Aug;468:177-200 [7504726] J Neurosci. 1994 Mar;14(3 Pt 2):1775-88 [8126570] J Physiol. 1952 May;117(1):109-28 [14946732] J Physiol. 1955 May 27;128(2):396-411 [14392617] Exp Cell Res. 1958;14(Suppl 5):294-322 [13586296] Nature. 1962 Mar 3;193:899-900 [14449017] J Physiol. 1960 Jan;150:134-44 [13800900] Brain Res. 1970 Oct 13;23(2):255-8 [5476767] J Cell Sci. 1970 Jul;7(1):91-123 [5476864] Brain Res. 1972 Dec 24;48:355-60 [4645210] J Neurosci. 1987 Jun;7(6):1866-86 [3037041] Eur J Pharmacol. 1988 Jun 10;150(3):277-86 [2843383] J Physiol. 1988 Jun;400:659-76 [3418542] J Physiol. 1988 Sep;403:41-55 [2908121] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Staurosporine inhibits phorbol 12-myristate 13-acetate- and insulin-stimulated translocation of GLUT1 and GLUT4 glucose transporters in rat adipose cells. AN - 76667924; 8068015 AB - Staurosporine, a widely used protein kinase C inhibitor, completely inhibited both phorbol 12-myristate 13-acetate (PMA)- and insulin-stimulated glucose transport activity in isolated rat adipocytes. The inhibition was non-competitive and was attributed to a blockade of the PMA- and insulin-induced translocation of both GLUT1 and GLUT4 glucose transporters. The PMA-stimulated glucose transport activity was more sensitive to inhibition by staurosporine than was insulin-stimulated transport activity (PMA, IC50 = 1.1 +/- 0.1 microM; insulin, IC50 = 6.4 +/- 0.7 microM; P < 0.05, n = 3). At 1 microM staurosporine the insulin-sensitivity was decreased, i.e. EC50 increased from 0.12 nM to 5.4 nM, but the maximum response to insulin and the time course for stimulation were unaffected. At 6 microM staurosporine the insulin-sensitivity was further decreased, the maximal stimulation was decreased by 25%, and the apparent half-time for stimulation was extended from 2.5 min in control cells to 9.4 min. Staurosporine (30 microM) was able to block insulin's ability to stimulate glucose transport, whether added before or after insulin, by a mechanism that did not alter the rate of GLUT4 internalization. In intact adipose cells, staurosporine (30 microM) induced a slight (30%) decrease in the maximal insulin-induced receptor autophosphorylation and a similar decrease in the tyrosine phosphorylation of pp60 and pp160 (insulin-receptor substrate-1: 'IRS-1'), but was without effect on insulin binding to its receptor. Conversely, staurosporine induced a concentration-dependent inhibition of the constitutively tyrosine-phosphorylated (pp120) protein and of an insulin-stimulated protein pp53 in the cytosol. The locus of staurosporine's action appears to be distal from the initial insulin-receptor signalling, at a step that regulates the specific translocation of the glucose transporters to the plasma membranes. JF - The Biochemical journal AU - Nishimura, H AU - Simpson, I A AD - Metabolism and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 271 EP - 277 VL - 302 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Alkaloids KW - 0 KW - Glucose Transporter Type 1 KW - Glucose Transporter Type 4 KW - Insulin KW - Insulin Antagonists KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - Slc2a1 protein, rat KW - Slc2a4 protein, rat KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Animals KW - Protein Kinase C -- antagonists & inhibitors KW - Blotting, Western KW - Biological Transport KW - Drug Antagonism KW - Male KW - Insulin Antagonists -- pharmacology KW - Monosaccharide Transport Proteins -- antagonists & inhibitors KW - Monosaccharide Transport Proteins -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Insulin -- pharmacology KW - Adipocytes -- metabolism KW - Adipocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76667924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Staurosporine+inhibits+phorbol+12-myristate+13-acetate-+and+insulin-stimulated+translocation+of+GLUT1+and+GLUT4+glucose+transporters+in+rat+adipose+cells.&rft.au=Nishimura%2C+H%3BSimpson%2C+I+A&rft.aulast=Nishimura&rft.aufirst=H&rft.date=1994-08-15&rft.volume=302+%28+Pt+1%29&rft.issue=&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-21 N1 - Date created - 1994-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1971 Oct 25;246(20):6210-6 [5127426] J Biol Chem. 1993 Dec 15;268(35):26422-7 [8253768] J Biol Chem. 1984 Jul 25;259(14):8758-63 [6086611] J Biol Chem. 1985 Mar 10;260(5):2646-52 [3882699] Biochem Biophys Res Commun. 1985 Apr 30;128(2):824-32 [3158314] Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402 [3457562] J Biol Chem. 1987 Mar 15;262(8):3633-9 [3546313] J Biol Chem. 1987 Jun 5;262(16):7796-801 [3108259] Int J Biochem. 1987;19(3):259-65 [3297842] J Biol Chem. 1987 Jul 15;262(20):9872-6 [3298262] Biochim Biophys Acta. 1987 Aug 7;902(1):154-8 [3300778] FEBS Lett. 1987 Aug 17;220(2):311-8 [3038619] J Antibiot (Tokyo). 1987 May;40(5):706-8 [3038816] Endocrinology. 1988 Jul;123(1):296-304 [2838257] Biochem Biophys Res Commun. 1988 Dec 30;157(3):955-62 [2974700] J Biol Chem. 1989 Mar 5;264(7):3859-63 [2537294] Biochem J. 1989 Feb 15;258(1):141-6 [2649084] Trends Pharmacol Sci. 1989 Jun;10(6):218-20 [2672462] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1052-6 [2105494] Curr Opin Cell Biol. 1990 Apr;2(2):192-7 [2194521] Metabolism. 1990 Nov;39(11):1170-9 [2233279] Nature. 1990 Nov 22;348(6299):302-8 [2123524] J Biol Chem. 1991 Jan 5;266(1):261-7 [1985898] J Biol Chem. 1991 Jun 15;266(17):10946-52 [2040611] Eur J Biochem. 1991 Aug 1;199(3):723-8 [1651243] Biochem J. 1991 Aug 15;278 ( Pt 1):235-41 [1883332] J Biol Chem. 1991 Nov 25;266(33):22260-5 [1939248] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11500-4 [1763064] Biochem J. 1992 Feb 1;281 ( Pt 3):809-17 [1536656] FEBS Lett. 1992 Mar 23;300(1):93-6 [1547896] Cell Signal. 1992 Mar;4(2):133-43 [1616820] Nature. 1992 Jul 30;358(6385):417-21 [1322500] J Biol Chem. 1992 Sep 5;267(25):17710-5 [1517217] Cell. 1992 Oct 16;71(2):335-42 [1330321] Biochem J. 1992 Nov 15;288 ( Pt 1):325-30 [1445278] J Biol Chem. 1993 Mar 5;268(7):5272-8 [7680348] J Biol Chem. 1993 Mar 25;268(9):6463-9 [8454619] Trends Biochem Sci. 1993 Apr;18(4):128-31 [8388132] J Biol Chem. 1993 Aug 25;268(24):17820-9 [8349666] J Biol Chem. 1993 Sep 15;268(26):19246-53 [7690030] Science. 1993 Sep 17;261(5128):1591-4 [8372354] J Biol Chem. 1982 Dec 10;257(23):14306-10 [6754726] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regio- and stereo-selective metabolism of phenanthrene by twelve cDNA-expressed human, rodent, and rabbit cytochromes P-450. AN - 76666604; 8062229 AB - The regio- and stereoselective metabolism of phenanthrene (PA) by seven cDNA-expressed human and five rodent and rabbit cytochromes P-450 has been examined using reverse-phase and chiral stationary phase high-pressure liquid chromatography (HPLC). Turnover numbers ranged from 0.2 to 55 nmol/min per nmol. Using vaccinia virus expression of P-450 enzymes in Hep G2 cells, m1A1 and m1A2 were found to be the most active P-450s. Of the human P-450s, 1A2 and 2B6 have the highest activity and 2C9 has moderate activity. Using cytochrome P-450s expressed in a lymphoblastoid cell line in presence of epoxide hydrolase (EH), human 1A1 had approximately twice the activity of human 1A2. Regioselectivities for PA metabolism were found to be both isozyme and species-dependent. Stereochemical analysis revealed that the P-450s 1A1, m1A1, m1A2, r2A1, r2B1, PB- and 3MC-treated rat liver microsomes preferentially formed 3R,4R-diol enantiomer (88-97%), whereas rabbit 4B formed the 3S,4S-diol enantiomer (72%). Eleven P-450s, 3MC and PB microsomes preferentially formed 1R,2R-diol enantiomer (80-96%). This is the same stereochemistry as the precursors to some diol epoxides that are potent carcinogens. JF - Cancer letters AU - Shou, M AU - Korzekwa, K R AU - Krausz, K W AU - Crespi, C L AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 305 EP - 313 VL - 83 IS - 1-2 SN - 0304-3835, 0304-3835 KW - DNA, Complementary KW - 0 KW - Phenanthrenes KW - Recombinant Proteins KW - phenanthrene KW - 448J8E5BST KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - In Vitro Techniques KW - Liver -- metabolism KW - Rabbits KW - Mice KW - Substrate Specificity KW - Phenanthrenes -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76666604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Regio-+and+stereo-selective+metabolism+of+phenanthrene+by+twelve+cDNA-expressed+human%2C+rodent%2C+and+rabbit+cytochromes+P-450.&rft.au=Shou%2C+M%3BKorzekwa%2C+K+R%3BKrausz%2C+K+W%3BCrespi%2C+C+L%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1994-08-15&rft.volume=83&rft.issue=1-2&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attributable risk: advantages of a broad definition of exposure. AN - 76659428; 8059765 AB - Classification of exposure into two levels--one consisting exclusively of unexposed individuals and the other consisting of exposed and perhaps unexposed ones--yields an unbiased estimate of attributable risk when misclassification is nondifferential. The authors advocate, therefore, the use of a broad definition of exposure when estimating attributable risk. Based on this idea, they justify a simple and robust method for estimating the overall attributable risk from several exposures that is based on a division of subjects into two groups, a baseline consisting of those unexposed to all exposures and everyone else. JF - American journal of epidemiology AU - Wacholder, S AU - Benichou, J AU - Heineman, E F AU - Hartge, P AU - Hoover, R N AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 303 EP - 309 VL - 140 IS - 4 SN - 0002-9262, 0002-9262 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Bias (Epidemiology) KW - Likelihood Functions KW - Mesothelioma -- epidemiology KW - Occupational Exposure -- classification KW - Mesothelioma -- classification KW - Mesothelioma -- chemically induced KW - Asbestos -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76659428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Attributable+risk%3A+advantages+of+a+broad+definition+of+exposure.&rft.au=Wacholder%2C+S%3BBenichou%2C+J%3BHeineman%2C+E+F%3BHartge%2C+P%3BHoover%2C+R+N&rft.aulast=Wacholder&rft.aufirst=S&rft.date=1994-08-15&rft.volume=140&rft.issue=4&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Am J Epidemiol 1994 Oct 1;140(7):668 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Invited commentary: lung cancer and exposure to residential radon. AN - 76656390; 8059767 JF - American journal of epidemiology AU - Lubin, J H AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20852. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 323 EP - 332 VL - 140 IS - 4 SN - 0002-9262, 0002-9262 KW - Air Pollutants, Occupational KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Bias (Epidemiology) KW - Research Design KW - Air Pollutants, Occupational -- adverse effects KW - Radon -- adverse effects KW - Occupational Diseases -- chemically induced KW - Air Pollution, Radioactive -- adverse effects KW - Population Surveillance KW - Air Pollution, Indoor -- adverse effects KW - Air Pollution, Indoor -- analysis KW - Lung Neoplasms -- epidemiology KW - Air Pollutants, Occupational -- analysis KW - Radon -- analysis KW - Occupational Diseases -- epidemiology KW - Lung Neoplasms -- chemically induced KW - Mining KW - Air Pollution, Radioactive -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76656390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Invited+commentary%3A+lung+cancer+and+exposure+to+residential+radon.&rft.au=Lubin%2C+J+H&rft.aulast=Lubin&rft.aufirst=J&rft.date=1994-08-15&rft.volume=140&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Am J Epidemiol. 1994 Aug 15;140(4):310-22 [8059766] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The regulatory element 3' to the A gamma-globin gene binds to the nuclear matrix and interacts with special A-T-rich binding protein 1 (SATB1), an SAR/MAR-associating region DNA binding protein. AN - 76631121; 8049444 AB - A cis-acting DNA regulatory element 3' to the A gamma-globin gene contains eight distinct regions of DNA-protein interaction distributed over 750 bp of DNA. The sequences of two foot-printed regions (sites I and IV) are A-T rich and generate a highly retarded complex on gel shift analysis with nuclear extract from human erythroleukemia (K562) cells. We have purified a 98-kD protein that reproduces this gel shift. Tryptic cleavage and peptide sequence analysis demonstrated that the 98-kD protein is identical to a recently cloned protein, special A-T-rich binding protein 1 (SATB1), that binds selectively to nuclear matrix/scaffold-associated regions of DNA (MARs/SARs). We have shown by functional analysis that the 3' A gamma regulatory element associates with the nuclear matrix. SATB1 mRNA was identified in K562 cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated its transcript in several other hematopoietic lines. Antisera to SATB1 caused ablation of the gel shift complex generated by both the crude nuclear extract and the purified 98-kD protein with the site I oligonucleotide. Furthermore, oligonucleotides that bind SATB1 inhibited formation of the site I gel shift complex when added as excess unlabeled competitor. An immunoblot analysis of the site I gel shift complex documented the presence of SATB1. Binding of SATB1 to two sites within the 3' A gamma regulatory element and its MAR/SAR activity suggests that this element may influence gene expression through interaction with the nuclear matrix. JF - Blood AU - Cunningham, J M AU - Purucker, M E AU - Jane, S M AU - Safer, B AU - Vanin, E F AU - Ney, P A AU - Lowrey, C H AU - Nienhuis, A W AD - Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 1298 EP - 1308 VL - 84 IS - 4 SN - 0006-4971, 0006-4971 KW - DNA-Binding Proteins KW - 0 KW - Matrix Attachment Region Binding Proteins KW - Oligodeoxyribonucleotides KW - Peptide Fragments KW - SATB1 protein, human KW - Globins KW - 9004-22-2 KW - Abridged Index Medicus KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Peptide Fragments -- isolation & purification KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis KW - Base Sequence KW - Leukemia, Erythroblastic, Acute KW - Peptide Fragments -- chemistry KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Cell Line KW - Regulatory Sequences, Nucleic Acid KW - Nuclear Matrix -- metabolism KW - Globins -- genetics KW - Globins -- metabolism KW - DNA-Binding Proteins -- isolation & purification KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76631121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+regulatory+element+3%27+to+the+A+gamma-globin+gene+binds+to+the+nuclear+matrix+and+interacts+with+special+A-T-rich+binding+protein+1+%28SATB1%29%2C+an+SAR%2FMAR-associating+region+DNA+binding+protein.&rft.au=Cunningham%2C+J+M%3BPurucker%2C+M+E%3BJane%2C+S+M%3BSafer%2C+B%3BVanin%2C+E+F%3BNey%2C+P+A%3BLowrey%2C+C+H%3BNienhuis%2C+A+W&rft.aulast=Cunningham&rft.aufirst=J&rft.date=1994-08-15&rft.volume=84&rft.issue=4&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-07 N1 - Date created - 1994-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelotype of endometrial carcinoma. AN - 76628737; 8044774 AB - An allelotype analysis of endometrial carcinoma was undertaken to identify chromosomal loci that are relevant to this tumor type. A total of 70 highly polymorphic microsatellite markers, distributed among all nonacrocentric chromosome arms, were examined for evidence of loss of heterozygosity or allelic imbalance in DNA samples from matched normal and tumor tissues. An average of 21 informative tumor cases were obtained for each marker. Allelic deletions or imbalance were observed on 31 of 41 chromosome arms with no marker showing an allelic loss ratio of greater than 33%. Those chromosome arms most frequently involved were 3p, 8p, 9p, 14q, 16q and 18q. There was a strong correlation between loss of heterozygosity on chromosome 14q and death from disease. These data indicate that the molecular genetic character of endometrial carcinoma is complex and that a relatively large number of different chromosomal loci are likely to play a role in the etiology and progression of this tumor type. JF - Cancer research AU - Fujino, T AU - Risinger, J I AU - Collins, N K AU - Liu, F S AU - Nishii, H AU - Takahashi, H AU - Westphal, E M AU - Barrett, J C AU - Sasaki, H AU - Kohler, M F AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 4294 EP - 4298 VL - 54 IS - 16 SN - 0008-5472, 0008-5472 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Genotype KW - Chromosomes, Human, Pair 18 KW - Chromosomes, Human, Pair 3 KW - Chromosomes, Human, Pair 16 KW - Humans KW - Prognosis KW - Chromosomes, Human, Pair 8 KW - Chromosomes, Human, Pair 9 KW - Chromosomes, Human, Pair 14 KW - Female KW - Endometrial Neoplasms -- pathology KW - Endometrial Neoplasms -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76628737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allelotype+of+endometrial+carcinoma.&rft.au=Fujino%2C+T%3BRisinger%2C+J+I%3BCollins%2C+N+K%3BLiu%2C+F+S%3BNishii%2C+H%3BTakahashi%2C+H%3BWestphal%2C+E+M%3BBarrett%2C+J+C%3BSasaki%2C+H%3BKohler%2C+M+F&rft.aulast=Fujino&rft.aufirst=T&rft.date=1994-08-15&rft.volume=54&rft.issue=16&rft.spage=4294&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 - 1994-08-31 N1 - Date created - 1994-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radioimmunotherapy of nude mice bearing a human interleukin 2 receptor alpha-expressing lymphoma utilizing the alpha-emitting radionuclide-conjugated monoclonal antibody 212Bi-anti-Tac. AN - 76625985; 8044783 AB - The efficacy, specificity, and toxicity of bismuth (212Bi) alpha particle-mediated radioimmunotherapy was evaluated in nude mice bearing a murine lymphoma transfected with the human CD25 [human Tac; interleukin 2 receptor alpha (IL-2R alpha)] gene. The therapeutic agent used was the tumor-specific humanized monoclonal antibody anti-Tac conjugated to 212Bi. The human IL-2R alpha-expressing cell line was produced by transfecting the gene encoding human Tac into the murine plasmacytoma cell line SP2/0. The resulting cell line, SP2/Tac, expressed approximately 18,000 human IL-2R alpha molecules/cell. Following s.c. or i.p. injection of 2 x 10(6) SP2/Tac cells into nude mice, rapidly growing tumors developed in all animals after a mean of 10 and 13 days, respectively. The bifunctional chelate cyclohexyldiethylenetriaminepentaacetic acid was used to couple 212Bi to the humanized anti-Tac monoclonal antibody. This immunoconjugate was shown to be stable in vivo. Specifically, in pharmacokinetic studies in nude mice, the blood clearance patterns of i.v. administered 205/206Bi-anti-Tac and coinjected 125I-anti-Tac were comparable. The toxicity and therapeutic efficacy of 212Bi-anti-Tac were evaluated in nude mouse ascites or solid tumor models wherein SP2/Tac cells were administered either i.p. or s.c., respectively. The i.p. administration of 212Bi-anti-Tac, 3 days following i.p. tumor inoculation, led to a dose-dependent, significant prolongation of tumor-free survival. Doses of 150 or 200 microCi prevented tumor occurrence in 75% (95% confidence interval, 41-93%) of the animals. In the second model, i.v. treatment with 212Bi-anti-Tac 3 days following s.c. tumor inoculation also resulted in a prolongation of the period before tumor development. However, prevention of tumor occurrence decreased to 30% (95% confidence interval, 11-60%). In both the i.p. and s.c. tumor trials, 212Bi-anti-Tac was significantly more effective for i.p. (P2 = 0.0128 50/100 microCi 212Bi-anti-Tac versus 50/100 microCi Mik beta; P2 = 0.0142 150/200 microCi anti-Tac versus 150/200 microCi Mik beta) and for s.c. tumors (P2 = 0.0018 100 microCi anti-Tac versus 100 microCi Mik beta; P2 = 0.0042 200 microCi anti-Tac versus 200 microCi Mik beta 1) than the control antibody Mik beta 1 coupled to 212Bi at comparable dose levels. In contrast to the efficacy observed in the adjuvant setting, therapy of large, established s.c. SP-2/Tac-expressing tumors with i.v. administered 212Bi-anti-Tac (at doses up to 200 microCi/animal) failed to induce tumor regression.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Hartmann, F AU - Horak, E M AU - Garmestani, K AU - Wu, C AU - Brechbiel, M W AU - Kozak, R W AU - Tso, J AU - Kosteiny, S A AU - Gansow, O A AU - Nelson, D L AD - Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/08/15/ PY - 1994 DA - 1994 Aug 15 SP - 4362 EP - 4370 VL - 54 IS - 16 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Radioisotopes KW - Receptors, Interleukin-2 KW - Bismuth KW - U015TT5I8H KW - Index Medicus KW - AIDS/HIV KW - Drug Screening Assays, Antitumor KW - Animals KW - Radiotherapy Dosage KW - Humans KW - Dose-Response Relationship, Immunologic KW - Mice, Nude KW - Mice KW - Tissue Distribution KW - Antibodies, Monoclonal -- metabolism KW - Leukemia-Lymphoma, Adult T-Cell -- metabolism KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Receptors, Interleukin-2 -- metabolism KW - Radioisotopes -- metabolism KW - Bismuth -- therapeutic use KW - Radioisotopes -- adverse effects KW - Leukemia-Lymphoma, Adult T-Cell -- radiotherapy KW - Radioimmunotherapy -- adverse effects KW - Radioisotopes -- therapeutic use KW - Bismuth -- adverse effects KW - Leukemia-Lymphoma, Adult T-Cell -- immunology KW - Antibodies, Monoclonal -- adverse effects KW - Bismuth -- metabolism KW - Radioimmunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76625985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Radioimmunotherapy+of+nude+mice+bearing+a+human+interleukin+2+receptor+alpha-expressing+lymphoma+utilizing+the+alpha-emitting+radionuclide-conjugated+monoclonal+antibody+212Bi-anti-Tac.&rft.au=Hartmann%2C+F%3BHorak%2C+E+M%3BGarmestani%2C+K%3BWu%2C+C%3BBrechbiel%2C+M+W%3BKozak%2C+R+W%3BTso%2C+J%3BKosteiny%2C+S+A%3BGansow%2C+O+A%3BNelson%2C+D+L&rft.aulast=Hartmann&rft.aufirst=F&rft.date=1994-08-15&rft.volume=54&rft.issue=16&rft.spage=4362&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 - 1994-08-31 N1 - Date created - 1994-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic component of lung cancer: cohort study of twins. AN - 76651449; 7914565 AB - Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15,924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur. JF - Lancet (London, England) AU - Braun, M M AU - Caporaso, N E AU - Page, W F AU - Hoover, R N AD - Epidemiology and Biostatistics Program, National Cancer Institute, National Institutes of Health, Rockville, MD 20852. Y1 - 1994/08/13/ PY - 1994 DA - 1994 Aug 13 SP - 440 EP - 443 VL - 344 IS - 8920 SN - 0140-6736, 0140-6736 KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Age Factors KW - Humans KW - Smoking -- adverse effects KW - Predictive Value of Tests KW - Twins, Dizygotic KW - Smoking -- epidemiology KW - Mass Screening KW - Survival Rate KW - Twins, Monozygotic KW - Military Personnel KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Registries KW - Lung Diseases -- genetics KW - Diseases in Twins -- epidemiology KW - Lung Diseases -- mortality KW - Diseases in Twins -- genetics KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76651449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Genetic+component+of+lung+cancer%3A+cohort+study+of+twins.&rft.au=Braun%2C+M+M%3BCaporaso%2C+N+E%3BPage%2C+W+F%3BHoover%2C+R+N&rft.aulast=Braun&rft.aufirst=M&rft.date=1994-08-13&rft.volume=344&rft.issue=8920&rft.spage=440&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - -mu opiate receptor. Charged transmembrane domain amino acids are critical for agonist recognition and intrinsic activity. AN - 76637424; 8051154 AB - The mu opiate receptor is a principal brain site for activities of morphine, other opiate drugs, and opioid peptides in modulating pain and altering mood. Recent cloning of cDNAs encoding rat and human mu receptors reveals charged amino acid residues within putative transmembrane domains (TMs) II, III, and VI, a substantial N-terminal extracellular domain, and a C-terminal intracellular domain. Deletion of 64 N-terminal amino acids produced little effect on receptor function (Wang, J.B., Imai, Y., Eppler, C.M., Gregor, P., Spivak, C.E., and Uhl, G.R. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10230-10234). Further deletion of 33 C-terminal amino acids yielded a receptor at which morphine, but not the substituted enkephalin DAMGO ([D-Ala2,MePhe4,Glyol5]enkephalin), inhibited adenylate cyclase. Alanine substitution for each charged TM residue in the N-terminally deleted receptor reduced affinities for morphine, DAMGO, and the opiate antagonist naloxone. Replacement of TM II Asp114 with asparagine or glutamic acid increased mu receptor affinity for naloxone. TM II and TM III glutamic acid substitutions for Asp114 and Asp147 reduced agonist binding affinities but allowed full inhibition of adenylate cyclase at high agonist concentrations. TM VI histidine substitution with alanine yielded a receptor that produced almost twice the cyclase inhibition displayed by the wild type receptor in parallel transient expression assays. These findings underscore the importance of charged residues in TM II, III, and VI for different receptor functions and the modest involvement of extensive portions of N- and C-terminal receptor domains in these processes. JF - The Journal of biological chemistry AU - Surratt, C K AU - Johnson, P S AU - Moriwaki, A AU - Seidleck, B K AU - Blaschak, C J AU - Wang, J B AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1994/08/12/ PY - 1994 DA - 1994 Aug 12 SP - 20548 EP - 20553 VL - 269 IS - 32 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Enkephalins KW - Receptors, Opioid, mu KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Naloxone -- pharmacology KW - Animals KW - Enkephalins -- pharmacology KW - Cells, Cultured KW - Humans KW - Cell Membrane -- metabolism KW - Structure-Activity Relationship KW - Sequence Deletion KW - Morphine -- pharmacology KW - Receptors, Opioid, mu -- drug effects KW - Receptors, Opioid, mu -- chemistry KW - Amino Acids -- metabolism KW - Receptors, Opioid, mu -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76637424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=-mu+opiate+receptor.+Charged+transmembrane+domain+amino+acids+are+critical+for+agonist+recognition+and+intrinsic+activity.&rft.au=Surratt%2C+C+K%3BJohnson%2C+P+S%3BMoriwaki%2C+A%3BSeidleck%2C+B+K%3BBlaschak%2C+C+J%3BWang%2C+J+B%3BUhl%2C+G+R&rft.aulast=Surratt&rft.aufirst=C&rft.date=1994-08-12&rft.volume=269&rft.issue=32&rft.spage=20548&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 - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of a multifunctional protein, with mRNA 5' cap-specific (nucleoside-2'-O-)-methyltransferase and 3'-adenylyltransferase stimulatory activities, encoded by vaccinia virus. AN - 76631419; 8051170 AB - The vaccinia virus-encoded protein VP39 is a poly(A) polymerase subunit that stimulates the formation of long poly(A) tails as well as a cap-specific mRNA (nucleoside-2'-O-)-methyltransferase. We have carried out mutagenesis studies aimed at locating regions of VP39 which are important for these activities. The open reading frame encoding VP39 was expressed in Escherichia coli as a glutathione S-transferase fusion protein. The affinity-purified protein had both mRNA modification activities, before and after removal of the glutathione S-transferase domain. Truncation, charge cluster-->Ala scanning, and Cys-->Ser substitution mutations of VP39 were made, and the proteins were synthesized, purified, and analyzed. Deletion of the RNA binding domain, experimentally localized within the carboxyl-terminal 112 amino acids, resulted in the loss of both mRNA modification activities. Eleven of the 21 charge cluster-->Ala mutated proteins had low to nondetectable methyltransferase activity. Four of those 11 also lacked adenylyl-transferase stimulatory function, whereas the remainder had amino acid substitutions that selectively affected methyltransferase activity. However, no mutated proteins lacking adenylyltransferase stimulatory function but possessing methyltransferase activity were isolated by the procedures used. Neither of the 2 cysteine residues in VP39 was necessary for either mRNA modification activity. JF - The Journal of biological chemistry AU - Schnierle, B S AU - Gershon, P D AU - Moss, B AD - Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08/12/ PY - 1994 DA - 1994 Aug 12 SP - 20700 EP - 20706 VL - 269 IS - 32 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - VP39 protein, Vaccinia virus KW - Viral Proteins KW - Methyltransferases KW - EC 2.1.1.- KW - cap I RNA (nucleoside-2'-)methyltransferase KW - cap II RNA(nucleoside-2'-)methyltransferase KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Polynucleotide Adenylyltransferase KW - EC 2.7.7.19 KW - Nucleotidases KW - EC 3.1.3.- KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Chromatography, Affinity KW - Glutathione Transferase -- metabolism KW - Recombinant Fusion Proteins -- isolation & purification KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Viral Proteins -- genetics KW - Vaccinia virus -- genetics KW - Polynucleotide Adenylyltransferase -- metabolism KW - Nucleotidases -- metabolism KW - DNA Mutational Analysis KW - Vaccinia virus -- metabolism KW - Methyltransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76631419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutational+analysis+of+a+multifunctional+protein%2C+with+mRNA+5%27+cap-specific+%28nucleoside-2%27-O-%29-methyltransferase+and+3%27-adenylyltransferase+stimulatory+activities%2C+encoded+by+vaccinia+virus.&rft.au=Schnierle%2C+B+S%3BGershon%2C+P+D%3BMoss%2C+B&rft.aulast=Schnierle&rft.aufirst=B&rft.date=1994-08-12&rft.volume=269&rft.issue=32&rft.spage=20700&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 - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Response of repair-competent and repair-deficient Escherichia coli to three O6-substituted guanines and involvement of methyl-directed mismatch repair in the processing of O6-methylguanine residues. AN - 76620300; 8049220 AB - Plasmids containing a site-specifically incorporated O6-methyl- (m6G), O6-ethyl- (e6G), or O6-benzylguanine (b6G) within the ATG initiation codon of the lacZ' gene were used to transform Escherichia coli that were repair proficient or deficient in one or both of the E. coli O6-alkylguanine-DNA alkyltransferases, the uvr(ABC) excision repair system, the recA-mediated recombination system, or the methylation-directed mismatch repair system. Colonies were scored phenotypically for adduct-induced mutations. With plasmids containing either e6G or b6G, the frequency of adduct-induced mutation was low and independent of the repair proficiency of the strain transformed. Plasmids containing an m6G residue elicited similar responses in all but the mismatch repair-deficient strain. The generally low mutagenicity of all the O6-substituted guanines was interpreted as reflecting an adduct-induced arrest of replication of the modified strand while the unmodified complementary strand was replicated normally. Studies of the involvement of mismatch repair in m6G mutagenesis showed that m6G:T base pairs were more readily processed than m6G:C base pairs, indicating that mismatch repair involving m6G residues occurs after replication. These data support a model in which the E. coli methylation-directed mismatch repair system diverts plasmids containing promutagenic m6G:T base pairs into replication-arrested complexes providing another line of defense against O6-methylguanine mutagenicity in addition to O6-alkylguanine-DNA alkyltransferase repair and excision repair mechanisms. JF - Biochemistry AU - Pauly, G T AU - Hughes, S H AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/08/09/ PY - 1994 DA - 1994 Aug 09 SP - 9169 EP - 9177 VL - 33 IS - 31 SN - 0006-2960, 0006-2960 KW - lacZ KW - recA KW - uvrA KW - uvrB KW - uvrC KW - Codon KW - 0 KW - O(6)-benzylguanine KW - 01KC87F8FE KW - 6-ethylguanine KW - 51866-19-4 KW - Guanine KW - 5Z93L87A1R KW - O-(6)-methylguanine KW - 9B710FV2AE KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Base Sequence KW - Models, Genetic KW - Molecular Sequence Data KW - Plasmids KW - Methyltransferases -- genetics KW - DNA Repair -- genetics KW - Genes, Bacterial KW - Escherichia coli -- genetics KW - Methyltransferases -- metabolism KW - Guanine -- analogs & derivatives KW - Guanine -- metabolism KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76620300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Response+of+repair-competent+and+repair-deficient+Escherichia+coli+to+three+O6-substituted+guanines+and+involvement+of+methyl-directed+mismatch+repair+in+the+processing+of+O6-methylguanine+residues.&rft.au=Pauly%2C+G+T%3BHughes%2C+S+H%3BMoschel%2C+R+C&rft.aulast=Pauly&rft.aufirst=G&rft.date=1994-08-09&rft.volume=33&rft.issue=31&rft.spage=9169&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-08 N1 - Date created - 1994-09-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - lacZ; recA; uvrA; uvrB; uvrC N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. AN - 76592443; 8028037 AB - Studies of human tumor-infiltrating lymphocytes (TILs) derived from patients with a variety of histologic types of cancer have demonstrated that cellular immune reactions against established malignancy exist in humans. We report the results of using autologous TILs plus high-dose bolus interleukin 2 (IL-2), with or without the concomitant administration of cyclophosphamide, in the treatment of 86 consecutive patients with metastatic melanoma. From May 1987 through December 1992, 86 patients (38 female and 48 male) with metastatic melanoma were treated (145 courses) with autologous TILs plus high-dose intravenous bolus IL-2 (720,000 IU/kg every 8 hours). TILs plus IL-2 were administered in two cycles separated by approximately 2 weeks. Two treatment cycles constituted one treatment course. Patients received a maximum of 15 doses of IL-2 per cycle given every 8 hours until grade 3 or 4 toxicity was reached that could not easily be reversed by standard supportive measures. All patients received concomitant medications to abrogate some of the side effects of IL-2 administration: acetaminophen (650 mg every 4 hours), indomethacin (50 mg every 8 hours), and ranitidine (150 mg every 12 hours). Fifty-seven of the 86 patients received a single intravenous dose of 25 mg/kg cyclophosphamide approximately 36 hours before receiving the first intravenous infusion of TILs plus IL-2. Six weeks after treatment, all known sites of disease were evaluated. The overall objective response rate in these patients was 34% and was similar in patients receiving TILs and IL-2 alone (31%) or in conjunction with cyclophosphamide (35%). There was no significant difference in the objective response rate in patients whose therapy with high-dose IL-2 had failed (32%) compared with patients not previously treated with IL-2 (34%). The frequency of response to treatment was greater in those patients who were treated with TILs from younger cultures (P = .0001), TILs with shorter doubling times (P = .03), and TILs that exhibited higher lysis against autologous tumor targets (P = .0008). Patients who received TILs generated from subcutaneous tumor deposits had higher response rates (49%) compared with those receiving TILs from lymph nodes (17%; P = .006). There was one treatment-related death due to respiratory insufficiency. Treatment with TILs and IL-2 with or without cyclophosphamide can result in objective responses in about one third of patients with metastatic melanoma. The side effects of treatment are transient in most patients, and this treatment can be safely administered. These results illustrate the potential value of immune lymphocytes for the treatment of patients with melanoma. JF - Journal of the National Cancer Institute AU - Rosenberg, S A AU - Yannelli, J R AU - Yang, J C AU - Topalian, S L AU - Schwartzentruber, D J AU - Weber, J S AU - Parkinson, D R AU - Seipp, C A AU - Einhorn, J H AU - White, D E AD - Surgery Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, Md. Y1 - 1994/08/03/ PY - 1994 DA - 1994 Aug 03 SP - 1159 EP - 1166 VL - 86 IS - 15 SN - 0027-8874, 0027-8874 KW - Interleukin-2 KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Cyclophosphamide -- therapeutic use KW - Tumor Cells, Cultured KW - Injections, Intravenous KW - Humans KW - Adult KW - Treatment Outcome KW - Combined Modality Therapy -- adverse effects KW - Middle Aged KW - Child KW - Adolescent KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Melanoma -- secondary KW - Interleukin-2 -- therapeutic use KW - Melanoma -- therapy KW - Lymphocytes, Tumor-Infiltrating -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76592443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+patients+with+metastatic+melanoma+with+autologous+tumor-infiltrating+lymphocytes+and+interleukin+2.&rft.au=Rosenberg%2C+S+A%3BYannelli%2C+J+R%3BYang%2C+J+C%3BTopalian%2C+S+L%3BSchwartzentruber%2C+D+J%3BWeber%2C+J+S%3BParkinson%2C+D+R%3BSeipp%2C+C+A%3BEinhorn%2C+J+H%3BWhite%2C+D+E&rft.aulast=Rosenberg&rft.aufirst=S&rft.date=1994-08-03&rft.volume=86&rft.issue=15&rft.spage=1159&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 - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1995 Feb 15;87(4):319 [7707427] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenic replication in human cell extracts of DNA containing site-specific N-2-acetylaminofluorene adducts. AN - 76643896; 8052656 AB - We have analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of bidirectional replication of double-stranded DNA in a human cell extract. Plasmid vectors were constructed containing the simian virus 40 origin of replication and single AAF adducts at one of three guanines in the Nar I sequence GGCGCC in a lacZ reporter gene. The presence of an AAF adduct diminishes replication efficiency in HeLa cell extracts by 70-80%. Replication product analyses reveal unique termination sites with each damaged vector, suggesting that when the replication fork encounters an AAF adduct, it often stops before incorporation opposite the adduct. We also observed a higher proportion of products representing replication of the undamaged strand compared to the damaged strand. This suggests that the undamaged strand is replicated more readily, either by uncoupling the first fork to encounter the lesion or by replication using the fork arriving from the other direction. Also included among replication products are covalently closed monomer-length molecules resistant to cleavage at the AAF-modified Nar I site. This resistance is characteristic of substrates containing the AAF adduct, suggesting that translesion bypass had occurred. Transformation of Escherichia coli cells with the replicated damaged DNA yielded lacZ alpha revertant frequencies significantly above values obtained with undamaged DNA or with damaged DNA not replicated in vitro. This increase was only seen with the substrate modified at the third guanine position. Analysis of mutant DNA demonstrated the loss of a GC dinucleotide at the Nar I sequence. Generation of this position-dependent AAF-induced frameshift error in a human replication system is consistent with previous observations in E. coli suggesting that, after incorporation of dCMP opposite modified guanine in the third position, realignment of the template-primer occurs to form an intermediate with two unpaired nucleotides in the template strand. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Thomas, D C AU - Veaute, X AU - Kunkel, T A AU - Fuchs, R P AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/08/02/ PY - 1994 DA - 1994 Aug 02 SP - 7752 EP - 7756 VL - 91 IS - 16 SN - 0027-8424, 0027-8424 KW - DNA KW - 9007-49-2 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Base Sequence KW - HeLa Cells KW - Humans KW - DNA -- metabolism KW - Molecular Sequence Data KW - Cell-Free System KW - DNA Replication -- genetics KW - 2-Acetylaminofluorene -- pharmacology KW - 2-Acetylaminofluorene -- metabolism KW - Mutagenesis -- genetics KW - DNA Damage -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76643896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenic+replication+in+human+cell+extracts+of+DNA+containing+site-specific+N-2-acetylaminofluorene+adducts.&rft.au=Thomas%2C+D+C%3BVeaute%2C+X%3BKunkel%2C+T+A%3BFuchs%2C+R+P&rft.aulast=Thomas&rft.aufirst=D&rft.date=1994-08-02&rft.volume=91&rft.issue=16&rft.spage=7752&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 - 1994-09-02 N1 - Date created - 1994-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1993 Jan;13(1):533-42 [8417349] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1310-4 [1741385] Science. 1993 Jul 30;261(5121):598-600 [8342022] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7744-8 [8356079] Biochemistry. 1993 Nov 2;32(43):11476-82 [8218213] Biochemistry. 1967 Jan;6(1):177-82 [6030315] Nature. 1979 Aug 2;280(5721):420-3 [223063] Proc Natl Acad Sci U S A. 1981 Jan;78(1):110-4 [6165985] Nature. 1981 Dec 17;294(5842):657-9 [7031481] Mol Cell Biol. 1985 Jun;5(6):1238-46 [2993858] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5953-7 [3461467] J Mol Biol. 1987 Feb 20;193(4):651-9 [3302272] Mol Gen Genet. 1989 Jan;215(2):306-11 [2651884] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4147-51 [2657743] J Mol Biol. 1989 May 20;207(2):355-64 [2754729] Carcinogenesis. 1990 Jul;11(7):1087-95 [2197010] Carcinogenesis. 1990 Dec;11(12):2103-9 [1702368] EMBO J. 1991 Dec;10(13):4351-60 [1721870] J Biol Chem. 1993 Jun 5;268(16):11703-10 [8505300] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A theoretical model for magneto-acoustic imaging of bioelectric currents. AN - 85244914; pmid-7927394 AB - A theoretical model of magneto-acoustic current imaging is derived, based on fundamental equations of continuum mechanics and electromagnetism. In electrically active tissue, the interaction between an applied magnetic field, B, and action currents, J, creates a pressure distribution. In the near field limit, this pressure obeys Poisson's equation, with a source term (delta x J).B. The displacement and pressure fields are calculated for a dipole (q), oriented either parallel or perpendicular to the applied magnetic field (B), at the center of an elastic, conducting sphere (radius a, shear modulus G). Surface displacements are on the order of qB/(4 pi Ga), which is about 1 nm for typical biological parameters. If the applied magnetic field is changing with time, eddy currents induced in the tissue may be larger than the action currents themselves. The frequency of the pressure and displacement arising from these eddy currents, however, is twice the frequency of the applied magnetic field, so it may be possible to eliminate this artifact by filtering or lock-in techniques. Magneto-acoustic and biomagnetic measurements both image delta x J in a similar way, although magneto-acoustic current imaging has the disadvantage that acoustic properties vary among tissues to a greater degree than do magnetic properties. JF - IEEE Transactions on Bio-Medical Engineering AU - Roth, B J AU - Basser, P J AU - Wikswo, J P AD - Biomedical Engineering and Instrumentation Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892. PY - 1994 SP - 723 EP - 728 VL - 41 IS - 8 SN - 0018-9294, 0018-9294 KW - Rheology KW - Viscosity KW - Electric Conductivity KW - Diagnostic Imaging KW - Microscopy KW - Electromagnetics KW - Poisson Distribution KW - Pressure KW - Surface Properties KW - Magnetics KW - Acoustics KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244914?accountid=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=IEEE+Transactions+on+Bio-Medical+Engineering&rft.atitle=A+theoretical+model+for+magneto-acoustic+imaging+of+bioelectric+currents.&rft.au=Roth%2C+B+J%3BBasser%2C+P+J%3BWikswo%2C+J+P&rft.aulast=Roth&rft.aufirst=B&rft.date=1994-08-01&rft.volume=41&rft.issue=8&rft.spage=723&rft.isbn=&rft.btitle=&rft.title=IEEE+Transactions+on+Bio-Medical+Engineering&rft.issn=00189294&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Minimal standards for a computerized endoscopic database. Ad hoc Task Force of the Committee for Minimal Standards of Digestive Endoscopy of the European Society of Gastrointestinal Endoscopy (ESGE). AN - 85227041; pmid-8048405 JF - The American Journal of Gastroenterology AU - Crespi, M AU - Delvaux, M AU - Schapiro, M AU - Venables, C AU - Zwiebel, F AD - National Cancer Institute Regina Elena, Rome, Italy. PY - 1994 SP - S144 EP - S153 VL - 89 IS - 8 Suppl SN - 0002-9270, 0002-9270 KW - Medical Records Systems, Computerized KW - Terminology KW - Human KW - Endoscopy, Digestive System UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227041?accountid=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+Gastroenterology&rft.atitle=Minimal+standards+for+a+computerized+endoscopic+database.+Ad+hoc+Task+Force+of+the+Committee+for+Minimal+Standards+of+Digestive+Endoscopy+of+the+European+Society+of+Gastrointestinal+Endoscopy+%28ESGE%29.&rft.au=Crespi%2C+M%3BDelvaux%2C+M%3BSchapiro%2C+M%3BVenables%2C+C%3BZwiebel%2C+F&rft.aulast=Crespi&rft.aufirst=M&rft.date=1994-08-01&rft.volume=89&rft.issue=8+Suppl&rft.spage=S144&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Lymphocyte-mediated cytotoxicity: two pathways and multiple effector molecules. AN - 77793673; 7882166 JF - Immunity AU - Henkart, P A AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 343 EP - 346 VL - 1 IS - 5 SN - 1074-7613, 1074-7613 KW - Cytotoxins KW - 0 KW - Membrane Glycoproteins KW - Pore Forming Cytotoxic Proteins KW - Perforin KW - 126465-35-8 KW - Index Medicus KW - Animals KW - Humans KW - Cytotoxins -- genetics KW - Membrane Glycoproteins -- pharmacology KW - Cytotoxins -- pharmacology KW - Membrane Glycoproteins -- genetics KW - Gene Deletion KW - T-Lymphocytes, Cytotoxic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77793673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunity&rft.atitle=Lymphocyte-mediated+cytotoxicity%3A+two+pathways+and+multiple+effector+molecules.&rft.au=Henkart%2C+P+A&rft.aulast=Henkart&rft.aufirst=P&rft.date=1994-08-01&rft.volume=1&rft.issue=5&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Immunity&rft.issn=10747613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-13 N1 - Date created - 1995-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The scientific fallacy of route specificity of carcinogenesis with particular reference to cadmium. AN - 77725796; 7838989 JF - Regulatory toxicology and pharmacology : RTP AU - Waalkes, M P AU - Infante, P AU - Huff, J AD - Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 119 EP - 121 VL - 20 IS - 1 Pt 1 SN - 0273-2300, 0273-2300 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Risk Assessment KW - Carcinogens -- administration & dosage KW - Cadmium -- administration & dosage KW - Carcinogens -- toxicity KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77725796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=The+scientific+fallacy+of+route+specificity+of+carcinogenesis+with+particular+reference+to+cadmium.&rft.au=Waalkes%2C+M+P%3BInfante%2C+P%3BHuff%2C+J&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1994-08-01&rft.volume=20&rft.issue=1+Pt+1&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral risks for HIV in adolescents. AN - 77700225; 7833570 AB - A psychosocial perspective on adolescent risk behavior is used to highlight aspects of psychological development and social environment that are relevant to sexual activity and substance use. Differences in behavior are also related to factors such as age and gender that have biological, developmental, and demographic implications. Sexual activity and substance use increase during adolescence, and are often interrelated. In the USA in 1992, 69% of 8th graders and 88% of 12th graders had drunk alcohol. In 1990, 54% of high school students had had sexual intercourse. Age of sexual initiation has decreased in recent cohorts, but condom use by adolescents has increased, with 35% of 15-19-year-old women reporting using condoms. Interventions that successfully change adolescent risk behavior take account of the teen's level of development and social context. JF - Acta paediatrica (Oslo, Norway : 1992). Supplement AU - Moss, N AD - Demographic and Behavioral Sciences Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 81 EP - 87 VL - 400 SN - 0803-5326, 0803-5326 KW - Index Medicus KW - AIDS/HIV KW - Condoms KW - Risk Factors KW - Humans KW - Adult KW - Substance-Related Disorders KW - Health Education KW - Adolescent KW - Male KW - Female KW - Sexual Partners KW - Models, Theoretical KW - Sexual Behavior KW - Contraception Behavior KW - Adolescent Behavior KW - Risk-Taking KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77700225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+paediatrica+%28Oslo%2C+Norway+%3A+1992%29.+Supplement&rft.atitle=Behavioral+risks+for+HIV+in+adolescents.&rft.au=Moss%2C+N&rft.aulast=Moss&rft.aufirst=N&rft.date=1994-08-01&rft.volume=400&rft.issue=&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Acta+paediatrica+%28Oslo%2C+Norway+%3A+1992%29.+Supplement&rft.issn=08035326&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-02 N1 - Date created - 1995-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic suicide genes in gene therapy. AN - 76919300; 7809180 AB - This article reviews uses of metabolic suicide genes in gene therapy. Suicide genes encode novel nonmammalian enzymes that can convert a relatively nontoxic prodrug into a highly toxic agent. Cells genetically transduced to express such genes essentially commit metabolic suicide in the presence of the appropriate prodrug. Three metabolic suicide genes are described: herpes simplex thymidine kinase, Escherichia coli cytosine deaminase and varicella zoster thymidine kinase. Transfer and expression of these genes into mammalian cells is described. Preclinical models of suicide gene therapy of cancer and human immunodeficiency virus are discussed, and several clinical trials employing suicide genes are described. JF - Pharmacology & therapeutics AU - Mullen, C A AD - Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 199 EP - 207 VL - 63 IS - 2 SN - 0163-7258, 0163-7258 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Genes, Bacterial KW - Herpes Simplex -- genetics KW - Humans KW - Herpesvirus 3, Human -- enzymology KW - Clinical Trials as Topic KW - Escherichia coli -- genetics KW - Mice KW - Escherichia coli -- enzymology KW - Mice, Transgenic KW - Gene Expression Regulation -- genetics KW - Herpesvirus 3, Human -- genetics KW - Herpes Simplex -- enzymology KW - Genes, Viral KW - Nucleoside Deaminases -- genetics KW - Neoplasms, Experimental -- therapy KW - HIV Infections -- therapy KW - Genetic Therapy KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76919300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+therapeutics&rft.atitle=Metabolic+suicide+genes+in+gene+therapy.&rft.au=Mullen%2C+C+A&rft.aulast=Mullen&rft.aufirst=C&rft.date=1994-08-01&rft.volume=63&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-31 N1 - Date created - 1995-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational cancer among women: a conference overview. AN - 76913864; 7807258 JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Pottern, L M AU - Zahm, S H AU - Sieber, S S AU - Schneider, I J AU - LaRosa, J H AU - Brown, D P AU - Collman, G W AU - Fingerhut, M A AU - Waters, M A AD - Occupational Studies Section, National Cancer Institute, Bethesda, MD 20892-7364. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 809 EP - 813 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Women, Working KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Female KW - Neoplasms KW - Women's Health KW - Occupational Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76913864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Occupational+cancer+among+women%3A+a+conference+overview.&rft.au=Pottern%2C+L+M%3BZahm%2C+S+H%3BSieber%2C+S+S%3BSchneider%2C+I+J%3BLaRosa%2C+J+H%3BBrown%2C+D+P%3BCollman%2C+G+W%3BFingerhut%2C+M+A%3BWaters%2C+M+A&rft.aulast=Pottern&rft.aufirst=L&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality patterns among female and male chrysotile asbestos textile workers. AN - 76913719; 7807269 AB - This study updates a retrospective cohort mortality analysis of workers from a South Carolina textile plant where chrysotile asbestos was the primary exposure. The update adds 15 years of observation to the original study, adds analyses of white women and black men, and allows comparison of mortality risks between race/gender groups. The total cohort includes 3,022 workers: 1,229 white women (363 deaths), 1,247 white men (607 deaths), and 546 black men (289 deaths). Statistically significant risks for lung cancer were observed among white women (standardized mortality ratio [SMR] = 2.07; 90% confidence interval [CI] = 1.55-2.71) and white men (SMR = 2.24; 90% CI = 1.83-2.72); both of these groups exhibited positive exposure-response trends. Although the lung cancer risk among black men was lower than expected (SMR = 0.70; 90% CI = 0.42-1.08), a statistically significant increase was observed at high levels of exposure. Statistically significant excess risk for pneumoconiosis and other respiratory diseases were observed for all race/gender groups. Despite the relatively high percentage of white women lost to follow-up and missing death certificates, both of which allow underestimation of the true relative risk, statistically significant excess risks were observed for lung cancer and pneumoconiosis among this group. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Brown, D P AU - Dement, J M AU - Okun, A AD - Office of Disease Prevention, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 882 EP - 888 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Asbestos, Serpentine KW - 0 KW - Index Medicus KW - Neoplasms -- mortality KW - Humans KW - Pneumoconiosis -- mortality KW - Retrospective Studies KW - Cause of Death KW - Risk KW - Women, Working KW - European Continental Ancestry Group KW - Cohort Studies KW - Neoplasms -- chemically induced KW - Lung Neoplasms -- mortality KW - Lung Neoplasms -- chemically induced KW - African Continental Ancestry Group KW - Female KW - Male KW - South Carolina -- epidemiology KW - Textile Industry KW - Occupational Diseases -- chemically induced KW - Occupational Diseases -- mortality KW - Asbestos, Serpentine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76913719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Mortality+patterns+among+female+and+male+chrysotile+asbestos+textile+workers.&rft.au=Brown%2C+D+P%3BDement%2C+J+M%3BOkun%2C+A&rft.aulast=Brown&rft.aufirst=D&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=882&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Women in the formaldehyde industry: their exposures and their jobs. AN - 76912260; 7807276 AB - Several studies have examined disease risks for women separately from risks for men, but few have examined exposure differences. This report used data from an epidemiological study of formaldehyde workers to compare formaldehyde exposures between men and women. Exposures were estimated from historical monitoring results, walk-through workplace surveys, interviews with long-term workers, and reviews of historical records. The mean of the exposures in the first job, the last job, and the highest exposed job were calculated by gender. Differences were found when all subjects were included in the analysis (men having higher exposures, on average, than women), but when nonexposed subjects were removed (40% of women, 6% of men), differences were minor. There was a substantial difference in the estimated peak exposure between men and women that decreased, but remained, when only exposed subjects were included. Evaluation of exposures in 1940 to 1945, 1965, and 1979 found that women had a higher average exposure than men in 1940 to 1945, but this pattern was reversed in 1965. By 1979, the average difference between the two genders had disappeared. A comparison of cumulative exposure found that exposed women had half the total exposure of exposed men. More men than women were exposed to other chemicals. Women tended to predominate in clerical, laboratory, assembly, finishing, inspecting, packing, and shipping jobs. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Stewart, P A AU - Blair, A AD - Environmental Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 918 EP - 923 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Women, Working KW - Women's Health KW - Humans KW - Adult KW - Male KW - Female KW - Risk Assessment KW - Occupational Exposure KW - Task Performance and Analysis KW - Chemical Industry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76912260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Women+in+the+formaldehyde+industry%3A+their+exposures+and+their+jobs.&rft.au=Stewart%2C+P+A%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=918&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent cancer patterns among men and women in the United States: clues for occupational research. AN - 76912231; 7807262 AB - Investigation of cancer rates--including trends over time, geographic variations, and differences by race, gender, and age--may identify patterns suggesting environmental exposures of potential occupational origin. National mortality data spanning the 40-year period from 1950 to 1989 were used to assess the patterns of several cancers for which occupational components have been identified among men, including cancers of the lung and bladder, non-Hodgkin's lymphoma, and leukemia, and for cancers of particular concern to women, such as breast and ovarian cancer, but for which occupational factors have not been well characterized. Newly available preliminary data show substantial geographic variation in cancer mortality rates at the county level during the 1970s and 1980s. Future analyses of the patterns, correlations with industrial indicators, and analytic studies should be fruitful in identifying occupational and other risk factors for cancers among women. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Devesa, S S AU - Grauman, D J AU - Blot, W J AD - Biostatistics Branch, Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 832 EP - 841 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Occupational Health KW - Humans KW - European Continental Ancestry Group KW - Urinary Bladder Neoplasms -- mortality KW - Lung Neoplasms -- mortality KW - United States -- epidemiology KW - African Continental Ancestry Group KW - Male KW - Female KW - Neoplasms -- mortality KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76912231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Recent+cancer+patterns+among+men+and+women+in+the+United+States%3A+clues+for+occupational+research.&rft.au=Devesa%2C+S+S%3BGrauman%2C+D+J%3BBlot%2C+W+J&rft.aulast=Devesa&rft.aufirst=S&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=832&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and ovarian cancer: a case-control study in the Washington, DC, metropolitan area, 1978-1981. AN - 76912002; 7807277 AB - Ovarian cancer risk factors may be genetic, reproductive, or hormonal in nature. Occupational exposure to talc and other carcinogenic substances has not been studied in relation to ovarian cancer risk. We therefore examined the job histories of 296 women aged 20 to 79 who were diagnosed with epithelial ovarian cancer in the Washington, DC area in 1978 to 1981, comparing them to 343 hospital controls, matched for age and race. A blind exposure assessment, evaluating each job/industry combination for potential exposure to talc, ionizing radiation, polycyclic aromatic hydrocarbons, and solvents was conducted by an industrial hygienist blind to case-control status. Women exposed to talc had a relative risk of ovarian cancer below the null, but the confidence interval was wide and there was no evidence of a trend. Women exposed to polycyclic aromatic hydrocarbons had an elevated relative risk, also with a wide confidence interval and no evidence of a trend with duration. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Hartge, P AU - Stewart, P AD - Environmental Epidemiology Branch, National Cancer Institute, Rockville, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 924 EP - 927 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Polycyclic Compounds KW - 0 KW - Talc KW - 14807-96-6 KW - Index Medicus KW - Occupational Exposure KW - Risk KW - Women, Working KW - Humans KW - Adult KW - Retrospective Studies KW - District of Columbia -- epidemiology KW - Confidence Intervals KW - Aged KW - Middle Aged KW - Polycyclic Compounds -- adverse effects KW - Female KW - Radiation, Ionizing KW - Ovarian Neoplasms -- etiology KW - Occupational Diseases -- etiology KW - Occupational Diseases -- epidemiology KW - Talc -- adverse effects KW - Ovarian Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76912002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Occupation+and+ovarian+cancer%3A+a+case-control+study+in+the+Washington%2C+DC%2C+metropolitan+area%2C+1978-1981.&rft.au=Hartge%2C+P%3BStewart%2C+P&rft.aulast=Hartge&rft.aufirst=P&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=924&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in animal bioassays for carcinogenicity. AN - 76911534; 7807265 AB - Animal bioassays for carcinogenicity are essential components of occupational health studies. Animal data that have been collected under controlled experimental conditions provide definitive information about the carcinogenic activities of individual substances or defined mixtures and their relative potencies in the test species. Such information serves as a frame of reference for clinical and epidemiologic studies, pointing to potential adverse health effects and to the types of substances that might produce them. This article alerts the occupational and environmental health communities to 20 substances that produced breast tumors, 13 substances that produced uterine tumors, and 8 substances that produced ovarian tumors in long-term National Toxicology Program animal studies. Each of the substances also produced neoplasms at other body sites. Follow-up studies of molecular measures of exposure and response in people and in animals will reduce the uncertainties of transspecies extrapolations. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Griesemer, R A AU - Eustis, S L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 855 EP - 859 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Carcinogens KW - 0 KW - Index Medicus KW - Mammary Neoplasms, Experimental -- chemically induced KW - Animals KW - Uterine Neoplasms -- chemically induced KW - Ovarian Neoplasms -- chemically induced KW - Male KW - Female KW - Sex Characteristics KW - Carcinogenicity Tests KW - Biological Assay UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Gender+differences+in+animal+bioassays+for+carcinogenicity.&rft.au=Griesemer%2C+R+A%3BEustis%2C+S+L&rft.aulast=Griesemer&rft.aufirst=R&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inclusion of women and minorities in occupational cancer epidemiologic research. AN - 76911298; 7807263 AB - A survey of published epidemiologic studies from eight journals during 1971 to 1990 was conducted to assess the proportion and characteristics of occupational cancer studies that have included women and minorities. A total of 1233 reports included 562 (46%) with subjects limited to white men. The remaining 671 (54%) had subjects from other race-gender groups. Thirty-five percent included white women, but only 14% presented any analyses of white women specifically and only 7% presented more than five risk estimates. The proportions with analyses of nonwhite women (any = 2%; detailed = 1%) or men (any = 7%; detailed = 3%) were also small. Studies with detailed analyses of women and minorities tended to use weaker methodologies (ie, proportionate mortality or cross-sectional design) than the studies of white men and were less able to provide convincing data on the occupational cancer risks of women and minorities. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Zahm, S H AU - Pottern, L M AU - Lewis, D R AU - Ward, M H AU - White, D W AD - Occupational Studies Section, National Cancer Institute, Rockville, Maryland 20892-7364. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 842 EP - 847 VL - 36 IS - 8 SN - 0096-1736, 0096-1736 KW - Bioethics KW - Index Medicus KW - Health Care and Public Health KW - Biomedical and Behavioral Research KW - Empirical Approach KW - United States KW - Periodicals as Topic KW - Women's Health KW - Humans KW - Research KW - Male KW - Female KW - Women, Working KW - Minority Groups KW - Epidemiologic Methods KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76911298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Inclusion+of+women+and+minorities+in+occupational+cancer+epidemiologic+research.&rft.au=Zahm%2C+S+H%3BPottern%2C+L+M%3BLewis%2C+D+R%3BWard%2C+M+H%3BWhite%2C+D+W&rft.aulast=Zahm&rft.aufirst=S&rft.date=1994-08-01&rft.volume=36&rft.issue=8&rft.spage=842&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-02 N1 - Date created - 1995-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age differences in the personality characteristics of suicide completers: preliminary findings from a psychological autopsy study. AN - 76906581; 7800770 JF - Psychiatry AU - Duberstein, P R AU - Conwell, Y AU - Caine, E D AD - Department of Psychiatry, University of Rochester Medical Center, UR-NIMH Clinical Research Center for the Study of Psychopathology of the Elderly, NY 14642. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 213 EP - 224 VL - 57 IS - 3 SN - 0033-2747, 0033-2747 KW - Index Medicus KW - Age Factors KW - Depressive Disorder -- psychology KW - Humans KW - Substance-Related Disorders -- mortality KW - Aged KW - Substance-Related Disorders -- psychology KW - Depressive Disorder -- mortality KW - Psychometrics KW - Cause of Death KW - Schizophrenia -- mortality KW - Risk Factors KW - Adult KW - Schizophrenic Psychology KW - Middle Aged KW - Female KW - Male KW - Personality Assessment -- statistics & numerical data KW - Suicide -- statistics & numerical data KW - Suicide -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76906581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Age+differences+in+the+personality+characteristics+of+suicide+completers%3A+preliminary+findings+from+a+psychological+autopsy+study.&rft.au=Duberstein%2C+P+R%3BConwell%2C+Y%3BCaine%2C+E+D&rft.aulast=Duberstein&rft.aufirst=P&rft.date=1994-08-01&rft.volume=57&rft.issue=3&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Psychiatry&rft.issn=00332747&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-20 N1 - Date created - 1995-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selected complications in the patient with cancer: spinal cord compression, malignant bowel obstruction, malignant ascites, and gastrointestinal bleeding. AN - 76904933; 7800973 AB - The growth rate of a tumor, patterns of tumor growth and metastatic spread, and toxicity of therapy contribute to the type and severity of complications. Four common critical care complications resulting from compressive and invasive properties of tumors include spinal cord compression, malignant bowel obstruction, malignant ascites, and gastrointestinal bleeding. Knowledge of the clinical presentations of each of these complications provides a foundation for nursing assessment. JF - Seminars in oncology nursing AU - Labovich, T M AD - National Institutes of Health, Bethesda, MD. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 189 EP - 197 VL - 10 IS - 3 SN - 0749-2081, 0749-2081 KW - Index Medicus KW - Nursing KW - Humans KW - Oncology Nursing KW - Critical Care KW - Ascites -- etiology KW - Gastrointestinal Hemorrhage -- diagnosis KW - Intestinal Obstruction -- etiology KW - Intestinal Obstruction -- nursing KW - Spinal Cord Compression -- physiopathology KW - Spinal Cord Compression -- etiology KW - Ascites -- physiopathology KW - Intestinal Obstruction -- diagnosis KW - Spinal Cord Compression -- nursing KW - Gastrointestinal Hemorrhage -- physiopathology KW - Gastrointestinal Hemorrhage -- nursing KW - Neoplasms -- complications KW - Gastrointestinal Hemorrhage -- etiology KW - Intestinal Obstruction -- physiopathology KW - Ascites -- nursing KW - Spinal Cord Compression -- diagnosis KW - Ascites -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76904933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology+nursing&rft.atitle=Selected+complications+in+the+patient+with+cancer%3A+spinal+cord+compression%2C+malignant+bowel+obstruction%2C+malignant+ascites%2C+and+gastrointestinal+bleeding.&rft.au=Labovich%2C+T+M&rft.aulast=Labovich&rft.aufirst=T&rft.date=1994-08-01&rft.volume=10&rft.issue=3&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology+nursing&rft.issn=07492081&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-20 N1 - Date created - 1995-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are men or women more likely to stop drinking because of alcohol problems? AN - 76876456; 7988360 AB - Using a national population sample of adults who had ever consumed at least 12 drinks per year, men and women were compared in terms of the proportions who had stopped drinking because of alcohol problems. Overall, 24% of the male drinkers and 31% of the female drinkers had stopped drinking as of the time of interview, but men were more likely than women to have stopped drinking because of alcohol-related problems (4.3 vs. 2.3%). After using survival techniques to adjust for women's greater competing risk of stopping drinking for other reasons and men's greater exposure time due to their earlier initiation of drinking, the conditional probabilities of having stopped drinking because of alcohol problems were almost identical for men and women during the first 15 years of their drinking histories. Thereafter, the conditional probabilities were about 50% higher for men than for women. The observed durations of drinking history were about five years longer for men than women. After controlling for sociodemographic characteristics, family history of alcoholism, and patterns of alcohol consumption, there was no gender difference in the hazard of stopping drinking because of alcohol problems among persons who drank alcohol on less than a daily basis during their period of heaviest consumption. However, among daily drinkers, the hazard of stopping drinking because of alcohol problems was greater for women than men, by a factor of 1.5 to 3, depending on quantity of consumption and interval since first drink. JF - Drug and alcohol dependence AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 57 EP - 64 VL - 36 IS - 1 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Sex Factors KW - Motivation KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Survival Analysis KW - Proportional Hazards Models KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76876456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Are+men+or+women+more+likely+to+stop+drinking+because+of+alcohol+problems%3F&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1994-08-01&rft.volume=36&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immature mouse uterine tissue in organ culture: estrogen-induced growth, morphology and biochemical parameters. AN - 76872066; 7987540 AB - Although estrogens have been shown to stimulate a variety of morphologic and biochemical changes in the uterus in vivo, no clear consistent demonstration of similar responses in vitro have been made; thus, a defined organ culture system using the immature mouse uterus was established to study the possibility of demonstrating estrogenic responses in vitro. Uterine tissue from immature outbred mice (17 to 24 days of age) were cut crosswise in 1-mm3 coins and cultured in a defined medium in the absence of serum, phenol red, or growth factor supplements. Diethylstilbestrol (DES), a synthetic estrogen, was added to the media at doses ranging from 1 to 100 ng/ml. The effect of DES on uterine cell proliferation was assessed by morphologic changes in uterine epithelial and stromal cells, increase in number of epithelial cells per unit basement membrane, increase in height of luminal epithelial cells, and [3H]thymidine incorporation. Functional changes were determined by measuring the amounts of the estrogen-inducible uterine protein, lactoferrin, that was localized in the epithelial cells and secreted into the media, and the localization of the estrogen receptor in the cultured tissues. Results indicate that under the described conditions of culture, estrogens like DES can induce morphologic and biochemical responses in the uterus that are similar to those seen in vivo. This organ culture system will aid in the investigation of various mechanisms involved in the hormonal regulation of growth and differentiation of estrogen target tissues. JF - In vitro cellular & developmental biology. Animal AU - Newbold, R R AU - Hanson, R B AU - Jefferson, W N AD - Developmental Endocrinology and Pharmacology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 519 EP - 528 VL - 30A IS - 8 SN - 1071-2690, 1071-2690 KW - Culture Media KW - 0 KW - Receptors, Estrogen KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Mice KW - Receptors, Estrogen -- metabolism KW - Epithelium -- drug effects KW - Epithelial Cells KW - Epithelium -- metabolism KW - Lactoferrin -- metabolism KW - Immunohistochemistry KW - Organ Culture Techniques KW - Female KW - Uterus -- metabolism KW - Uterus -- growth & development KW - Diethylstilbestrol -- pharmacology KW - Diethylstilbestrol -- administration & dosage KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76872066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vitro+cellular+%26+developmental+biology.+Animal&rft.atitle=Immature+mouse+uterine+tissue+in+organ+culture%3A+estrogen-induced+growth%2C+morphology+and+biochemical+parameters.&rft.au=Newbold%2C+R+R%3BHanson%2C+R+B%3BJefferson%2C+W+N&rft.aulast=Newbold&rft.aufirst=R&rft.date=1994-08-01&rft.volume=30A&rft.issue=8&rft.spage=519&rft.isbn=&rft.btitle=&rft.title=In+vitro+cellular+%26+developmental+biology.+Animal&rft.issn=10712690&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-12 N1 - Date created - 1995-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of toxoplasmosis. AN - 76869311; 7527323 AB - Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans. In immunocompetent hosts, the infection is usually asymptomatic and benign. Toxoplasmosis is either congenital or acquired. In general, prenatal therapy of congenital toxoplasmosis is beneficial in reducing the frequency of infant infection. Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentrations achieved in the placenta. Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection. The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides. Toxoplasmic encephalitis is the most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal. However, because of toxicity, the therapeutic efficacy of pyrimethamine-sulphonamide combinations may be seriously limited in immunodeficient patients. A number of novel and less toxic agents are being currently studied in clinical settings, including macrolide antibiotics (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole). Maintenance or prophylactic therapy is essential in many patients with acquired immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of a pre-existent latent infection. JF - Drugs AU - Georgiev, V S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 179 EP - 188 VL - 48 IS - 2 SN - 0012-6667, 0012-6667 KW - Anti-Infective Agents KW - 0 KW - Antiprotozoal Agents KW - Sulfonamides KW - Spiramycin KW - 8025-81-8 KW - Pyrimethamine KW - Z3614QOX8W KW - Index Medicus KW - Drug Therapy, Combination KW - Pyrimethamine -- therapeutic use KW - Sulfonamides -- pharmacology KW - Spiramycin -- therapeutic use KW - Humans KW - Spiramycin -- pharmacology KW - Infant, Newborn KW - Pyrimethamine -- pharmacology KW - Drug Synergism KW - Sulfonamides -- therapeutic use KW - Anti-Infective Agents -- therapeutic use KW - Toxoplasmosis, Congenital -- prevention & control KW - Antiprotozoal Agents -- pharmacology KW - Toxoplasmosis -- prevention & control KW - Anti-Infective Agents -- pharmacology KW - Antiprotozoal Agents -- therapeutic use KW - Toxoplasmosis, Congenital -- drug therapy KW - Toxoplasmosis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76869311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs&rft.atitle=Management+of+toxoplasmosis.&rft.au=Georgiev%2C+V+S&rft.aulast=Georgiev&rft.aufirst=V&rft.date=1994-08-01&rft.volume=48&rft.issue=2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Drugs&rft.issn=00126667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice. AN - 76867440; 7985194 AB - Toxicity studies of riddelliine, a member of a class of pyrrolizidine alkaloids, were conducted because riddelliine has been found to contaminate human food sources. Groups of male and female Fischer rats were administered riddelliine by gavage in phosphate buffer at doses up to 10 mg/kg, and B6C3F1 mice at doses up to 25 mg/kg, five times a week. The animals were necropsied after 13 weeks of treatment or after a 7 or 14 week recovery period. Body weight gains were inversely related to dose in both rats and mice. Body weight of the 1.0 and 3.3 mg/kg female rats and 10.0 and 25.0 mg/kg mice remained depressed during the 14 week recovery period. At 13 weeks, significant findings included dose-related hepatopathy and intravascular macrophage accumulation in rats and hepatocytomegaly in mice. During the 14 week recovery period these lesions persisted and hepatic foci of cellular alteration in male rats and bile duct proliferation in female rats and male and female mice increased in severity. In the 10 mg/kg group of female rats adenomas of the liver occurred in two of ten at 13 weeks and in one of five at the 14 week recovery period. In separate studies, the frequency of micronucleated erythrocytes in peripheral blood was increased in male mice administered a single dose (150 mg/kg) of riddelliine. Increases in unscheduled DNA and S-phase syntheses were detected in primary hepatocytes from rats and mice treated with riddelliine at doses up to 25.0 mg/kg for 5 or 30 days. In mating trials in rats and mice, pup weights from treated dams at birth and during suckling were lower than controls. Thus, riddelliine is genotoxic and carcinogenic and may cross the placenta and/or be found in milk, causing developmental toxicity in rodents. JF - Toxicon : official journal of the International Society on Toxinology AU - Chan, P C AU - Mahler, J AU - Bucher, J R AU - Travlos, G S AU - Reid, J B AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 891 EP - 908 VL - 32 IS - 8 SN - 0041-0101, 0041-0101 KW - Carcinogens KW - 0 KW - Pyrrolizidine Alkaloids KW - riddelliine KW - 23246-96-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Mutation -- drug effects KW - Administration, Oral KW - Animals KW - Reproduction -- drug effects KW - Dose-Response Relationship, Drug KW - Mice KW - Macrophages -- drug effects KW - DNA -- biosynthesis KW - Rats KW - Microscopy, Fluorescence KW - Rats, Inbred F344 KW - Micronucleus Tests KW - Cells, Cultured KW - Body Weight -- drug effects KW - DNA -- genetics KW - Mutation -- genetics KW - Image Processing, Computer-Assisted KW - Female KW - Male KW - Organ Size -- drug effects KW - Macrophages -- metabolism KW - Liver -- ultrastructure KW - Liver -- pathology KW - Liver -- cytology KW - Carcinogens -- administration & dosage KW - Liver -- drug effects KW - Liver Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Pyrrolizidine Alkaloids -- administration & dosage KW - Adenoma, Liver Cell -- chemically induced KW - Pyrrolizidine Alkaloids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76867440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.atitle=Toxicity+and+carcinogenicity+of+riddelliine+following+13+weeks+of+treatment+to+rats+and+mice.&rft.au=Chan%2C+P+C%3BMahler%2C+J%3BBucher%2C+J+R%3BTravlos%2C+G+S%3BReid%2C+J+B&rft.aulast=Chan&rft.aufirst=P&rft.date=1994-08-01&rft.volume=32&rft.issue=8&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.issn=00410101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-30 N1 - Date created - 1994-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of a diverged homeobox gene, MOX1, from the BRCA1 region on 17q21 by solution hybrid capture. AN - 76865502; 7987315 AB - Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study. JF - Human molecular genetics AU - Futreal, P A AU - Cochran, C AU - Rosenthal, J AU - Miki, Y AU - Swenson, J AU - Hobbs, M AU - Bennett, L M AU - Haugen-Strano, A AU - Marks, J AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 1359 EP - 1364 VL - 3 IS - 8 SN - 0964-6906, 0964-6906 KW - BRCA1 KW - MOX1 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Transcription, Genetic KW - Amino Acid Sequence KW - Chromosome Mapping KW - Chromosomes, Human, Pair 17 KW - Nucleic Acid Hybridization KW - Genes, Homeobox -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76865502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Isolation+of+a+diverged+homeobox+gene%2C+MOX1%2C+from+the+BRCA1+region+on+17q21+by+solution+hybrid+capture.&rft.au=Futreal%2C+P+A%3BCochran%2C+C%3BRosenthal%2C+J%3BMiki%2C+Y%3BSwenson%2C+J%3BHobbs%2C+M%3BBennett%2C+L+M%3BHaugen-Strano%2C+A%3BMarks%2C+J%3BBarrett%2C+J+C&rft.aulast=Futreal&rft.aufirst=P&rft.date=1994-08-01&rft.volume=3&rft.issue=8&rft.spage=1359&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - BRCA1; MOX1 N1 - Genetic sequence - U10493; GENBANK; U10492 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity studies of oxazepam in mice. AN - 76864592; 7982536 AB - Oxazepam is a benzodiazepine widely used as a sedative-hypnotic and antianxiety drug. In chronic studies, groups of 60 male and 60 female Swiss-Webster (SW) or B6C3F1 mice received oxazepam in feed at concentrations of 0,2500, or 5000 ppm. Additional groups of 60 male and female B6C3F1 mice received 125 ppm in feed to allow for study of mice with serum concentrations of oxazepam similar to those achieved in humans taking a therapeutic dose. At 57 weeks, treatment-related mortality of exposed SW mice caused the study to be terminated. Enhanced systemic amyloidosis contributing to heart failure was considered the principal cause of death. Hepatocellular adenomas and carcinomas were increased in exposed SW mice. Survival of B6C3F1 mice receiving 2500 and 5000 ppm oxazepam was also lower than that of controls. Early deaths were due to increased incidences of hepatoblastoma and hepatocellular carcinoma, and nearly all mice receiving 2500 or 5000 ppm developed hepatocellular neoplasia. An increase in follicular cell hyperplasia of the thyroid gland occurred in all exposed groups of B6C3F1 mice, and thyroid gland follicular cell adenoma was increased in exposed females. Further studies of the capacity of oxazepam to induce liver cell mitogenesis and an evaluation of the frequency of activated H- and K-ras oncogenes in the liver tumors of B6C3F1 mice has shown that many of the neoplastic and nonneoplastic responses of mice to oxazepam resemble those observed with phenobarbital. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Bucher, J R AU - Shackelford, C C AU - Haseman, J K AU - Johnson, J D AU - Kurtz, P J AU - Persing, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 280 EP - 297 VL - 23 IS - 2 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Animals KW - Carcinogenicity Tests -- methods KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Species Specificity KW - Male KW - Female KW - Behavior, Animal -- drug effects KW - Liver -- pathology KW - Oxazepam -- toxicity KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Oxazepam -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76864592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Carcinogenicity+studies+of+oxazepam+in+mice.&rft.au=Bucher%2C+J+R%3BShackelford%2C+C+C%3BHaseman%2C+J+K%3BJohnson%2C+J+D%3BKurtz%2C+P+J%3BPersing%2C+R+L&rft.aulast=Bucher&rft.aufirst=J&rft.date=1994-08-01&rft.volume=23&rft.issue=2&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-30 N1 - Date created - 1994-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans, European-Americans and Taiwanese. AN - 76864156; 7987402 AB - Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is involved in metabolism of many known carcinogens including N-nitrosodimethylamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variability in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environmental. Recently, two restriction fragment length polymorphisms (RFLPs) within the CYP2E1 gene have been suggested as genetic markers of risk for cancer. The first was a Rsa I polymorphism in the 5' regulatory region that appeared to alter transcriptional activation of the gene and the second was a Dra I polymorphism located approximately 7000 bp downstream in an intron. Rare alleles at each of these loci have been associated with a reduced risk for lung cancer in Japanese and Swedish populations. We have used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotype frequency for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, African-American or European-American background. Genotype and allele frequencies for Taiwanese were significantly different from those of African-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Americans were significantly different at the Rsa I site (p = 0.03). The rare alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiwanese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in European-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have been caused by a recombination event between these markers.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Pharmacogenetics AU - Stephens, E A AU - Taylor, J A AU - Kaplan, N AU - Yang, C H AU - Hsieh, L L AU - Lucier, G W AU - Bell, D A AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 185 EP - 192 VL - 4 IS - 4 SN - 0960-314X, 0960-314X KW - DNA Primers KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - GTAC-specific type II deoxyribonucleases KW - TTTAAA -specific type II deoxyribonucleases KW - Index Medicus KW - United States KW - Taiwan KW - Humans KW - Asian Continental Ancestry Group -- genetics KW - European Continental Ancestry Group -- genetics KW - Genotype KW - African Continental Ancestry Group -- genetics KW - Haplotypes KW - Molecular Sequence Data KW - Europe -- ethnology KW - Oxidoreductases, N-Demethylating -- genetics KW - Polymorphism, Restriction Fragment Length KW - Cytochrome P-450 Enzyme System -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76864156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ethnic+variation+in+the+CYP2E1+gene%3A+polymorphism+analysis+of+695+African-Americans%2C+European-Americans+and+Taiwanese.&rft.au=Stephens%2C+E+A%3BTaylor%2C+J+A%3BKaplan%2C+N%3BYang%2C+C+H%3BHsieh%2C+L+L%3BLucier%2C+G+W%3BBell%2C+D+A&rft.aulast=Stephens&rft.aufirst=E&rft.date=1994-08-01&rft.volume=4&rft.issue=4&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-10 N1 - Date created - 1995-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired sideroblastic anaemia following progesterone therapy. AN - 76863002; 7986730 AB - We report a case of acquired sideroblastic anaemia precipitated by progesterone. On two separate occasions, over 15 years apart, the patient developed sideroblastic anaemia with iron overload shortly after the administration of progesterone. No other cause for sideroblastic anaemia was found, and treatment with folic acid, pyridoxine or androgens corrected the anaemia. In both instances removal of the progestational agent led to prompt disappearance of the anaemia as well as the ringed sideroblasts. Using a two-phase liquid culture procedure in which human peripheral blood-derived progenitor cells undergo erythroid proliferation and differentiation, we demonstrated enhanced sensitivity of the patient's erythroid progenitors to progesterone. We conclude that progesterone should be added to the list of medications known to be associated with acquired sideroblastic anaemia. JF - British journal of haematology AU - Brodsky, R A AU - Hasegawa, S AU - Fibach, E AU - Dunbar, C E AU - Young, N S AU - Rodgers, G P AD - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 859 EP - 862 VL - 87 IS - 4 SN - 0007-1048, 0007-1048 KW - Progesterone Congeners KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Index Medicus KW - Erythroid Precursor Cells -- drug effects KW - Bone Marrow -- pathology KW - Cells, Cultured KW - Progesterone -- pharmacology KW - Humans KW - Adult KW - Cell Division -- drug effects KW - Follow-Up Studies KW - Cell Differentiation -- drug effects KW - Female KW - Progesterone Congeners -- adverse effects KW - Anemia, Sideroblastic -- pathology KW - Anemia, Sideroblastic -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76863002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acquired+sideroblastic+anaemia+following+progesterone+therapy.&rft.au=Brodsky%2C+R+A%3BHasegawa%2C+S%3BFibach%2C+E%3BDunbar%2C+C+E%3BYoung%2C+N+S%3BRodgers%2C+G+P&rft.aulast=Brodsky&rft.aufirst=R&rft.date=1994-08-01&rft.volume=87&rft.issue=4&rft.spage=859&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 - 1995-01-09 N1 - Date created - 1995-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to chlorinated aliphatic hydrocarbons and risk of astrocytic brain cancer. AN - 76851094; 7977393 AB - Chlorinated aliphatic hydrocarbons (CAHs) were evaluated as potential risk factors for astrocytic brain tumors. Job-exposure matrices for six individual CAHs and for the general class of organic solvents were applied to data from a case-control study of brain cancer among white men. The matrices indicated whether the CAHs were likely to have been used in each industry and occupation by decade (1920-1980), and provided estimates of probability and intensity of exposure for "exposed" industries and occupations. Cumulative exposure indices were calculated for each subject. Associations of astrocytic brain cancer were observed with likely exposure to carbon tetrachloride, methylene chloride, tetrachloroethylene, and trichloroethylene, but were strongest for methylene chloride. Exposure to chloroform or methyl chloroform showed little indication of an association with brain cancer. Risk of astrocytic brain tumors increased with probability and average intensity of exposure, and with duration of employment in jobs considered exposed to methylene chloride, but not with a cumulative exposure score. These trends could not be explained by exposures to the other solvents. JF - American journal of industrial medicine AU - Heineman, E F AU - Cocco, P AU - Gómez, M R AU - Dosemeci, M AU - Stewart, P A AU - Hayes, R B AU - Zahm, S H AU - Thomas, T L AU - Blair, A AD - Occupational Studies Section, National Cancer Institute, Rockville, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 155 EP - 169 VL - 26 IS - 2 SN - 0271-3586, 0271-3586 KW - Hydrocarbons, Chlorinated KW - 0 KW - Trichloroethylene KW - 290YE8AR51 KW - Methylene Chloride KW - 588X2YUY0A KW - Tetrachloroethylene KW - TJ904HH8SN KW - Index Medicus KW - Astrocytoma -- epidemiology KW - Trichloroethylene -- poisoning KW - Tetrachloroethylene -- poisoning KW - New Jersey -- epidemiology KW - Methylene Chloride -- poisoning KW - Risk Factors KW - Humans KW - Carbon Tetrachloride Poisoning -- epidemiology KW - Astrocytoma -- chemically induced KW - Philadelphia -- epidemiology KW - Male KW - Louisiana -- epidemiology KW - Occupational Exposure KW - Hydrocarbons, Chlorinated -- poisoning KW - Glioblastoma -- chemically induced KW - Glioblastoma -- epidemiology KW - Brain Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76851094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+exposure+to+chlorinated+aliphatic+hydrocarbons+and+risk+of+astrocytic+brain+cancer.&rft.au=Heineman%2C+E+F%3BCocco%2C+P%3BG%C3%B3mez%2C+M+R%3BDosemeci%2C+M%3BStewart%2C+P+A%3BHayes%2C+R+B%3BZahm%2C+S+H%3BThomas%2C+T+L%3BBlair%2C+A&rft.aulast=Heineman&rft.aufirst=E&rft.date=1994-08-01&rft.volume=26&rft.issue=2&rft.spage=155&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 - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ind Med. 1996 Oct;30(4):504-9 [8892559] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to chlorinated aliphatic hydrocarbons: job exposure matrix. AN - 76849992; 7977394 AB - A job exposure matrix combining features to increase the accuracy of exposure assessment was developed to evaluate cancer risks from workplace exposures to six chlorinated aliphatic hydrocarbons (CAHs). A detailed description of the matrix is provided to satisfy the need for more in-depth discussion of exposure assessment methods than is typical in today's epidemiologic literature. The matrix assigns semiquantitative estimates of the probability and intensity of exposure to each four-digit Standard Industrial Classification (SIC) and Standard Occupational Classification (SOC) code potentially associated with exposure to each CAH. The matrix also accounts for the changing patterns of use of the CAHs by decade from the 1920s to the 1980s. An algorithm combines these parameters to assign each study subject a unique lifetime probability of exposure and an estimated score of cumulative exposure for each CAH. These assignments can then become the subjects of analyses. The ability of the matrix to reduce the number of false positive exposure assessments is discussed and illustrated. A companion paper describes the detailed epidemiologic findings of this application of the matrix. JF - American journal of industrial medicine AU - Gomez, M R AU - Cocco, P AU - Dosemeci, M AU - Stewart, P A AD - Occupational Studies Section, National Cancer Institute, Rockville, MD. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 171 EP - 183 VL - 26 IS - 2 SN - 0271-3586, 0271-3586 KW - Hydrocarbons, Chlorinated KW - 0 KW - Index Medicus KW - Probability KW - Humans KW - Algorithms KW - Statistics as Topic KW - Occupations KW - Occupational Exposure KW - Hydrocarbons, Chlorinated -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76849992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+exposure+to+chlorinated+aliphatic+hydrocarbons%3A+job+exposure+matrix.&rft.au=Gomez%2C+M+R%3BCocco%2C+P%3BDosemeci%2C+M%3BStewart%2C+P+A&rft.aulast=Gomez&rft.aufirst=M&rft.date=1994-08-01&rft.volume=26&rft.issue=2&rft.spage=171&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 - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ind Med. 1996 Oct;30(4):504-9 [8892559] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High in vitro and in vivo survival of day 3 mouse embryos vitrified or frozen in a non-toxic solution of glycerol and albumin. AN - 76829214; 7966026 AB - A vitrification solution consisting of 6.5 mol glycerol l-1 and 6% (w/v) BSA in a modified Dulbecco's PBS (designated solution VS3a) was examined for the cryopreservation of 8-12-cell mouse embryos. Solution VS3a vitrified when cooled to -196 degrees C at rates of 10-2500 degrees C min-1 and vitrified suspensions did not crystallize when warmed at 200 or 2000 degrees C min-1. However, slow cooling at 5 degrees C min-1 or slow warming at 20 degrees C min-1 resulted in visible crystallization of solution VS3a. Embryos were equilibrated in solution VS3a in three steps at room temperature and placed into a 0.25 ml plastic straw in a way that permitted in-straw dilution with 1 mol sucrose l-1. Embryos equilibrated in solution VS3a and diluted immediately exhibited high rates of development in vitro to blastocysts (> 90%) if the total time of exposure to 100% solution VS3a did not exceed 5 min. Embryos exhibited high rates of development in vitro (75-97%) when equilibrated in 100% solution VS3a for 1 min and then cryopreserved using all combinations of three rates of cooling (5200 or 2500 degrees C min-1) and three rates of warming (20,000 or 2000 degrees C min-1). Although embryo suspensions visibly crystallized during slow cooling at 5 degrees C min-1, the rate of cooling was not a significant source of variance (P > 0.26). However, the rate of warming was found to have a small but significant effect on embryo survival (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of reproduction and fertility AU - Rall, W F AU - Wood, M J AD - Veterinary Resources Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 681 EP - 688 VL - 101 IS - 3 SN - 0022-4251, 0022-4251 KW - Culture Media KW - 0 KW - Serum Albumin, Bovine KW - Glycerol KW - PDC6A3C0OX KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Embryo Transfer KW - Mice KW - Blastocyst KW - Freeze Substitution -- methods KW - Fetal Viability KW - Cryopreservation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76829214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+and+fertility&rft.atitle=High+in+vitro+and+in+vivo+survival+of+day+3+mouse+embryos+vitrified+or+frozen+in+a+non-toxic+solution+of+glycerol+and+albumin.&rft.au=Rall%2C+W+F%3BWood%2C+M+J&rft.aulast=Rall&rft.aufirst=W&rft.date=1994-08-01&rft.volume=101&rft.issue=3&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Journal+of+reproduction+and+fertility&rft.issn=00224251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate]. AN - 76807374; 7956313 AB - The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6. JF - Current eye research AU - Dastgheib, K AU - Hikita, N AU - Sredni, B AU - Albeck, M AU - Sredni, D AU - Nussenblatt, R B AU - Chan, C C AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 603 EP - 610 VL - 13 IS - 8 SN - 0271-3683, 0271-3683 KW - Adjuvants, Immunologic KW - 0 KW - Ethylenes KW - Histocompatibility Antigens Class II KW - Interleukin-6 KW - ammonium trichloro(dioxoethylene-O,O'-)tellurate KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Interleukin-6 -- metabolism KW - Eye Diseases -- chemically induced KW - Anterior Eye Segment -- pathology KW - Inflammation KW - Rats KW - Eye Diseases -- metabolism KW - Histocompatibility Antigens Class II -- metabolism KW - Anterior Eye Segment -- drug effects KW - Eye Diseases -- pathology KW - Anterior Eye Segment -- metabolism KW - Injections KW - Female KW - Intercellular Adhesion Molecule-1 -- metabolism KW - Iridocyclitis -- pathology KW - Vitreous Body -- drug effects KW - Iridocyclitis -- chemically induced KW - Vitreous Body -- metabolism KW - Vitreous Body -- pathology KW - Iridocyclitis -- metabolism KW - Adjuvants, Immunologic -- pharmacology KW - Ethylenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76807374?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=Ocular+inflammation+stimulated+by+the+immunomodulator+AS101+%5Bammonium+trichloro%28dioxyethelene-O-O%27%29+tellurate%5D.&rft.au=Dastgheib%2C+K%3BHikita%2C+N%3BSredni%2C+B%3BAlbeck%2C+M%3BSredni%2C+D%3BNussenblatt%2C+R+B%3BChan%2C+C+C&rft.aulast=Dastgheib&rft.aufirst=K&rft.date=1994-08-01&rft.volume=13&rft.issue=8&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emphysema and airway obstruction in non-smoking South African gold miners with long exposure to silica dust. AN - 76799161; 7951782 AB - Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. 242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease. JF - Occupational and environmental medicine AU - Hnizdo, E AU - Sluis-Cremer, G K AU - Baskind, E AU - Murray, J AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 557 EP - 563 VL - 51 IS - 8 SN - 1351-0711, 1351-0711 KW - Dust KW - 0 KW - Gold KW - 7440-57-5 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Autopsy KW - Bronchitis -- etiology KW - Vital Capacity KW - Humans KW - Aged KW - Forced Expiratory Volume KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - South Africa KW - Dust -- adverse effects KW - Time Factors KW - Male KW - Silicosis -- etiology KW - Lung Diseases, Obstructive -- physiopathology KW - Lung Diseases, Obstructive -- etiology KW - Emphysema -- etiology KW - Occupational Diseases -- etiology KW - Occupational Diseases -- physiopathology KW - Emphysema -- physiopathology KW - Mining KW - Silicon Dioxide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76799161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Emphysema+and+airway+obstruction+in+non-smoking+South+African+gold+miners+with+long+exposure+to+silica+dust.&rft.au=Hnizdo%2C+E%3BSluis-Cremer%2C+G+K%3BBaskind%2C+E%3BMurray%2C+J&rft.aulast=Hnizdo&rft.aufirst=E&rft.date=1994-08-01&rft.volume=51&rft.issue=8&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-08 N1 - Date created - 1994-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Ind Med. 1992 Jul;49(7):472-9 [1322158] Am J Ind Med. 1993 Oct;24(4):447-57 [8250063] Am Rev Respir Dis. 1985 Jan;131(1):139-43 [3966701] Am Rev Respir Dis. 1987 Jun;135(6):1234-41 [3592399] Int Arch Occup Environ Health. 1992;63(6):387-91 [1544686] Am Rev Respir Dis. 1991 Jan;143(1):80-4 [1986688] Chest. 1991 Feb;99(2):265-6 [1989778] Am Rev Respir Dis. 1991 Jun;143(6):1241-7 [1646580] Exp Lung Res. 1989 Dec;15(6):813-22 [2558880] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contemporary approaches in the investigation and treatment of malignant pleural mesothelioma. AN - 76798627; 7953481 AB - The cellular and molecular biology of mesothelioma is a complicated, multifactorial, incompletely understood process of carcinogenesis. Normal mesothelial cells can be transformed into a malignant phenotype by multiple factors, usually asbestos. Several tumor suppressor genes may be lost, and several oncogenes can be activated. A local environment of inflammation with associated release of cytokines may promote deregulated cell growth. The release of immunosuppressive substances such as nitric oxide may contribute to this process. The interaction of asbestos and viral DNA incorporation is unclear but warrants further investigation. In the majority of mesothelioma patients, present standard therapies have little effect on survival. Clinical trials studying a variety of innovative treatment strategies are being performed at centers with a significant referral base for the disease. Future treatments, however, must be based on understanding of the biology of mesothelioma. JF - Chest surgery clinics of North America AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 497 EP - 515 VL - 4 IS - 3 SN - 1052-3359, 1052-3359 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Asbestos -- adverse effects KW - Mesothelioma -- therapy KW - Mesothelioma -- etiology KW - Mesothelioma -- genetics KW - Pleural Neoplasms -- therapy KW - Pleural Neoplasms -- genetics KW - Pleural Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76798627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chest+surgery+clinics+of+North+America&rft.atitle=Contemporary+approaches+in+the+investigation+and+treatment+of+malignant+pleural+mesothelioma.&rft.au=Pass%2C+H+I&rft.aulast=Pass&rft.aufirst=H&rft.date=1994-08-01&rft.volume=4&rft.issue=3&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Chest+surgery+clinics+of+North+America&rft.issn=10523359&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-08 N1 - Date created - 1994-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oligonucleotides protect cells from the cytotoxicity of several anti-cancer chemotherapeutic drugs. AN - 76796036; 7949248 AB - The possibility of inhibiting gene expression with antisense oligonucleotides (AS ODNs) in combination with more conventional chemotherapy is a very attractive modality in oncology. However, possible interaction between the ODN and drug must be considered. Here we show that ODNs protect cells from the cytostatic/cytotoxic action of actinomycin D (AMD), adriamycin, daunomycin or quinacrine, but not mitomycin, camptothecin, vincristine, cisplatin, etoposide (VP-16) or cycloheximide. The cytoprotective effect depends on ODN length as well as ability to interact directly with the cytotoxic drug and is only slightly sequence selective. JF - Anti-cancer drugs AU - Blagosklonny, M V AU - Neckers, L M AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 437 EP - 442 VL - 5 IS - 4 SN - 0959-4973, 0959-4973 KW - Antineoplastic Agents KW - 0 KW - Oligonucleotides, Antisense KW - Receptors, Tumor Necrosis Factor KW - Dactinomycin KW - 1CC1JFE158 KW - Doxorubicin KW - 80168379AG KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Animals KW - Drug Interactions KW - Dactinomycin -- toxicity KW - Base Sequence KW - Doxorubicin -- metabolism KW - Dactinomycin -- metabolism KW - Cell Survival -- drug effects KW - Daunorubicin -- toxicity KW - Humans KW - Daunorubicin -- metabolism KW - Molecular Sequence Data KW - Doxorubicin -- toxicity KW - Receptors, Tumor Necrosis Factor -- drug effects KW - Oligonucleotides, Antisense -- therapeutic use KW - Antineoplastic Agents -- metabolism KW - Antineoplastic Agents -- toxicity KW - Oligonucleotides, Antisense -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76796036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Oligonucleotides+protect+cells+from+the+cytotoxicity+of+several+anti-cancer+chemotherapeutic+drugs.&rft.au=Blagosklonny%2C+M+V%3BNeckers%2C+L+M&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1994-08-01&rft.volume=5&rft.issue=4&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality among workers in the meat department of supermarkets. AN - 76791835; 7951779 AB - The aim was to study the risk of dying from cancer among workers in the meat department of supermarkets potentially exposed to oncogenic retroviruses and fumes during the wrapping and labelling of meat. Cancer mortality for the period 1949 to 1989 was compared in a previously studied cohort of 10,841 members of a local meatcutters' union in Baltimore, Maryland who worked in the meat department of supermarkets, after an extended follow up of nine years (1981-9). Person-years and deaths were apportioned in five-year intervals by sex, age, and calendar year, and standardised mortality ratio (SMR) and proportional mortality ratio (PMR) analyses were conducted. The United States general population was used as the comparison group. Analyses of SMR and PMR were also conducted for a control group of workers from the same union who worked exclusively in non-meat companies. Among women, an SMR of 1.6 (95% confidence interval (95% CI) 1.1-2.2) and a PMR of 1.5 (95% CI 1.0-2.0) for lung cancer were found. For men, the SMR for cancer of the buccal cavity and pharynx was 1.8 (95% CI 1.0-3.0), and for colon cancer it was 1.5 (95% CI 1.1-2.1). The respective PMRs were 1.9 (95% CI 1.1-3.1) and 1.5 (95% CI 1.1-2.1). Whereas the role of non-occupational factors needs to be taken into account before occupational factors can be implicated in the occurrence of the excess of cancer of the buccal cavity and pharynx, and colon cancer in men, there is reason to suspect that occupational factors may be responsible for the lung cancer excess in women. Thus exposures that occur predominantly in women, such as exposure to fumes during wrapping and labelling, should be investigated as to their role in this excess. JF - Occupational and environmental medicine AU - Johnson, E S AD - Environmental and Molecular Epidemiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 541 EP - 547 VL - 51 IS - 8 SN - 1351-0711, 1351-0711 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Incidence KW - Baltimore -- epidemiology KW - Male KW - Female KW - Cause of Death KW - Neoplasms -- mortality KW - Meat-Packing Industry KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76791835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Cancer+mortality+among+workers+in+the+meat+department+of+supermarkets.&rft.au=Johnson%2C+E+S&rft.aulast=Johnson&rft.aufirst=E&rft.date=1994-08-01&rft.volume=51&rft.issue=8&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-08 N1 - Date created - 1994-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Ind Med. 1986 Mar;43(3):214-5 [3947587] Br J Ind Med. 1993 Nov;50(11):1008-16 [8280626] Br J Ind Med. 1986 Sep;43(9):597-604 [3756110] Scand J Work Environ Health. 1986 Dec;12(6):614-8 [3823811] N Engl J Med. 1987 Apr 23;316(17):1044-50 [3561457] Br J Ind Med. 1987 Jun;44(6):382-95 [3606967] Med Lav. 1987 Jul-Aug;78(4):263-71 [3683274] Cancer Surv. 1987;6(1):39-54 [2825987] J Occup Med. 1989 Mar;31(3):270-2 [2918412] Scand J Work Environ Health. 1989 Feb;15(1):24-9 [2922585] Br J Ind Med. 1989 Mar;46(3):188-91 [2930728] Nature. 1973 Sep 14;245(5420):104-5 [4582759] JAMA. 1973 Nov 5;226(6):639-41 [4800606] Arch Environ Health. 1975 Jun;30(6):269-71 [1137432] Int J Cancer. 1975 Apr 15;15(4):617-31 [1140864] J Occup Med. 1977 Mar;19(3):188-91 [839290] Am Ind Hyg Assoc J. 1980 Jul;41(7):508-12 [7415972] Environ Health Perspect. 1981 Jun;39:93-103 [6786872] Lancet. 1982 Feb 13;1(8268):399 [6120378] J Occup Med. 1982 Apr;24(4):299-304 [7069522] Lancet. 1982 Apr 17;1(8277):913-4 [6122132] Environ Health Perspect. 1982 Nov;45:129-33 [7140685] J Natl Cancer Inst. 1983 Feb;70(2):343-52 [6571941] Lancet. 1983 Mar 5;1(8323):527-8 [6131232] Am Ind Hyg Assoc J. 1983 Mar;44(3):176-83 [6846143] Cancer Lett. 1983 May;19(1):55-60 [6303561] J Occup Med. 1983 Apr;25(4):290-4 [6602212] Environ Health Perspect. 1989 Jul;82:109-24 [2792037] Science. 1990 Jun 29;248(4963):1656-60 [2163544] J Occup Med. 1986 Jan;28(1):23-32 [3485192] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Degradation and disposal of some enzyme inhibitors. Scientific note. AN - 76784153; 7944352 AB - Five enzyme inhibitors (phenylmethylsulfonyl fluoride, 4-amidinophenylmethanesulfonyl fluoride, 4-(2-aminoethyl)benzenesulfonyl fluoride, N alpha-p-tosyl-L-lysine chloromethyl ketone, and N-tosyl-L-phenylalanine chloromethyl ketone) in buffer, DMSO, or stock solutions were completely degraded by adding 1M NaOH and the final reaction mixtures were not mutagenic. The stability of these compounds decreased as the pH increased. JF - Applied biochemistry and biotechnology AU - Lunn, G AU - Sansone, E B AD - Program Resources, Inc./DynCorp, Environmental Control and Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 57 EP - 59 VL - 48 IS - 2 SN - 0273-2289, 0273-2289 KW - Enzyme Inhibitors KW - 0 KW - Mutagens KW - Tosyl Compounds KW - Tosyllysine Chloromethyl Ketone KW - 2104-86-1 KW - Tosylphenylalanyl Chloromethyl Ketone KW - 402-71-1 KW - Sodium Hydroxide KW - 55X04QC32I KW - Phenylmethylsulfonyl Fluoride KW - 57KD15003I KW - Index Medicus KW - Drug Stability KW - Tosyl Compounds -- chemistry KW - Hydrogen-Ion Concentration KW - Sodium Hydroxide -- pharmacology KW - Tosylphenylalanyl Chloromethyl Ketone -- chemistry KW - Tosyllysine Chloromethyl Ketone -- chemistry KW - Chromatography, High Pressure Liquid KW - Phenylmethylsulfonyl Fluoride -- chemistry KW - Enzyme Inhibitors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76784153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+biochemistry+and+biotechnology&rft.atitle=Degradation+and+disposal+of+some+enzyme+inhibitors.+Scientific+note.&rft.au=Lunn%2C+G%3BSansone%2C+E+B&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-08-01&rft.volume=48&rft.issue=2&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Applied+biochemistry+and+biotechnology&rft.issn=02732289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Numt, a recent transfer and tandem amplification of mitochondrial DNA to the nuclear genome of the domestic cat. AN - 76756228; 7932781 AB - The mitochondrial DNA of plant and animal cells is a transcriptionally active genome that traces its origins to a symbiotic infection of eucaryotic cells by bacterial progenitors. As prescribed by the Serial Endosymbiosis Theory, symbiotic organelles have gradually transferred their genes to the eucaryotic genome, producing a functional interaction of nuclear and mitochondrial genes in organelle function. We report here a recent remarkable transposition of 7.9 kb of a typically 17.0-kb mitochondrial genome to a specific nuclear chromosomal position in the domestic cat. The intergrated segment has subsequently become amplified 38-76 times and now occurs as a tandem repeat macrosatellite with multiple-length alleles resolved by pulse-field gel electrophoresis (PFGE) segregating in cat populations. Sequence determination of the nuclear mitochondrial DNA segment, Numt, revealed a d(CA)-rich 8-bp motif [ACACACGT] repeated imperfectly five times at the deletion junction that is a likely target for recombination. The extent and pattern of sequence divergence of Numt genes from the cytoplasmic mtDNA homologues plus the occurrence of Numt in other species of the family Felidae allowed an estimate for the origins of Numt at 1.8-2.0 million years ago in an ancestor of four modern species in the genus Felis. Numt genes do not function in cats; rather, the locus combines properties of nuclear minisatellites and pseudogenes. These observations provide an empirical glimpse of historic genomic events that may parallel the accommodation of organelles in eucaryotes. JF - Journal of molecular evolution AU - Lopez, J V AU - Yuhki, N AU - Masuda, R AU - Modi, W AU - O'Brien, S J AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 174 EP - 190 VL - 39 IS - 2 SN - 0022-2844, 0022-2844 KW - DNA, Complementary KW - 0 KW - DNA, Mitochondrial KW - Index Medicus KW - Pseudogenes KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Symbiosis KW - Sequence Alignment KW - Cells, Cultured KW - Models, Genetic KW - Cats KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Genome KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76756228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Numt%2C+a+recent+transfer+and+tandem+amplification+of+mitochondrial+DNA+to+the+nuclear+genome+of+the+domestic+cat.&rft.au=Lopez%2C+J+V%3BYuhki%2C+N%3BMasuda%2C+R%3BModi%2C+W%3BO%27Brien%2C+S+J&rft.aulast=Lopez&rft.aufirst=J&rft.date=1994-08-01&rft.volume=39&rft.issue=2&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - S75332; GENBANK; S75331; S75326; S75323; S75321; S75083; S75096; S75317; S75329; S75098; S75328; S75099; S75319; S75064; S75063; S75101; S75066; S75065 N1 - SuppNotes - Erratum In: J Mol Evol 1994 Nov;39(5):544 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid evolution of a heteroplasmic repetitive sequence in the mitochondrial DNA control region of carnivores. AN - 76755008; 7932782 AB - We describe a repetitive DNA region at the 3' end of the mitochondrial DNA (mtDNA) control region and compare it in 21 carnivore species representing eight carnivore families. The sequence and organization of the repetitive motifs can differ extensively between arrays; however, all motifs appear to be derived from the core motif "ACGT." Sequence data and Southern blot analysis demonstrate extensive heteroplasmy. The general form of the array is similar between heteroplasmic variants within an individual and between individuals within a species (varying primarily in the length of the array, though two clones from the northern elephant seal are exceptional). Within certain families, notably ursids, the array structure is also similar between species. Similarity between species was not apparent in other carnivore families, such as the mustelids, suggesting rapid changes in the organization and sequence of some arrays. The pattern of change seen within and between species suggests that a dominant mechanism involved in the evolution of these arrays is DNA slippage. A comparative analysis shows that the motifs that are being reiterated or deleted vary within and between arrays, suggesting a varying rate of DNA turnover. We discuss the evolutionary implications of the observed patterns of variation and extreme levels of heteroplasmy. JF - Journal of molecular evolution AU - Hoelzel, A R AU - Lopez, J V AU - Dover, G A AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 191 EP - 199 VL - 39 IS - 2 SN - 0022-2844, 0022-2844 KW - DNA, Complementary KW - 0 KW - DNA, Mitochondrial KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Blotting, Southern KW - Biological Evolution KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Carnivora -- genetics KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76755008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Rapid+evolution+of+a+heteroplasmic+repetitive+sequence+in+the+mitochondrial+DNA+control+region+of+carnivores.&rft.au=Hoelzel%2C+A+R%3BLopez%2C+J+V%3BDover%2C+G+A%3BO%27Brien%2C+S+J&rft.aulast=Hoelzel&rft.aufirst=A&rft.date=1994-08-01&rft.volume=39&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convergent evolution of crystallin gene regulation in squid and chicken: the AP-1/ARE connection. AN - 76752020; 7932777 AB - Previous experiments have shown that the minimal promoters required for function of the squid SL20-1 and SL11 crystallin genes in transfected rabbit lens epithelial cells contain an overlapping AP-1/antioxidant responsive element (ARE) upstream of the TATA box. This region resembles the PL-1 and PL-2 elements of the chicken beta B1-crystallin promoter which are essential for promoter function in transfected primary chicken lens epithelial cells. Here we demonstrate by site-directed mutagenesis that the AP-1/ARE sequence is essential for activity of the squid SL20-1 and SL11 promoters in transfected embryonic chicken lens cells and fibroblasts. Promoter activity was higher in transfected lens cells than in fibroblasts. Electrophoretic mobility shift and DNase protection experiments demonstrated the formation of numerous complexes between nuclear proteins of the embryonic chicken lens and the AP-1/ARE sequences of the squid SL20-1 and SL11 crystallin promoters. One of these complexes comigrated and cross-competed with that formed with the PL-1 element of the chicken beta B1-crystallin promoter. This complex formed with nuclear extracts from the lens, heart, brain, and skeletal muscle of embryonic chickens and was eliminated by competition with a consensus AP-1 sequence. The nonfunctional mutant AP-1/ARE sequences did not compete for complex formation. These data raise the intriguing possibility that entirely different, nonhomologous crystallin genes of the chicken and squid have convergently evolved a similar cis-acting regulatory element (AP-1/ARE) for high expression in the lens. JF - Journal of molecular evolution AU - Tomarev, S I AU - Duncan, M K AU - Roth, H J AU - Cvekl, A AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 134 EP - 143 VL - 39 IS - 2 SN - 0022-2844, 0022-2844 KW - AP-1 KW - Crystallins KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Sequence Alignment KW - Transfection KW - Cells, Cultured KW - Biological Evolution KW - Molecular Sequence Data KW - Promoter Regions, Genetic -- genetics KW - Gene Expression Regulation KW - DNA Fingerprinting KW - Crystallins -- genetics KW - Decapodiformes -- genetics KW - Chickens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76752020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Convergent+evolution+of+crystallin+gene+regulation+in+squid+and+chicken%3A+the+AP-1%2FARE+connection.&rft.au=Tomarev%2C+S+I%3BDuncan%2C+M+K%3BRoth%2C+H+J%3BCvekl%2C+A%3BPiatigorsky%2C+J&rft.aulast=Tomarev&rft.aufirst=S&rft.date=1994-08-01&rft.volume=39&rft.issue=2&rft.spage=134&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-31 N1 - Date created - 1994-10-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - AP-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of oral mucosal lesions in United States schoolchildren: 1986-87. AN - 76727738; 7924239 AB - Oral mucosal lesion findings from a national multistage probability oral health survey of United States schoolchildren in kindergarten through grade 12 are reported. In the 1986-87 school year 39,206 children aged 5-17 yr were examined by 14 dentists trained in standardized clinical diagnostic criteria for dental caries, periodontal conditions and oral mucosal lesions. In addition all children were asked whether or not they ever had "cold sores," "fever blisters," or "canker sores", and adolescents (grades 6-12) were questioned about their history of tobacco use. About 4% of the children had one or more oral mucosal lesions present at the time of the examination, while 33 and 37% reported a history of recurrent herpes labialis and recurrent aphthous ulcers, respectively. The most prevalent lesions clinically observed were recurrent aphthous ulcers (1.23%), recurrent herpes labialis (0.78), smokeless tobacco lesions (0.71), and geographic tongue (0.60). Differences in prevalence were analyzed by age, sex, race, metropolitan area, and geographic region. Almost 10% of 12-17-yr-olds reported current use of some type of tobacco product. In adolescents the current use of tobacco products had a marked effect on the prevalence of oral lesions. JF - Community dentistry and oral epidemiology AU - Kleinman, D V AU - Swango, P A AU - Pindborg, J J AD - National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 243 EP - 253 VL - 22 IS - 4 SN - 0301-5661, 0301-5661 KW - Dentistry KW - Index Medicus KW - Probability KW - Age Factors KW - Stomatitis, Aphthous -- epidemiology KW - Sex Factors KW - Humans KW - Smoking -- adverse effects KW - Child KW - Dental Health Surveys KW - Child, Preschool KW - Glossitis, Benign Migratory -- epidemiology KW - Herpes Labialis -- epidemiology KW - Ethnic Groups KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Plants, Toxic KW - Mouth Mucosa -- pathology KW - Tobacco, Smokeless -- adverse effects KW - Mouth Diseases -- epidemiology KW - Mouth Mucosa -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76727738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Community+dentistry+and+oral+epidemiology&rft.atitle=Epidemiology+of+oral+mucosal+lesions+in+United+States+schoolchildren%3A+1986-87.&rft.au=Kleinman%2C+D+V%3BSwango%2C+P+A%3BPindborg%2C+J+J&rft.aulast=Kleinman&rft.aufirst=D&rft.date=1994-08-01&rft.volume=22&rft.issue=4&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Community+dentistry+and+oral+epidemiology&rft.issn=03015661&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-02 N1 - Date created - 1994-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unassembled (soluble) vimentin in human myeloid leukemia cell line HL60. AN - 76708997; 7522191 AB - The intermediate filament proteins which include vimentin, desmin, and the keratins are one of three major classes of cytoskeletal proteins in eukaryotic cells. In this study we found that most of the vimentin of undifferentiated HL60 and cells induced to differentiate either along the monocytoid pathway by 12-O-tetradecanoylphorbol-13-acetate (TPA) or along the granulocytic pathway by retinoic acid was soluble in a buffer containing 1% Triton X-100/0.6 mol/l KCl in which the intermediate filament proteins usually are not soluble. HL60 vimentin separated on polyacrylamide gel electrophoresis into two proteins of Mr 55,000 and 54,000 that we detected by immunoblotting. The Mr 55,000 species was the major form in undifferentiated HL60 cells and cells induced by retinoic acid. The distribution of both forms of vimentin changed during induction of differentiation by TPA and after 24 h the Mr 54,000 species was predominant. After an additional 24 h exposure to TPA the relative levels of the two forms of vimentin approached equivalence and a high level of vimentin degradation products was seen. These results suggest that TPA may increase vimentin degradation along a pathway that has a Mr 54,000 intermediate. In addition, the high levels of soluble vimentin in HL60 cells suggests that these cells may be a good model for studying components involved in vimentin assembly. JF - European journal of haematology AU - Takahashi, N AU - Breitman, T R AD - Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 78 EP - 84 VL - 53 IS - 2 SN - 0902-4441, 0902-4441 KW - Antibodies, Monoclonal KW - 0 KW - Desmin KW - Vimentin KW - Tretinoin KW - 5688UTC01R KW - Keratins KW - 68238-35-7 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Keratins -- metabolism KW - Tretinoin -- pharmacology KW - Immunoblotting KW - Tumor Cells, Cultured -- chemistry KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Desmin -- metabolism KW - Keratins -- analysis KW - Cell Differentiation -- drug effects KW - Time Factors KW - Desmin -- analysis KW - Vimentin -- analysis KW - Leukemia, Myeloid -- metabolism KW - Vimentin -- metabolism KW - Vimentin -- chemistry KW - Leukemia, Myeloid -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76708997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+haematology&rft.atitle=Unassembled+%28soluble%29+vimentin+in+human+myeloid+leukemia+cell+line+HL60.&rft.au=Takahashi%2C+N%3BBreitman%2C+T+R&rft.aulast=Takahashi&rft.aufirst=N&rft.date=1994-08-01&rft.volume=53&rft.issue=2&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=European+journal+of+haematology&rft.issn=09024441&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-19 N1 - Date created - 1994-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide production during endotoxic shock in carbon tetrachloride-treated rats. AN - 76693626; 8078502 AB - Earlier studies showed that hepatotoxicant-treated experimental animals were more susceptible than controls to the lethal effects of bacterial endotoxin. The exact mechanisms of this effect were not understood. In this paper we showed that nitric oxide (.NO) was produced in whole blood and in liver tissues of rats that had been treated with a nonlethal dose of CCl4 (1.3 g/kg) followed by a low dose of lipopolysaccharide (LPS) (100 micrograms/kg). EPR spectroscopy was used in this study to detect nitrosyl-protein complexes. Hemoglobin-nitrosyl complexes were detected in both whole blood and liver. By performing analyses of EPR spectra obtained from hepatocytes exposed to .NO, we were able to identify EPR signals attributable to nitrosyl-cytochrome P420 in rat liver. We found that nitrosyl complex formation in red blood cells and liver was inhibited by treatment with NG-mono-methyl-L-arginine, suggesting enzymatic biosynthesis of .NO. A small but significant inhibition of nitrosyl complex formation by gadolinium trichloride pretreatment was found in the liver, suggesting that Kupffer cells were also involved in .NO biosynthesis, because this treatment decreased Kupffer cells. There was a synergistic effect of CCl4 and LPS on the serum levels of the hepatic enzymes aspartate aminotransferase, alanine amino-transferase, lactate dehydrogenase, and sorbitol dehydrogenase, which are indices of parenchymal cell damage. NG-Mono-methyl-L-arginine treatment increased these hepatic enzyme activities, suggesting a protective role for .NO. EPR resonances at g approximately 2.48, 2.29, and 1.91, due to low-spin cytochromes P450/P420 (FE3+), were decreased in the livers of LPS-induced rats that had been previously treated with CCl4, indicating cytochrome P450/P420 destruction or at least a change in the valence state of the cytochrome P450/P420 heme groups to Fe2+ in the presence of .NO. Because nitrosyl-cytochrome P450 is not stable, the concomitant detection of nitrosyl-cytochrome P420 (Fe2+) could account, at least in part, for the decrease of the ferric low-spin heme groups. Our novel observations of hepatic nitrosyl species suggest that .NO plays an important role during hepatic injury caused by CCl4 in hosts exposed to endotoxin. JF - Molecular pharmacology AU - Chamulitrat, W AU - Jordan, S J AU - Mason, R P AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 391 EP - 397 VL - 46 IS - 2 SN - 0026-895X, 0026-895X KW - Cytochromes KW - 0 KW - Lipopolysaccharides KW - Nitric Oxide KW - 31C4KY9ESH KW - cytochrome P420 KW - 9035-49-8 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - L-Iditol 2-Dehydrogenase KW - EC 1.1.1.14 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Rats KW - Aspartate Aminotransferases -- blood KW - Rats, Sprague-Dawley KW - Alanine Transaminase -- blood KW - L-Iditol 2-Dehydrogenase -- blood KW - Liver -- drug effects KW - Electron Spin Resonance Spectroscopy KW - L-Lactate Dehydrogenase -- blood KW - Lipopolysaccharides -- toxicity KW - Male KW - Cytochromes -- metabolism KW - Nitric Oxide -- biosynthesis KW - Carbon Tetrachloride -- toxicity KW - Shock, Septic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76693626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide+production+during+endotoxic+shock+in+carbon+tetrachloride-treated+rats.&rft.au=Chamulitrat%2C+W%3BJordan%2C+S+J%3BMason%2C+R+P&rft.aulast=Chamulitrat&rft.aufirst=W&rft.date=1994-08-01&rft.volume=46&rft.issue=2&rft.spage=391&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 - 1994-10-05 N1 - Date created - 1994-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in the regulation of phosphatidylinositol-specific phospholipase C in normal and neoplastic keratinocytes. AN - 76664458; 8068182 AB - The induction of epidermal differentiation by Ca2+ in vitro is associated with enhanced activity of phosphatidylinositol-specific phospholipase C (PLC). Neoplastic keratinocyte cell lines expressing a mutant c-Ha-ras gene and normal keratinocytes transformed to the neoplastic phenotype by transduction with the v-Ha-ras gene (v-Ha-ras keratinocytes) have elevated constitutive activity of PLC that increases further in response to Ca2+, but the cells do not differentiate normally. PLC-gamma 1 (145 kDa) is the major isoform detected by immunoblotting of extracts from control, v-Ha-ras, and neoplastic keratinocyte cell lines cultured in 0.05 mM Ca2+ medium. The amount of PLC-gamma 1 protein was higher in neoplastic cell lines than in normal and v-Ha-ras keratinocytes that had similar PLC-gamma 1 protein levels. Thus, higher PLC-gamma 1 protein levels cannot account for the elevated constitutive activity PLC in v-Ha-ras keratinocytes. After induction of differentiation by Ca2+, the amount of PLC-gamma 1 protein increased in all cell types, and PLC-delta 1 (85 kDa), barely detectable in 0.05 mM Ca2+, increased. PLC-beta 1 was not detected at any Ca2+ concentration. PLC-gamma 1 and PLC-delta 1 mRNA did not increase after elevation of extracellular Ca2+, suggesting that posttranscriptional mechanisms can regulate PLC-gamma 1 and PLC-delta 1 protein levels in normal and neoplastic keratinocytes. Activation of protein kinase C by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the stimulation of inositol phosphate (InsP) formation by Ca2+ but did not alter basal InsP levels in normal keratinocytes. In contrast, TPA treatment reduced both Ca(2+)-stimulated and basal InsP formation in neoplastic cells lines and v-Ha-ras keratinocytes. In both normal and v-Ha-ras keratinocytes labeled with [32P]orthophosphate, antibodies against PLC-gamma 1 immunoprecipitated a complex of 32P-labeled proteins. The relative labeling of the PLC-gamma 1 band was greater in normal than in v-Ha-ras keratinocytes. Furthermore, treatment with TPA specifically increased the relative phosphorylation of PLC-gamma 1 in v-Ha-ras keratinocytes but not in normal keratinocytes. These results suggest that the negative regulation of constitutive activity of PLC by protein kinase C differs in normal and neoplastic keratinocytes and that this could be the mechanism of increased PLC activity produced by an oncogenic ras gene in keratinocytes. JF - Molecular carcinogenesis AU - Punnonen, K AU - Denning, M F AU - Rhee, S G AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 216 EP - 225 VL - 10 IS - 4 SN - 0899-1987, 0899-1987 KW - Inositol Phosphates KW - 0 KW - Isoenzymes KW - RNA, Messenger KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - Phosphoinositide Phospholipase C KW - EC 3.1.4.11 KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Inositol Phosphates -- metabolism KW - Gene Expression KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Isoenzymes -- metabolism KW - Calcium -- metabolism KW - Phosphorylation KW - Cells, Cultured KW - In Vitro Techniques KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Phosphoric Diester Hydrolases -- genetics KW - Keratinocytes -- enzymology KW - Phosphoric Diester Hydrolases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76664458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differences+in+the+regulation+of+phosphatidylinositol-specific+phospholipase+C+in+normal+and+neoplastic+keratinocytes.&rft.au=Punnonen%2C+K%3BDenning%2C+M+F%3BRhee%2C+S+G%3BYuspa%2C+S+H&rft.aulast=Punnonen&rft.aufirst=K&rft.date=1994-08-01&rft.volume=10&rft.issue=4&rft.spage=216&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 - 1994-09-27 N1 - Date created - 1994-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation and characterization of novel plasmid-encoded umuC mutants. AN - 76640954; 8051014 AB - Most inducible mutagenesis in Escherichia coli is dependent upon the activity of the UmuDC proteins. The role of UmuC in this process is poorly understood, possibly because of the limited number of genetically characterized umuC mutants. To better understand the function of the UmuC protein in mutagenic DNA repair, we have isolated several novel plasmid-encoded umuC mutants. A multicopy plasmid that expressed UmuC at physiological levels was constructed and randomly mutagenized in vitro by exposure to hydroxylamine. Mutated plasmids were introduced into the umu tester strain RW126, and 16 plasmids that were unable to promote umuC-dependent spontaneous mutator activity were identified by a colorimetric papillation assay. Interestingly, these plasmid mutants fell into two classes: (i) 5 were expression mutants that produced either too little or too much wild-type UmuC protein, and (ii) 11 were plasmids with structural changes in the UmuC protein. Although hydroxylamine mutagenesis was random, most of the structural mutants identified in the screen were localized to two regions of the UmuC protein; four mutations were found in a stretch of 30 amino acids (residues 133 to 162) in the middle of the protein, while four other mutations (three of which resulted in a truncated UmuC protein) were localized in the last 50 carboxyl-terminal amino acid residues. These new plasmid umuC mutants, together with the previously identified chromosomal umuC25, umuC36, and umuC104 mutations that we have also cloned, should prove extremely useful in dissecting the genetic and biochemical activities of UmuC in mutagenic DNA repair. JF - Journal of bacteriology AU - Woodgate, R AU - Singh, M AU - Kulaeva, O I AU - Frank, E G AU - Levine, A S AU - Koch, W H AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 5011 EP - 5021 VL - 176 IS - 16 SN - 0021-9193, 0021-9193 KW - impB KW - mucB KW - samB KW - umuC KW - Bacterial Proteins KW - 0 KW - DNA Primers KW - Escherichia coli Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Base Sequence KW - Sequence Alignment KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Plasmids KW - Mutation KW - DNA Replication KW - DNA Primers -- chemistry KW - Bacterial Proteins -- genetics KW - SOS Response (Genetics) KW - Escherichia coli -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76640954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Isolation+and+characterization+of+novel+plasmid-encoded+umuC+mutants.&rft.au=Woodgate%2C+R%3BSingh%2C+M%3BKulaeva%2C+O+I%3BFrank%2C+E+G%3BLevine%2C+A+S%3BKoch%2C+W+H&rft.aulast=Woodgate&rft.aufirst=R&rft.date=1994-08-01&rft.volume=176&rft.issue=16&rft.spage=5011&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 - 1994-09-07 N1 - Date created - 1994-09-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - impB; mucB; samB; umuC N1 - SuppNotes - Cited By: Science. 1968 Apr 12;160(3824):149-59 [4868223] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9685-9 [1946387] Mol Gen Genet. 1977 Nov 14;156(2):121-31 [340898] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Mol Gen Genet. 1978 Sep 20;165(1):87-93 [362169] Proc Natl Acad Sci U S A. 1981 Sep;78(9):5749-53 [7029544] J Mol Biol. 1983 Feb 25;164(2):175-92 [6302271] Microbiol Rev. 1984 Mar;48(1):60-93 [6371470] Gene. 1984 Nov;31(1-3):165-71 [6098521] J Bacteriol. 1985 Apr;162(1):155-61 [2984171] Mol Gen Genet. 1985;199(1):133-40 [3889546] Proc Natl Acad Sci U S A. 1985 May;82(10):3325-9 [3159017] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4193-7 [3889923] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4331-5 [2989816] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4336-40 [2989817] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6226-30 [2994067] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6805-9 [3309946] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1806-10 [3126496] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811-5 [3279417] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1816-20 [3279418] J Bacteriol. 1988 May;170(5):2163-73 [2834329] Microbiol Rev. 1988 Sep;52(3):354-74 [3054467] 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] Mol Gen Genet. 1988 Nov;214(3):467-73 [2851096] J Bacteriol. 1989 May;171(5):2415-23 [2651400] Proc Natl Acad Sci U S A. 1989 Oct;86(19):7301-5 [2552436] J Bacteriol. 1989 Nov;171(11):6117-25 [2572581] Proc Natl Acad Sci U S A. 1989 Nov;86(21):8363-7 [2554312] Mutat Res. 1990 Mar;229(1):79-87 [2179713] J Bacteriol. 1990 Apr;172(4):2105-12 [2180917] Nucleic Acids Res. 1990 Apr 25;18(8):2153-7 [2186377] Mutat Res. 1992 Mar;281(3):221-5 [1371846] J Bacteriol. 1992 Apr;174(8):2517-24 [1556072] J Bacteriol. 1992 May;174(10):3133-9 [1349601] Mol Gen Genet. 1992 Apr;232(3):489-97 [1534140] Mol Gen Genet. 1992 Jun;233(3):443-8 [1320188] J Bacteriol. 1992 Nov;174(21):6844-51 [1400235] Mol Microbiol. 1992 Aug;6(16):2213-8 [1406263] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10777-81 [1438275] Mutat Res. 1993 Jan;285(1):95-9 [7678139] J Bacteriol. 1993 Sep;175(17):5411-9 [8366028] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8169-73 [8367479] J Mol Biol. 1994 Jan 14;235(2):465-71 [8289275] Mol Microbiol. 1993 Dec;10(5):963-71 [7934872] J Bacteriol. 1990 Jun;172(6):3030-6 [2188949] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7190-4 [2205854] Mol Gen Genet. 1990 Jun;222(1):166-8 [2233676] Mol Gen Genet. 1991 Sep;229(1):10-6 [1654503] Biochimie. 1991 Apr;73(4):437-48 [1911944] Biochimie. 1991 Apr;73(4):479-84 [1911948] Mutat Res. 1991 Sep-Oct;250(1-2):183-97 [1944335] Mutat Res. 1991 Sep-Oct;250(1-2):199-204 [1944336] Mol Gen Genet. 1972;119(2):93-102 [4565757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. AN - 76634716; 8053698 AB - The frequency of melanoma and nonmelanoma skin cancer is increasing rapidly in the United States. However, the linkage of these cancers to sun exposure has been questioned because of differences in anatomic site distribution. To obtain insights into the development of these skin cancers, we examined reports of 132 patients with xeroderma pigmentosum (XP), an inherited cancer-prone, DNA repair-deficient disorder with marked clinical and laboratory UV hypersensitivity. Malignant skin neoplasms were present in 70% of the patients with XP at a median age of 8 years, which is 50 years earlier than in the US white population. Fifty-seven percent of the patients had basal cell or squamous cell carcinoma, and 22% had melanoma. The frequency of melanomas, like the frequency of nonmelanoma skin cancers (basal cell and squamous cell carcinomas), anterior eye cancers, and tongue cancers, but unlike that of internal neoplasms, was increased 1000-fold or more in patients with XP who were younger than 20 years. As in the general population, the anatomic distribution of melanomas was different from that of nonmelanomas in the patients with XP. These data suggest that (1) DNA repair plays a major role in the prevention of cutaneous cancers in the general population and (2) sunlight exposure is responsible for the induction of melanoma as well as nonmelanoma skin cancer in patients with XP, although acting by different mechanisms for the two types of skin cancer. JF - Archives of dermatology AU - Kraemer, K H AU - Lee, M M AU - Andrews, A D AU - Lambert, W C AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Md. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 1018 EP - 1021 VL - 130 IS - 8 SN - 0003-987X, 0003-987X KW - Abridged Index Medicus KW - Index Medicus KW - Tongue Neoplasms -- epidemiology KW - Age Factors KW - Carcinoma, Squamous Cell -- epidemiology KW - Cocarcinogenesis KW - Neoplasms, Multiple Primary -- epidemiology KW - Eye Neoplasms -- epidemiology KW - Humans KW - Carcinoma, Basal Cell -- epidemiology KW - Child KW - Child, Preschool KW - Infant KW - Adult KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Skin Neoplasms -- genetics KW - DNA Repair KW - Melanoma -- genetics KW - Xeroderma Pigmentosum -- epidemiology KW - Sunlight -- adverse effects KW - Skin Neoplasms -- etiology KW - Melanoma -- etiology KW - Skin Neoplasms -- epidemiology KW - Xeroderma Pigmentosum -- genetics KW - Xeroderma Pigmentosum -- complications KW - Melanoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76634716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dermatology&rft.atitle=The+role+of+sunlight+and+DNA+repair+in+melanoma+and+nonmelanoma+skin+cancer.+The+xeroderma+pigmentosum+paradigm.&rft.au=Kraemer%2C+K+H%3BLee%2C+M+M%3BAndrews%2C+A+D%3BLambert%2C+W+C&rft.aulast=Kraemer&rft.aufirst=K&rft.date=1994-08-01&rft.volume=130&rft.issue=8&rft.spage=1018&rft.isbn=&rft.btitle=&rft.title=Archives+of+dermatology&rft.issn=0003987X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Platelet-activating factor induces airway mucin release via activation of protein kinase C: evidence for translocation of protein kinase C to membranes. AN - 76630996; 8049080 AB - Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent assay using a monoclonal antibody raised against airway mucin-type glycoproteins. Coincubation of FTEC with PAF (5 microM) and pharmacologic PKC inhibitors, sphingosine, H7, or calphostin C, inhibited PAF-induced mucin secretion at 30 min. The PKC inhibitors produced a concentration-dependent, noncytotoxic inhibition. Exposure of FTEC with the PKC activator phorbol 12-myristate 13-acetate (PMA), failed to increase the release of mucin. Stimulation of FTEC with PAF caused a transient increase of membrane-bound PKC activity after 5 min of stimulation. PMA also induced the translocation of PKC activity from the cytosol to the membrane fraction, which was still present after 15 min of exposure. Determination of the specific PKC isozyme(s) involved in PAF-induced mucin release was performed by immunoblot analysis of the subcellular fractions using a battery of antibodies against various PKC isozymes (anti-PKC alpha, beta, delta, gamma, epsilon, and zeta). We found that PKC zeta (mol wt approximately 70 kD) was a major identifiable PKC isozyme present in the cytosolic fraction of FTEC. Furthermore, PKC zeta isozyme was also found to translocate to the membrane fraction following PAF exposure. Thus, these results demonstrate the crucial role of PKC in the intracellular events that culminate in mucin release following PAF stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) JF - American journal of respiratory cell and molecular biology AU - Larivée, P AU - Levine, S J AU - Martinez, A AU - Wu, T AU - Logun, C AU - Shelhamer, J H AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 199 EP - 205 VL - 11 IS - 2 SN - 1044-1549, 1044-1549 KW - Isoenzymes KW - 0 KW - Isoquinolines KW - Mucins KW - Piperazines KW - Platelet Activating Factor KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Sphingosine KW - NGZ37HRE42 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Centrifugation, Density Gradient KW - Animals KW - Cell Membrane -- enzymology KW - Enzyme Activation KW - Piperazines -- pharmacology KW - Molecular Weight KW - Isoenzymes -- metabolism KW - Epithelium -- drug effects KW - Cell Fractionation KW - Isoenzymes -- antagonists & inhibitors KW - Isoquinolines -- pharmacology KW - Isoenzymes -- isolation & purification KW - Cells, Cultured KW - Kinetics KW - Cats KW - Epithelium -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Sphingosine -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Platelet Activating Factor -- pharmacology KW - Mucins -- secretion KW - Protein Kinase C -- isolation & purification KW - Trachea -- drug effects KW - Trachea -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76630996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Platelet-activating+factor+induces+airway+mucin+release+via+activation+of+protein+kinase+C%3A+evidence+for+translocation+of+protein+kinase+C+to+membranes.&rft.au=Lariv%C3%A9e%2C+P%3BLevine%2C+S+J%3BMartinez%2C+A%3BWu%2C+T%3BLogun%2C+C%3BShelhamer%2C+J+H&rft.aulast=Lariv%C3%A9e&rft.aufirst=P&rft.date=1994-08-01&rft.volume=11&rft.issue=2&rft.spage=199&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 - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Constitutive expression of inducible nitric oxide synthase in human bronchial epithelial cells induces c-fos and stimulates the cGMP pathway. AN - 76630271; 7519434 AB - Two major roles have been defined for nitric oxide (NO): cell-cell communication mediated by the stimulation of cyclic guanosine 3',5'-monophosphate (cGMP) synthesis and cytotoxicity by direct or indirect interaction of the free radical NO with cellular targets. Thus, pathologic states might result from an alteration of NO pathways, e.g., by deregulated activity of NO synthase. To investigate this hypothesis, we introduced the murine-inducible NO synthase (iNOS) sequence into immortalized human bronchial epithelial cells (BEAS-2B). iNOS activity, measured by conversion of [14C]arginine to [14C]citrulline in the presence of 1 mM EGTA, was higher than 100 pmol/min/mg protein in early passages of iNOS-transfected cells but decreased with cell subculturing. No iNOS activity could be detected in control vector-transfected cells. NO stimulated cGMP production in iNOS-transfected cells, and this effect was inhibited by the iNOS inhibitor NG-monomethyl-L-arginine. In addition, NO production induced c-fos expression and did not interfere with clonal cell growth. These results suggest that BEAS-2B cells constitute a suitable model to study the consequences of iNOS activity on signal transduction pathways in bronchial epithelium. JF - American journal of respiratory cell and molecular biology AU - Felley-Bosco, E AU - Ambs, S AU - Lowenstein, C J AU - Keefer, L K AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 159 EP - 164 VL - 11 IS - 2 SN - 1044-1549, 1044-1549 KW - c-fos KW - Antigens, Polyomavirus Transforming KW - 0 KW - Carbon Radioisotopes KW - DNA Primers KW - Proto-Oncogene Proteins c-fos KW - Citrulline KW - 29VT07BGDA KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Cyclic GMP KW - H2D2X058MU KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Arginine -- metabolism KW - Simian virus 40 -- genetics KW - Humans KW - Mice KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Antigens, Polyomavirus Transforming -- biosynthesis KW - Kinetics KW - Molecular Sequence Data KW - Enzyme Induction KW - Epithelium -- metabolism KW - Cell Line, Transformed KW - Citrulline -- metabolism KW - Cell Division KW - Cyclic GMP -- metabolism KW - Amino Acid Oxidoreductases -- biosynthesis KW - Gene Expression KW - Genes, fos KW - Bronchi -- metabolism KW - Proto-Oncogene Proteins c-fos -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76630271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Constitutive+expression+of+inducible+nitric+oxide+synthase+in+human+bronchial+epithelial+cells+induces+c-fos+and+stimulates+the+cGMP+pathway.&rft.au=Felley-Bosco%2C+E%3BAmbs%2C+S%3BLowenstein%2C+C+J%3BKeefer%2C+L+K%3BHarris%2C+C+C&rft.aulast=Felley-Bosco&rft.aufirst=E&rft.date=1994-08-01&rft.volume=11&rft.issue=2&rft.spage=159&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 - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose selegiline in treatment-resistant older depressive patients. AN - 76627849; 7519005 AB - We examined the effect of high-dose selegiline in 16 treatment-resistant older depressive patients. We hypothesized that selegiline, at a dosage of 60 mg/d, would be at least partially effective but that the higher doses would not maintain the monoamine oxidase B selectivity observed with the lower doses of selegiline. Sixteen treatment-resistant subjects (mean [+/- SD] age, 65.6 +/- 9.3 years) entered a double-blind, randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of mood and behavior were obtained in all subjects, and 10 of the subjects underwent repeated lumbar punctures for analysis of monoamine metabolites in the cerebrospinal fluid. Objective measures of mood and behavior revealed significant improvement in the Hamilton Depression Rating Scale score (37.4% decrease), the Global Depression score (22.7% decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures, however, did not show significant improvement during the 3-week medication trial. Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of systolic blood pressure on standing (15%), but these changes were not accompanied by clinical side effects. Our results suggest that high-dose selegiline can be an effective antidepressant in treatment-resistant older depressive patients. While the selegiline dose required has nonselective monoamine oxidase effects and thus would not be free of possible tyramine interactions, other advantages suggest that further investigations with selegiline are warranted in this population. JF - Archives of general psychiatry AU - Sunderland, T AU - Cohen, R M AU - Molchan, S AU - Lawlor, B A AU - Mellow, A M AU - Newhouse, P A AU - Tariot, P N AU - Mueller, E A AU - Murphy, D L AD - Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, Md. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 607 EP - 615 VL - 51 IS - 8 SN - 0003-990X, 0003-990X KW - Placebos KW - 0 KW - Selegiline KW - 2K1V7GP655 KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Drug Administration Schedule KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Psychiatric Status Rating Scales KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Treatment Outcome KW - Hypotension, Orthostatic -- chemically induced KW - Middle Aged KW - Blood Pressure -- drug effects KW - Female KW - Male KW - Selegiline -- administration & dosage KW - Selegiline -- therapeutic use KW - Depressive Disorder -- psychology KW - Depressive Disorder -- drug therapy KW - Depressive Disorder -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76627849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=High-dose+selegiline+in+treatment-resistant+older+depressive+patients.&rft.au=Sunderland%2C+T%3BCohen%2C+R+M%3BMolchan%2C+S%3BLawlor%2C+B+A%3BMellow%2C+A+M%3BNewhouse%2C+P+A%3BTariot%2C+P+N%3BMueller%2C+E+A%3BMurphy%2C+D+L&rft.aulast=Sunderland&rft.aufirst=T&rft.date=1994-08-01&rft.volume=51&rft.issue=8&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-24 N1 - Date created - 1994-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. AN - 76625848; 8040669 AB - A randomized prospective study was performed to compare the efficacy and toxicity of high-dose intravenous bolus interleukin-2 (IL-2) and a lower-dose intravenous bolus regimen for the treatment of metastatic renal cell carcinoma (RCC). Between March 1991 and April 1993, 125 patients with metastatic RCC were randomized to receive IL-2 by intravenous bolus every 8 hours at either 720,000 IU/kg (high-dose) or 72,000 IU/kg (low-dose) to the maximum-tolerated number of doses (or a maximum of 15 doses). After approximately 7 to 10 days, both treatment groups were re-treated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5 to 6 weeks later went on to receive re-treatment with another course (two cycles) of therapy. Response rates and toxicity were determined for the two treatment arms. One hundred twenty-five patients received a total of 208 courses of therapy. Sixty patients were randomized to receive low-dose, and 65 to receive high-dose IL-2. There were no treatment-related deaths in either arm. There was a greater incidence of grade III or IV thrombocytopenia, malaise, and hypotension in patients who received high-dose IL-2, while patients who received low-dose IL-2 had significantly more infections. Three percent of treatment courses with low-dose IL-2 required vasopressor support, compared with 52% of courses with high-dose IL-2. Patients who received low-dose IL-2 had a 7% complete response (CR) and an 8% partial response (PR) rate, and patients who received high-dose IL-2 had a 3% CR and a 17% PR rate. Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU). JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Yang, J C AU - Topalian, S L AU - Parkinson, D AU - Schwartzentruber, D J AU - Weber, J S AU - Ettinghausen, S E AU - White, D E AU - Steinberg, S M AU - Cole, D J AU - Kim, H I AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 1572 EP - 1576 VL - 12 IS - 8 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Drug Administration Schedule KW - Prospective Studies KW - Injections, Intravenous KW - Infusions, Intravenous KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Kidney Neoplasms -- therapy KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Carcinoma, Renal Cell -- therapy KW - Carcinoma, Renal Cell -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76625848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Randomized+comparison+of+high-dose+and+low-dose+intravenous+interleukin-2+for+the+therapy+of+metastatic+renal+cell+carcinoma%3A+an+interim+report.&rft.au=Yang%2C+J+C%3BTopalian%2C+S+L%3BParkinson%2C+D%3BSchwartzentruber%2C+D+J%3BWeber%2C+J+S%3BEttinghausen%2C+S+E%3BWhite%2C+D+E%3BSteinberg%2C+S+M%3BCole%2C+D+J%3BKim%2C+H+I&rft.aulast=Yang&rft.aufirst=J&rft.date=1994-08-01&rft.volume=12&rft.issue=8&rft.spage=1572&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 - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion. AN - 76616607; 7913721 AB - A phase I study of paclitaxel infused over 96-hours was performed to determine toxicity, maximum-tolerated dose (MTD), and pharmacokinetics in patients with incurable lymphomas and solid tumors. A phase II study was performed at the MTD of paclitaxel in patients with doxorubicin/mitoxantrone-refractory metastatic breast cancer. In the phase I study, paclitaxel dose levels ranged from 120 to 160 mg/m2, administered on a 21-day cycle. Patients with metastatic breast cancer who had either no response or a partial response (PR) to doxorubicin or mitoxantrone and had measurable disease were eligible for the phase I and II studies. Expression of the multidrug resistance (mdr-1) gene was determined in tumor biopsies by mRNA quantitative polymerase chain reaction. Twelve patients received a total of 73 cycles of paclitaxel on the phase I study. Dose-limiting mucositis and/or grade IV granulocytopenia was reached at 160 mg/m2, and 140 mg/m2 was selected as the phase II dose. Thirty-six consecutive patients with metastatic breast cancer were treated, of whom three were not assessable. The median age was 49 years, with disease in the liver and/or lung in 76%. Patients received a median of two prior regimens for metastatic disease, and 73% had no response to prior doxorubicin or mitoxantrone. Of 33 patients treated with paclitaxel, 16 patients (48%) achieved a PR and five (15%) achieved a minor response (MR). With a median potential follow-up duration of 60 weeks, the median progression-free and overall survival durations were 27 and 43 weeks, respectively. No correlation was found between extent of prior treatment or prior response to doxorubicin/mitoxantrone, and response to paclitaxel. Paclitaxel pharmacokinetics showed a correlation between both granulocyte and mucosal toxicity, and serum steady-state concentrations (Css) more than 0.07 mumol/L. Patients with liver metastases had significantly decreased paclitaxel clearance and higher paclitaxel Css. Levels of mdr-1 were uniformly low in all tumor biopsies studied. The recommended phase II dose of paclitaxel is 140 mg/m2 in patients without liver metastases and 105 mg/m2 in patients with liver metastases. Ninety-six-hour infusions of paclitaxel were effective and well tolerated in patients with doxorubicin/mitoxantrone-refractory breast cancer. Prolonged infusion schedules may be more effective than shorter schedules and deserve further study. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Wilson, W H AU - Berg, S L AU - Bryant, G AU - Wittes, R E AU - Bates, S AU - Fojo, A AU - Steinberg, S M AU - Goldspiel, B R AU - Herdt, J AU - O'Shaughnessy, J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 1621 EP - 1629 VL - 12 IS - 8 SN - 0732-183X, 0732-183X KW - mdr-1 KW - Doxorubicin KW - 80168379AG KW - Mitoxantrone KW - BZ114NVM5P KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Administration Schedule KW - Drug Resistance -- genetics KW - Mouth Mucosa KW - Humans KW - Aged KW - Agranulocytosis -- chemically induced KW - Stomatitis -- chemically induced KW - Mitoxantrone -- therapeutic use KW - Adult KW - Doxorubicin -- therapeutic use KW - Middle Aged KW - Female KW - Male KW - Paclitaxel -- administration & dosage KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- mortality KW - Paclitaxel -- adverse effects KW - Paclitaxel -- pharmacokinetics KW - Lung Neoplasms -- drug therapy KW - Lymphoma -- drug therapy KW - Breast Neoplasms -- metabolism KW - Lymphoma -- metabolism KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76616607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Paclitaxel+in+doxorubicin-refractory+or+mitoxantrone-refractory+breast+cancer%3A+a+phase+I%2FII+trial+of+96-hour+infusion.&rft.au=Wilson%2C+W+H%3BBerg%2C+S+L%3BBryant%2C+G%3BWittes%2C+R+E%3BBates%2C+S%3BFojo%2C+A%3BSteinberg%2C+S+M%3BGoldspiel%2C+B+R%3BHerdt%2C+J%3BO%27Shaughnessy%2C+J&rft.aulast=Wilson&rft.aufirst=W&rft.date=1994-08-01&rft.volume=12&rft.issue=8&rft.spage=1621&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 - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr-1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Some perspectives on the nutritional aspects of breast cancer research. Food-derived heterocyclic amines as etiologic agents in human mammary cancer. AN - 76615743; 8039141 AB - Epidemiologic and experimental evidence indicates that dietary factors influence the incidence of mammary gland cancer. The dietary causes of this cancer, however, remain largely unknown. This paper reviews the experimental studies implicating the food-derived heterocyclic amines (HAs) in human breast cancer. Heterocyclic amines are formed at the parts-per-billion levels in meats, such as beef, chicken, pork, and fish, cooked by ordinary methods. 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is among the most prevalent of the HAs in fried and barbecued beef, a staple of the American diet. Chronic administration of PhIP in the diet has been shown to cause mammary gland cancer in rats. Two other food-derived HAs, 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, also have been shown to be mammary carcinogens in rodent models. In rats, heterocyclic amines produce DNA adducts in the mammary gland after metabolic activation. Studies examining human urine for HAs and metabolites confirm that humans who consume cooked meats are exposed to HAs. Studies also reveal that humans can activate HAs metabolically. Therefore, the experimental evidence suggests that the food-derived HAs may be etiologic agents in human breast cancer. Humans, however, are exposed to a complex mixture of carcinogenic and anticarcinogenic agents through their diets. Experimental studies examining the interaction between HAs and other dietary factors with respect to mammary carcinogenesis are warranted. JF - Cancer AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/08/01/ PY - 1994 DA - 1994 Aug 01 SP - 1070 EP - 1077 VL - 74 IS - 3 Suppl SN - 0008-543X, 0008-543X KW - Amines KW - 0 KW - Carcinogens KW - Heterocyclic Compounds KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Abridged Index Medicus KW - Index Medicus KW - Amines -- analysis KW - Humans KW - Cooking KW - Meat -- analysis KW - Imidazoles -- analysis KW - Female KW - Amines -- adverse effects KW - Food Analysis KW - Heterocyclic Compounds -- analysis KW - Carcinogens -- analysis KW - Heterocyclic Compounds -- adverse effects KW - Breast Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76615743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Some+perspectives+on+the+nutritional+aspects+of+breast+cancer+research.+Food-derived+heterocyclic+amines+as+etiologic+agents+in+human+mammary+cancer.&rft.au=Snyderwine%2C+E+G&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1994-08-01&rft.volume=74&rft.issue=3+Suppl&rft.spage=1070&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-24 N1 - Date created - 1994-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequences homologous to 5' splice sites are required for the inhibitory activity of papillomavirus late 3' untranslated regions. AN - 76606243; 8035806 AB - Expression of bovine papillomavirus type 1 (BPV-1) late genes is limited to terminally differentiated keratinocytes in an infected epithelium. We have previously shown that although the BPV-1 late polyadenylation site is functional in nonpermissive cells, a 53-nucleotide (nt) fragment of the late 3' untranslated region acts posttranscriptionally to reduce polyadenylated cytoplasmic RNA levels. This 53-nt fragment does not appear to function by destabilizing polyadenylated cytoplasmic RNA (P. A. Furth and C. C. Baker, J. Virol. 65:5806-5812, 1991). In this study, we used site-directed mutagenesis and deletion analysis to demonstrate that the sequence AAG/GUAAGU, which is identical to the consensus 5' splice site sequence, was both necessary and sufficient for the inhibitory activity of the 53-nt fragment. Furthermore, base pairing between the 5' end of the U1 small nuclear RNA and this 5' splice site-like sequence was shown to be required for the inhibitory activity in vivo. We have also further mapped the human papillomavirus type 16 late 3' inhibitory element (I. M. Kennedy, J. K. Haddow, and J. B. Clements, J. Virol. 65:2093-2097, 1991) to a 51-nt region containing four overlapping sequence motifs with partial homology to 5' splice sites. Mutation of each of these motifs demonstrated that only one of these motifs is required for the inhibitory activity. However, the presence of the other motifs may contribute to the full inhibitory activity of the element. No BPV-1 or human papillomavirus type 16 mRNAs which are spliced by using the potential 5' splice sites present in the viral late 3' untranslated regions have been identified. This suggests that the primary function of these 5' splice site-like sequences is the inhibition of late gene expression. The most likely mechanism of action of these elements is reduction of polyadenylation efficiency, perhaps through interference with 3'-terminal exon definition. JF - Molecular and cellular biology AU - Furth, P A AU - Choe, W T AU - Rex, J H AU - Byrne, J C AU - Baker, C C AD - Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 5278 EP - 5289 VL - 14 IS - 8 SN - 0270-7306, 0270-7306 KW - RNA, Messenger KW - 0 KW - RNA, Small Nuclear KW - RNA, Viral KW - Poly A KW - 24937-83-5 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - RNA Splicing KW - Molecular Sequence Data KW - Papillomaviridae -- genetics KW - RNA, Viral -- genetics KW - Consensus Sequence KW - RNA, Small Nuclear -- genetics KW - Hydrogen Bonding KW - RNA Processing, Post-Transcriptional KW - Poly A -- metabolism KW - Structure-Activity Relationship KW - Gene Expression Regulation, Viral KW - RNA, Messenger -- genetics KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76606243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sequences+homologous+to+5%27+splice+sites+are+required+for+the+inhibitory+activity+of+papillomavirus+late+3%27+untranslated+regions.&rft.au=Furth%2C+P+A%3BChoe%2C+W+T%3BRex%2C+J+H%3BByrne%2C+J+C%3BBaker%2C+C+C&rft.aulast=Furth&rft.aufirst=P&rft.date=1994-08-01&rft.volume=14&rft.issue=8&rft.spage=5278&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11224-8 [1454802] Mol Cell Biol. 1993 Jan;13(1):289-300 [8417332] Mol Cell Biol. 1993 Jan;13(1):578-87 [8417354] Cell. 1993 Mar 26;72(6):881-92 [8458082] Genes Dev. 1993 Apr;7(4):647-59 [8384583] Science. 1993 Apr 9;260(5105):219-22 [8385799] Mol Cell Biol. 1993 May;13(5):2993-3001 [8474457] Mol Cell Biol. 1993 Aug;13(8):5085-98 [8336736] J Virol. 1993 Sep;67(9):5605-16 [8394463] Mol Cell Biol. 1993 Nov;13(11):6841-8 [8413277] Genes Dev. 1992 Dec;6(12B):2554-68 [1285125] Mol Cell Biol. 1993 Dec;13(12):7734-46 [8246990] EMBO J. 1993 Dec 15;12(13):5191-200 [8262062] Mol Cell Biol. 1994 Jan;14(1):77-86 [7903422] Nucleic Acids Res. 1990 Feb 25;18(4):937-47 [1690394] J Virol. 1990 Apr;64(4):1825-9 [2157064] Nucleic Acids Res. 1990 Jun 11;18(11):3161-70 [2356116] Science. 1990 Aug 10;249(4969):614-5 [2143313] Trends Biochem Sci. 1990 Jul;15(7):277-81 [1974368] Virology. 1990 Sep;178(1):254-62 [2167553] Mol Cell Biol. 1990 Dec;10(12):6299-305 [2247057] Genes Dev. 1990 Sep;4(9):1552-9 [1701407] Science. 1991 Jan 4;251(4989):33-4 [1824726] EMBO J. 1991 Jan;10(1):215-9 [1671216] Cell. 1991 Feb 22;64(4):671-4 [1671760] Science. 1991 Mar 1;251(4997):1045-50 [1825520] J Virol. 1991 Apr;65(4):2093-7 [1848319] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2108-12 [1848693] EMBO J. 1991 Jul;10(7):1833-42 [2050120] Science. 1991 Jun 28;252(5014):1823-8 [2063195] Science. 1991 Jun 28;252(5014):1842-5 [2063196] J Mol Biol. 1991 Jul 5;220(1):49-65 [2067018] Trends Biochem Sci. 1991 May;16(5):187-90 [1882420] New Biol. 1991 Jun;3(6):531-7 [1680384] J Virol. 1991 Nov;65(11):5806-12 [1717710] Mol Cell Biol. 1991 Oct;11(10):5291-300 [1656228] J Virol. 1991 Dec;65(12):6677-85 [1682508] Mol Cell Biol. 1991 Dec;11(12):5977-84 [1944273] Int J Cancer. 1992 Feb 1;50(3):356-64 [1310488] Trends Biochem Sci. 1991 Dec;16(12):452-3 [1781021] EMBO J. 1992 Apr;11(4):1513-24 [1373376] J Virol. 1992 Jul;66(7):4242-51 [1318403] Genes Dev. 1992 Aug;6(8):1386-401 [1322855] Mol Cell Biol. 1992 Sep;12(9):3699-705 [1508176] EMBO J. 1992 Dec;11(12):4419-28 [1425577] Cell. 1994 Feb 11;76(3):531-41 [8313473] Mol Cell Biol. 1994 Mar;14(3):2140-6 [8114744] Genes Dev. 1994 Mar 1;8(5):576-86 [7926751] J Virol. 1988 Aug;62(8):2537-43 [2839684] EMBO J. 1988 Aug;7(8):2533-8 [3056718] Nucleic Acids Res. 1988 Nov 11;16(21):9893-908 [3057449] Genes Dev. 1988 Oct;2(10):1258-67 [3060402] J Virol. 1989 Aug;63(8):3529-34 [2545923] Mol Cell Biol. 1989 Aug;9(8):3429-37 [2477685] Mol Cell Biol. 1989 Oct;9(10):4248-58 [2573828] Cell. 1989 Dec 1;59(5):789-95 [2686839] Mol Cell Biol. 1990 Jan;10(1):84-94 [2136768] J Mol Biol. 1990 Jan 5;211(1):103-15 [2299664] Genes Dev. 1989 Dec;3(12B):2180-90 [2628166] Methods Enzymol. 1990;183:252-78 [2314278] Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408-12 [4504350] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Virology. 1981 Jan 30;108(2):251-5 [6258289] Nucleic Acids Res. 1981 Jan 10;9(1):133-48 [6163133] J Virol. 1981 Jun;38(3):973-81 [6264167] Proc Natl Acad Sci U S A. 1981 May;78(5):2727-31 [6265905] J Cell Biochem. 1983;21(3):239-47 [6195168] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):45-52 [6198623] EMBO J. 1984 May;3(5):1083-90 [6203743] Proc Natl Acad Sci U S A. 1985 Feb;82(4):1030-4 [2983327] Cell. 1985 Jul;41(3):845-55 [2408761] J Mol Biol. 1985 Apr 20;182(4):541-54 [2989533] Science. 1985 Jul 19;229(4710):272-5 [2409601] Proc Natl Acad Sci U S A. 1985 Nov;82(22):7590-4 [3865180] Cell. 1986 Sep 12;46(6):827-35 [3757028] Cell. 1986 Nov 21;47(4):555-65 [3779836] Cell. 1987 Jul 17;50(2):237-46 [3647844] EMBO J. 1987 Apr;6(4):1027-35 [3036488] J Virol. 1992 Dec;66(12):7589-96 [1279209] Nature. 1992 Nov 19;360(6401):277-80 [1359430] Mol Cell Biol. 1992 Dec;12(12):5386-93 [1333042] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of N-(4-hydroxyphenyl)retinamide supplementation on vitamin A metabolism. AN - 76599828; 8033144 AB - The efficacy of the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been demonstrated in the inhibition of cancers in a variety of tissues. Moreover, toxicity effects following administration of 4-HPR have been found to be reduced or absent when compared to other retinoids. Pharmacokinetic studies in both animals and humans have focused on the metabolism of 4-HPR and its metabolites, and relatively little information has been published detailing the effects of long-term administration of 4-HPR upon normal endogenous vitamin A metabolism. Thus, the present study was carried out to examine the effects of long-term administration of 4-HPR upon plasma and tissue vitamin A kinetics. Male Sprague-Dawley rats were fed either a control diet sufficient in vitamin A [CON group; 1.0 retinol (ROH) equivalents/g diet] or a CON diet supplemented with 4-HPR (CON+4HPR group; 1173 micrograms 4-HPR/g diet). Following i.v. injection of a physiologically radiolabeled dose of ROH, ROH tracer and tracee kinetics were monitored in plasma and tissues over a 41-day period. Kinetic parameters were determined using the SAAM/CONSAM computer modeling programs to carry out graphical analysis of the tracer concentration curves. Mean plasma ROH levels measured for the CON+4HPR group were reduced to one-third of those of the CON group. Most of the kinetic parameters calculated were found to be significantly altered by the inclusion of 4-HPR in the diet. The fraction of the plasma ROH being catabolized per day (fractional catabolic rate) was nearly twice as high in the CON+4HPR treated group (3.61 +/- 0.49 day-1; mean +/- SD) as compared to the CON group (2.00 +/- 0.68 day-1). The amount of time that vitamin A molecules spent in the body before being lost irreversibly from the system (system residence time) was decreased by half in the CON+4HPR group (19.20 +/- 7.13 days) versus the CON group (38.63 +/- 9.62 days). Despite the increased catabolic rates and decreased system residence times measured for the CON+4HPR group, the estimated vitamin A use in these animals (11.01 +/- 3.10 micrograms/day) was 33% less than that used by the CON group (16.31 +/- 2.47 micrograms/day). Studies investigating the mechanisms by which 4-HPR alters vitamin A kinetics are presently under way in our laboratory. Nevertheless, these results suggest that long-term administration of 4-HPR markedly perturbs normal vitamin A metabolism in rats. Whether 4-HPR similarly alters human vitamin A metabolism with untoward clinical consequences deserves careful evaluation. JF - Cancer research AU - Lewis, K C AU - Zech, L A AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/08/01/ PY - 1994 DA - 1994 Aug 01 SP - 4112 EP - 4117 VL - 54 IS - 15 SN - 0008-5472, 0008-5472 KW - Retinol-Binding Proteins KW - 0 KW - Retinol-Binding Proteins, Plasma KW - Vitamin A KW - 11103-57-4 KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Kidney -- metabolism KW - Liver -- metabolism KW - Male KW - Fenretinide -- adverse effects KW - Vitamin A -- blood KW - Retinol-Binding Proteins -- metabolism KW - Fenretinide -- administration & dosage KW - Vitamin A -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76599828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+N-%284-hydroxyphenyl%29retinamide+supplementation+on+vitamin+A+metabolism.&rft.au=Lewis%2C+K+C%3BZech%2C+L+A%3BPhang%2C+J+M&rft.aulast=Lewis&rft.aufirst=K&rft.date=1994-08-01&rft.volume=54&rft.issue=15&rft.spage=4112&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of T cell differentiation and lymphomagenesis in the thymus of mice with severe combined immune deficiency (SCID). AN - 76594047; 7913108 AB - Severe combined immune deficiency (SCID) mice have a defect in their recombinase system and cannot productively rearrange their immune receptor genes. Thus, SCID thymocytes are arrested at the immature "triple negative" phase, not expressing CD3, CD4, or CD8 surface markers. Whole body irradiation of SCID mice induced maturation of their thymocytes to the CD4+/CD8+ double positive, CD3+low stage of differentiation, and resulted in the generation of a thymic cortical region on histologic examination. No mature single positive T cells were detected in the thymus or the periphery. VDJ rearrangements of TCR-beta with restricted clonality were observed in the double positive cells from a given individual. The CD3 complex was expressed on some of these cells, but the cells failed to mobilize intracellular calcium after cross-linking with CD3 Abs. The double positive cells appeared several weeks after irradiation, persisted for many months in the thymus, and by 6 mo generally developed into metastatic lymphoma. Retroviral activation was undetectable in both the preneoplastic and transformed thymocytes. Thus, it appears that the earliest steps in T cell development can be induced in SCID mice by inducing DNA breaks with radiation. This system represents a model of early thymic development, preneoplasia, and neoplasia. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Murphy, W J AU - Durum, S K AU - Anver, M R AU - Ferris, D K AU - McVicar, D W AU - O'Shea, J J AU - Ruscetti, S K AU - Smith, M R AU - Young, H A AU - Longo, D L AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/08/01/ PY - 1994 DA - 1994 Aug 01 SP - 1004 EP - 1014 VL - 153 IS - 3 SN - 0022-1767, 0022-1767 KW - Antigens, CD3 KW - 0 KW - Antigens, CD8 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - CD4-Positive T-Lymphocytes -- cytology KW - Apoptosis KW - Gamma Rays KW - Antigens, CD8 -- analysis KW - Cell Differentiation KW - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor KW - Mice KW - Mice, Inbred BALB C KW - Calcium -- metabolism KW - Antigens, CD3 -- analysis KW - Whole-Body Irradiation KW - Time Factors KW - T-Lymphocyte Subsets -- cytology KW - Thymus Gland -- cytology KW - Mice, SCID -- immunology KW - T-Lymphocyte Subsets -- immunology KW - Thymus Gland -- pathology KW - Thymus Gland -- microbiology KW - Thymoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76594047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Induction+of+T+cell+differentiation+and+lymphomagenesis+in+the+thymus+of+mice+with+severe+combined+immune+deficiency+%28SCID%29.&rft.au=Murphy%2C+W+J%3BDurum%2C+S+K%3BAnver%2C+M+R%3BFerris%2C+D+K%3BMcVicar%2C+D+W%3BO%27Shea%2C+J+J%3BRuscetti%2C+S+K%3BSmith%2C+M+R%3BYoung%2C+H+A%3BLongo%2C+D+L&rft.aulast=Murphy&rft.aufirst=W&rft.date=1994-08-01&rft.volume=153&rft.issue=3&rft.spage=1004&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-09 N1 - Date created - 1994-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats. AN - 76593991; 8027525 AB - We are studying the development of fibrogenic lesions in the lungs of rats exposed briefly to an aerosol of chrysotile asbestos fibers. This model of asbestosis has enabled us to establish very early cellular events at the specific locations where interstitial fibrosis will develop. These sites, the first alveolar duct bifurcations, are where the fibers are initially deposited and where macrophages first accumulate. In the studies presented here, we used immunohistochemical techniques to show that these macrophages exhibit strong localization of transforming growth factor-beta. In the adjacent developing fibrogenic lesions a clear increase in fibronectin staining was demonstrated and morphological analysis indicated a significant increase in amounts of smooth muscle actin. Such studies are essential in furthering our understanding of the distribution of potential mediators of the fibrogenic process and the cellular responses they elicit during the pathogenesis of disease. JF - The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society AU - Perdue, T D AU - Brody, A R AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 1061 EP - 1070 VL - 42 IS - 8 SN - 0022-1554, 0022-1554 KW - Actins KW - 0 KW - Asbestos, Serpentine KW - Fibronectins KW - Transforming Growth Factor beta KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Analysis of Variance KW - Immunohistochemistry KW - Male KW - Pulmonary Fibrosis -- etiology KW - Asbestos, Serpentine -- toxicity KW - Fibronectins -- metabolism KW - Actins -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Pulmonary Fibrosis -- metabolism KW - Muscle, Smooth -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76593991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.atitle=Distribution+of+transforming+growth+factor-beta+1%2C+fibronectin%2C+and+smooth+muscle+actin+in+asbestos-induced+pulmonary+fibrosis+in+rats.&rft.au=Perdue%2C+T+D%3BBrody%2C+A+R&rft.aulast=Perdue&rft.aufirst=T&rft.date=1994-08-01&rft.volume=42&rft.issue=8&rft.spage=1061&rft.isbn=&rft.btitle=&rft.title=The+journal+of+histochemistry+and+cytochemistry+%3A+official+journal+of+the+Histochemistry+Society&rft.issn=00221554&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene. AN - 76590575; 8033154 AB - A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after injection, the normal SHE cells were readily retrieved from the mice and grew well in culture. In contrast, few sup +I cells were retrieved 5 days after injection and no viable cells were retrieved after 21 days. Sup -II cells were not retrieved at either the 5-day or 21-day harvest, and histological examinations of the sites of injection showed the presence of macrophages, eosinophils, and neutrophils, indicating an inflammatory response associated with necrotic cell death.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Preston, G A AU - Lang, J E AU - Maronpot, R R AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1994/08/01/ PY - 1994 DA - 1994 Aug 01 SP - 4214 EP - 4223 VL - 54 IS - 15 SN - 0008-5472, 0008-5472 KW - Culture Media KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Cell Death -- physiology KW - Animals KW - Precancerous Conditions -- genetics KW - Necrosis KW - Resting Phase, Cell Cycle KW - Mesocricetus KW - Mice, Nude KW - Mice KW - G1 Phase KW - Flow Cytometry KW - Cell Line, Transformed KW - Precancerous Conditions -- pathology KW - Culture Media -- chemistry KW - Cricetinae KW - Apoptosis -- genetics KW - Cell Transformation, Neoplastic -- pathology KW - Genes, Tumor Suppressor KW - Apoptosis -- physiology KW - DNA Replication -- physiology KW - DNA, Neoplasm -- physiology KW - Cell Transformation, Neoplastic -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+apoptosis+by+low+serum+in+cells+of+different+stages+of+neoplastic+progression%3A+enhanced+susceptibility+after+loss+of+a+senescence+gene+and+decreased+susceptibility+after+loss+of+a+tumor+suppressor+gene.&rft.au=Preston%2C+G+A%3BLang%2C+J+E%3BMaronpot%2C+R+R%3BBarrett%2C+J+C&rft.aulast=Preston&rft.aufirst=G&rft.date=1994-08-01&rft.volume=54&rft.issue=15&rft.spage=4214&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production. AN - 76589380; 8035531 AB - The matrix protein of human immunodeficiency virus type 1 is encoded by the amino-terminal portion of the Gag precursor and is postulated to be involved in a variety of functions in the virus life cycle. To define domains and specific amino acid residues of the matrix protein that are involved in virus particle assembly, we introduced 35 amino acid substitution mutations in the human immunodeficiency virus type 1 matrix protein. Using reverse transcriptase and radioimmunoprecipitation analyses and transmission electron microscopy, we assessed the mutants for their ability to form virus particles and to function in the infection process. This study has identified several domains of the matrix protein in which single amino acid substitutions dramatically reduce the efficiency of virus particle production. These domains include the six amino-terminal residues of matrix, the region of matrix between amino acids 55 and 59, and the region between amino acids 84 and 95. Single amino acid substitutions in one of these domains (between matrix amino acids 84 and 88) result in a redirection of the majority of virus particle formation to sites within cytoplasmic vacuoles. JF - Journal of virology AU - Freed, E O AU - Orenstein, J M AU - Buckler-White, A J AU - Martin, M A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 5311 EP - 5320 VL - 68 IS - 8 SN - 0022-538X, 0022-538X KW - Gene Products, gag KW - 0 KW - HIV Antigens KW - Protein Precursors KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - Index Medicus KW - AIDS/HIV KW - HeLa Cells KW - Protein Precursors -- chemistry KW - Humans KW - Molecular Sequence Data KW - Microscopy, Electron KW - Amino Acid Sequence KW - Virus Replication -- physiology KW - Mutagenesis, Insertional KW - Cell Line KW - Radioimmunoprecipitation Assay KW - HIV Antigens -- physiology KW - HIV-1 -- chemistry KW - Gene Products, gag -- physiology KW - HIV Antigens -- chemistry KW - Gene Products, gag -- chemistry KW - HIV-1 -- physiology KW - HIV-1 -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76589380?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Single+amino+acid+changes+in+the+human+immunodeficiency+virus+type+1+matrix+protein+block+virus+particle+production.&rft.au=Freed%2C+E+O%3BOrenstein%2C+J+M%3BBuckler-White%2C+A+J%3BMartin%2C+M+A&rft.aulast=Freed&rft.aufirst=E&rft.date=1994-08-01&rft.volume=68&rft.issue=8&rft.spage=5311&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1988 Jan;62(1):139-47 [3257102] J Virol. 1988 Feb;62(2):479-87 [2826810] Methods Enzymol. 1987;154:367-82 [3323813] J Virol. 1993 Nov;67(11):6387-94 [8411340] J Virol. 1993 Nov;67(11):6499-506 [8411353] Nature. 1993 Oct 14;365(6447):666-9 [8105392] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Jan;68(1):111-22 [8254720] J Virol. 1994 Feb;68(2):1029-39 [7904656] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Apr;68(4):2556-69 [8139035] Nature. 1994 May 12;369(6476):107-8 [8192816] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1989 May;63(5):2370-3 [2649693] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] Arch Virol. 1989;106(1-2):1-13 [2669684] J Virol. 1989 Oct;63(10):4331-43 [2550669] Cell. 1989 Oct 6;59(1):103-12 [2676191] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8964-7 [2479031] Virology. 1978 Jan;84(1):19-31 [202077] Virology. 1980 Apr 15;102(1):205-10 [6245502] Proc Natl Acad Sci U S A. 1981 Dec;78(12):7575-8 [6278479] J Mol Biol. 1984 Apr 5;174(2):297-317 [6325711] J Virol. 1984 Oct;52(1):145-53 [6090691] Mol Cell Biol. 1984 Sep;4(9):1834-42 [6092942] Nature. 1985 Mar 28-Apr 3;314(6009):374-7 [3920530] Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623-7 [2984663] Virology. 1984 Apr 30;134(2):389-97 [6336230] J Virol. 1986 Aug;59(2):284-91 [3016298] J Virol. 1987 Apr;61(4):1045-53 [3493352] Virology. 1987 May;158(1):248-50 [3554734] J Virol. 1987 Sep;61(9):2852-6 [3039173] J Virol. 1988 May;62(5):1808-9 [3357211] J Virol. 1988 Aug;62(8):2578-86 [3260631] J Virol. 1988 Sep;62(9):3217-23 [2841473] Annu Rev Biochem. 1988;57:69-99 [3052287] Annu Rev Cell Biol. 1988;4:611-47 [3058168] Cell. 1989 Nov 17;59(4):591-601 [2573430] EMBO J. 1989 Sep;8(9):2653-60 [2684654] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] Virology. 1990 Mar;175(1):139-48 [1689917] J Virol. 1990 May;64(5):1934-45 [2157861] J Virol. 1990 May;64(5):2265-79 [2109101] J Virol. 1990 Jun;64(6):2653-9 [2186175] J Virol. 1990 Jun;64(6):2743-50 [1692347] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] Nature. 1990 Jul 5;346(6279):84-6 [2164157] J Virol. 1990 Aug;64(8):3995-4001 [2164607] Cell. 1990 Oct 5;63(1):77-86 [2170021] J Virol. 1990 Nov;64(11):5306-16 [1698996] Virology. 1990 Nov;179(1):321-9 [2219727] Virology. 1990 Dec;179(2):874-80 [2238477] EMBO J. 1991 Mar;10(3):535-46 [1705884] 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 Virol. 1991 Jul;65(7):3804-12 [1710290] J Gen Virol. 1991 Jun;72 ( Pt 6):1243-51 [2045790] J Virol. 1991 Aug;65(8):4350-8 [2072454] New Biol. 1990 Nov;2(11):1044-6 [2129296] J Virol. 1991 Sep;65(9):5111-7 [1870215] AIDS Res Hum Retroviruses. 1991 May;7(5):475-83 [1873082] AIDS. 1991 Jun;5(6):617-37 [1652977] AIDS. 1991 Jun;5(6):639-54 [1883539] Virology. 1992 Jan;186(1):25-39 [1727601] J Virol. 1992 May;66(5):3230-5 [1560545] Protein Seq Data Anal. 1991 Dec;4(6):375-6 [1812494] J Virol. 1992 Jul;66(7):4479-87 [1318415] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Sep;66(9):5667-70 [1501299] AIDS Res Hum Retroviruses. 1992 Oct;8(10):1795-801 [1457192] J Gen Virol. 1992 Dec;73 ( Pt 12):3079-86 [1469349] J Virol. 1993 Jul;67(7):4264-73 [7685414] J Virol. 1993 Aug;67(8):4972-80 [8331736] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Different abilities of Friend murine leukemia virus (MuLV) and Moloney MuLV to induce promonocytic leukemia are due to determinants in both psi-gag-PR and env regions. AN - 76589328; 7518530 AB - Moloney murine leukemia virus (M-MuLV) is capable of inducing promonocytic leukemia in 50% of adult BALB/c mice that have received peritoneal injections of pristane, but Friend MuLV strain 57 (F-MuLV) is nonleukemogenic under similar conditions. It was shown earlier that these differences could not be mapped to the U3 region of the virus long terminal repeat, indicating the probable influence of structural genes and/or R-U5 sequences. In this study, reciprocal chimeras containing exchanged structural genes and R-U5 sequences from these two closely related viruses were analyzed for differences in ability to induce disease. Results showed that two regions of F-MuLV, psi-gag-PR and env, when substituted for those of M-MuLV were dramatically disease attenuating. The 5'-most region, which is widely distributed, overlaps with the 5' end of the env intron and includes the RNA packaging region, psi, the entire gag coding region, and the viral protease coding region (PR) of pol. It was also found that reciprocal constructs having substitutions of both of these regions of M-MuLV in an F-MuLV background allowed full reestablishment of promonocytic leukemia. These leukemias were positive for c-myb rearrangements which are characteristic of M-MuLV-induced promonocytic leukemias. Neither region alone, however, was sufficient to produce disease with a greater incidence than 13%. Further studies demonstrated that the inability of viruses with psi, gag, PR, or env sequences from F-MuLV to induce leukemia in this model system was not due to their inability to replicate in hematopoietic tissue, to integrate into the c-myb locus early on after infection in vivo, or to express gag-myb mRNA characteristic of M-MuLV-induced preleukemic cells and acute leukemia. JF - Journal of virology AU - Mukhopadhyaya, R AU - Richardson, J AU - Nazarov, V AU - Corbin, A AU - Koller, R AU - Sitbon, M AU - Wolff, L AD - Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 5100 EP - 5107 VL - 68 IS - 8 SN - 0022-538X, 0022-538X KW - c-myb KW - env KW - gag KW - DNA, Viral KW - 0 KW - Epitopes KW - Gene Products, gag KW - Viral Envelope Proteins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - 3T3 Cells KW - Precancerous Conditions -- microbiology KW - Base Sequence KW - Molecular Sequence Data KW - Mice KW - Mice, Inbred BALB C KW - Mutagenesis, Insertional KW - Female KW - Gene Products, gag -- genetics KW - Leukemia Virus, Murine -- genetics KW - Gene Products, gag -- physiology KW - Viral Envelope Proteins -- physiology KW - Gene Products, gag -- immunology KW - Tumor Virus Infections -- microbiology KW - Leukemia, Myeloid -- microbiology KW - Friend murine leukemia virus -- genetics KW - Viral Envelope Proteins -- immunology KW - Friend murine leukemia virus -- immunology KW - Leukemia Virus, Murine -- pathogenicity KW - Leukemia Virus, Murine -- immunology KW - Friend murine leukemia virus -- pathogenicity KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76589328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Different+abilities+of+Friend+murine+leukemia+virus+%28MuLV%29+and+Moloney+MuLV+to+induce+promonocytic+leukemia+are+due+to+determinants+in+both+psi-gag-PR+and+env+regions.&rft.au=Mukhopadhyaya%2C+R%3BRichardson%2C+J%3BNazarov%2C+V%3BCorbin%2C+A%3BKoller%2C+R%3BSitbon%2C+M%3BWolff%2C+L&rft.aulast=Mukhopadhyaya&rft.aufirst=R&rft.date=1994-08-01&rft.volume=68&rft.issue=8&rft.spage=5100&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myb; env; gag N1 - Genetic sequence - X02794; GENBANK N1 - SuppNotes - Cited By: Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] J Virol. 1993 Sep;67(9):5478-86 [8350407] Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408-11 [6308622] Nature. 1984 May 17-23;309(5965):276-9 [6325950] J Virol. 1984 Oct;52(1):248-54 [6090701] J Virol. 1984 Nov;52(2):448-56 [6092670] Nature. 1984 Nov 8-14;312(5990):159-62 [6095084] Virology. 1985 Feb;141(1):110-8 [2983493] Virology. 1985 Feb;141(1):119-29 [2983494] Proc Natl Acad Sci U S A. 1986 May;83(10):3204-8 [3010282] Mol Cell Biol. 1985 Oct;5(10):2832-5 [3016518] Virology. 1986 Aug;153(1):145-9 [3016984] EMBO J. 1986 Jul;5(7):1615-23 [3462001] Cell. 1986 Dec 26;47(6):851-9 [3465451] Mol Cell Biol. 1987 Jan;7(1):388-97 [3031470] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] J Virol. 1987 Dec;61(12):3721-5 [2824810] J Virol. 1988 Feb;62(2):614-8 [2826819] J Immunol. 1988 Jul 15;141(2):681-9 [2838552] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5698-702 [3165197] J Virol. 1989 Jan;63(1):328-37 [2783259] Nucleic Acids Res. 1989 Mar 11;17(5):2141 [2928127] Curr Top Microbiol Immunol. 1989;149:79-87 [2659284] Nucleic Acids Res. 1989 Jun 26;17(12):4902 [2473446] J Virol. 1990 Jan;64(1):155-60 [2403439] J Virol. 1990 May;64(5):2135-40 [2182908] Virology. 1970 Dec;42(4):1136-9 [4099080] J Virol. 1980 Jan;33(1):475-86 [6245244] Proc Natl Acad Sci U S A. 1980 Jul;77(7):3932-6 [6449003] J Virol. 1981 Apr;38(1):239-48 [6165830] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4874-8 [2352955] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5932-6 [2062871] Virology. 1991 Nov;185(1):99-108 [1656608] Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1619-23 [7679511] J Virol. 1993 Jul;67(7):4056-61 [8510216] J Virol. 1993 Sep;67(9):5146-52 [8394442] Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203-7 [6308605] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coordinate actions of calcium and protein kinase-C in the expression of primary response genes in pituitary gonadotrophs. AN - 76576985; 7518388 AB - Activation of GnRH receptors in cultured pituitary cells and alpha T3-1 gonadotrophs caused prominent, but transient, increases in messenger RNAs for primary response genes (PRGs) including c-fos, c-jun, and junB. GnRH-induced stimulation peaked at 30 min and was dose related, with similar EC50 values (approximately 1 nM) for all three PRGs and higher maximum responses for junB than for c-jun and c-fos. The agonist-induced expression of PRGs was mimicked by activation of protein kinase-C with the phorbol ester phorbol 12-myristate 13-acetate (PMA), which acted additively with GnRH at low concentrations of both stimuli. Depletion of cellular protein kinase-C by prior treatment with PMA reduced GnRH- and PMA-induced expression of PRGs. The protein kinase-C inhibitor staurosporine also attenuated agonist- and phorbol ester-induced PRG expression. Activation of Ca2+ entry by the calcium channel agonist BayK 8644 or high K(+)-induced depolarization caused a concentration-dependent rise in intracellular Ca2+ ([Ca2+]i) and a concentration-dependent and transient expression of PRGs, albeit of smaller amplitudes than those elicited by GnRH and PMA. Ca(2+)-dependent PRG expression was abolished by the calmodulin inhibitor W-7. Parallel measurements of [Ca2+]i and steady-state levels of PRG messenger RNAs indicated that intracellular Ca2+ exerted both additive and suppressive actions over its physiological concentration range on GnRH- and PMA-induced PRG expression. At lower intracellular calcium concentrations, calcium acted additively with low concentrations of GnRH and PMA. However, high calcium concentrations suppressed high agonist- and phorbol ester-induced PRG expression. In contrast, omission of Ca2+ from the extracellular medium significantly enhanced induction of PRGs. These findings indicate that GnRH-induced PRG expression in gonadotrophs is mediated by protein kinase-C and calcium, and that protein kinase-C-dependent induction of PRGs is modulated both positively and negatively by physiological changes in [Ca2+]i. Such coordinate actions of the two signaling molecules provide a mechanism for the control of PRG expression by preferential integration of low strength, and attenuation of high strength, extracellular signals. JF - Endocrinology AU - Cesnjaj, M AU - Catt, K J AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of health, Bethesda, Maryland 20892. Y1 - 1994/08// PY - 1994 DA - August 1994 SP - 692 EP - 701 VL - 135 IS - 2 SN - 0013-7227, 0013-7227 KW - c-fos KW - c-jun KW - junB KW - Receptors, LHRH KW - 0 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester KW - 71145-03-4 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Blood KW - Hypothalamus -- metabolism KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Potassium -- pharmacology KW - Genes, fos KW - Gonadotropin-Releasing Hormone -- pharmacology KW - Signal Transduction KW - Cell Line KW - Genes, jun KW - Receptors, LHRH -- physiology KW - Protein Kinase C -- metabolism KW - Gene Expression -- drug effects KW - Receptors, LHRH -- genetics KW - Calcium -- pharmacology KW - Pituitary Gland -- metabolism KW - Protein Kinase C -- pharmacology KW - Pituitary Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76576985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Coordinate+actions+of+calcium+and+protein+kinase-C+in+the+expression+of+primary+response+genes+in+pituitary+gonadotrophs.&rft.au=Cesnjaj%2C+M%3BCatt%2C+K+J%3BStojilkovic%2C+S+S&rft.aulast=Cesnjaj&rft.aufirst=M&rft.date=1994-08-01&rft.volume=135&rft.issue=2&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-18 N1 - Date created - 1994-08-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun; junB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of intraoperative radiotherapy on vascular grafts in a canine model. AN - 76693267; 8083070 AB - The effects of intraoperative radiotherapy +/- external beam radiotherapy on prosthetic vascular grafts were investigated in a canine model. In 1986 and 1987, 30 adult beagles underwent laparotomy with transection and segmental resection of the infrarenal aorta followed by immediate reconstruction with a prosthetic graft. Intraoperative radiotherapy at varying doses from 0-30 Gy was then administered to all animals. Half of the dogs received 36 Gy external beam radiotherapy in 10 fractions postoperatively. Animals were sacrificed and necropsied at predetermined intervals and as clinically indicated to assess early ( 6 months) effects to the vascular graft and surrounding normal tissue. Histopathologic analyses of irradiated vascular structures were performed and correlations were made with the clinical outcome. The most frequent early clinical toxicity was graft thrombosis, occurring in 7 of 10 animals followed for 6 months. Late (> 6 months) graft stenosis was correlated with intraoperative radiotherapy dose. At 25 Gy, five of six animals developed late occlusion. On histopathologic review, increasing intraoperative dose and increasing total radiotherapy dose (intraoperative+external beam) appeared to correspond with increasing severity of graft changes seen after 6 months of follow-up. Thrombus formation is a frequent early complication of vascular graft placement of the infrarenal aorta in our beagle dog model. Intraoperative doses up to 20 Gy appear to contribute minimally to late graft occlusion, while doses > or = 25 Gy contribute to late occlusion with high likelihood. Both intraoperative dose and total radiotherapy dose correlated with late graft occlusion, and with histopathologic changes in the graft and anastomoses. JF - International journal of radiation oncology, biology, physics AU - Johnstone, P A AU - Sprague, M AU - DeLuca, A M AU - Bacher, J D AU - Hampshire, V A AU - Terrill, R E AU - Kinsella, T J AU - Sindelar, W F AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/30/ PY - 1994 DA - 1994 Jul 30 SP - 1015 EP - 1025 VL - 29 IS - 5 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Animals KW - Dogs KW - Thrombosis -- etiology KW - Radiation Tolerance KW - Radiation Injuries, Experimental -- etiology KW - Graft Occlusion, Vascular -- etiology KW - Female KW - Intraoperative Care KW - Blood Vessel Prosthesis KW - Aorta, Abdominal -- radiation effects KW - Models, Biological KW - Aorta, Abdominal -- surgery KW - Aorta, Abdominal -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76693267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Effects+of+intraoperative+radiotherapy+on+vascular+grafts+in+a+canine+model.&rft.au=Johnstone%2C+P+A%3BSprague%2C+M%3BDeLuca%2C+A+M%3BBacher%2C+J+D%3BHampshire%2C+V+A%3BTerrill%2C+R+E%3BKinsella%2C+T+J%3BSindelar%2C+W+F&rft.aulast=Johnstone&rft.aufirst=P&rft.date=1994-07-30&rft.volume=29&rft.issue=5&rft.spage=1015&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-11 N1 - Date created - 1994-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saliva of Lutzomyia longipalpis sibling species differs in its composition and capacity to enhance leishmaniasis. AN - 76842910; 7972360 AB - Leishmania donovani chagasi parasites, transmitted by sandflies of the Lutzomyia longipalpis species complex, normally cause visceral leishmaniasis. However, in Central America infections frequently result in cutaneous disease. We undertook experiments to investigate the possible influence of sandfly saliva on the course of infection. Erythemas caused by feeding sandflies correlated well with the levels of the erythema-inducing peptide, maxadilan, in their saliva. Saliva of Brazilian flies was the most potent, that of Colombian flies less so, and Costa Rican saliva had very little maxadilan and lacked activity. Nucleotide sequence differences in the maxadilan gene of the three species were detected by 'single strand conformational polymorphism' electrophoresis. Leishmania infections proliferated fastest when coinjected with the saliva of Costa Rican flies. Brazilian flies had less influence, and Colombian flies only a slight effect. Thus Costa Rican Lutzomyia longipalpis, vectors of non-ulcerative cutaneous disease, have very low vasodilatory activity and very little maxadilan, but their saliva strongly enhances cutaneous proliferation of Leishmania infections. Conversely, flies from Colombia and Brazil, vectors of visceral disease, have more maxadilan, but exacerbate cutaneous infections to a lesser degree. These coincidental observations suggest that species of Lutzomyia longipalpis differ in their propensity to modulate the pathology of the disease they transmit. JF - Philosophical transactions of the Royal Society of London. Series B, Biological sciences AU - Warburg, A AU - Saraiva, E AU - Lanzaro, G C AU - Titus, R G AU - Neva, F AD - Laboratory of Malaria Research, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/07/29/ PY - 1994 DA - 1994 Jul 29 SP - 223 EP - 230 VL - 345 IS - 1312 SN - 0962-8436, 0962-8436 KW - DNA Primers KW - 0 KW - Insect Hormones KW - Insect Proteins KW - maxadilan protein, insect KW - 135374-80-0 KW - Index Medicus KW - Animals KW - DNA Primers -- genetics KW - Costa Rica KW - Humans KW - Mice -- parasitology KW - Colombia KW - Base Sequence KW - Brazil KW - Leishmania -- genetics KW - Molecular Sequence Data KW - Insect Hormones -- analysis KW - Mesocricetus -- parasitology KW - Bites and Stings -- parasitology KW - Insect Hormones -- genetics KW - Female KW - Genes, Protozoan -- genetics KW - Cricetinae KW - Leishmaniasis -- transmission KW - Saliva -- chemistry KW - Psychodidae -- parasitology KW - Saliva -- parasitology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76842910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.atitle=Saliva+of+Lutzomyia+longipalpis+sibling+species+differs+in+its+composition+and+capacity+to+enhance+leishmaniasis.&rft.au=Warburg%2C+A%3BSaraiva%2C+E%3BLanzaro%2C+G+C%3BTitus%2C+R+G%3BNeva%2C+F&rft.aulast=Warburg&rft.aufirst=A&rft.date=1994-07-29&rft.volume=345&rft.issue=1312&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.issn=09628436&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-05 N1 - Date created - 1994-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eukaryotic damaged DNA-binding proteins. DNA repair proteins or transcription factors? AN - 76726893; 8092697 JF - Annals of the New York Academy of Sciences AU - Protić, M AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/29/ PY - 1994 DA - 1994 Jul 29 SP - 333 EP - 335 VL - 726 SN - 0077-8923, 0077-8923 KW - DNA-Binding Proteins KW - 0 KW - Transcription Factors KW - Index Medicus KW - Animals KW - DNA Damage KW - Humans KW - Eukaryotic Cells KW - DNA Repair KW - Transcription Factors -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76726893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Eukaryotic+damaged+DNA-binding+proteins.+DNA+repair+proteins+or+transcription+factors%3F&rft.au=Proti%C4%87%2C+M&rft.aulast=Proti%C4%87&rft.aufirst=M&rft.date=1994-07-29&rft.volume=726&rft.issue=&rft.spage=333&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 - 1994-10-18 N1 - Date created - 1994-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Close similarity of baculovirus-expressed n-chimaerin and protein kinase C alpha as phorbol ester receptors. AN - 76587094; 7518459 AB - n-Chimaerin is a recently described phorbol ester receptor that shares homology in its N-terminal region with the cysteine-rich zinc finger domain of protein kinase C. We have expressed n-chimaerin in insect cells using the baculovirus system and have used the isolated, recombinant n-chimaerin to characterize phorbol ester binding and structure-activity relations, lipid requirements, and inhibitor sensitivity. We find that n-chimaerin expressed in the baculovirus system bound [3H]phorbol 12,13-dibutyrate with high affinity (0.17 +/- 0.01 nM). Although having only a single cysteine-rich zinc finger region compared to two for protein kinase C, n-chimaerin thus closely resembled protein kinase C alpha. n-Chimaerin was likewise virtually indistinguishable from protein kinase C alpha in phorbol ester structure-activity relations, in phospholipid requirements, and in inhibition of binding by sphingosine and calphostin C, protein kinase C inhibitors acting on the regulatory domain. We conclude that a number of typical approaches used to implicate protein kinase C in biological function in cells do not discriminate between the n-chimaerin and protein kinase C classes of phorbol ester receptors. JF - The Journal of biological chemistry AU - Areces, L B AU - Kazanietz, M G AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/29/ PY - 1994 DA - 1994 Jul 29 SP - 19553 EP - 19558 VL - 269 IS - 30 SN - 0021-9258, 0021-9258 KW - Caenorhabditis elegans Proteins KW - 0 KW - Carrier Proteins KW - Chimerin 1 KW - Isoenzymes KW - Naphthalenes KW - Nerve Tissue Proteins KW - Phosphatidylserines KW - Phospholipids KW - Polycyclic Compounds KW - Receptors, Drug KW - phorbol ester binding protein KW - phorbol ester receptor KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-alpha KW - calphostin C KW - I271P23G24 KW - Sphingosine KW - NGZ37HRE42 KW - Index Medicus KW - Animals KW - Phospholipids -- pharmacology KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Polycyclic Compounds -- pharmacology KW - Amino Acid Sequence KW - Baculoviridae -- genetics KW - Base Sequence KW - Cells, Cultured KW - Phosphatidylserines -- pharmacology KW - Molecular Sequence Data KW - Sphingosine -- pharmacology KW - Moths -- cytology KW - Protein Kinase C -- metabolism KW - Nerve Tissue Proteins -- drug effects KW - Receptors, Drug -- metabolism KW - Protein Kinase C -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76587094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Close+similarity+of+baculovirus-expressed+n-chimaerin+and+protein+kinase+C+alpha+as+phorbol+ester+receptors.&rft.au=Areces%2C+L+B%3BKazanietz%2C+M+G%3BBlumberg%2C+P+M&rft.aulast=Areces&rft.aufirst=L&rft.date=1994-07-29&rft.volume=269&rft.issue=30&rft.spage=19553&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 - 1994-08-18 N1 - Date created - 1994-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laminin chain assembly. Specific sequences at the C terminus of the long arm are required for the formation of specific double- and triple-stranded coiled-coil structures. AN - 76587739; 8034675 AB - The assembly of laminin chains into double- and triple-stranded structures was studied with recombinant proteins derived from the C-terminal alpha-helical region of the long arm of laminin. Both affinity assays and structural studies demonstrated chain-specific assembly of the B1, B2, and A chains, while associations between homotypic and homologous chains could not be observed. These results suggest that chain selection is controlled by the C-terminal region. Deletion mapping in the B1e and B2e chains identified two sites important for dimer and trimer formation. These two sites were separated by 23 amino acids in the B1e chain, whereas they were adjacent in the B2e chain. The Ae and Am chains contained only one site for trimerization. Site-directed mutagenesis revealed that charged amino acid residues within these sites were essential for association. These results suggest that distinct sites within the C-terminal alpha-helical region of the laminin long arm are critical for the chain-specific assembly of these macro-molecules. JF - The Journal of biological chemistry AU - Utani, A AU - Nomizu, M AU - Timpl, R AU - Roller, P P AU - Yamada, Y AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/22/ PY - 1994 DA - 1994 Jul 22 SP - 19167 EP - 19175 VL - 269 IS - 29 SN - 0021-9258, 0021-9258 KW - Laminin KW - 0 KW - Macromolecular Substances KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - Humans KW - Molecular Sequence Data KW - Microscopy, Electron KW - Mice KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Protein Conformation KW - Cloning, Molecular KW - Laminin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76587739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Laminin+chain+assembly.+Specific+sequences+at+the+C+terminus+of+the+long+arm+are+required+for+the+formation+of+specific+double-+and+triple-stranded+coiled-coil+structures.&rft.au=Utani%2C+A%3BNomizu%2C+M%3BTimpl%2C+R%3BRoller%2C+P+P%3BYamada%2C+Y&rft.aulast=Utani&rft.aufirst=A&rft.date=1994-07-22&rft.volume=269&rft.issue=29&rft.spage=19167&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional role in ligand binding and receptor activation of an asparagine residue present in the sixth transmembrane domain of all muscarinic acetylcholine receptors. AN - 76581490; 8034642 AB - The molecular mechanisms through which muscarinic receptors are activated upon binding of the neurotransmitter acetylcholine (ACh) are still poorly understood. Classical structure-function relationship studies have previously established that the ACh ester moiety plays a key role in muscarinic receptor recognition and activation. Consistent with this notion, all recently proposed three-dimensional muscarinic receptor models predict that an asparagine residue present in transmembrane domain VI of all muscarinic receptors is critically involved in the binding of the ACh ester moiety by means of hydrogen bonding. To test the correctness of this hypothesis, we created several mutant m3 muscarinic receptors in which this residue (Asn507) was replaced with alanine, serine, or aspartic acid. Radioligand binding studies with transfected COS-7 cells showed that, in contrast to the predictions made based on molecular modeling studies, all three mutant receptors were able to bind ACh and the structurally related muscarinic agonist, carbachol, with high affinities which differed from the corresponding wild type values by less than 5-fold. However, all three mutations led to dramatic reductions (235-28,300-fold) in binding affinities for certain subclasses of muscarinic antagonists including atropine-like agents and pirenzepine. The m3(Asn507-->Ala) and m3(Asn507-->Asp) mutant receptors were able to mediate carbachol-induced phosphatidylinositol hydrolysis in a fashion similar to that of the wild type receptor. Interestingly, the m3(Asn507-->Ser) mutant receptor displayed about 2-fold increased basal inositol phosphate levels, raising the possibility that it is constitutively active. In conclusion, our data suggest that the asparagine residue present in transmembrane domain VI of all muscarinic receptors is not critical for ACh binding and agonist-induced receptor activation, but plays a key role in the binding of certain subclasses of muscarinic antagonists. JF - The Journal of biological chemistry AU - Blüml, K AU - Mutschler, E AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/22/ PY - 1994 DA - 1994 Jul 22 SP - 18870 EP - 18876 VL - 269 IS - 29 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Phosphatidylinositols KW - Receptors, Muscarinic KW - Scopolamine Derivatives KW - Quinuclidinyl Benzilate KW - 6581-06-2 KW - Asparagine KW - 7006-34-0 KW - Carbachol KW - 8Y164V895Y KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Acetylcholine KW - N9YNS0M02X KW - N-Methylscopolamine KW - VDR09VTQ8U KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Scopolamine Derivatives -- metabolism KW - Enzyme Activation KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Rats KW - Mutagenesis, Site-Directed KW - Acetylcholine -- metabolism KW - Quinuclidinyl Benzilate -- metabolism KW - Sequence Alignment KW - GTP-Binding Proteins -- metabolism KW - Binding, Competitive KW - In Vitro Techniques KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Carbachol -- pharmacology KW - Asparagine -- chemistry KW - Receptors, Muscarinic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76581490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+role+in+ligand+binding+and+receptor+activation+of+an+asparagine+residue+present+in+the+sixth+transmembrane+domain+of+all+muscarinic+acetylcholine+receptors.&rft.au=Bl%C3%BCml%2C+K%3BMutschler%2C+E%3BWess%2C+J&rft.aulast=Bl%C3%BCml&rft.aufirst=K&rft.date=1994-07-22&rft.volume=269&rft.issue=29&rft.spage=18870&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of plasmacytomas with silicone gel in genetically susceptible strains of mice. AN - 76583589; 8021954 AB - Plasmacytomas can be induced in high frequency in susceptible strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10,14-tetramethylpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcription. Because silicone gels are in widespread medical use and share many of the characteristics of other materials known to be inducers of plasmacytomas, we wished to determine their capacity to induce plasmacytomas in mice. In a series of parallel experiments, corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraperitoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB/cAnPt.DBA/2-Idh1-Pep3 mice, as well as into plasmacytoma-resistant C57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were examined at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for peritoneal plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohistochemical techniques. Metaphase chromosome spreads were made from ascitic plasmacytomas without Colcemid treatment, and metaphase plates were G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsied 125-400 days after the injection of test material. Gas chromatography and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. The silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Neither corn oil used as a control nor 1000-centistoke or 12,500-centistoke dimethylpolysiloxane induced plasmacytomas in these mice. The plasmacytomas were transplantable in syngeneic hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas showed that 30 had t(12;15) translocations, eight had t(6;15) translocations, and three had no translocations. The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials. JF - Journal of the National Cancer Institute AU - Potter, M AU - Morrison, S AU - Wiener, F AU - Zhang, X K AU - Miller, F W AD - Division of Cancer Biology, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/07/20/ PY - 1994 DA - 1994 Jul 20 SP - 1058 EP - 1065 VL - 86 IS - 14 SN - 0027-8874, 0027-8874 KW - Gels KW - 0 KW - Silicones KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Disease Susceptibility KW - Mice KW - Granuloma, Foreign-Body -- pathology KW - Translocation, Genetic KW - Male KW - Female KW - Plasmacytoma -- genetics KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Silicones -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76583589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+plasmacytomas+with+silicone+gel+in+genetically+susceptible+strains+of+mice.&rft.au=Potter%2C+M%3BMorrison%2C+S%3BWiener%2C+F%3BZhang%2C+X+K%3BMiller%2C+F+W&rft.aulast=Potter&rft.aufirst=M&rft.date=1994-07-20&rft.volume=86&rft.issue=14&rft.spage=1058&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 - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1994 Jul 20;86(14):1040-1 [8021949] J Natl Cancer Inst. 1995 Feb 15;87(4):315-6 [7707424] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by lactating Fischer 344 rats and their nursing pups. AN - 76576145; 8021955 AB - An important class of dietary mutagens and carcinogens are the heterocyclic arylamine compounds that have been identified in a variety of cooked, protein-containing foods. Among these heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) is potentially the most important carcinogen for human cancer risk. We have recently observed that PhIP-derived radioactivity is excreted into the breast milk of lactating rats administered [3H]PhIP. To better assess the significance of breast milk as a route of exposure of the newborn to dietary heterocyclic amines, we examined the metabolites of PhIP in breast milk and in urine of nursing pups. Lactating Fischer 344 rats with 5-day-old pups were given a single oral dose of 10 mg/kg of [3H]PhIP. We collected milk from the dams and urine from the pups and then analyzed the samples for metabolites of PhIP, using high-pressure liquid chromatography (HPLC). PhIP-DNA adduct levels in the tissues of the pups were determined by 32P-postlabeling analysis. Three radioactive peaks were observed by HPLC separation of milk samples: an unidentified early eluting peak, 4'-hydroxy-PhIP, and PhIP. Four metabolites and the parent compound were found in urine of the pups nursed by dams given radiolabeled PhIP: PhIP-4'-O-glucuronide, PhIP-4'-sulfate, 4'-hydroxy-PhIP, and N2-hydroxy-PhIP-N3-glucuronide. 4'-Hydroxy-PhIP and its conjugates contributed approximately 60% of the radioactivity found in the urine. By 32P-postlabeling analysis, PhIP-DNA adducts were detected in spleen, lung, heart, kidney, liver, and stomach of pups at mean levels ranging from 0.06 to 0.55 adducts/10(7) nucleotides. The large percentage of 4-hydroxy-PhIP and its conjugates in the urine indicates that 5-day-old pups detoxify PhIP and further metabolize 4'-hydroxy-PhIP obtained from the breast milk. The presence of the glucuronide conjugate of N-hydroxy-PhIP in the urine of pups and the lack of detectable conjugate or N-hydroxylamine itself in breast milk suggest that PhIP from breast milk undergoes metabolic activation via N-hydroxylation in 5-day-old rat pups. This conclusion was further supported by the observation that hepatic S9 fractions from the pups activated PhIP to a mutagen in the Ames Salmonella mutagenicity assay and by the presence of PhIP-DNA adducts in the tissues of the pups. The findings reported here may have carcinogenic and toxicologic implications for the offspring of women who breast-feed and consume a diet rich in cooked meat. JF - Journal of the National Cancer Institute AU - Davis, C D AU - Ghoshal, A AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/07/20/ PY - 1994 DA - 1994 Jul 20 SP - 1065 EP - 1070 VL - 86 IS - 14 SN - 0027-8874, 0027-8874 KW - Carcinogens KW - 0 KW - Imidazoles KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Time Factors KW - Female KW - Milk -- metabolism KW - Carcinogens -- metabolism KW - Imidazoles -- metabolism KW - Lactation -- metabolism KW - Animals, Suckling -- urine KW - Imidazoles -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76576145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Metabolism+of+the+food-derived+carcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+by+lactating+Fischer+344+rats+and+their+nursing+pups.&rft.au=Davis%2C+C+D%3BGhoshal%2C+A%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1994-07-20&rft.volume=86&rft.issue=14&rft.spage=1065&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 - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1994 Jul 20;86(14):1041-2 [8021950] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dimerization of thiol-specific antioxidant and the essential role of cysteine 47. AN - 76632049; 8041739 AB - Thiol-specific antioxidant (TSA) from yeast contains cysteine residues at amino acid positions 47 and 170 but is not associated with obvious redox cofactors. These two cysteines are highly conserved in a family of proteins that exhibit sequence identity of 23-98% with TSA. The roles of Cys-47 and Cys-170 in yeast TSA were investigated by replacing them individually with serine and expressing the mutant TSA proteins (RC47S and RC170S, respectively), as well as wild-type TSA (RWT), in Escherichia coli. Wild-type TSA purified from yeast (YWT) and RWT were both shown to exist predominantly as dimers, whereas RC47S and RC170S existed mainly as monomers under a denaturing condition. This observation suggests that the dimerization of YWT and RWT requires disulfide linkage of Cys-47 and Cys-170. The presence of the Cys-47-Cys-170 linkage in YWT was directly shown by isolation of dimeric tryptic peptides, one monomer of which contained Cys-47 and the other contained Cys-170. A small percentage of YWT, RWT, RC47S, and RC170S molecules formed dimers linked by Cys-47-Cys-47 or Cys-170-Cys-170 disulfide bonds. The antioxidant activity of the various TSA proteins was evaluated from their ability to protect glutamine synthetase against the dithiothreitol/Fe3+/O2 oxidation system. YWT, RWT, and RC170S were equally protective, whereas RC47S was completely ineffective. Thus, Cys-47, but not Cys-170, constitutes the site of oxidation by putative substrate. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chae, H Z AU - Uhm, T B AU - Rhee, S G AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/19/ PY - 1994 DA - 1994 Jul 19 SP - 7022 EP - 7026 VL - 91 IS - 15 SN - 0027-8424, 0027-8424 KW - Antioxidants KW - 0 KW - Biopolymers KW - DNA, Fungal KW - Disulfides KW - Proteins KW - Peroxidases KW - EC 1.11.1.- KW - Peroxiredoxins KW - EC 1.11.1.15 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Immunoblotting KW - Amino Acid Sequence KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Oxidation-Reduction KW - Base Sequence KW - Conserved Sequence KW - Escherichia coli KW - Molecular Sequence Data KW - Cysteine -- chemistry KW - Proteins -- chemistry KW - Saccharomyces cerevisiae -- chemistry KW - Antioxidants -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76632049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dimerization+of+thiol-specific+antioxidant+and+the+essential+role+of+cysteine+47.&rft.au=Chae%2C+H+Z%3BUhm%2C+T+B%3BRhee%2C+S+G&rft.aulast=Chae&rft.aufirst=H&rft.date=1994-07-19&rft.volume=91&rft.issue=15&rft.spage=7022&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 - 1994-08-22 N1 - Date created - 1994-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1988 Apr 5;263(10):4704-11 [2895105] J Biol Chem. 1989 Jan 25;264(3):1488-96 [2643600] J Bacteriol. 1989 Apr;171(4):2049-55 [2649484] Eur J Biochem. 1972 Feb;25(3):420-30 [4402915] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6018-22 [2668950] J Biol Chem. 1993 Aug 5;268(22):16815-21 [8344960] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7017-21 [8041738] J Biol Chem. 1989 Aug 25;264(24):13963-6 [2668278] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. AN - 76628097; 8041788 AB - The iron-responsive element binding protein/cytosolic aconitase functions as either an RNA binding protein that regulates the uptake, sequestration, and utilization of iron or an enzyme that interconverts citrate and isocitrate. These mutually exclusive functions are regulated by changes in cellular iron levels. By site-directed mutagenesis we show that (i) ligation of a [4Fe-4S] cluster is necessary to inactivate RNA binding and activate enzyme function in vivo, (ii) three of four arginine residues of the aconitase active site participate in RNA binding, and (iii) aconitase activity is not required for iron-mediated regulation of RNA binding. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Philpott, C C AU - Klausner, R D AU - Rouault, T A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/19/ PY - 1994 DA - 1994 Jul 19 SP - 7321 EP - 7325 VL - 91 IS - 15 SN - 0027-8424, 0027-8424 KW - Iron-Regulatory Proteins KW - 0 KW - Ligands KW - RNA, Messenger KW - RNA-Binding Proteins KW - Iron KW - E1UOL152H7 KW - Aconitate Hydratase KW - EC 4.2.1.3 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Cytosol -- enzymology KW - Mice KW - Cell Line KW - Cloning, Molecular KW - Binding Sites KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - RNA, Messenger -- metabolism KW - Aconitate Hydratase -- metabolism KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76628097?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bifunctional+iron-responsive+element+binding+protein%2Fcytosolic+aconitase%3A+the+role+of+active-site+residues+in+ligand+binding+and+regulation.&rft.au=Philpott%2C+C+C%3BKlausner%2C+R+D%3BRouault%2C+T+A&rft.aulast=Philpott&rft.aufirst=C&rft.date=1994-07-19&rft.volume=91&rft.issue=15&rft.spage=7321&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 - 1994-08-22 N1 - Date created - 1994-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] EMBO J. 1994 Jan 15;13(2):453-61 [7508861] EMBO J. 1988 Apr;7(4):913-8 [3402439] Proc Natl Acad Sci U S A. 1989 May;86(10):3639-43 [2726740] J Biol Chem. 1989 Jul 5;264(19):11204-10 [2661555] Proteins. 1989;5(4):289-312 [2798408] Mol Cell Biol. 1989 Nov;9(11):5055-61 [2601708] Proc Natl Acad Sci U S A. 1990 Oct;87(20):7958-62 [2172968] J Biol Chem. 1991 Oct 15;266(29):19328-33 [1655783] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10109-13 [1946430] Biochemistry. 1992 Mar 17;31(10):2735-48 [1547214] J Biol Chem. 1992 Apr 15;267(11):7895-903 [1313811] Genes Dev. 1992 Aug;6(8):1357-72 [1379562] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7536-40 [1502165] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11730-4 [1334546] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11735-9 [1281544] Science. 1993 Jan 15;259(5093):365-8 [8420004] Cell. 1993 Jan 15;72(1):19-28 [8380757] Mol Biol Cell. 1993 Jan;4(1):1-5 [8443405] Biochem J. 1954 Dec;58(4):685-92 [13230022] Nature. 1970 Jul 25;227(5256):331-2 [5428426] Anal Biochem. 1980 Sep 1;107(1):220-39 [6254391] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1787-91 [3162307] J Biol Chem. 1993 Mar 15;268(8):5974-8 [8449958] Nucleic Acids Res. 1993 Mar 25;21(6):1457-61 [8464737] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3680-4 [7682716] Cell. 1993 Jun 4;73(5):1031-40 [7684657] Biochemistry. 1993 Jun 1;32(21):5497-502 [8504070] J Biol Chem. 1993 Jun 15;268(17):12699-705 [8509404] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5603-7 [8390672] Science. 1993 Aug 6;261(5122):715-25 [8342038] J Biol Chem. 1993 Aug 25;268(24):17655-8 [8349646] EMBO J. 1993 Sep;12(9):3643-9 [7504626] EMBO J. 1993 Sep;12(9):3651-7 [7504627] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):574-8 [8290565] Science. 1989 Apr 21;244(4902):357-9 [2711187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A circularly permuted recombinant interleukin 4 toxin with increased activity. AN - 76625926; 8041715 AB - Fusion of ligands such as growth factors to other proteins often dramatically reduces the affinity of the ligand for its receptor. With recombinant DNA techniques, the attachment point between the two proteins has until now been restricted to either the amino or the carboxyl terminus of the ligand. However, binding may be greatly compromised if both ends are close to the site at which the ligand binds to its receptor. To construct a single-chain growth factor fusion protein with the connection at a new site on the growth factor, we constructed a DNA fragment encoding circularly permuted interleukin 4 (IL4), termed IL4(38-37). This was accomplished by placing a start codon before position 38, connecting codons 1 and 129 with a sequence encoding a peptide linker, and placing a stop codon after codon 37 of IL4. IL4(38-37) was fused via its new carboxyl terminus, Lys37, to a truncated form of Pseudomonas exotoxin. The purified circularly permuted IL4-toxin bound to the IL4 receptor with 10-fold higher affinity than an IL4-toxin in which the toxin was fused to the carboxyl terminus of IL4. Circular permuteins of growth factors can improve the effectiveness of recombinant fusion proteins, because the junction can be moved to a site on the growth factor which allows it to bind with higher affinity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kreitman, R J AU - Puri, R K AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/19/ PY - 1994 DA - 1994 Jul 19 SP - 6889 EP - 6893 VL - 91 IS - 15 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Bacterial Toxins KW - Codon KW - Exotoxins KW - IL-4-PE40 protein, recombinant KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Interleukin-4 KW - 207137-56-2 KW - DNA KW - 9007-49-2 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- toxicity KW - Protein Conformation KW - Cloning, Molecular KW - Bacterial Proteins -- toxicity KW - Interleukin-4 -- metabolism KW - Interleukin-4 -- toxicity KW - Bacterial Proteins -- metabolism KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Interleukin-4 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76625926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+circularly+permuted+recombinant+interleukin+4+toxin+with+increased+activity.&rft.au=Kreitman%2C+R+J%3BPuri%2C+R+K%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1994-07-19&rft.volume=91&rft.issue=15&rft.spage=6889&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 - 1994-08-22 N1 - Date created - 1994-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5809-13 [1829529] J Immunol. 1991 Apr 1;146(7):2446-52 [1706402] Biochemistry. 1991 Oct 8;30(40):9576-82 [1911743] Biochemistry. 1992 Feb 18;31(6):1621-30 [1737018] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3075-9 [1557415] Gene. 1992 May 1;114(1):103-7 [1316865] Protein Eng. 1991 Dec;4(8):989-94 [1817263] Science. 1992 Jun 19;256(5064):1673-7 [1609277] J Mol Biol. 1983 Apr 5;165(2):407-13 [6188846] J Mol Biol. 1983 Jun 25;167(2):443-60 [6864804] Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 [3006045] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8258-62 [3095831] Science. 1989 Jan 13;243(4888):206-10 [2643160] Mol Cell Biol. 1989 Jul;9(7):2860-7 [2779550] Protein Eng. 1990 Mar;3(4):249-58 [2188262] Annu Rev Biochem. 1992;61:331-54 [1497314] Protein Eng. 1992 Jul;5(5):427-31 [1518791] J Biol Chem. 1992 Oct 5;267(28):20371-6 [1400355] Protein Eng. 1992 Sep;5(6):583-91 [1438170] J Immunol. 1993 Apr 1;150(7):2774-82 [8454854] Gene. 1993 Mar 30;125(2):111-4 [7681803] Biochemistry. 1993 Apr 13;32(14):3549-56 [7682108] FEBS Lett. 1993 Apr 26;321(2-3):163-8 [8386677] Cancer Res. 1993 May 1;53(9):2123-7 [8481914] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5167-71 [7685117] J Biol Chem. 1993 Jul 5;268(19):14065-70 [8314773] Biochemistry. 1993 Jul 6;32(26):6744-62 [8329398] J Biol Chem. 1993 Sep 25;268(27):20668-75 [8376416] Protein Sci. 1993 Sep;2(9):1373-82 [8401223] Biochemistry. 1993 Nov 23;32(46):12311-8 [8241117] Blood. 1993 Dec 1;82(11):3229-40 [8241495] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11980-4 [8265657] Blood. 1994 Jan 15;83(2):426-34 [8286741] Science. 1994 Mar 4;263(5151):1273-6 [8122109] Bioconjug Chem. 1993 Mar-Apr;4(2):112-20 [7873642] J Biol Chem. 1990 Jul 15;265(20):11885-9 [2195027] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9491-4 [2251289] Cancer Res. 1991 Jan 1;51(1):174-80 [1846308] Biochemistry. 1991 Feb 12;30(6):1515-23 [1993171] Eur J Biochem. 1991 Jul 15;199(2):361-9 [2070793] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calorie restriction delays spontaneous tumorigenesis in p53-knockout transgenic mice. AN - 76623642; 8041741 AB - Transgenic mice with both alleles of the p53 tumor suppressor gene (frequently mutated in human tumors) knocked out by gene targeting provide a potentially useful tumorigenesis model because these mice rapidly develop spontaneous tumors. To determine whether tumorigenesis in p53-knockout mice is sensitive to experimental manipulation, tumor development in response to calorie restriction (CR; a potent inhibitor of rodent tumors) was evaluated. Tumor development was monitored for 48 weeks in male nullizygous p53-knockout and wild-type littermate mice (28-30 per treatment group) fed ad libitum (AL) or restricted to 60% of AL carbohydrate calorie intake. CR:p53-knockout mice (median survival = 25 weeks) experienced a delay in tumor onset and subsequent mortality (P = 0.0002) relative to AL:p53-knockout mice (median survival = 16 weeks). Tumor development and mortality in wild-type littermates on either diet treatment were < 4% through 48 weeks. Cell cycle analyses were performed on splenocytes from p53-knockout mice and wild-type littermates after 4 weeks of AL feeding or CR (5 per group). The percentage of splenocytes in S phase of the cell cycle was 3-fold higher for p53-knockout mice than wild-type mice (P < 0.001), and CR reduced the percentage of S-phase splenocytes in both p53-knockout and wild-type mice (P = 0.012). These data demonstrate that tumor development in p53-knockout mice genetically predisposed to tumors can be delayed by CR (possibly via cell cycle modulation) and suggest that these mice provide a very useful model of spontaneous tumorigenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hursting, S D AU - Perkins, S N AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/07/19/ PY - 1994 DA - 1994 Jul 19 SP - 7036 EP - 7040 VL - 91 IS - 15 SN - 0027-8424, 0027-8424 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Animals KW - Alleles KW - Mice, Inbred C57BL KW - Mice KW - Mice, Transgenic KW - Time Factors KW - Male KW - Mutagenesis KW - Mice, Knockout KW - Neoplasms, Experimental -- genetics KW - Energy Intake KW - Neoplasms, Experimental -- prevention & control KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76623642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calorie+restriction+delays+spontaneous+tumorigenesis+in+p53-knockout+transgenic+mice.&rft.au=Hursting%2C+S+D%3BPerkins%2C+S+N%3BPhang%2C+J+M&rft.aulast=Hursting&rft.aufirst=S&rft.date=1994-07-19&rft.volume=91&rft.issue=15&rft.spage=7036&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 - 1994-08-22 N1 - Date created - 1994-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Comput Biomed Res. 1977 Aug;10(4):373-81 [891148] Cancer Res. 1994 Mar 1;54(5):1169-74 [8118801] Gastroenterology. 1990 Feb;98(2):387-91 [2295393] Cancer Lett. 1990 May 15;51(1):67-73 [2337899] Nature. 1990 Dec 20-27;348(6303):747-9 [2259385] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jul 5;253(5015):49-53 [1905840] Nature. 1991 Jul 25;352(6333):345-7 [1852210] Nature. 1992 Mar 19;356(6366):215-21 [1552940] J Nutr. 1992 Jul;122(7):1446-53 [1619471] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 [1323840] Cell. 1992 Nov 13;71(4):587-97 [1423616] Am J Gastroenterol. 1993 Feb;88(2):174-86 [8424417] Cancer Res. 1993 Jun 15;53(12):2750-7 [8389243] FASEB J. 1993 Jul;7(10):938-43 [8344491] Nature. 1993 Sep 2;365(6441):17-8 [8361531] Oncogene. 1994 Feb;9(2):603-9 [8290271] Cytometry. 1980 Nov;1(3):229-37 [6167410] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelin-1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c-fos mRNA in cerebellar granule cells. AN - 76579938; 8034051 AB - Endothelin-1 (ET-1) induced a time- and dose-dependent increase in the levels of mRNA of m2- and m3-muscarinic acetylcholine receptors (mAChRs) in cultured cerebellar granule cells. The levels of immunoprecipitable m3-mAChR protein and total mAChR binding sites were also increased by ET-1 treatment. The up-regulation of m2- and m3-mAChR was blocked by phorbol ester pretreatment to inhibit ET-1-stimulated phosphoinositide hydrolysis and was preceded by an increase in c-fos mRNA levels. Treatments that prevented ET-1-induced c-fos mRNA increase also abolished the subsequent m2- and m3-mAChR mRNA up-regulation, suggesting that c-Fos protein is involved in the ET-1-induced mAChR expression. JF - FEBS letters AU - Fukamauchi, F AU - Chuang, D M AD - Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/18/ PY - 1994 DA - 1994 Jul 18 SP - 263 EP - 267 VL - 348 IS - 3 SN - 0014-5793, 0014-5793 KW - c-fos KW - Endothelins KW - 0 KW - RNA, Messenger KW - Receptors, Muscarinic KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - 2-Aminopurine KW - 452-06-2 KW - Cycloheximide KW - 98600C0908 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Northern KW - Cycloheximide -- pharmacology KW - Immunosorbent Techniques KW - 2-Aminopurine -- pharmacology KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Receptors, Muscarinic -- genetics KW - Endothelins -- pharmacology KW - RNA, Messenger -- metabolism KW - Genes, fos KW - Receptors, Muscarinic -- metabolism KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76579938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endothelin-1+increases+the+levels+of+mRNA+and+protein+of+muscarinic+acetylcholine+receptors+and+c-fos+mRNA+in+cerebellar+granule+cells.&rft.au=Fukamauchi%2C+F%3BChuang%2C+D+M&rft.aulast=Fukamauchi&rft.aufirst=F&rft.date=1994-07-18&rft.volume=348&rft.issue=3&rft.spage=263&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 - 1994-08-17 N1 - Date created - 1994-08-17 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The calcitonin gene-related peptide (CGRP) phenotype is expressed early and up-regulated by resiniferatoxin (RTX) in mouse sensory neurons. AN - 76808641; 7955356 AB - Calcitonin gene-related peptide (CGRP) immunoreactivity was detected at day 2 in vitro (embryonic day 15) in developing mouse dorsal root ganglion (DRG) neurons in primary culture. During 2 weeks of culture the proportion of CGRP-immunoreactive (CGRP-IR) neurons remained around 65-70%, much higher than usually found in adult animals (45-50%). Treatment of cultures with the capsaicin analog resiniferatoxin (RTX; 0.3-30 nM) significantly augmented CGRP immunoreactivity per neuron at all ages investigated without increasing the number of CGRP-immunoreactive cells. The increased CGRP immunoreactivity was observed both in the axonal varicosities and in the perinuclear region of cell bodies. This RTX-induced increase in CGRP immunoreactivity was completely blocked by Ruthenium red (RR). Treatment with the non-esterified form of RTX (resiniferol 9, 13, 14 orthophenylacetate, ROPA) produced no increase. These results suggest that: (1) early expression of the CGRP phenotype is regulated in a cell-autonomous way in developing mouse DRG neurons in vitro; and (2) the RTX-induced increase in CGRP biosynthesis is most likely the result of activating the capsaicin/RTX receptor rather than directly activating the protein kinase C (PKC) pathway in vitro. The results may also reflect qualitative and quantitative differences in capsaicin/RTX sensitivity of sensory neurons between embryonal and adult ages. JF - Brain research. Developmental brain research AU - Jakab, G AU - Szallasi, A AU - Agoston, D AD - Laboratory of Experimental Neuropathology, NINDS, NIH, Bethesda, MD 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 290 EP - 294 VL - 80 IS - 1-2 SN - 0165-3806, 0165-3806 KW - Diterpenes KW - 0 KW - Neurotoxins KW - Calcitonin Gene-Related Peptide KW - 83652-28-2 KW - resiniferatoxin KW - A5O6P1UL4I KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Phenotype KW - Gene Expression -- drug effects KW - Ganglia, Spinal -- cytology KW - Animals KW - Axons -- drug effects KW - Ganglia, Spinal -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Axons -- ultrastructure KW - Mice KW - Ganglia, Spinal -- drug effects KW - Capsaicin -- pharmacology KW - Neurons, Afferent -- metabolism KW - Diterpenes -- pharmacology KW - Calcitonin Gene-Related Peptide -- genetics KW - Calcitonin Gene-Related Peptide -- biosynthesis KW - Up-Regulation -- drug effects KW - Neurotoxins -- pharmacology KW - Neurons, Afferent -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76808641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=The+calcitonin+gene-related+peptide+%28CGRP%29+phenotype+is+expressed+early+and+up-regulated+by+resiniferatoxin+%28RTX%29+in+mouse+sensory+neurons.&rft.au=Jakab%2C+G%3BSzallasi%2C+A%3BAgoston%2C+D&rft.aulast=Jakab&rft.aufirst=G&rft.date=1994-07-15&rft.volume=80&rft.issue=1-2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased phospholipase D activity in multidrug resistant breast cancer cells. AN - 76611804; 8037714 AB - An adriamycin-resistant MCF-7 cell line (300-fold increased resistance vs. wild type MCF-7) showed an increased phorbol ester-stimulated phospholipase D activity of approximately 4-6 times over that found in wild type cells. Phospholipase D activity was assessed by monitoring the mass of phorbol ester-induced phosphatidylethanol. The cellular phospholipase D activity was time- and phorbol ester-concentration-dependent and was obvious whether measured as an increase in the mass of PEt or in the production of 3H-labeled phosphatidylethanol in cells prelabeled with [3H]myristic acid. Phorbol ester also stimulated increases in the production of the mass of cellular diacylglycerol and phosphatidic acid in the adriamycin-resistant cells vs. the wild-type cells. Tests with a series of drug-resistant MCF-7 cell lines revealed a positive correlation between increased drug resistance and phorbol ester-stimulated phospholipase D activity. JF - Biochemical and biophysical research communications AU - Welsh, C J AU - Yeh, G C AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 211 EP - 217 VL - 202 IS - 1 SN - 0006-291X, 0006-291X KW - Diglycerides KW - 0 KW - Fatty Acids, Nonesterified KW - Myristic Acids KW - Phosphatidic Acids KW - Myristic Acid KW - 0I3V7S25AW KW - Doxorubicin KW - 80168379AG KW - Phospholipase D KW - EC 3.1.4.4 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Phosphatidic Acids -- metabolism KW - Tumor Cells, Cultured KW - Kinetics KW - Humans KW - Time Factors KW - Myristic Acids -- metabolism KW - Female KW - Cell Line KW - Fatty Acids, Nonesterified -- metabolism KW - Diglycerides -- metabolism KW - Phospholipase D -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Drug Resistance KW - Doxorubicin -- toxicity KW - Breast Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76611804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+phospholipase+D+activity+in+multidrug+resistant+breast+cancer+cells.&rft.au=Welsh%2C+C+J%3BYeh%2C+G+C%3BPhang%2C+J+M&rft.aulast=Welsh&rft.aufirst=C&rft.date=1994-07-15&rft.volume=202&rft.issue=1&rft.spage=211&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 - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human DNA repair gene, ERCC2 (XPD), corrects ultraviolet hypersensitivity and ultraviolet hypermutability of a shuttle vector replicated in xeroderma pigmentosum group D cells. AN - 76599638; 8033104 AB - To determine the contribution of a human DNA repair gene, ERCC2 (XPD), to mutagenesis in human cells, two ERCC2 (XPD)-transformed xeroderma pigmentosum complementation group D (XPD) cell lines with increased UV survival compared to XP6BE(SV40), the original XPD line, were studied: D6BE-ER2-2 with slightly increased UV survival; and D6BE-ER2-9 with normal UV survival. ERCC2 (XPD) antibody-reactive protein levels were elevated 4.8-fold in D6BE-ER2-2 and 17.6-fold in D6BE-ER2-9 relative to XP6BE(SV40). DNA repair ability was assessed by measuring the ability of the cells to restore expression to UV-treated plasmids. Transfection of pRSVcat exposed to 1000 J/m2 UV resulted in 0.3% chloramphenicol acetyltransferase activity in XP6BE(SV40) cells but 20-80% in D6BE-ER2-2, D6BE-ER2-9, and repair-proficient cells compared to untreated control plasmids. The UV hypersensitivity of the mutagenesis shuttle vector pSP189 in XP6BE(SV40) cells was partially corrected and the UV hypermutability and excess of G:C-->A:T mutations of pSP189 fell to the normal range in D6BE-ER2-2 and D6BE-ER2-9 cells. However, the frequency of plasmids recovered with multiple base substitution mutations was significantly reduced with XP6BE(SV40) cells and remained low in D6BE-ER2-2 and D6BE-ER2-9 cells, when compared with the normal fibroblasts. The human DNA excision repair gene, ERCC2 (XPD), substantially corrected the plasmid UV hypersensitivity and UV hypermutability of xeroderma pigmentosum complementation group D cells; however, the dose response relationship varied for different end points. JF - Cancer research AU - Gözükara, E M AU - Parris, C N AU - Weber, C A AU - Salazar, E P AU - Seidman, M M AU - Watkins, J F AU - Prakash, L AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 3837 EP - 3844 VL - 54 IS - 14 SN - 0008-5472, 0008-5472 KW - ERCC2 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - Transcription Factors KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Ultraviolet Rays KW - Base Sequence KW - Humans KW - Genetic Vectors KW - Adult KW - Molecular Sequence Data KW - Plasmids KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Female KW - Cell Line KW - Cell Survival KW - DNA Repair KW - Xeroderma Pigmentosum -- genetics KW - Proteins -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76599638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+human+DNA+repair+gene%2C+ERCC2+%28XPD%29%2C+corrects+ultraviolet+hypersensitivity+and+ultraviolet+hypermutability+of+a+shuttle+vector+replicated+in+xeroderma+pigmentosum+group+D+cells.&rft.au=G%C3%B6z%C3%BCkara%2C+E+M%3BParris%2C+C+N%3BWeber%2C+C+A%3BSalazar%2C+E+P%3BSeidman%2C+M+M%3BWatkins%2C+J+F%3BPrakash%2C+L%3BKraemer%2C+K+H&rft.aulast=G%C3%B6z%C3%BCkara&rft.aufirst=E&rft.date=1994-07-15&rft.volume=54&rft.issue=14&rft.spage=3837&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 - 1994-08-16 N1 - Date created - 1994-08-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ERCC2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenic specificity of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the supF shuttle vector system. AN - 76591159; 8033094 AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amine mutagens/carcinogens formed from the cooking of meat. Here we used the pSP189 shuttle vector developed by Parris and Seidman (Gene, 117: 1-5, 1992) to study and compare the mutation spectra induced by these compounds. pSP189 was adducted by reaction with the N-acetoxy derivatives of IQ or PhIP. 32P-Postlabeling analysis was used to measure the C8-guanine adduct level and the total adduct levels formed in the plasmid. Plasmids were replicated and mutagenized in repair-proficient [GM0637(SV40)] or repair-deficient [XP12Be(SV40)] human fibroblasts. Resulting inactivation mutations in the supF gene were determined by the formation of white or light blue colonies on indicator bacteria (carrying a lacZ amber mutation) and cycle sequencing. With both compounds in either cell line, 85-93% of the mutations induced were base substitutions and the remainder of the mutations were base deletions. The majority of the substitution mutations involved a single base, and nearly all base substitution mutations (> 97%) were at guanine. This latter finding is consistent with the results from 32P-postlabeling showing that both compounds adduct to the guanine base with the major adduct being formed at the C8-guanine position. The predominant mutation found with IQ and PhIP in either cell line was G:C to T:A transversion, followed by G:C to A:T transition, and then G:C to C:G transversion; these mutations accounted for 59-72%, 19-27%, and 6-14% of total base substitution mutations, respectively. There was a preference seen with both compounds to induce mutations at a guanine base having a neighboring guanine or cytosine (i.e., GG and GC sites). However, despite the striking similarity in the kinds of base substitution mutations induced by IQ and PhIP, their mutation spectra were distinct. For example, in repair-proficient cells, 26% of the mutations induced with PhIP, but not with IQ, also involved a GA site, containing the 5-base pair sequence 5'-GCAGA-3'. Mutation spectra for IQ and PhIP were also different between repair-deficient and repair-proficient cells. The findings shown here may serve to be predictive of the kinds of mutations induced by the adducts of IQ and PhIP in oncogenes and tumor suppressor genes altered during heterocyclic amine-induced carcinogenesis. JF - Cancer research AU - Endo, H AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-0037. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 3745 EP - 3751 VL - 54 IS - 14 SN - 0008-5472, 0008-5472 KW - supF KW - Imidazoles KW - 0 KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Base Sequence KW - Humans KW - DNA -- metabolism KW - Molecular Sequence Data KW - Plasmids KW - Mutation KW - Cell Line KW - Quinolines -- toxicity KW - Quinolines -- metabolism KW - Imidazoles -- toxicity KW - Imidazoles -- metabolism KW - Genetic Vectors KW - Mutagens -- toxicity KW - Genes, Suppressor UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76591159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenic+specificity+of+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+and+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+in+the+supF+shuttle+vector+system.&rft.au=Endo%2C+H%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Endo&rft.aufirst=H&rft.date=1994-07-15&rft.volume=54&rft.issue=14&rft.spage=3745&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 - 1994-08-16 N1 - Date created - 1994-08-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The murine Ig 3' alpha enhancer is a target site with repressor function for the B cell lineage-specific transcription factor BSAP (NF-HB, S alpha-BP). AN - 76590214; 8021508 AB - Using electrophoretic mobility shift assays (EMSAs) we have identified several target sites for nuclear proteins in the murine heavy chain Ig 3' alpha enhancer. Two of these sites, denoted oligo-H and oligo-K, were shown by several criteria, including cell distribution and stimulation experiments, EMSA cross-competition studies, and proteolytic clipping bandshift assays, to bind to the same protein identical to the transcription factor B cell lineage-specific activator protein (BSAP) (NF-HB, S alpha-BP). To assess the possible functional role of these BSAP binding sites in the 3' alpha enhancer, we transiently transfected a construct containing a 314-bp 3' alpha enhancer fragment upstream of a luciferase reporter gene in MOPC-315 cells, a plasmacytoma line lacking BSAP. In these cells, co-transfection with a vector expressing recombinant BSAP led to significant reduction in the activity of the 3' alpha enhancer fragment. Conversely, in the mature B lymphoma cell line CH12.LX, a cell line that expresses BSAP and has a less active 3' alpha enhancer, selective BSAP down-regulation by an antisense phosphorothioate oligonucleotide was sufficient to considerably up-regulate 3' alpha enhancer activity, as were mutations of both binding sites that prevented binding of BSAP to the 3' alpha enhancer. Our findings thus suggest that the natural loss of BSAP expression in terminally differentiated plasma cells contributes to the activation of the murine Ig 3' alpha enhancer. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Neurath, M F AU - Strober, W AU - Wakatsuki, Y AD - Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 730 EP - 742 VL - 153 IS - 2 SN - 0022-1767, 0022-1767 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Oligonucleotides, Antisense KW - PAX5 Transcription Factor KW - Pax5 protein, mouse KW - Repressor Proteins KW - Transcription Factors KW - Abridged Index Medicus KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Cell Line KW - Binding Sites KW - Transcription Factors -- physiology KW - Nuclear Proteins -- genetics KW - Repressor Proteins -- physiology KW - Enhancer Elements, Genetic KW - Genes, Immunoglobulin KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Nuclear Proteins -- physiology KW - B-Lymphocytes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=The+murine+Ig+3%27+alpha+enhancer+is+a+target+site+with+repressor+function+for+the+B+cell+lineage-specific+transcription+factor+BSAP+%28NF-HB%2C+S+alpha-BP%29.&rft.au=Neurath%2C+M+F%3BStrober%2C+W%3BWakatsuki%2C+Y&rft.aulast=Neurath&rft.aufirst=M&rft.date=1994-07-15&rft.volume=153&rft.issue=2&rft.spage=730&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea. AN - 76588383; 8033099 AB - Temozolomide, a methylating agent with clinical activity against brain tumors, demonstrated excellent antitumor activity following p.o. administration to athymic mice bearing human brain tumor xenografts. In the early stage s.c. implanted SNB-75 astrocytoma model, a 400-mg/kg dose administered on Day 5 produced 10 of 10 Day 54 tumor-free mice. In later staged s.c. U251 and SF-295 glioblastoma models, a single 600-mg/kg dose produced 9 of 10 Day 86 and 2 of 10 Day 40 tumor-free mice, respectively. In the latter group, a tumor growth delay of > 315% was attained. Similar levels of activity were attained with equal total doses on schedules of daily for 5 doses and every fourth day for 3 doses. A single 40-mg/kg i.v. dose of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) also demonstrated excellent activity, producing 9 of 10 tumor-free mice in the SNB-75 model and growth delays of 283 and 301% in the U251 and SF-295 models, respectively. Temozolomide was also highly effective against intracerebral implants of the U251 and SF-295 glioblastomas. Administration of either 600 mg/kg on Day 1 or 200 mg/kg on Days 1, 5, and 9 produced 7 of 9 Day 90 tumor-free mice in the U251 model. In the SF-295 model, a single 400-mg/kg dose or three 200-mg/kg doses produced 3 and 4 of 10 Day 90 tumor-free mice, respectively, and prolonged survival by 127%. A single 40-mg/kg i.v. dose of BCNU was more effective than temozolomide in the intracerebral SF-295 model, and less effective in the intracerebral U251 model. The synergistic potential of temozolomide and BCNU in combination was evaluated in an advanced stage s.c. implanted SF-295 model. When temozolomide was administered 2 h after BCNU on a single treatment day, a dramatic synergistic therapeutic effect was observed in two experiments. For example, single agent doses of temozolomide (600 mg/kg) and BCNU (60 mg/kg) and a combination (400 mg/kg + 27 mg/kg) demonstrating equivalent toxicity produced growth delays of 190, 258, and > 492% (includes 5 of 10 Day 51 tumor-free mice), respectively. Analysis of the data by a quadratic dose response model indicated synergism with significance at P = 0.0001 in both experiments. Synergism also was demonstrated by the isobole method. The reverse sequence was more toxic, but at lower combination doses a synergistic effect was still observed (P = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Plowman, J AU - Waud, W R AU - Koutsoukos, A D AU - Rubinstein, L V AU - Moore, T D AU - Grever, M R AD - Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 3793 EP - 3799 VL - 54 IS - 14 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Dacarbazine KW - 7GR28W0FJI KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Carmustine KW - U68WG3173Y KW - temozolomide KW - YF1K15M17Y KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Mice KW - Methyltransferases -- metabolism KW - Carmustine -- administration & dosage KW - Dacarbazine -- therapeutic use KW - Brain Neoplasms -- drug therapy KW - Dacarbazine -- analogs & derivatives KW - Dacarbazine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76588383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preclinical+antitumor+activity+of+temozolomide+in+mice%3A+efficacy+against+human+brain+tumor+xenografts+and+synergism+with+1%2C3-bis%282-chloroethyl%29-1-nitrosourea.&rft.au=Plowman%2C+J%3BWaud%2C+W+R%3BKoutsoukos%2C+A+D%3BRubinstein%2C+L+V%3BMoore%2C+T+D%3BGrever%2C+M+R&rft.aulast=Plowman&rft.aufirst=J&rft.date=1994-07-15&rft.volume=54&rft.issue=14&rft.spage=3793&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 - 1994-08-16 N1 - Date created - 1994-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Improved binding and antitumor activity of a recombinant anti-erbB2 immunotoxin by disulfide stabilization of the Fv fragment. AN - 76581805; 7913461 AB - e23(dsFv)-PE38KDEL is a recombinant immunotoxin composed of the Fv region of anti-erbB2 monoclonal antibody e23 connected to a truncated form of Pseudomonas exotoxin (PE38KDEL), in which the inherently unstable Fv heterodimer (composed of VH and VL) is stabilized by a disulfide bond engineered between structurally conserved framework positions of VH and VL. We have now found that e23(dsFv)-PE38KDEL is considerably more cytotoxic to antigen-positive cell lines than the corresponding single-chain immunotoxin. The basis for the enhanced cytotoxic activity is that the e23 dsFv-immunotoxin binds to erbB2 with greater affinity than the single-chain counterpart. The dsFv-immunotoxin had 4-fold increased binding compared to the scFv and almost identical to the binding affinity of e23 Fab. e23(dsFv)-PE38KDEL was also considerably more stable at 37 degrees C than the single-chain immunotoxin. The therapeutic potential of the disulfide-stabilized immunotoxin was compared with its single-chain counterpart using two animal models of immunodeficient mice bearing subcutaneous tumor xenografts of human gastric tumor N87 cells or human A431 epidermoid carcinoma cells. The antitumor effect of e23(dsFv)-PE38KDEL was significantly better than that of the single-chain immunotoxin. e23(dsFv)-PE38KDEL caused complete regression of tumors at doses which caused no toxic effects in mice, whereas the single-chain immunotoxin did not cause complete regressions at the same doses. JF - The Journal of biological chemistry AU - Reiter, Y AU - Brinkmann, U AU - Jung, S H AU - Lee, B AU - Kasprzyk, P G AU - King, C R AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 18327 EP - 18331 VL - 269 IS - 28 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fab Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Oncogene Proteins, Viral KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Humans KW - Mice, Nude KW - Mice KW - Amino Acid Sequence KW - Bacterial Toxins -- metabolism KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Bacterial Toxins -- therapeutic use KW - Binding, Competitive KW - Immunoglobulin Fab Fragments -- metabolism KW - Transplantation, Heterologous KW - Pseudomonas aeruginosa KW - Recombinant Proteins -- therapeutic use KW - Cell Line KW - Stomach Neoplasms -- drug therapy KW - Stomach Neoplasms -- pathology KW - Carcinoma, Squamous Cell -- pathology KW - Oncogene Proteins, Viral -- immunology KW - Exotoxins -- metabolism KW - Immunotoxins -- therapeutic use KW - Immunotoxins -- metabolism KW - Exotoxins -- therapeutic use KW - Carcinoma, Squamous Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76581805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Improved+binding+and+antitumor+activity+of+a+recombinant+anti-erbB2+immunotoxin+by+disulfide+stabilization+of+the+Fv+fragment.&rft.au=Reiter%2C+Y%3BBrinkmann%2C+U%3BJung%2C+S+H%3BLee%2C+B%3BKasprzyk%2C+P+G%3BKing%2C+C+R%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1994-07-15&rft.volume=269&rft.issue=28&rft.spage=18327&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 - 1994-08-17 N1 - Date created - 1994-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behçet's disease. AN - 76565758; 8023874 AB - Behçet's disease is a multisystem disorder that may cause profound ocular inflammation and blindness. We reviewed 19 patients with severe ocular Behçet's disease treated with combined cyclosporine and corticosteroid therapy. Previous treatment with corticosteroids alone failed to control the uveitis in all patients. Ten patients were given cyclosporine therapy alone (mean dosage, 8.6 mg/kg of body weight per day), and nine patients were given lower dosages of cyclosporine (mean dosage, 6.2 mg/kg of body weight per day) in combination with prednisone (mean dosage, 29.4 mg per day). The mean follow-up on therapy was 51 months. After three months of therapy, a trend toward greater improvement in visual acuity was noted in patients treated with combined cyclosporine and prednisone compared to those receiving cyclosporine alone (17.8 letters vs 10.2 letters, P = .2379), but after one year little difference was observed in the improvement between the two groups (5.8 letters vs 3.3 letters, P = .7984). However, a trend toward greater renal toxicity was seen in patients treated with cyclosporine alone after both three months and one year of therapy. Because of either a suboptimal therapeutic response or adverse effects, all patients treated with cyclosporine alone at baseline had prednisone added to their regimen after a mean time of 23.5 months. Overall, visual acuity remained stable or improved in 28 of 37 eyes (75.7%) over the course of therapy. These data suggest that combined cyclosporine and prednisone therapy is an effective treatment for Behçet's uveitis and may be less toxic than therapy with cyclosporine alone. A prospective, randomized trial with a larger sample size is needed to provide definitive data. JF - American journal of ophthalmology AU - Whitcup, S M AU - Salvo, E C AU - Nussenblatt, R B AD - Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/15/ PY - 1994 DA - 1994 Jul 15 SP - 39 EP - 45 VL - 118 IS - 1 SN - 0002-9394, 0002-9394 KW - Cyclosporine KW - 83HN0GTJ6D KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Glomerular Filtration Rate KW - Humans KW - Adult KW - Kidney -- drug effects KW - Hemodynamics KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Visual Acuity KW - Male KW - Female KW - Cyclosporine -- adverse effects KW - Prednisone -- therapeutic use KW - Cyclosporine -- therapeutic use KW - Uveitis -- drug therapy KW - Behcet Syndrome -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76565758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=Combined+cyclosporine+and+corticosteroid+therapy+for+sight-threatening+uveitis+in+Beh%C3%A7et%27s+disease.&rft.au=Whitcup%2C+S+M%3BSalvo%2C+E+C%3BNussenblatt%2C+R+B&rft.aulast=Whitcup&rft.aufirst=S&rft.date=1994-07-15&rft.volume=118&rft.issue=1&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prediction of an rRNA methyltransferase domain in human tumor-specific nucleolar protein P120. AN - 19369333; 8744771 AB - Using computer methods for identification of amino acid motifs in sequence databases and multiple alignment, it is shown that human proliferation-associated nucleolar protein P120 contains a putative methyltransferase domain that is conserved in a group of bacterial proteins. It is hypothesized that P120 and the related prokaryotic proteins are rRNA methylases required for division of all types of cells. JF - Nucleic Acids Research AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894. Y1 - 1994/07/11/ PY - 1994 DA - 1994 Jul 11 SP - 2476 EP - 2478 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 22 IS - 13 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - rRNA KW - Databases KW - Nucleoli KW - Methyltransferase KW - Methylase KW - Computers KW - Conserved sequence KW - rRNA methyltransferase KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19369333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Prediction+of+an+rRNA+methyltransferase+domain+in+human+tumor-specific+nucleolar+protein+P120.&rft.au=Koonin%2C+E+V&rft.aulast=Koonin&rft.aufirst=E&rft.date=1994-07-11&rft.volume=22&rft.issue=13&rft.spage=2476&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 - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Databases; rRNA; Nucleoli; Methylase; Methyltransferase; Computers; Conserved sequence; rRNA methyltransferase; Amino acid sequence ER - TY - JOUR T1 - Cleavage of pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. AN - 76594512; 8027078 AB - Pseudomonas exotoxin (PE) is cleaved within mammalian cells between Arg279 and Gly280 to generate an enzymatically active COOH-terminal fragment of 37 kDa which translocates to the cytosol and ADP-ribosylates elongation factor 2. A protease, with toxin cleaving activity, was prepared from beef liver and subsequently characterized. After achieving a 500-fold enrichment in several chromatographic steps, a soluble form of this protease was identified as a furin-like enzyme. It cleaved PE on the COOH-terminal side of the sequence of RQPR (amino acids 276-279) producing the same fragments as those generated within cells. Cleavage had a pH optimum of 5.0-5.5, was inhibited by EDTA or p-hydroxymercuribenzoate but not by O-phenanthroline,N-ethylmaleimide, trans-epoxysuccinyl-L-leukcylamido-(4-guanidino)-butane, or PMSF (or other well known inhibitors of serine proteases). The beef protease cleaved PE with an apparent Km of 7 microM. A mutant form of PE, PEala281, was cleaved at the same site, with the same pH optimum, a similar Km (9 microM) but with a Vmax 150 times faster than was seen with the native toxin. Mutational analysis of the amino acids located just before the site of cleavage, confirmed the importance of arginines at P-1 and P-4. It was also noted that the introduction of a dibasic pair at 278-279 did not increase toxicity or appreciably improve the rate of cleavage. Unnicked diphtheria toxin (DT) was also cleaved by the beef protease; cleavage was on the COOH-terminal side of the sequence RVRR (amino acids 190-193), was seen at pH values ranging from 5.5 to 8.5 and had an optimum at pH 8.0. Recombinant furin cleaved PE, PEala281, and DT with the same characteristics as the beef protease. In addition, Western blot analysis revealed that anti-furin antibodies reacted specifically with components in the beef protease preparation. Immunodepletion experiments showed that all toxin-cleavage activity could be removed from the beef protease using anti-furin antibodies. The relevance of furin-mediated cleavage was further assessed by adding nicked toxins to intact cells. Nicked PE and DT both killed cells at a faster rate than their unnicked counterparts. JF - The Journal of biological chemistry AU - Chiron, M F AU - Fryling, C M AU - FitzGerald, D J AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/07/08/ PY - 1994 DA - 1994 Jul 08 SP - 18167 EP - 18176 VL - 269 IS - 27 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Diphtheria Toxin KW - Exotoxins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Subtilisins KW - EC 3.4.21.- KW - Furin KW - EC 3.4.21.75 KW - Index Medicus KW - Animals KW - Cattle KW - Kinetics KW - Hydrogen-Ion Concentration KW - Mice KW - Mutation KW - Cell Line KW - Liver -- enzymology KW - Diphtheria Toxin -- toxicity KW - Diphtheria Toxin -- metabolism KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity KW - Subtilisins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76594512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cleavage+of+pseudomonas+exotoxin+and+diphtheria+toxin+by+a+furin-like+enzyme+prepared+from+beef+liver.&rft.au=Chiron%2C+M+F%3BFryling%2C+C+M%3BFitzGerald%2C+D+J&rft.aulast=Chiron&rft.aufirst=M&rft.date=1994-07-08&rft.volume=269&rft.issue=27&rft.spage=18167&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 - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer risk and radiation dose among women treated for breast cancer. AN - 76559376; 8007020 AB - Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects. JF - Journal of the National Cancer Institute AU - Inskip, P D AU - Stovall, M AU - Flannery, J T AD - Radiation Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, Bethesda, Md. Y1 - 1994/07/06/ PY - 1994 DA - 1994 Jul 06 SP - 983 EP - 988 VL - 86 IS - 13 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - Risk KW - Logistic Models KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Female KW - Radiotherapy -- adverse effects KW - Lung Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Second Primary -- etiology KW - Breast Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76559376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lung+cancer+risk+and+radiation+dose+among+women+treated+for+breast+cancer.&rft.au=Inskip%2C+P+D%3BStovall%2C+M%3BFlannery%2C+J+T&rft.aulast=Inskip&rft.aufirst=P&rft.date=1994-07-06&rft.volume=86&rft.issue=13&rft.spage=983&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 - 1994-07-21 N1 - Date created - 1994-07-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1995 Jan 4;87(1):60-1 [7666469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity. AN - 76588625; 8022819 AB - Inositol phospholipid-specific phospholipase C (PLC) is involved in several signaling pathways leading to cellular growth and differentiation. Our previous studies reported the induction of DNA synthesis in quiescent NIH 3T3 cells after microinjection of PLC and the inhibition of serum- or Ras-stimulated DNA synthesis by a mixture of monoclonal antibodies to PLC-gamma 1. In the course of our investigation of anti-PLC-gamma 1 monoclonal antibodies, we found that each antibody exerts different inhibitory effects on the phosphatidylinositol-hydrolyzing activity of PLC-gamma 1 and that the inhibition of enzymatic activity does not correlate with the inhibition of DNA synthesis observed in the microinjection assay. PLC-gamma 1 with defective enzymatic activity was synthesized by substituting phenylalanine for histidine within the PLC-gamma 1 catalytic domain at amino acids 335 and 380, and mutant enzymes were expressed using a vaccinia expression system. The mutant enzymes were purified and microinjected into quiescent NIH 3T3 cells to evaluate their mitogenic activity. A moderate induction of DNA synthesis occurred after injection of mutant PLC-gamma 1. This mitogenic activity was inhibited by an antibody (alpha E 8-4) that does not significantly inhibit PLC-gamma 1 enzyme activity, which indicates that something else has to be inhibited. Furthermore, the partial induction of DNA synthesis observed with mutant PLC-gamma 1 was increased to levels seen with wild-type PLC-gamma 1 by coinjection of mutant PLC-gamma 1 with two second messengers, diacylglycerol and inositol trisphosphate. These results suggest that the mitogenic activity of PLC-gamma 1 does not exclusively result from the enzymatic activity of the lipase and that another activity inherent to the PLC-gamma 1 molecule can also induce DNA synthesis in quiescent cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Smith, M R AU - Liu, Y L AU - Matthews, N T AU - Rhee, S G AU - Sung, W K AU - Kung, H F AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/07/05/ PY - 1994 DA - 1994 Jul 05 SP - 6554 EP - 6558 VL - 91 IS - 14 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Diglycerides KW - Isoenzymes KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Tritium KW - 10028-17-8 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - DNA KW - 9007-49-2 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - S Phase -- physiology KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Microinjections KW - Inositol 1,4,5-Trisphosphate -- pharmacology KW - Thymidine -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Diglycerides -- pharmacology KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- antagonists & inhibitors KW - Isoenzymes -- antagonists & inhibitors KW - Type C Phospholipases -- antagonists & inhibitors KW - Point Mutation KW - Cell Division -- physiology KW - Cell Division -- drug effects KW - DNA -- biosynthesis KW - Signal Transduction KW - Isoenzymes -- metabolism KW - DNA Replication -- drug effects KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76588625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phospholipase+C-gamma+1+can+induce+DNA+synthesis+by+a+mechanism+independent+of+its+lipase+activity.&rft.au=Smith%2C+M+R%3BLiu%2C+Y+L%3BMatthews%2C+N+T%3BRhee%2C+S+G%3BSung%2C+W+K%3BKung%2C+H+F&rft.aulast=Smith&rft.aufirst=M&rft.date=1994-07-05&rft.volume=91&rft.issue=14&rft.spage=6554&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 - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1984 Sep 21;225(4668):1365-70 [6147898] Mol Cell Biol. 1992 Dec;12(12):5843-56 [1448108] J Neurochem. 1987 Apr;48(4):999-1017 [3029333] Methods Enzymol. 1987;154:367-82 [3323813] Nature. 1988 Mar 17;332(6161):269-72 [2831461] J Biol Chem. 1988 Oct 5;263(28):14497-504 [2459119] Proc Natl Acad Sci U S A. 1989 May;86(10):3659-63 [2726744] Science. 1990 Mar 2;247(4946):1074-7 [2408147] Mol Cell Biol. 1990 Apr;10(4):1307-18 [2108315] Science. 1990 Nov 16;250(4983):979-82 [2173144] Science. 1990 Nov 30;250(4985):1253-6 [1700866] Cell. 1991 May 3;65(3):435-41 [1708307] Science. 1991 May 3;252(5006):668-74 [1708916] Mol Cell Biol. 1991 Oct;11(10):5068-78 [1656221] Mol Cell Biol. 1992 Apr;12(4):1451-9 [1312663] Mol Cell Biol. 1992 Apr;12(4):1835-45 [1549129] J Biol Chem. 1992 Jun 25;267(18):12393-6 [1319994] Mol Cell Biol. 1992 Dec;12(12):5816-23 [1333046] Nature. 1984 Nov 22-28;312(5992):315-21 [6095092] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-level expression and deletion mutagenesis of human tryptophan hydroxylase. AN - 76574493; 8022832 AB - Human tryptophan hydroxylase has been expressed as a soluble and active form in Escherichia coli by fusion with an affinity tag, maltose-binding protein. The fusion protein has been purified to near homogeneity by affinity chromatography on crosslinked amylose resin. The purified fusion protein has a specific activity of 86 nmol of 5-hydroxytryptophan per min per mg of fusion protein. A series of truncation mutants have also been made to explore the domain organization of tryptophan hydroxylase. All deletion mutants were subject to affinity purification and kinetic characterization. While removal of the N-terminal 164 amino acids completely inactivates the enzyme, deletion of the first 91 residues results in a 7-fold reduction in specific activity. From the C terminus, deletion of 36, 55, or 112 amino acids abolishes the activity, whereas deletion of 19 residues decreases the specific activity by approximately 11-fold. These results are consistent with a model for tryptophan hydroxylase in which the enzyme consists of an N-terminal regulatory domain, a catalytic core, and a small C-terminal region of uncertain but important function. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Yang, X J AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/05/ PY - 1994 DA - 1994 Jul 05 SP - 6659 EP - 6663 VL - 91 IS - 14 SN - 0027-8424, 0027-8424 KW - Carrier Proteins KW - 0 KW - DNA Primers KW - Escherichia coli Proteins KW - Maltose-Binding Proteins KW - Monosaccharide Transport Proteins KW - Recombinant Fusion Proteins KW - maltose transport system, E coli KW - Tryptophan Hydroxylase KW - EC 1.14.16.4 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Escherichia coli -- metabolism KW - Carrier Proteins -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Escherichia coli -- genetics KW - Plasmids KW - Carrier Proteins -- biosynthesis KW - Carrier Proteins -- isolation & purification KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Blotting, Western KW - Genetic Vectors KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Mutagenesis, Site-Directed KW - Tryptophan Hydroxylase -- biosynthesis KW - Tryptophan Hydroxylase -- metabolism KW - ATP-Binding Cassette Transporters KW - Tryptophan Hydroxylase -- isolation & purification KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76574493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-level+expression+and+deletion+mutagenesis+of+human+tryptophan+hydroxylase.&rft.au=Yang%2C+X+J%3BKaufman%2C+S&rft.aulast=Yang&rft.aufirst=X&rft.date=1994-07-05&rft.volume=91&rft.issue=14&rft.spage=6659&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 - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1988 Jul;51(1):312-6 [3379411] J Biol Chem. 1964 Sep;239:2910-7 [14216443] Gene. 1988 Dec 30;74(2):365-73 [3073105] J Biol Chem. 1990 Feb 5;265(4):2042-7 [1967606] Genomics. 1990 May;7(1):88-96 [2110547] Nucleic Acids Res. 1990 Jul 25;18(14):4257 [2377472] Science. 1990 Dec 7;250(4986):1400-3 [2147779] Brain Res Mol Brain Res. 1991 Mar;9(4):277-83 [1645430] J Mol Neurosci. 1991;2(4):203-15 [1676292] Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8779-83 [1681542] J Biol Chem. 1992 Apr 15;267(11):7520-8 [1559990] J Biol Chem. 1992 Jun 25;267(18):12639-46 [1352289] Protein Expr Purif. 1992 Apr;3(2):93-100 [1422220] J Biol Chem. 1993 Jan 25;268(3):1590-5 [8420934] J Biol Chem. 1993 Apr 15;268(11):8046-52 [8385134] Protein Sci. 1993 Sep;2(9):1452-60 [8104613] J Mol Neurosci. 1993 Summer;4(2):125-39 [8105857] Biochem Biophys Res Commun. 1964 Aug 11;16(6):586-92 [5297063] Science. 1967 Jan 13;155(3759):217-9 [6015530] Mol Pharmacol. 1967 May;3(3):274-8 [6037686] J Biol Chem. 1971 Mar 10;246(5):1330-40 [5545077] J Biol Chem. 1972 Jul 10;247(13):4165-73 [4402511] Mol Pharmacol. 1972 Sep;8(5):501-10 [4404334] J Biol Chem. 1973 Jun 25;248(12):4345-53 [4145799] J Biol Chem. 1975 Jun 10;250(11):4152-8 [1126946] Arch Biochem Biophys. 1980 Feb;199(2):355-61 [6767445] J Biol Chem. 1980 May 10;255(9):4137-43 [7372670] Eur J Biochem. 1982 Feb;122(1):41-7 [7060568] J Biol Chem. 1986 Feb 15;261(5):2051-6 [3944127] Adv Enzyme Regul. 1986;25:37-64 [3028051] Methods Enzymol. 1987;142:83-7 [3600387] Methods Enzymol. 1987;142:88-92 [3110558] Proc Natl Acad Sci U S A. 1987 Aug;84(16):5530-4 [3475690] Biochem Biophys Res Commun. 1988 Mar 30;151(3):1446-53 [2895648] Biochem Biophys Res Commun. 1993 Dec 30;197(3):1543-8 [7904160] Annu Rev Neurosci. 1989;12:415-61 [2564757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Fenton oxidation mechanism: reactivities of biologically relevant substrates with two oxidizing intermediates differ from those predicted for the hydroxyl radical. AN - 76569771; 8022825 AB - The application of kinetic probes that allow one to determine relative reactivities of biologically relevant substrates with oxidizing intermediates in the Fenton reagent (H2O2 plus Fe2+ in acidic aqueous solution) is described. These results lead to the conclusion that there are two key intermediates with very different reactivity patterns. One (X) is proposed to be an iron complex formed via direct reaction of H2O2 with Fe2+, which reacts with N-nitrosodimethylamine to generate a strong transient absorption at 450 nm. This provides a sensitive spectrophotometric probe of the competitive reactivities toward X of biologically relevant substrates such as nucleic acid components and amino acids. The second intermediate (Y) is probed by its oxidation of the Ru(bpy)2+3 ion (bpy = 2,2'-bipyridine) to a product with an absorption band centered at 500 nm. In the absence of other substrates, Ru(bpy)2+3 is oxidized at rates independent of the Ru concentration, but the product yield is diminished by competing reactions with substrates that can intercept X. Competition studies demonstrate reactivity patterns for X and Y that are clearly distinct from the pattern predicted for the hydroxyl radical, the intermediate commonly invoked in discussions of Fenton oxidations. These data require reevaluation of the mechanisms by which the Fenton reagent oxidizes biological substrates. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wink, D A AU - Nims, R W AU - Saavedra, J E AU - Utermahlen, W E AU - Ford, P C AD - Chemistry Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/07/05/ PY - 1994 DA - 1994 Jul 05 SP - 6604 EP - 6608 VL - 91 IS - 14 SN - 0027-8424, 0027-8424 KW - Amino Acids KW - 0 KW - Carcinogens KW - Deoxyribonucleosides KW - Deoxyribonucleotides KW - Fenton's reagent KW - Hydroxyl Radical KW - 3352-57-6 KW - Deoxyribose KW - 533-67-5 KW - Ribose KW - 681HV46001 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Iron KW - E1UOL152H7 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Oxidation-Reduction KW - Kinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76569771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Fenton+oxidation+mechanism%3A+reactivities+of+biologically+relevant+substrates+with+two+oxidizing+intermediates+differ+from+those+predicted+for+the+hydroxyl+radical.&rft.au=Wink%2C+D+A%3BNims%2C+R+W%3BSaavedra%2C+J+E%3BUtermahlen%2C+W+E%3BFord%2C+P+C&rft.aulast=Wink&rft.aufirst=D&rft.date=1994-07-05&rft.volume=91&rft.issue=14&rft.spage=6604&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 - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858-62 [6947260] Biochem J. 1984 Apr 1;219(1):1-14 [6326753] Arch Biochem Biophys. 1986 May 1;246(2):501-14 [3010861] Chem Res Toxicol. 1991 Sep-Oct;4(5):510-2 [1665352] Arch Biochem Biophys. 1987 Aug 1;256(2):462-71 [3113335] Science. 1988 Apr 29;240(4852):640-2 [2834821] Chem Res Toxicol. 1989 Jul-Aug;2(4):247-53 [2519780] J Free Radic Biol Med. 1985;1(1):3-25 [3013969] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A clinical study of infants presenting to a mental retardation clinic. AN - 85256422; pmid-8002066 AB - Early detection has a central role in the prevention and management of mental retardation. The purpose of this present study is to delinerate the characteristics of developmentally delayed infants and their families attending Mental Retardation Clinic. The sample consisted of 101 infants who were registered in Mental Retardation Clinic of NIMHANS, Bangalore in 1988 constituting 12.5% of total registrations. Data was collected from case records. Majority of subjects were males, first or second born, 7 months or older, from a consanguineous lower or middle class family. Along with developmental delay, 60% had other complaints. Medical problems were reported in about half of the subjects and most had abnormalities on physical examination. Aetiology was discernible in 77.1%. Majority had associated physical disorder such as cerebral palsy, seizures and hearing and/or visual impairment. Around 17% came for follow-up thrice or more, 43% dropped out after work-up. The main conclusions are that; (i) certain socio-demographic, personal and clinical variables influence treatment seeking, and (ii) developmental delay recognised in infancy tends to be associated with clear aetiologic factors and significant medical/neurologic problems. JF - Indian Journal of Pediatrics AU - Girimaji, S R AU - Srinath, S AU - Seshadri, S P AD - Department of Psychiatry, National Institute of Mental Health and Neuro-Sciences, Bangalore. PY - 1994 SP - 373 EP - 378 VL - 61 IS - 4 SN - 0019-5456, 0019-5456 KW - Parity KW - Vision Disorders KW - Sex Factors KW - Human KW - Seizures KW - India KW - Registries KW - Infant KW - Mental Retardation KW - Consanguinity KW - Hearing Disorders KW - Cerebral Palsy KW - Patient Acceptance of Health Care KW - Patient Compliance KW - Social Class KW - Follow-Up Studies KW - Male KW - Female KW - Abnormalities UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85256422?accountid=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=Indian+Journal+of+Pediatrics&rft.atitle=A+clinical+study+of+infants+presenting+to+a+mental+retardation+clinic.&rft.au=Girimaji%2C+S+R%3BSrinath%2C+S%3BSeshadri%2C+S+P&rft.aulast=Girimaji&rft.aufirst=S&rft.date=1994-07-01&rft.volume=61&rft.issue=4&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Indian+Journal+of+Pediatrics&rft.issn=00195456&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Antiviral activity in vitro of Kutapressin against human herpesvirus-6. AN - 77796207; 7893985 AB - The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Kutapressin (KU), a drug that has been available to practicing physicians for over 50 years, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus, under various conditions. Either pretreatment of the cells prior to infection or treatment shortly after infection, inhibited viral replication by > 90%. Indirect evidence suggests that KU may inhibit viral attachment to cellular receptors, and inhibit intracellular maturation of the virus. Given these in vitro findings, and the low frequency of toxicity reported with the use of KU, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted. JF - In vivo (Athens, Greece) AU - Ablashi, D V AU - Berneman, Z N AU - Lawyer, C AU - Kramarsky, B AU - Ferguson, D M AU - Komaroff, A L AD - National Cancer Institute, Bethesda, MD 20892. PY - 1994 SP - 581 EP - 586 VL - 8 IS - 4 SN - 0258-851X, 0258-851X KW - Antimicrobial Cationic Peptides KW - 0 KW - Antiviral Agents KW - Liver Extracts KW - Peptides KW - kutapressin KW - Index Medicus KW - Swine KW - Antiviral Agents -- therapeutic use KW - Animals KW - Virus Replication -- drug effects KW - Humans KW - T-Lymphocytes -- virology KW - Cell Line KW - Herpesvirus 6, Human -- drug effects KW - Herpesvirus 6, Human -- physiology KW - Peptides -- pharmacology KW - Liver Extracts -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77796207?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Antiviral+activity+in+vitro+of+Kutapressin+against+human+herpesvirus-6.&rft.au=Ablashi%2C+D+V%3BBerneman%2C+Z+N%3BLawyer%2C+C%3BKramarsky%2C+B%3BFerguson%2C+D+M%3BKomaroff%2C+A+L&rft.aulast=Ablashi&rft.aufirst=D&rft.date=1994-07-01&rft.volume=8&rft.issue=4&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ampligen inhibits human herpesvirus-6 in vitro. AN - 77770837; 7893986 AB - The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Ampligen [Poly (1): Poly (C12U), a synthetic, mismatched, double-stranded RNA, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus and treated with Ampligen under various conditions. When cells were pretreated with Ampligen (concentrations of 100 or 200 micrograms/ml) prior to infection or treated shortly after infection, viral replication was inhibited by 46-98%. At 100 and 200 micrograms/ml, Ampligen also inhibited the DNA polymerase activity of HHV-6 by 42-98%. When lower concentrations of Ampligen (10 and 50 micrograms/ml) were used, only pretreatment of cells, with Ampligen, followed by virus infection and carrying the infected cells with Ampligen, significantly inhibited HHV-6 infection (83.7 and 89.1% respectively). Indirect evidence suggests that Ampligen may inhibit viral attachment to cellular receptors and/or inhibit intracellular maturation of the virus. The above concentrations of Ampligen were not toxic to the cells used in the study. Given these in vitro findings, and the low frequency of toxicity reported with the use of Ampligen, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted. JF - In vivo (Athens, Greece) AU - Ablashi, D V AU - Berneman, Z N AU - Williams, M AU - Strayer, D R AU - Kramarsky, B AU - Suhadolnik, R J AU - Reichenbach, N AU - Hiltzges, P AU - Komaroff, A L AD - National Cancer Institute, Bethesda, MD 20892. PY - 1994 SP - 587 EP - 591 VL - 8 IS - 4 SN - 0258-851X, 0258-851X KW - Antigens, Viral KW - 0 KW - Antiviral Agents KW - Culture Media KW - Nucleic Acid Synthesis Inhibitors KW - RNA, Double-Stranded KW - poly(I).poly(c12,U) KW - Poly I-C KW - 24939-03-5 KW - Poly U KW - 27416-86-0 KW - Index Medicus KW - Antigens, Viral -- biosynthesis KW - Humans KW - RNA, Double-Stranded -- pharmacology KW - Time Factors KW - T-Lymphocytes -- virology KW - Cell Line KW - Poly U -- pharmacology KW - Virus Replication -- drug effects KW - Herpesvirus 6, Human -- drug effects KW - Antiviral Agents -- pharmacology KW - Herpesvirus 6, Human -- physiology KW - Herpesvirus 6, Human -- enzymology KW - Poly I-C -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77770837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+vivo+%28Athens%2C+Greece%29&rft.atitle=Ampligen+inhibits+human+herpesvirus-6+in+vitro.&rft.au=Ablashi%2C+D+V%3BBerneman%2C+Z+N%3BWilliams%2C+M%3BStrayer%2C+D+R%3BKramarsky%2C+B%3BSuhadolnik%2C+R+J%3BReichenbach%2C+N%3BHiltzges%2C+P%3BKomaroff%2C+A+L&rft.aulast=Ablashi&rft.aufirst=D&rft.date=1994-07-01&rft.volume=8&rft.issue=4&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=In+vivo+%28Athens%2C+Greece%29&rft.issn=0258851X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-27 N1 - Date created - 1995-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic lymphocytic leukemia and hairy-cell leukemia. AN - 77116223; 9371293 AB - In recent years, major advances in our understanding of the biology of the chronic lymphoid leukemias have been accompanied by the emergence of new therapeutic options. Chronic lymphocytic leukemia, the most common of these disorders, appears to be related to a failure of apoptosis, leading to accumulation of functionally abnormal lymphocytes. Fludarabine, a nucleoside analogue that may activate apoptosis, has emerged as the most effective agent for newly diagnosed as well as relapsed patients with chronic lymphocytic leukemia. Nevertheless, few if any patients are cured with this agent. Unique chemotherapeutic and biologic therapies are being explored, and new strategies combining several approaches will likely be established. For patients with hairy-cell leukemia, pentostatin and 2-chlorodeoxyadenosine achieve durable complete remissions in 65% to 85% of patients, with comparable toxicity. JF - Current opinion in hematology AU - Cheson, B D AD - National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 268 EP - 277 VL - 1 IS - 4 SN - 1065-6251, 1065-6251 KW - Index Medicus KW - Humans KW - Leukemia, Hairy Cell -- physiopathology KW - Leukemia, Hairy Cell -- therapy KW - Leukemia, Lymphocytic, Chronic, B-Cell -- physiopathology KW - Leukemia, Lymphocytic, Chronic, B-Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77116223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+hematology&rft.atitle=Chronic+lymphocytic+leukemia+and+hairy-cell+leukemia.&rft.au=Cheson%2C+B+D&rft.aulast=Cheson&rft.aufirst=B&rft.date=1994-07-01&rft.volume=1&rft.issue=4&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+hematology&rft.issn=10656251&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1997-12-31 N1 - Date created - 1997-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug sensitization, substance abuse, and chemical sensitivity. AN - 77100325; 7778108 AB - Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. Much has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper. JF - Toxicology and industrial health AU - Newlin, D B AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. PY - 1994 SP - 463 EP - 480 VL - 10 IS - 4-5 SN - 0748-2337, 0748-2337 KW - Index Medicus KW - Animals KW - Humans KW - Adaptation, Physiological KW - Alcoholism -- physiopathology KW - Substance-Related Disorders -- physiopathology KW - Multiple Chemical Sensitivity -- etiology KW - Multiple Chemical Sensitivity -- physiopathology KW - Substance-Related Disorders -- psychology KW - Multiple Chemical Sensitivity -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77100325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+industrial+health&rft.atitle=Drug+sensitization%2C+substance+abuse%2C+and+chemical+sensitivity.&rft.au=Newlin%2C+D+B&rft.aulast=Newlin&rft.aufirst=D&rft.date=1994-07-01&rft.volume=10&rft.issue=4-5&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caveats in the use of the kindling model of affective disorders. AN - 77096340; 7778106 JF - Toxicology and industrial health AU - Weiss, S R AU - Post, R M AD - Biological Psychiatry Branch, NIMH, Bethesda, MD 20892, USA. PY - 1994 SP - 421 EP - 447 VL - 10 IS - 4-5 SN - 0748-2337, 0748-2337 KW - Lithium KW - 9FN79X2M3F KW - Index Medicus KW - Stimulation, Chemical KW - Animals KW - Multiple Chemical Sensitivity -- psychology KW - Electric Stimulation KW - Lithium -- pharmacology KW - Behavior, Animal -- drug effects KW - Kindling, Neurologic -- drug effects KW - Mood Disorders -- physiopathology KW - Disease Models, Animal KW - Kindling, Neurologic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77096340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+industrial+health&rft.atitle=Caveats+in+the+use+of+the+kindling+model+of+affective+disorders.&rft.au=Weiss%2C+S+R%3BPost%2C+R+M&rft.aulast=Weiss&rft.aufirst=S&rft.date=1994-07-01&rft.volume=10&rft.issue=4-5&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+industrial+health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-10 N1 - Date created - 1995-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemoprevention research at the U.S. National Cancer Institute. AN - 76933988; 7816223 AB - The use of specific chemicals to prevent the development or retard the progression of carcinogenesis--known as chemoprevention--is a rapidly growing area in cancer research. Developed through the integration of strong laboratory and epidemiologic evidence, chemoprevention research has moved successfully into the clinical research setting, with diverse agents being tested for their efficacy in individuals at high risk of developing certain cancers. The public health potential for reducing cancer incidence and mortality through chemical intervention provides a unique and promising opportunity, and continued support of this multidisciplinary approach to cancer prevention remains a high priority for the U.S. National Cancer Institute. JF - Military medicine AU - Greenwald, P AD - Division of Cancer Prevention and Control, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 505 EP - 512 VL - 159 IS - 7 SN - 0026-4075, 0026-4075 KW - Antineoplastic Agents KW - 0 KW - Antioxidants KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Clinical Trials as Topic KW - Research KW - Antineoplastic Agents -- therapeutic use KW - Male KW - Female KW - Antioxidants -- administration & dosage KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76933988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Chemoprevention+research+at+the+U.S.+National+Cancer+Institute.&rft.au=Greenwald%2C+P&rft.aulast=Greenwald&rft.aufirst=P&rft.date=1994-07-01&rft.volume=159&rft.issue=7&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-06 N1 - Date created - 1995-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissimilar frequency of hepatoblastomas and hepatic cystadenomas and adenocarcinomas arising in hepatocellular neoplasms of D2B6F1 mice initiated with N-nitrosodiethylamine and subsequently given Aroclor-1254, dichlorodiphenyltrichloroethane, or phenobarbital. AN - 76932088; 7817132 AB - Aroclor-1254 (Ar-1254) and dichlorodiphenyltrichloroethane (DDT) were compared to phenobarbital (PB) for their ability to promote hepatocellular proliferative lesions to hepatocellular adenomas and carcinomas and to hepatoblastomas in D2B6F1 male mice initiated with N-nitrosodiethylamine (NDEA). Hepatocellular neoplasms developed in all mice given NDEA and were more numerous in mice fed promoters. Multiplicities decreased in the order Ar-1254 > PB > DDT, indicating that Ar-1254 was more potent than either PB or DDT at the dosage levels used. PB was the most effective of the 3 agents in stimulating the evolution of hepatocellular neoplasms to hepatoblastoma. The incidence of hepatoblastomas in the NDEA.PB group was 72% but was only 27% in NDEA-initiated, DDT-promoted mice and 33% in low-dose and only 9% in high-dose Ar-1254-promoted mice. In contrast, lesions resembling benign and malignant cholangiocellular neoplasms were frequently found within hepatocellular tumors in Ar-1254-promoted mice but not in mice fed PB or DDT, either alone or after NDEA. Some cystic glandular structures in Ar-1254-promoted mice contained mucous cells, argentaffin cells, and Paneth cells and thus constituted intestinal metaplasia. Hepatoblastoma and intestinal metaplasia/cholangiocellular tumor morphology appear to constitute different patterns of genetic programming induced by certain promoters in expanding clones of initiated hepatocytes, on favorable genetic backgrounds such as that of D2B6F1 male mice. JF - Toxicologic pathology AU - Diwan, B A AU - Ward, J M AU - Kurata, Y AU - Rice, J M AD - Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201. PY - 1994 SP - 430 EP - 439 VL - 22 IS - 4 SN - 0192-6233, 0192-6233 KW - Aroclors KW - 0 KW - Carcinogens KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - DDT KW - CIW5S16655 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Cystadenoma -- chemically induced KW - Animals KW - Adenocarcinoma -- chemically induced KW - Metaplasia -- chemically induced KW - Mice KW - Hepatoblastoma -- chemically induced KW - Mice, Inbred DBA KW - Cell Transformation, Neoplastic -- chemically induced KW - Mice, Inbred C57BL KW - Phenobarbital -- toxicity KW - Female KW - Male KW - Liver Neoplasms, Experimental -- pathology KW - DDT -- toxicity KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Aroclors -- toxicity KW - Liver Neoplasms, Experimental -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76932088?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Dissimilar+frequency+of+hepatoblastomas+and+hepatic+cystadenomas+and+adenocarcinomas+arising+in+hepatocellular+neoplasms+of+D2B6F1+mice+initiated+with+N-nitrosodiethylamine+and+subsequently+given+Aroclor-1254%2C+dichlorodiphenyltrichloroethane%2C+or+phenobarbital.&rft.au=Diwan%2C+B+A%3BWard%2C+J+M%3BKurata%2C+Y%3BRice%2C+J+M&rft.aulast=Diwan&rft.aufirst=B&rft.date=1994-07-01&rft.volume=22&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-08 N1 - Date created - 1995-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-1 alpha reduces the severity of the vascular leak syndrome produced by interleukin-2 and interleukin-2 plus interferon-alpha. AN - 76931445; 7817127 AB - Histological and ultrastructural changes were investigated in lung, liver, and heart of mice given interleukin-2 (IL-2), either alone or in combination with other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree with infiltration of lymphoid cells, moderate endothelial damage, mild hepatic parenchymal damage, and minimal myocardial alterations. Interferon-alpha (IFN-alpha) produced infiltration mainly of monocytes/macrophages in liver and heart; endothelial cell damage was absent in lung and heart and minimal in liver. Interleukin-1 alpha (IL-1 alpha) caused an increased number of neutrophils in liver and lung; VLS and parenchymal cell and endothelial damage were not found. The VLS and the cellular damage caused by the combination of IL-2 and IFN were much more severe than those produced by IL-2 alone. In animals treated with IL-2, IFN-alpha, and IL-1 alpha, VLS was minimal and parenchymal and endothelial cell damage were less severe than after IL-2 alone or IL-2 plus IFN-alpha. Taken together, these observations show that IL-1 alpha reduces ultrastructural changes produced by IL-2 and IFN-alpha. This reduction may be clinically useful in the treatment of neoplasms. JF - Toxicologic pathology AU - Fujita, S AU - Puri, R AU - Yu, Z X AU - Travis, W AU - Yamaguchi, M AU - Ferrans, V J AD - Pathology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Maryland 20892. PY - 1994 SP - 381 EP - 397 VL - 22 IS - 4 SN - 0192-6233, 0192-6233 KW - Interferon-alpha KW - 0 KW - Interleukin-1 KW - Interleukin-2 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Myocardium -- pathology KW - Liver -- drug effects KW - Syndrome KW - Mice, Inbred C57BL KW - Lung -- drug effects KW - Mice KW - Capillary Permeability -- drug effects KW - Lung -- pathology KW - Female KW - Interleukin-2 -- antagonists & inhibitors KW - Interferon-alpha -- toxicity KW - Edema -- chemically induced KW - Interleukin-1 -- pharmacology KW - Edema -- prevention & control KW - Interferon-alpha -- antagonists & inhibitors KW - Edema -- pathology KW - Interleukin-2 -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76931445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Interleukin-1+alpha+reduces+the+severity+of+the+vascular+leak+syndrome+produced+by+interleukin-2+and+interleukin-2+plus+interferon-alpha.&rft.au=Fujita%2C+S%3BPuri%2C+R%3BYu%2C+Z+X%3BTravis%2C+W%3BYamaguchi%2C+M%3BFerrans%2C+V+J&rft.aulast=Fujita&rft.aufirst=S&rft.date=1994-07-01&rft.volume=22&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-08 N1 - Date created - 1995-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Independent and coordinate regulation of beta 1- and beta 2-adrenergic receptors in rat C6 glioma cells. AN - 76928775; 7815386 AB - Rat C6 glioma cells have both beta 1- and beta 2-adrenergic receptors in approximately 7:3 ratio. When the cells were exposed to the beta-adrenergic agonist isoproterenol, there was a rapid sequestration of up to 50% of the surface receptor population over a 30-min period as measured by the loss of binding of the hydrophilic ligand [3H] CGP-12177 to intact cells. Using the beta 1-selective antagonist CGP 20712A to quantify the proportion of the two subtypes, it was found that although both beta 1 and beta 2 receptors were sequestered, the latter were sequestered initially twice as fast as the former. More prolonged agonist exposure led to a down-regulation of approximately 90% of the total receptor population by 6 h as measured by the loss of binding of the more hydrophobic ligand [125I]iodocyanopindolol to cell lysates. The two subtypes, however, underwent down-regulation with similar kinetics. Treatment of the cells with agents that raise cyclic AMP levels such as cholera toxin and forskolin resulted in a slower, but still coordinated down-regulation of both subtypes. Thus, there appears to be both independent and coordinate regulation of endogenous beta 1-and beta 2-adrenergic receptors in the same cell line. JF - Journal of receptor research AU - Fishman, P H AU - Miller, T AU - Curran, P K AU - Feussner, G K AD - Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 281 EP - 296 VL - 14 IS - 5 SN - 0197-5110, 0197-5110 KW - Receptors, Adrenergic, beta-1 KW - 0 KW - Receptors, Adrenergic, beta-2 KW - Colforsin KW - 1F7A44V6OU KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Rats KW - Oligodendroglia -- metabolism KW - Animals KW - Oligodendroglia -- drug effects KW - Colforsin -- pharmacology KW - Down-Regulation -- physiology KW - Tumor Cells, Cultured KW - Astrocytes -- drug effects KW - Cyclic AMP -- metabolism KW - Cholera Toxin -- pharmacology KW - Down-Regulation -- drug effects KW - Cell Differentiation -- drug effects KW - Isoproterenol -- pharmacology KW - Astrocytes -- metabolism KW - Receptors, Adrenergic, beta-1 -- metabolism KW - Glioma -- metabolism KW - Receptors, Adrenergic, beta-2 -- drug effects KW - Receptors, Adrenergic, beta-1 -- drug effects KW - Receptors, Adrenergic, beta-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76928775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+receptor+research&rft.atitle=Independent+and+coordinate+regulation+of+beta+1-+and+beta+2-adrenergic+receptors+in+rat+C6+glioma+cells.&rft.au=Fishman%2C+P+H%3BMiller%2C+T%3BCurran%2C+P+K%3BFeussner%2C+G+K&rft.aulast=Fishman&rft.aufirst=P&rft.date=1994-07-01&rft.volume=14&rft.issue=5&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Journal+of+receptor+research&rft.issn=01975110&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-08 N1 - Date created - 1995-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of NO synthase increases the severity of kainic acid-induced seizures in rodents. AN - 76916151; 7528658 AB - The nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (NNA) and the putative brain-selective NO synthase inhibitor 7-nitroindazole (7-NI) were used to determine the role of endogenous NO on seizures induced by kainic acid (KA) in rats and KA, pilocarpine, bicuculline, picrotoxin and pentylenetetrazole (PTZ) in mice. Rats given a subconvulsant dose of KA (6 mg/kg, i.p.) had seizures after they had been pretreated with NNA (50 mg/kg, i.p.). With a higher dose of KA (12 mg/kg, i.p.), NNA caused an increase in wild running seizures and mortality. Unlike NNA, 7-NI had no effect on KA-induced seizures. Similarly, NNA but not 7-NI caused a worsening of seizures in mice measured as a shortening of seizure latency and an increase in wild running and mortality. The effect of NNA on seizure latency was completely reversed by the competitive substrate for NO synthase, L-arginine. NNA had no effect on seizure latency following any of the other convulsants and increased mortality following pilocarpine and picrotoxin alone. Our results indicate that NNA may enhance the severity of KA-induced seizures through suppression of NO synthase activity in the vascular endothelium. The resulting impairment of cerebrovascular autoregulation may cause a mismatch between metabolic demand and blood flow during seizures leading to facilitation of spread. The absence of a comparable effect of NNA on other seizure models may indicate differences in the degree to which seizure activity in different models is influenced by the metabolic impairment secondary to decreased blood flow. JF - Epilepsy research AU - Penix, L P AU - Davis, W AU - Subramaniam, S AD - Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 177 EP - 184 VL - 18 IS - 3 SN - 0920-1211, 0920-1211 KW - Enzyme Inhibitors KW - 0 KW - Indazoles KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Kainic Acid KW - SIV03811UC KW - 7-nitroindazole KW - UX0N37CMVH KW - Pentylenetetrazole KW - WM5Z385K7T KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Pentylenetetrazole -- pharmacology KW - Nitric Oxide -- antagonists & inhibitors KW - Cerebrovascular Circulation -- drug effects KW - Indazoles -- pharmacology KW - Mice KW - Arginine -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Enzyme Inhibitors -- pharmacology KW - Arginine -- analogs & derivatives KW - Male KW - Seizures -- chemically induced KW - Kainic Acid -- pharmacology KW - Seizures -- physiopathology KW - Amino Acid Oxidoreductases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76916151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Inhibition+of+NO+synthase+increases+the+severity+of+kainic+acid-induced+seizures+in+rodents.&rft.au=Penix%2C+L+P%3BDavis%2C+W%3BSubramaniam%2C+S&rft.aulast=Penix&rft.aufirst=L&rft.date=1994-07-01&rft.volume=18&rft.issue=3&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy of advanced gastrointestinal cancer. AN - 76908253; 7803544 AB - Pancreatic, gastric, and colorectal carcinomas are diagnosed in 200,000 Americans each year. Therapeutic options for patients with advanced disease are limited; conventional chemotherapy is palliative and produces complete responses in only a few patients. Clinical research has focused on the evaluation of investigational new drugs, combination regimens, and biochemical modulation of fluorouracil. Unfortunately, the results of recent phase II studies of new agents have been disappointing. The exception is CPT-11, a topoisomerase I inhibitor, which showed promising activity in colorectal cancer (in including patients who had failed prior fluorouracil therapy). Modified regimens of fluorouracil and methotrexate with either doxorubicin alone or with epirubicin and cisplatin were associated with response rates approaching 50% in patients with gastric cancer, but appeared to be less toxic than previously published regimens. A randomized trial comparing fluororacil alone or with oral leucovorin allowed early dose escalation according to individual tolerance; the response rate to fluorouracil alone (23%) was higher than that reported in previous phase III trials, suggesting the importance of using adequate doses to produce toxicity in terms of clinical response. Hepatic arterial infusion of floxuridine was associated with a 39% response rate in colorectal cancer patients with disease confined to the liver for whom systemic fluorouracil therapy had failed, suggesting this approach is a reasonable therapeutic option in carefully selected patients. JF - Current opinion in oncology AU - Geoffroy, F AU - Grem, J L AD - National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, MD 20899-5105. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 427 EP - 434 VL - 6 IS - 4 SN - 1040-8746, 1040-8746 KW - Antineoplastic Agents KW - 0 KW - Drugs, Investigational KW - Immunologic Factors KW - irinotecan KW - 0H43101T0J KW - Leucovorin KW - Q573I9DVLP KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Pancreatic Neoplasms -- mortality KW - Humans KW - Gastrointestinal Neoplasms -- therapy KW - Gastrointestinal Neoplasms -- drug therapy KW - Camptothecin -- therapeutic use KW - Drugs, Investigational -- therapeutic use KW - Treatment Outcome KW - Neoplasm Metastasis KW - Gastrointestinal Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Immunologic Factors -- adverse effects KW - Infusions, Intra-Arterial KW - Double-Blind Method KW - Combined Modality Therapy KW - Clinical Trials as Topic KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Pancreatic Neoplasms -- pathology KW - Pancreatic Neoplasms -- therapy KW - Prospective Studies KW - Survival Rate KW - Immunologic Factors -- therapeutic use KW - Gastrointestinal Neoplasms -- mortality KW - Camptothecin -- analogs & derivatives KW - Pancreatic Neoplasms -- drug therapy KW - Leucovorin -- therapeutic use KW - Digestive System Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Digestive System Neoplasms -- therapy KW - Digestive System Neoplasms -- mortality KW - Digestive System Neoplasms -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76908253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+oncology&rft.atitle=Chemotherapy+of+advanced+gastrointestinal+cancer.&rft.au=Geoffroy%2C+F%3BGrem%2C+J+L&rft.aulast=Geoffroy&rft.aufirst=F&rft.date=1994-07-01&rft.volume=6&rft.issue=4&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-27 N1 - Date created - 1995-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive brain potential alterations in boys exposed to opiates: in utero and lifestyle comparisons. AN - 76882062; 7992677 AB - Several studies have observed that intrauterine exposure to opiates results in emotional and cognitive complications for the child, but genetic and postnatal social-environmental factors may also affect the CNS development of these children. To assess the relative contribution of the in utero and social-environmental (lifestyle) effects of opiate exposure, event-related potentials (ERPs) and performance were studied in three groups of 7- to 12-year-old boys: (1) the in utero/lifestyle group (IU/LS) contained 16 boys who were exposed to opiates (in utero and lived with opiate-abusing mothers, (2) the lifestyle group (LS) included 14 boys who lived with opiate-abusing mothers, and (3) the control group (CON) composed of 13 boys. The cognitive ERP components and task performance were recorded in the Auditory Rare Event Monitoring (AREM) task and the Sternberg Memory task (Sternberg, 1975). On the AREM and Sternberg Memory tasks, P200 component was significantly decreased for the IU/LS and LS groups. On the Sternberg Memory task, percent correct was also significantly impaired in IU/LS and LS groups. The ERP alterations in the boys living with opiate-abusing mothers with and without intrauterine opiate exposure were similar. A dysfunctional social environment may contribute to the cognitive deficits seen in the sons of opiate-abusing mothers. JF - Addictive behaviors AU - Guo, X AU - Spencer, J W AU - Suess, P E AU - Hickey, J E AU - Better, W E AU - Herning, R I AD - Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224. PY - 1994 SP - 429 EP - 441 VL - 19 IS - 4 SN - 0306-4603, 0306-4603 KW - Narcotics KW - 0 KW - Index Medicus KW - Humans KW - Child of Impaired Parents -- psychology KW - Child KW - Male KW - Female KW - Social Environment KW - Pregnancy KW - Life Style KW - Arousal -- drug effects KW - Evoked Potentials, Auditory -- drug effects KW - Narcotics -- adverse effects KW - Attention -- drug effects KW - Mental Recall -- drug effects KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76882062?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Cognitive+brain+potential+alterations+in+boys+exposed+to+opiates%3A+in+utero+and+lifestyle+comparisons.&rft.au=Guo%2C+X%3BSpencer%2C+J+W%3BSuess%2C+P+E%3BHickey%2C+J+E%3BBetter%2C+W+E%3BHerning%2C+R+I&rft.aulast=Guo&rft.aufirst=X&rft.date=1994-07-01&rft.volume=19&rft.issue=4&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-09 N1 - Date created - 1995-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. AN - 76864219; 7981423 AB - Diclofenac is a nonsteroidal anti-inflammatory agent that is reported to cause serious hepatic injury in some patients. To investigate the possibility that protein adducts derived from reactive intermediates of diclofenac might be responsible for the hepatotoxicity produced by this drug, we recently developed polyclonal antisera that recognized protein adducts of diclofenac. In the present study, we have characterized further the diclofenac adducts in rat liver. Immunoblotting studies showed that diclofenac-labeled hepatic proteins were formed in a dose- and time-dependent manner in rats given diclofenac. Subcellular fractionation of liver homogenates from diclofenac-treated rats showed that a 50-kDa microsomal protein and 110-, 140-, and 200-kDa plasma membrane proteins were labeled preferentially. Immunofluorescence studies of isolated hepatocytes and immunohistochemical analysis of liver slices from diclofenac-treated mice and rats confirmed that plasma membrane proteins were labeled by diclofenac metabolites and showed that the bile canalicular domain of the plasma membrane was a major site of diclofenac adduct formation. Additionally, we found that cytochrome P-450 and UDP-glucuronosyltransferase, but not acyl-CoA synthase, catalyzed the formation of reactive intermediates of diclofenac that were bound covalently to proteins in vitro. The metabolites catalyzed by cytochrome P-450 in vitro were bound exclusively to a 50-kDa microsomal protein, even in the presence of albumin. In contrast, the 110-, 140-, and 200-kDa plasma membrane proteins as well as others appeared to be labeled when diclofenac was activated by UDP-glucuronosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Chemical research in toxicology AU - Hargus, S J AU - Amouzedeh, H R AU - Pumford, N R AU - Myers, T G AU - McCoy, S C AU - Pohl, L R AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 575 EP - 582 VL - 7 IS - 4 SN - 0893-228X, 0893-228X KW - Proteins KW - 0 KW - Diclofenac KW - 144O8QL0L1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Index Medicus KW - Rats KW - Cytosol -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Cell Membrane -- drug effects KW - Biotransformation KW - Glucuronosyltransferase -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cell Membrane -- metabolism KW - Proteins -- metabolism KW - Fluorescent Antibody Technique KW - Male KW - Diclofenac -- toxicity KW - Microsomes, Liver -- metabolism KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - Diclofenac -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76864219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Metabolic+activation+and+immunochemical+localization+of+liver+protein+adducts+of+the+nonsteroidal+anti-inflammatory+drug+diclofenac.&rft.au=Hargus%2C+S+J%3BAmouzedeh%2C+H+R%3BPumford%2C+N+R%3BMyers%2C+T+G%3BMcCoy%2C+S+C%3BPohl%2C+L+R&rft.aulast=Hargus&rft.aufirst=S&rft.date=1994-07-01&rft.volume=7&rft.issue=4&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-03 N1 - Date created - 1995-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A further attenuated derivative of a cold-passaged temperature-sensitive mutant of human respiratory syncytial virus retains immunogenicity and protective efficacy against wild-type challenge in seronegative chimpanzees. AN - 76855973; 7975856 AB - A cold-passage (cp), temperature-sensitive (ts) RSV mutant designated RSV cpts-248 (shut-off temperature 38 degrees C), which possesses host-range mutations acquired during 52 passages at low temperature in bovine tissue culture and a ts phenotype introduced by subsequent chemical mutagenesis, was found previously to be attenuated, immunogenic, and protective against wild-type challenge in seronegative chimpanzees. We sought to introduce additional attenuating mutations such as small-plaque (sp) and ts mutations into RSV cpts-248 by chemical mutagenesis with 5-fluorouracil with the intent of obtaining cpts-248 derivatives that are more attenuated in mice or chimpanzees and that are more genetically stable following replication in vivo. Ten mutants of RSV cpts-248 which had acquired a sp phenotype or a second ts mutation were generated by chemical mutagenesis. Five cpts-248 derivatives which had acquired mutations that specified a 36 degrees C shut-off temperature for plaque formation and one which had acquired only a sp phenotype were more restricted in replication in Balb/c mice than the cpts-248 parental strain. One mutant, designated RSV cpts-248/404 (shut-off temperature 36 degrees C), was 100 times more restricted in replication in the nasal turbinates of mice and 100 times more restricted in the nasopharynx of seronegative chimpanzees than its cpts-248 parent. The cpts-248/404 mutant was completely restricted in replication in the lower respiratory tract of chimpanzees even following direct intratracheal administration. The ts phenotype of the cpts-248/404 mutant was stable during replication in vivo in mice and chimpanzees.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Vaccine AU - Crowe, J E AU - Bui, P T AU - Davis, A R AU - Chanock, R M AU - Murphy, B R AD - Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 783 EP - 790 VL - 12 IS - 9 SN - 0264-410X, 0264-410X KW - Vaccines, Attenuated KW - 0 KW - Viral Vaccines KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Mutagenesis -- drug effects KW - Animals KW - Humans KW - Mice KW - Cold Temperature KW - Mutagenesis -- genetics KW - Mice, Inbred BALB C KW - Pan troglodytes KW - Phenotype KW - Virus Replication -- genetics KW - Cattle KW - Culture Techniques KW - Epithelial Cells KW - Vaccines, Attenuated -- immunology KW - Serial Passage KW - Cercopithecus aethiops KW - Vaccines, Attenuated -- genetics KW - Fluorouracil -- pharmacology KW - Vero Cells KW - Epithelium -- immunology KW - Cell Line, Transformed KW - Virus Replication -- immunology KW - Female KW - Male KW - Respiratory Syncytial Viruses -- immunology KW - Respiratory Syncytial Viruses -- genetics KW - Viral Vaccines -- genetics KW - Viral Vaccines -- immunology KW - Respiratory Syncytial Virus Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76855973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=A+further+attenuated+derivative+of+a+cold-passaged+temperature-sensitive+mutant+of+human+respiratory+syncytial+virus+retains+immunogenicity+and+protective+efficacy+against+wild-type+challenge+in+seronegative+chimpanzees.&rft.au=Crowe%2C+J+E%3BBui%2C+P+T%3BDavis%2C+A+R%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=J&rft.date=1994-07-01&rft.volume=12&rft.issue=9&rft.spage=783&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-28 N1 - Date created - 1994-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and safety of weekly dapsone and dapsone plus pyrimethamine for prevention of pneumocystis pneumonia. AN - 76855254; 7979291 AB - The safety and pharmacokinetics of weekly dapsone and weekly dapsone plus pyrimethamine were examined in adult patients with human immunodeficiency virus infection who were at risk for pneumocystis pneumonia because of a prior episode or a CD4+ T-cell count less than 250 cells per mm3. Groups of patients received 100, 200, and 300 mg of dapsone as a single weekly dose. The maximum tolerated dose of weekly dapsone was established as 200 mg per week in patients receiving at least 500 mg of zidovudine concomitantly. This dose of dapsone was then found to be well tolerated when combined with pyrimethamine at 25 mg. Further patients were randomized to dapsone at 200 mg or dapsone at 200 mg plus pyrimethamine at 25 mg once weekly. Twenty-six patients each were followed for a median of 33 weeks on dapsone alone and 45 weeks on the combination. Seven patients in each group withdrew because of toxicity. Five patients receiving dapsone developed documented pneumocystis pneumonia, while four and two patients receiving dapsone plus pyrimethamine developed documented and presumptive pneumocystis pneumonia, respectively. To evaluate the tolerability of a higher dose of pyrimethamine, 11 patients had their regimen changed to dapsone at 200 mg plus pyrimethamine at 75 mg, which was well tolerated by 10 of the patients for a median period of 11 weeks. The pharmacokinetics of dapsone and pyrimethamine were examined by using a population pharmacokinetic model. Decreases in the apparent volume of the peripheral compartment were observed when multiple-dose regimens of dapsone were compared with single-dose dapsone and when multiple-dose regimens of dapsone with pyrimethamine were compared with multiple-dose dapsone alone. When administered weekly, dapsone at 200 mg and dapsone at 200 mg with pyrimethamine at 25 mg are both well-tolerated regimens. This preliminary study suggests that the efficacy of these regimens in preventing pneumocystis pneumonia, however, may be less than that of trimethoprim-sulfamethoxazole. JF - Antimicrobial agents and chemotherapy AU - Falloon, J AU - Lavelle, J AU - Ogata-Arakaki, D AU - Byrne, A AU - Graziani, A AU - Morgan, A AU - Amantea, M A AU - Ownby, K AU - Polis, M AU - Davey, R T AD - Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 1580 EP - 1587 VL - 38 IS - 7 SN - 0066-4804, 0066-4804 KW - Dapsone KW - 8W5C518302 KW - Pyrimethamine KW - Z3614QOX8W KW - Index Medicus KW - AIDS/HIV KW - Drug Therapy, Combination KW - Humans KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Biological Availability KW - Dapsone -- adverse effects KW - Pneumonia, Pneumocystis -- prevention & control KW - Pyrimethamine -- therapeutic use KW - Dapsone -- administration & dosage KW - Pyrimethamine -- adverse effects KW - Pyrimethamine -- administration & dosage KW - Dapsone -- pharmacokinetics KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Pyrimethamine -- pharmacokinetics KW - Dapsone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76855254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Pharmacokinetics+and+safety+of+weekly+dapsone+and+dapsone+plus+pyrimethamine+for+prevention+of+pneumocystis+pneumonia.&rft.au=Falloon%2C+J%3BLavelle%2C+J%3BOgata-Arakaki%2C+D%3BByrne%2C+A%3BGraziani%2C+A%3BMorgan%2C+A%3BAmantea%2C+M+A%3BOwnby%2C+K%3BPolis%2C+M%3BDavey%2C+R+T&rft.aulast=Falloon&rft.aufirst=J&rft.date=1994-07-01&rft.volume=38&rft.issue=7&rft.spage=1580&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-29 N1 - Date created - 1994-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: AIDS. 1992 Oct;6(10):1169-74 [1466849] N Engl J Med. 1991 Sep 5;325(10):737 [1908060] Am J Med. 1993 Dec;95(6):573-83 [8018144] Br J Clin Pharmacol. 1978 Nov;6(5):421-7 [728285] Comput Programs Biomed. 1979 Mar;9(2):115-34 [761456] Br J Clin Pharmacol. 1980 Nov;10(5):519-24 [7437265] Drug Metab Rev. 1984;15(1-2):265-92 [6745083] Clin Pharmacokinet. 1986 Jul-Aug;11(4):299-315 [3530584] J Exp Med. 1987 Mar 1;165(3):926-31 [2950200] Arch Intern Med. 1992 Mar;152(3):523-8 [1546914] J Acquir Immune Defic Syndr. 1992;5(4):341-7 [1548570] Lancet. 1992 Sep 26;340(8822):788 [1356193] Lancet. 1992 Oct 31;340(8827):1099 [1357487] N Engl J Med. 1992 Dec 24;327(26):1842-8 [1448121] Antimicrob Agents Chemother. 1988 May;32(5):623-5 [3260765] Ann Intern Med. 1989 Apr 15;110(8):606-11 [2784648] Med J Aust. 1989 Jul 3;151(1):30-3 [2528052] N Engl J Med. 1990 Jan 18;322(3):161-5 [1967190] J Clin Invest. 1990 Feb;85(2):371-9 [2298911] Lancet. 1990 Oct 27;336(8722):1066 [1977035] AIDS. 1990 Nov;4(11):1145-8 [2282188] Lancet. 1991 May 11;337(8750):1162-3 [1674036] AIDS. 1991 May;5(5):601-2 [1863415] N Engl J Med. 1993 May 27;328(21):1514-20 [8479488] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluctuations in plasma levodopa and motor responses with liquid and tablet levodopa/carbidopa. AN - 76834271; 7969216 AB - To evaluate the ability of orally administered liquid levodopa/carbidopa (LD/CD) to stabilize plasma levodopa levels and reduce motor response fluctuations in Parkinson's disease, five patients received LD/CD hourly, as standard tablets or as an aqueous solution on two separate days in a double-blind, placebo-controlled, cross-over design. Except for a slightly earlier peak plasma levodopa level, no significant advantage of the liquid formulation over tablet therapy was found. However, liquid LD/CD could be helpful in quickly resolving "off" states and by facilitating small dose adjustments that are not possible with tablets. JF - Movement disorders : official journal of the Movement Disorder Society AU - Metman, L V AU - Hoff, J AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 463 EP - 465 VL - 9 IS - 4 SN - 0885-3185, 0885-3185 KW - Antiparkinson Agents KW - 0 KW - Drug Combinations KW - Solutions KW - Tablets KW - carbidopa, levodopa drug combination KW - Levodopa KW - 46627O600J KW - Carbidopa KW - MNX7R8C5VO KW - Index Medicus KW - Administration, Oral KW - Double-Blind Method KW - Humans KW - Aged KW - Biological Availability KW - Therapeutic Equivalency KW - Cross-Over Studies KW - Neurologic Examination -- drug effects KW - Middle Aged KW - Female KW - Male KW - Carbidopa -- administration & dosage KW - Antiparkinson Agents -- adverse effects KW - Levodopa -- administration & dosage KW - Levodopa -- pharmacokinetics KW - Antiparkinson Agents -- administration & dosage KW - Motor Skills -- drug effects KW - Carbidopa -- adverse effects KW - Carbidopa -- pharmacokinetics KW - Levodopa -- adverse effects KW - Parkinson Disease -- drug therapy KW - Antiparkinson Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76834271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&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=Fluctuations+in+plasma+levodopa+and+motor+responses+with+liquid+and+tablet+levodopa%2Fcarbidopa.&rft.au=Metman%2C+L+V%3BHoff%2C+J%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Metman&rft.aufirst=L&rft.date=1994-07-01&rft.volume=9&rft.issue=4&rft.spage=463&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 - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-14 N1 - Date created - 1994-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic toxic and carcinogenic effects of cadmium chloride in male DBA/2NCr and NFS/NCr mice: strain-dependent association with tumors of the hematopoietic system, injection site, liver, and lung. AN - 76816589; 7958559 AB - Although the acute toxic effects of cadmium in mice vary greatly with strain, relatively little is known about strain differences in cadmium carcinogenesis. Therefore, this work was performed to assess the chronic toxic and carcinogenic effects of cadmium in two strains of mice generally thought to be susceptible to the acute effects of cadmium. Male DBA/2NCr (DBA) and NFS/NCr (NFS) mice were given CdCl2 (40 mumol/kg, sc) either as a single dose (1 x 40) or as weekly doses for 16 weeks (16 x 40) starting at 8 weeks of age. Controls received saline. The animals were observed for the next 104 weeks and mice at risk were defined as those surviving to the time of appearance of a particular tumor. Cadmium-induced dose-related increases in lymphoma (primarily follicular center cell) incidence (1 x 40, 11 cases/23 mice at risk; 16 x 40, 16/28) over control (7/27) in DBA mice but not in NFS mice. Only NFS mice receiving repeated cadmium injections (16 x 40) showed sarcoma development at the injection site (9/35), as no sarcomas occurred in control NFS mice or any group of DBA mice. On the other hand, cadmium-treated (16 x 40) NFS mice, but not DBA mice, had more hepatocellular adenomas and carcinomas (9/27) than control (1/15) but only at the high dose (16 x 40). More cadmium-treated NFS mice had pulmonary tumors than controls, but only at the lower dose (1 x 40). Although testicular tumors were rare, nonneoplastic lesions (fibrosis and mineralization) were induced by cadmium to a similar extent in both strains. Clearly cadmium carcinogenicity varies widely with strain, indicating a genetic basis to susceptibility. The basis of these strain differences deserves further study. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Waalkes, M P AU - Rehm, S AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 21 EP - 31 VL - 23 IS - 1 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Skin Neoplasms -- chemically induced KW - Injections, Subcutaneous KW - Carcinogenicity Tests KW - Lymphoma -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Lung Neoplasms -- chemically induced KW - Species Specificity KW - Male KW - Mice, Inbred DBA KW - Carcinogens -- administration & dosage KW - Cadmium -- administration & dosage KW - Carcinogens -- toxicity KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76816589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Chronic+toxic+and+carcinogenic+effects+of+cadmium+chloride+in+male+DBA%2F2NCr+and+NFS%2FNCr+mice%3A+strain-dependent+association+with+tumors+of+the+hematopoietic+system%2C+injection+site%2C+liver%2C+and+lung.&rft.au=Waalkes%2C+M+P%3BRehm%2C+S&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1994-07-01&rft.volume=23&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of individual housing and other experimental design factors on tumor incidence in B6C3F1 mice. AN - 76809225; 7958562 AB - The effects of individual housing and other experimental design factors on body weight, survival, and tumor incidence in 72 control groups of B6C3F1 mice were evaluated. Individually housed males showed a greatly reduced incidence of dermal/subcutaneous tumors and an improved survival relative to group-housed animals. However, there were significant body weight increases in individually housed males and females and an associated marked increase in liver tumor incidence in both sexes and a lesser increase in lung neoplasms in males. Body weights of mice as young as 19 weeks of age were predictive of subsequent liver tumor incidence. There were no major differences in tumor rates among the various types of control groups, and differences in tumor rates among laboratories were not significant for most tumors. Differences among animal suppliers may have contributed to the time-related decreased incidence of malignant lymphoma observed in control mice, particularly in females. Comparisons with earlier control tumor rates suggest that there has been little change in tumor incidence for control groups having approximately equivalent body weights. However, control groups with heavier animals have shown a striking increase in the incidence of liver tumors. The National Toxicology Program recently returned to its earlier practice of group-housing female mice, and this should reduce the incidence of liver tumors in this sex-species group. However, if measures are not taken to reduce body weights, male mice (which continue to be individually housed because of fighting problems among group-housed animals) will likely continue to show a high incidence of liver tumors and possibly also lung neoplasms. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Haseman, J K AU - Bourbina, J AU - Eustis, S L AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 44 EP - 52 VL - 23 IS - 1 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - Neoplasms, Experimental -- epidemiology KW - Mice, Inbred Strains KW - Animals KW - Body Weight -- physiology KW - Mice KW - Neoplasms, Experimental -- pathology KW - Research Design KW - Male KW - Female KW - Survival Analysis KW - Housing, Animal KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76809225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Effect+of+individual+housing+and+other+experimental+design+factors+on+tumor+incidence+in+B6C3F1+mice.&rft.au=Haseman%2C+J+K%3BBourbina%2C+J%3BEustis%2C+S+L&rft.aulast=Haseman&rft.aufirst=J&rft.date=1994-07-01&rft.volume=23&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-01 N1 - Date created - 1994-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure and transcriptional regulation of the GFAP gene. AN - 76807290; 7952266 AB - Transcriptional regulation of the GFAP gene is intimately connected with astrocyte function: its initial activation marks the differentiation of astrocytes, and its up-regulation accompanies the reactive response to CNS injury. Studies of GFAP transcription should thus provide insights into multiple regulatory pathways operating in these cells. In addition, they should identify DNA elements that could be used to direct synthesis of other proteins to astrocytes in transgenic animals, permitting creation of disease models, and the testing of cause and effect relationships. This review describes several GFAP cDNA and genomic clones that have been isolated, including homology comparisons of the encoded RNAs and proteins. Cell transfection studies by several laboratories are summarized that have identified a DNA segment immediately upstream of the RNA start site that is essential for transcriptional activity, but which have yielded conflicting results concerning the importance of other segments located both further upstream and downstream of the RNA start site. Two procedures are recounted that have led to the successful expression of GFAP-transgenes in astrocytes in mice. One of these incorporates the transgene into the first exon of a fragment spanning the entire GFAP gene, while the other links it to a 2 kb 5'-flanking segment. Results already produced by GFAP-transgenic studies include demonstration of a neurotoxic effect of the HIV-1 gp120 coat protein, and creation of a hydrocephalic mouse model. JF - Brain pathology (Zurich, Switzerland) AU - Brenner, M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 245 EP - 257 VL - 4 IS - 3 SN - 1015-6305, 1015-6305 KW - Glial Fibrillary Acidic Protein KW - 0 KW - HIV Envelope Protein gp120 KW - Neurotoxins KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Sequence Homology, Nucleic Acid KW - Astrocytes -- drug effects KW - Humans KW - Transcription, Genetic KW - Mice KW - Animals, Genetically Modified KW - HIV-1 KW - Neurotoxins -- toxicity KW - Rats KW - Base Sequence KW - Promoter Regions, Genetic KW - Transfection KW - Molecular Sequence Data KW - HIV Envelope Protein gp120 -- toxicity KW - TATA Box KW - Astrocytes -- metabolism KW - Gene Expression Regulation KW - Brain -- metabolism KW - Glial Fibrillary Acidic Protein -- biosynthesis KW - Glial Fibrillary Acidic Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76807290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathology+%28Zurich%2C+Switzerland%29&rft.atitle=Structure+and+transcriptional+regulation+of+the+GFAP+gene.&rft.au=Brenner%2C+M&rft.aulast=Brenner&rft.aufirst=M&rft.date=1994-07-01&rft.volume=4&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Brain+pathology+%28Zurich%2C+Switzerland%29&rft.issn=10156305&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-20 N1 - Date created - 1994-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of two lysine residues in the CDR loops of a recombinant immunotoxin that reduce its sensitivity to chemical derivatization. AN - 76793731; 7948099 AB - B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of monoclonal antibody B3 is connected to a truncated form of Pseudomonas exotoxin. It would be desirable to use the lysine residues of the molecule for chemical modification so that it can be derivatized with poly(ethylene glycol) to achieve reduced immunogenicity or with the Bolton-Hunter reagent for biodistribution studies. We found that derivatizing lysine residues of B3(Fv)-PE38 causes a marked loss of specific target cell cytotoxicity and/or immunoreactivity. Here we show that two lysine residues in the antibody-combining region of B3(Fv)-PE38 can be replaced with arginines, with only a small loss of cytotoxicity and no change in specificity. This mutant molecule is 3-fold more resistant to inactivation by derivatization with succinimidyl 4-(N-maleimidomethyl)cyclohexane 1-carboxylate (SMCC) or Bolton-Hunter reagent. JF - Bioconjugate chemistry AU - Benhar, I AU - Brinkmann, U AU - Webber, K O AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 321 EP - 326 VL - 5 IS - 4 SN - 1043-1802, 1043-1802 KW - Immunoglobulin Variable Region KW - 0 KW - Immunotoxins KW - Iodine Radioisotopes KW - Recombinant Proteins KW - Glutamine KW - 0RH81L854J KW - Arginine KW - 94ZLA3W45F KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - Arginine -- metabolism KW - Glutamine -- metabolism KW - Humans KW - Amino Acid Sequence KW - Mice KW - Recombinant Proteins -- genetics KW - Plasmids KW - Recombinant Proteins -- toxicity KW - Antibody Specificity KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Pseudomonas -- metabolism KW - Mutation KW - Immunotoxins -- chemistry KW - Immunotoxins -- toxicity KW - Immunoglobulin Variable Region -- chemistry KW - Immunotoxins -- genetics KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76793731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioconjugate+chemistry&rft.atitle=Mutations+of+two+lysine+residues+in+the+CDR+loops+of+a+recombinant+immunotoxin+that+reduce+its+sensitivity+to+chemical+derivatization.&rft.au=Benhar%2C+I%3BBrinkmann%2C+U%3BWebber%2C+K+O%3BPastan%2C+I&rft.aulast=Benhar&rft.aufirst=I&rft.date=1994-07-01&rft.volume=5&rft.issue=4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+chemistry&rft.issn=10431802&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-23 N1 - Date created - 1994-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiretroviral therapy for infection due to human immunodeficiency virus in children. AN - 76788220; 7948527 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Pizzo, P A AU - Wilfert, C AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 177 EP - 196 VL - 19 IS - 1 SN - 1058-4838, 1058-4838 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Child Health Services KW - Retroviridae -- drug effects KW - Humans KW - Infant, Newborn KW - Child KW - Child, Preschool KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- pharmacokinetics KW - HIV Infections -- drug therapy KW - Antiviral Agents -- adverse effects KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76788220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Antiretroviral+therapy+for+infection+due+to+human+immunodeficiency+virus+in+children.&rft.au=Pizzo%2C+P+A%3BWilfert%2C+C&rft.aulast=Pizzo&rft.aufirst=P&rft.date=1994-07-01&rft.volume=19&rft.issue=1&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-12 N1 - Date created - 1994-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral vector-mediated overexpression of the RII beta subunit of the cAMP-dependent protein kinase induces differentiation in human leukemia cells and reverts the transformed phenotype of mouse fibroblasts. AN - 76787929; 7947390 AB - We have recently shown, using antisense strategy, that the RII beta regulatory subunit of cAMP-dependent protein kinase is essential for cAMP-induced growth inhibition and differentiation of HL-60 human leukemia cells. We constructed a retroviral vector for RII beta (MT-RII beta) by inserting human RII beta complementary DNA into the OT1521 retroviral vector plasmid that contains an internal mouse metallothionein-1 promoter and a neomycin resistance gene. The PA317 packaging cell line was then transfected with MT-RII beta plasmid to produce the amphotrophic stock of MT-RII beta retroviral vector. The infection with MT-RII beta and treatment with CdCl2 brought about growth arrest in HL-60 human leukemia and Ki-ras-transformed NIH 3T3 clone DT cells in monolayer culture with no sign of toxicity. The growth inhibition correlated with the expression of RII beta and accompanied changes in cell morphology; cells became flat, exhibiting enlarged cytoplasm. The growth of these cells in semisolid medium (anchorage-independent growth) was almost completely suppressed. In contrast, overexpression of the RI alpha subunit of protein kinase enhanced the cell proliferation in DT cells. The MT-RII beta-infected cells exhibited an increased sensitivity toward treatment with cAMP analogues, such as 8-Cl-cAMP and N6-benzyl-cAMP, as compared with the parental noninfected cells. In MT-RII beta HL-60 cells, N6-benzyl-cAMP treatment greatly enhanced the expression of monocytic surface markers. These results suggest that the RII beta cAMP receptor, by binding to its ligand, cAMP, acts as a tumor suppressor protein exerting growth inhibition, differentiation, and reverse transformation. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Tortora, G AU - Budillon, A AU - Yokozaki, H AU - Clair, T AU - Pepe, S AU - Merlo, G AU - Rohlff, C AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 753 EP - 759 VL - 5 IS - 7 SN - 1044-9523, 1044-9523 KW - v-Ki-ras KW - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit KW - 0 KW - Isoenzymes KW - PRKAR2B protein, human KW - Prkar2b protein, mouse KW - Recombinant Fusion Proteins KW - Cadmium KW - 00BH33GNGH KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - N(6)-benzyl-cyclic adenosine 5'-monophosphate KW - 32115-08-5 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Metallothionein KW - 9038-94-2 KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - 3T3 Cells KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Animals KW - Humans KW - Metallothionein -- genetics KW - Mice KW - Leukemia, Promyelocytic, Acute -- pathology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Phenotype KW - Cadmium -- pharmacology KW - Tumor Cells, Cultured KW - Promoter Regions, Genetic -- drug effects KW - Genetic Vectors KW - Retroviridae -- genetics KW - Allosteric Site KW - Cell Division KW - Isoenzymes -- chemistry KW - Gene Expression Regulation, Neoplastic KW - Signal Transduction -- physiology KW - Isoenzymes -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Cell Differentiation -- physiology KW - Cyclic AMP -- pharmacology KW - Cyclic AMP -- analogs & derivatives KW - Cyclic AMP-Dependent Protein Kinases -- chemistry KW - Cyclic AMP-Dependent Protein Kinases -- genetics KW - Cyclic AMP -- physiology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76787929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Retroviral+vector-mediated+overexpression+of+the+RII+beta+subunit+of+the+cAMP-dependent+protein+kinase+induces+differentiation+in+human+leukemia+cells+and+reverts+the+transformed+phenotype+of+mouse+fibroblasts.&rft.au=Tortora%2C+G%3BBudillon%2C+A%3BYokozaki%2C+H%3BClair%2C+T%3BPepe%2C+S%3BMerlo%2C+G%3BRohlff%2C+C%3BCho-Chung%2C+Y+S&rft.aulast=Tortora&rft.aufirst=G&rft.date=1994-07-01&rft.volume=5&rft.issue=7&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-Ki-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of hepatitis B surface and core antigens and transforming growth factor-alpha in "oval cells" of the liver in patients with hepatocellular carcinoma. AN - 76760624; 7523580 AB - Recent studies have identified epithelial cell populations in human livers that are similar to the "oval cells" and "transitional cells" seen in rat livers during the early stages of chemical carcinogenesis. It has been suggested that these cells might be precursors of hepatocytes and theoretically could be involved in hepatocarcinogenesis. The hepatitis B virus (HBV) also is believed to play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients from China to determine whether HBV antigens could be identified in oval cells and transitional cells using an immunohistochemical technique. Hepatitis B surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%) patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or ductule cells. Transforming growth factor-alpha (TGF-alpha) was expressed in oval cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-alpha was identified in the same cells in populations of oval cells and transitional cells of selected patients. Because of the possibility that oval cells could be a source of evolving HCC, these findings suggest that expression of TGF-alpha associated with HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites) where HBV participates in the development of HCC. JF - Journal of medical virology AU - Hsia, C C AU - Thorgeirsson, S S AU - Tabor, E AD - Biological Carcinogenesis Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 216 EP - 221 VL - 43 IS - 3 SN - 0146-6615, 0146-6615 KW - Hepatitis B Core Antigens KW - 0 KW - Hepatitis B Surface Antigens KW - Transforming Growth Factor alpha KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Keratins -- metabolism KW - Epithelium -- virology KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Epithelium -- metabolism KW - Transforming Growth Factor alpha -- metabolism KW - Epithelium -- pathology KW - Immunohistochemistry KW - Male KW - Female KW - Carcinoma, Hepatocellular -- virology KW - Liver Neoplasms -- pathology KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Liver Neoplasms -- virology KW - Hepatitis B Core Antigens -- metabolism KW - Carcinoma, Hepatocellular -- pathology KW - Hepatitis B Surface Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76760624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+virology&rft.atitle=Expression+of+hepatitis+B+surface+and+core+antigens+and+transforming+growth+factor-alpha+in+%22oval+cells%22+of+the+liver+in+patients+with+hepatocellular+carcinoma.&rft.au=Hsia%2C+C+C%3BThorgeirsson%2C+S+S%3BTabor%2C+E&rft.aulast=Hsia&rft.aufirst=C&rft.date=1994-07-01&rft.volume=43&rft.issue=3&rft.spage=216&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+virology&rft.issn=01466615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-18 N1 - Date created - 1994-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Violent behavior by individuals with serious mental illness. AN - 76748737; 7927289 AB - The perceived association between violent behavior and serious mental illness was explored to determine the validity of claims by mental health advocates that individuals with serious mental illness are no more dangerous than members of the general population. The author reviewed recent studies and media accounts of violent behavior by individuals with serious mental illness, with emphasis given to the most recent studies. Although the vast majority of individuals with serious mental illness are not more dangerous than members of the general population, recent findings suggest the existence of a subgroup that is more dangerous. A history of violent behavior, noncompliance with medications, and substance abuse are important predictors of violent behavior in this subgroup. The findings imply that the criteria for involuntary hospitalization, involuntary medication, outpatient commitment, the monitoring of medication compliance, and other mandated follow-up procedures may need to be revised. The existence of a subgroup of seriously mentally ill patients who exhibit violent behavior undermines efforts by mental health advocates to reduce the stigma of mental illness by denying an association with violence. Until the problem of violence by this subgroup is addressed, it will be difficult to substantially decrease the stigma associated with serious mental illness. JF - Hospital & community psychiatry AU - Torrey, E F AD - National Institute of Mental Health Neuroscience Center at St. Elizabeths Hospital, Washington, DC 20032. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 653 EP - 662 VL - 45 IS - 7 SN - 0022-1597, 0022-1597 KW - Index Medicus KW - Stereotyping KW - Risk Factors KW - Humans KW - Substance-Related Disorders -- psychology KW - Treatment Refusal KW - Family Health KW - Mass Media KW - Male KW - Female KW - Mental Disorders -- psychology KW - Violence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76748737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hospital+%26+community+psychiatry&rft.atitle=Violent+behavior+by+individuals+with+serious+mental+illness.&rft.au=Torrey%2C+E+F&rft.aulast=Torrey&rft.aufirst=E&rft.date=1994-07-01&rft.volume=45&rft.issue=7&rft.spage=653&rft.isbn=&rft.btitle=&rft.title=Hospital+%26+community+psychiatry&rft.issn=00221597&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Psychiatr Serv. 1995 Apr;46(4):406-8 [7788468] Hosp Community Psychiatry. 1994 Nov;45(11):1146 [7835866] Hosp Community Psychiatry. 1994 Jul;45(7):711-3 [7927297] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of inducible nitric oxide synthase by neurones following exposure to endotoxin and cytokine. AN - 76744016; 7522856 AB - In the CNS, nitric oxide (NO) has been implicated as both a mediator of neurotoxicity and a neuromodulator. The inducible NO synthase (iNOS), thought to mediate toxic effects of NO, has been attributed to glial cells in the CNS. We now report that cerebellar granule cell neurones can be stimulated by lipopolysaccharide and interferon-gamma to express iNOS in vitro, as demonstrated by reverse transcription-polymerase chain reaction and fluorescent in situ hybridisation. The expression of both constitutive NO synthase (cNOS) and iNOS by neurones suggests that NO has diverse functions in the brain, and supports the possibility that iNOS plays a role in neuronal damage and inflammation following activation of brain microglia and production of cytokines. JF - British journal of pharmacology AU - Minc-Golomb, D AU - Tsarfaty, I AU - Schwartz, J P AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 720 EP - 722 VL - 112 IS - 3 SN - 0007-1188, 0007-1188 KW - Cytokines KW - 0 KW - Endotoxins KW - RNA KW - 63231-63-0 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - In Situ Hybridization KW - Cerebellum -- cytology KW - Enzyme Induction -- drug effects KW - Neuroglia -- enzymology KW - Cerebellum -- drug effects KW - Cerebellum -- enzymology KW - RNA -- biosynthesis KW - Cytokines -- pharmacology KW - Neurons -- drug effects KW - Amino Acid Oxidoreductases -- biosynthesis KW - Neurons -- enzymology KW - Endotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76744016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Expression+of+inducible+nitric+oxide+synthase+by+neurones+following+exposure+to+endotoxin+and+cytokine.&rft.au=Minc-Golomb%2C+D%3BTsarfaty%2C+I%3BSchwartz%2C+J+P&rft.aulast=Minc-Golomb&rft.aufirst=D&rft.date=1994-07-01&rft.volume=112&rft.issue=3&rft.spage=720&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-09 N1 - Date created - 1994-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1975 Feb;114(2 pt 2):894-7 [1167564] Brain Res. 1988 Jun 7;451(1-2):205-12 [2472189] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368-71 [1648740] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] Trends Neurosci. 1993 Aug;16(8):323-8 [7691008] Biotechniques. 1991 Dec;11(6):760-3 [1725598] Trends Pharmacol Sci. 1992 Jul;13(7):286-91 [1509523] Science. 1992 Aug 28;257(5074):1258-61 [1387731] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3024-7 [7681993] Eur J Pharmacol. 1991 Nov 12;204(3):339-40 [1773832] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ. AN - 76733379; 7921612 AB - 1. Administration of the irreversible antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, (EEDQ, 2 mg kg-1, i.p.) to mice reduced binding of [3H]-RX 821002 (2-methoxy-idazoxan) to alpha 2-adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2. EEDQ administration also resulted in the loss of the sedative effect of the alpha 2-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post EEDQ administration. 3. EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg-1, i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration. 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ. 5. The results of these experiments indicate that there is significant receptor reserve for alpha 2-adrenoceptor-mediated behavioural and physiological responses. JF - British journal of pharmacology AU - Durcan, M J AU - Morgan, P F AU - Van Etten, M L AU - Linnoila, M AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 855 EP - 860 VL - 112 IS - 3 SN - 0007-1188, 0007-1188 KW - Adrenergic alpha-2 Receptor Antagonists KW - 0 KW - Adrenergic alpha-Agonists KW - Adrenergic alpha-Antagonists KW - Dioxanes KW - Hypnotics and Sedatives KW - Imidazoles KW - Quinolines KW - Receptors, Adrenergic, alpha-2 KW - 2-methoxyidazoxan KW - 102575-24-6 KW - EEDQ KW - 60O971AN19 KW - Medetomidine KW - MR15E85MQM KW - Idazoxan KW - Y310PA316B KW - Index Medicus KW - Animals KW - Drug Interactions KW - Imidazoles -- pharmacology KW - Adrenergic alpha-Agonists -- pharmacology KW - Body Temperature -- drug effects KW - Mice KW - Radioligand Assay KW - Hypnotics and Sedatives -- pharmacology KW - Idazoxan -- analogs & derivatives KW - Exploratory Behavior -- drug effects KW - Motor Activity -- drug effects KW - Male KW - Dioxanes -- pharmacokinetics KW - Quinolines -- pharmacology KW - Receptors, Adrenergic, alpha-2 -- metabolism KW - Adrenergic alpha-Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76733379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Covariation+of+alpha+2-adrenoceptor+density+and+function+following+irreversible+antagonism+with+EEDQ.&rft.au=Durcan%2C+M+J%3BMorgan%2C+P+F%3BVan+Etten%2C+M+L%3BLinnoila%2C+M&rft.aulast=Durcan&rft.aufirst=M&rft.date=1994-07-01&rft.volume=112&rft.issue=3&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-09 N1 - Date created - 1994-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Am Chem Soc. 1968 Jan 31;90(3):823-4 [5638314] J Neurochem. 1993 Nov;61(5):1602-10 [8228980] Life Sci. 1983 May 9;32(19):2247-55 [6133202] J Pharmacol Exp Ther. 1985 Jun;233(3):656-62 [2861276] J Med Chem. 1985 Aug;28(8):1054-62 [2862284] Eur J Pharmacol. 1985 Oct 8;116(1-2):175-8 [2865161] J Pharmacol Exp Ther. 1987 Feb;240(2):508-15 [3027315] Adv Exp Med Biol. 1988;235:121-36 [2906517] Neuropharmacology. 1989 Mar;28(3):275-81 [2566945] Clin Exp Pharmacol Physiol. 1989 Jun;16(6):545-8 [2670361] Brain Res. 1989 Jul 24;493(1):8-13 [2570619] Am J Med. 1989 Sep 18;87(3C):10S-13S [2571290] Life Sci. 1989;45(10):917-29 [2529407] Life Sci. 1989;45(18):1609-15 [2573811] Trends Pharmacol Sci. 1989 Sep;10(9):342-4 [2690423] Mol Pharmacol. 1990 Jun;37(6):876-85 [1972775] Eur J Pharmacol. 1990 Apr 25;188(4-5):261-72 [1973120] Brain Res. 1990 Nov 26;534(1-2):273-82 [1981482] J Neurochem. 1991 Sep;57(3):754-9 [1677675] J Pharmacol Exp Ther. 1992 Mar;260(3):1000-7 [1545372] Eur J Pharmacol. 1992 Feb 25;212(1):109-11 [1348228] Mol Pharmacol. 1992 Nov;42(5):846-55 [1359398] Br J Pharmacol. 1993 Feb;108(2):370-5 [8095417] Biochem Pharmacol. 1969 May;18(5):1039-44 [5789772] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck. AN - 76732148; 7918123 AB - Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Pinnarò, P AU - Cercato, M C AU - Giannarelli, D AU - Carlini, P AU - Del Vecchio, M R AU - Impiombato, F A AU - Marzetti, F AU - Milella, M AU - Cognetti, F AD - Regina Elena National Cancer Institute, Rome, Italy. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 513 EP - 519 VL - 5 IS - 6 SN - 0923-7534, 0923-7534 KW - Cisplatin KW - Q20Q21Q62J KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Disease-Free Survival KW - Drug Administration Schedule KW - Phlebitis -- chemically induced KW - Chi-Square Distribution KW - Humans KW - Aged KW - Cisplatin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Patient Compliance KW - Leukopenia -- chemically induced KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Cisplatin -- adverse effects KW - Male KW - Female KW - Remission Induction KW - Alopecia -- chemically induced KW - Carcinoma, Squamous Cell -- pathology KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Head and Neck Neoplasms -- drug therapy KW - Carcinoma, Squamous Cell -- radiotherapy KW - Carcinoma, Squamous Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76732148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Technology+Transfer+%26+Commercialisation&rft.atitle=The+impact+of+technology+absorptive+capacity+on+technology+transfer+performance&rft.au=Lin%2C+Chinho%3BChang%2C+Shofang%3BCheung-Shung%2C+Chang&rft.aulast=Lin&rft.aufirst=Chinho&rft.date=2004-10-01&rft.volume=3&rft.issue=4&rft.spage=384&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Technology+Transfer+%26+Commercialisation&rft.issn=14706075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clonazepam as an augmenting agent in the treatment of childhood-onset obsessive-compulsive disorder. AN - 76716909; 8083135 AB - This case study is of a young man with childhood onset of severe obsessive-compulsive disorder (OCD). The patient had no clinical improvement during therapeutic trials of clomipramine, fluoxetine, and fluvoxamine, including buspirone augmentation. The patient consumed 50 tablets of fluoxetine in a suicide attempt and experienced a total remission of his OCD symptoms for the first time in his life. This remission lasted approximately 1 month and raises interesting questions about the mechanism of action of the serotonin reuptake inhibitors. Subsequently, the patient was able to achieve a 75% improvement in symptomatology when treated with a combination of fluoxetine and clonazepam. This open report suggests that clonazepam may be an effective augmentation agent to a serotonin reuptake inhibitor in the treatment of OCD. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Leonard, H L AU - Topol, D AU - Bukstein, O AU - Hindmarsh, D AU - Allen, A J AU - Swedo, S E AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. PY - 1994 SP - 792 EP - 794 VL - 33 IS - 6 SN - 0890-8567, 0890-8567 KW - Serotonin Uptake Inhibitors KW - 0 KW - Fluoxetine KW - 01K63SUP8D KW - Clonazepam KW - 5PE9FDE8GB KW - Thioridazine KW - N3D6TG58NI KW - Clomipramine KW - NUV44L116D KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Suicide, Attempted KW - Diazepam -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Fluoxetine -- metabolism KW - Thioridazine -- metabolism KW - Clomipramine -- therapeutic use KW - Thioridazine -- therapeutic use KW - Diazepam -- therapeutic use KW - Clomipramine -- metabolism KW - Fluoxetine -- therapeutic use KW - Adolescent KW - Drug Synergism KW - Male KW - Serotonin Uptake Inhibitors -- metabolism KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Obsessive-Compulsive Disorder -- psychology KW - Obsessive-Compulsive Disorder -- drug therapy KW - Clonazepam -- administration & dosage KW - Clonazepam -- therapeutic use KW - Clonazepam -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76716909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Clonazepam+as+an+augmenting+agent+in+the+treatment+of+childhood-onset+obsessive-compulsive+disorder.&rft.au=Leonard%2C+H+L%3BTopol%2C+D%3BBukstein%2C+O%3BHindmarsh%2C+D%3BAllen%2C+A+J%3BSwedo%2C+S+E&rft.aulast=Leonard&rft.aufirst=H&rft.date=1994-07-01&rft.volume=33&rft.issue=6&rft.spage=792&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-11 N1 - Date created - 1994-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2. AN - 76703157; 8081560 AB - Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine3 receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Kim, H AU - Rosenberg, S A AU - Steinberg, S M AU - Cole, D J AU - Weber, J S AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 60 EP - 65 VL - 16 IS - 1 SN - 1067-5582, 1067-5582 KW - Interleukin-2 KW - 0 KW - Ondansetron KW - 4AF302ESOS KW - Droperidol KW - O9U0F09D5X KW - Index Medicus KW - Lymphoma, Non-Hodgkin -- therapy KW - Carcinoma, Renal Cell -- therapy KW - Humans KW - Lymphoma, Non-Hodgkin -- complications KW - Adult KW - Neoplasm Metastasis KW - Melanoma -- complications KW - Aged KW - Middle Aged KW - Melanoma -- therapy KW - Carcinoma, Renal Cell -- complications KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Ondansetron -- therapeutic use KW - Nausea -- prevention & control KW - Interleukin-2 -- therapeutic use KW - Droperidol -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76703157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=A+randomized+double-blinded+comparison+of+the+antiemetic+efficacy+of+ondansetron+and+droperidol+in+patients+receiving+high-dose+interleukin-2.&rft.au=Kim%2C+H%3BRosenberg%2C+S+A%3BSteinberg%2C+S+M%3BCole%2C+D+J%3BWeber%2C+J+S&rft.aulast=Kim&rft.aufirst=H&rft.date=1994-07-01&rft.volume=16&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Locus-specific analysis of human leukocyte antigen class I expression in melanoma cell lines. AN - 76701495; 8081556 AB - Surface expression of human leukocyte antigen (HLA) class I antigens on melanoma lines was evaluated by locus-specific monoclonal antibodies (mAbs) with three different techniques: Fluorescence-activated cell sorting (FACS), immunohistochemistry with cytospin preparation (ICP), and complement-mediated cytotoxicity (CMC). Eleven HLA class I-expressing cell lines developed from metastases were used. Specific expression of HLA loci was examined under routine culture conditions and after 48-h incubation in interferon-gamma (IFN-gamma; 500 U/ml). Loss of allelic expression was seen in one line (586-MEL): Products of genes coding for HLA-A29 and -B44, in strong linkage disequilibrium, were not detectable. HLA-A antigens were consistently detected by all methodologies and minimally affected by pretreatment with IFN-gamma. HLA-B antigens were detectable in 8 of 11 lines by ICP and 3 of 11 lines by CMC. By FACS the supratypic specificity HLA-Bw6 was expressed at low levels in most lines (mean fluorescence 47.2 +/- 13.4 and rose to 259.8 +/- 45.9 after incubation with IFN-gamma; p < 0.001). HLA-Cw antigen detection by CMC correlated with HLA-B (p < 0.01), suggesting that down-regulation and sensitivity to IFN-gamma are shared by the two loci. This low expression of the HLA-B antigens may play a role in the evasion of the host immune response and its up-regulation may be useful in allowing tumor antigen recognition. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Marincola, F M AU - Shamamian, P AU - Simonis, T B AU - Abati, A AU - Hackett, J AU - O'Dea, T AU - Fetsch, P AU - Yannelli, J AU - Restifo, N P AU - Mulé, J J AD - Surgery Branch, Clinical Oncology Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 13 EP - 23 VL - 16 IS - 1 SN - 1067-5582, 1067-5582 KW - HLA-A Antigens KW - 0 KW - HLA-B Antigens KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Lymphocytes -- immunology KW - Tumor Cells, Cultured KW - Humans KW - Neoplasm Metastasis KW - Lymphocytes -- metabolism KW - Interferon-gamma -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Flow Cytometry KW - Immunohistochemistry KW - HLA-A Antigens -- blood KW - HLA-A Antigens -- analysis KW - HLA-B Antigens -- analysis KW - Melanoma -- immunology KW - Melanoma -- metabolism KW - HLA-B Antigens -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76701495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=Locus-specific+analysis+of+human+leukocyte+antigen+class+I+expression+in+melanoma+cell+lines.&rft.au=Marincola%2C+F+M%3BShamamian%2C+P%3BSimonis%2C+T+B%3BAbati%2C+A%3BHackett%2C+J%3BO%27Dea%2C+T%3BFetsch%2C+P%3BYannelli%2C+J%3BRestifo%2C+N+P%3BMul%C3%A9%2C+J+J&rft.aulast=Marincola&rft.aufirst=F&rft.date=1994-07-01&rft.volume=16&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-13 N1 - Date created - 1994-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1982 Jun;128(6):2804-6 [6176653] Hybridoma. 1982;1(2):87-90 [6208124] Hum Immunol. 1985 Apr;12(4):191-211 [3921497] Int J Cancer. 1985 Jul 15;36(1):29-35 [3860479] Hum Immunol. 1986 Mar;15(3):316-9 [2420768] Int J Cancer. 1987 Apr 15;39(4):466-71 [3104215] J Immunol Methods. 1987 Aug 24;102(1):127-41 [3305708] Nature. 1988 Feb 25;331(6158):719-21 [2830541] Pathology. 1987 Oct;19(4):339-46 [3328139] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] J Natl Cancer Inst. 1981 Jun;66(6):1003-12 [7017212] J Invest Dermatol. 1989 May;92(5 Suppl):243S-247S [2654298] J Exp Med. 1989 Sep 1;170(3):621-35 [2788705] J Exp Med. 1989 Sep 1;170(3):797-810 [2788708] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6719-23 [2672003] Adv Cancer Res. 1989;53:181-245 [2678947] J Natl Cancer Inst. 1990 May 2;82(9):755-61 [2109092] J Immunol. 1991 Aug 15;147(4):1453-9 [1907999] J Immunother (1991). 1991 Jun;10(3):153-64 [1868040] Int J Cancer Suppl. 1991;6:138-45 [1906051] Int J Cancer Suppl. 1991;6:123-30 [1906050] Int J Cancer Suppl. 1991;6:106-16 [2066176] J Immunol. 1991 Mar 1;146(5):1692-9 [1671580] J Clin Invest. 1991 Jan;87(1):284-92 [1898655] J Immunol. 1990 Jun 1;144(11):4487-95 [2160503] Int J Cancer. 1990 Nov 15;46(5):813-23 [2228310] J Immunol. 1982 Jan;128(1):129-35 [6172474] J Exp Med. 1992 Oct 1;176(4):937-50 [1383381] Int J Cancer. 1992 May 28;51(3):379-85 [1592528] Cancer Res. 1992 Mar 1;52(5):1201-4 [1737380] Science. 1991 Dec 13;254(5038):1643-7 [1840703] Cancer Res. 1991 Dec 1;51(23 Pt 1):6372-80 [1933900] J Immunol. 1991 Oct 1;147(7):2384-90 [1717558] Semin Cancer Biol. 1991 Feb;2(1):35-45 [1912517] J Immunol. 1989 Jan 1;142(1):352-8 [2462591] Cancer. 1977 Jul;40(1):36-41 [69483] J Immunother Emphasis Tumor Immunol. 1993 Oct;14(3):182-90 [8297900] Cancer Res. 1993 Jul 15;53(14):3349-54 [7686817] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2842-5 [8464898] J Exp Med. 1993 Feb 1;177(2):265-72 [8426105] J Clin Invest. 1993 Feb;91(2):684-92 [8432869] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Library of human chromosomes in mouse cells for mapping genes by function. AN - 76670657; 8071106 JF - Japanese journal of cancer research : Gann AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/07// PY - 1994 DA - July 1994 VL - 85 IS - 7 SN - 0910-5050, 0910-5050 KW - Genetic Markers KW - 0 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Gene Transfer Techniques KW - Humans KW - Hybrid Cells KW - Mice KW - Chromosomes, Human KW - Chromosome Mapping KW - Gene Library UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76670657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Library+of+human+chromosomes+in+mouse+cells+for+mapping+genes+by+function.&rft.au=Barrett%2C+J+C&rft.aulast=Barrett&rft.aufirst=J&rft.date=1994-07-01&rft.volume=85&rft.issue=7&rft.spage=inside+front+cover&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exchanges of short polymorphic DNA segments predating speciation in feline major histocompatibility complex class I genes. AN - 76664881; 8064870 AB - Sequence comparisons of 14 distinct MHC class I cDNA clones isolated from species representing the three major taxonomic lineages of Felidae (domestic cat lineage, ocelot lineage, and pantherine lineage) revealed that feline MHC class I alleles have highly mosaic structures with short polymorphic sequence motifs that are rearranged between alleles of individual MHC loci, between MHC class I genes within cat species, and between homologous MHC loci in different species. The pattern of sequence variation in felids supports the role of the following factors in production and maintenance of MHC variation: (1) gradual spontaneous mutation; (2) selective pressure to conserve certain residues but also to vary in hypervariable regions, notably residues that functionally participate in antigen recognition and presentation; and (3) recombination-mediated gene exchange between alleles and between related genes. The overall amount of genetic variation observed among MHC class I genes in the Felidae family is no greater than the amount of variation within any outbred cat species (i.e., domestic cat, ocelot). The occurrence of equivalent levels of polymorphism plus the simultaneous persistence of the same sequence motifs in divergent feline species suggest that most MHC class I nucleotide site polymorphism predated species divergences. Ancient polymorphisms have been transmitted through the speciation events and modern feline MHC class I alleles were derived by recombinational exchange of polymorphic sequence motifs. Moreover, some of these sequence motifs were found in other mammalian MHC class I genes, such as classical human HLA-B5, nonclassical human HLA-E class I genes, and bovine class I genes. These results raise the prospect of an ancient origin for some motifs, although the possibility of convergence in parallel mammalian radiations cannot be excluded. JF - Journal of molecular evolution AU - Yuhki, N AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 22 EP - 33 VL - 39 IS - 1 SN - 0022-2844, 0022-2844 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Polymerase Chain Reaction KW - Genetic Variation KW - Animals KW - Base Sequence KW - Time KW - Sequence Homology, Nucleic Acid KW - Humans KW - Recombination, Genetic KW - DNA -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Species Specificity KW - Cloning, Molecular KW - Carnivora -- immunology KW - Carnivora -- genetics KW - Polymorphism, Genetic KW - Cats -- genetics KW - Biological Evolution KW - Genes, MHC Class I -- genetics KW - Cats -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76664881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+evolution&rft.atitle=Exchanges+of+short+polymorphic+DNA+segments+predating+speciation+in+feline+major+histocompatibility+complex+class+I+genes.&rft.au=Yuhki%2C+N%3BO%27Brien%2C+S+J&rft.aulast=Yuhki&rft.aufirst=N&rft.date=1994-07-01&rft.volume=39&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+evolution&rft.issn=00222844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-20 N1 - Date created - 1994-09-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U07668; GENBANK; U07669; U07677; U07678; U07665; U07666; U07675; U07667; U07676; U07673; U07674; U07671; U07672; U07670 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance. AN - 76660029; 8059438 AB - The organochlorine insecticide, endosulfan was administered (6 mg/kg body weight) to Wistar rat pups of both sexes by gastric intubation daily from post-natal days 2-25. Its effect on levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) was assayed in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), brainstem (BS) and cerebellum (CB) on days 10 and 25 using high-performance liquid chromatography (HPLC). The activity of acetylcholinesterase (AChE) was also estimated in the same regions of the brain. Performance in operant conditioning for solid food reward was assessed in 25-day-old rats. NA levels were increased in OB (12%, P < 0.01) and BS (10%, P < 0.05) at 10 days of age and in HI (20%, P < 0.01) and CB (12%, P < 0.05) at 25 days of age. DA level was decreased in HI at both 10 (42%, P < 0.001) and 25 (45%, P < 0.001) days. Serotonin levels were increased in OB (12%, P < 0.05), HI (41%, P < 0.001), VC (30%, P < 0.01) and BS (15%, P < 0.01) at 10 days of age but at 25 days, levels were decreased in BS (20%, P < 0.05) and CB (31%, P < 0.01). The activity of AChE was not different from the control groups in any of the regions studied. These data suggest that monoaminergic systems in the developing rat brain respond to endosulfan by undergoing something like a 'reorganization'. However, such changes do not ameliorate certain functional losses following the exposure to endosulfan as operant conditioning revealed deficits in acquisition as well as retention of memory. JF - Toxicology AU - Lakshmana, M K AU - Raju, T R AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 139 EP - 150 VL - 91 IS - 2 SN - 0300-483X, 0300-483X KW - Serotonin KW - 333DO1RDJY KW - Acetylcholinesterase KW - EC 3.1.1.7 KW - Sodium-Potassium-Exchanging ATPase KW - EC 3.6.3.9 KW - Endosulfan KW - OKA6A6ZD4K KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals, Newborn KW - Animals KW - Sodium-Potassium-Exchanging ATPase -- metabolism KW - Acetylcholinesterase -- metabolism KW - Rats, Wistar KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Conditioning, Operant -- drug effects KW - Brain -- enzymology KW - Norepinephrine -- metabolism KW - Brain -- drug effects KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Endosulfan -- toxicity KW - Serotonin -- metabolism KW - Norepinephrine -- analysis KW - Brain -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76660029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Endosulfan+induces+small+but+significant+changes+in+the+levels+of+noradrenaline%2C+dopamine+and+serotonin+in+the+developing+rat+brain+and+deficits+in+the+operant+learning+performance.&rft.au=Lakshmana%2C+M+K%3BRaju%2C+T+R&rft.aulast=Lakshmana&rft.aufirst=M&rft.date=1994-07-01&rft.volume=91&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukemia induced in rats but not mice by dimethyl morpholinophosphoramidate, a simulant anticholinesterase agent. AN - 76643364; 8059437 AB - Dimethyl morpholinophosphoramidate (DMMPA), an organophosphate, caused leukemia in male and female Fischer 344/N rats. DMMPA was administered in corn oil by oral intubation to groups of 50 male and 50 female rats at 0, 150, 300, or 600 mg/kg body weight, five times per week for 2 years. B6C3F1 mice were given 0, 150 (males only), 300, and 600 (females only) mg/kg body weight under the same schedule. DMMPA induced a dose-related enhancement in the incidence of mononuclear cell leukemia in rats--males: controls = 14/50, 150 mg group = 21/50; 300 mg group = 19/50; 600 mg group = 25/50; females: controls = 9/50, 150 mg group = 13/50; 300 mg group = 12/49; 600 mg group = 18/50. Survival-adjusted rates strengthen the DMMPA effect: males--31%, 50%, 47%, and 63%; females--20%, 32%, 30%, 50%. Latent periods for mononuclear cell leukemia development in exposed rats were not shortened compared to controls. No carcinogenic effects in mice were detected. DMMPA was not mutagenic in Salmonella, was mutagenic for mouse lymphoma cells, and induced both chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. JF - Toxicology AU - Chan, P AU - Cardy, R AU - Haseman, J AU - Moe, J AU - Huff, J AD - Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 127 EP - 137 VL - 91 IS - 2 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - Glycerophospholipids KW - Phosphatidic Acids KW - dimyristoylmethylphosphatidic acid KW - 54672-40-1 KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Liver -- pathology KW - Sex Factors KW - Liver -- drug effects KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Mice KW - Species Specificity KW - Male KW - Female KW - Phosphatidic Acids -- toxicity KW - Leukemia, Experimental -- classification KW - Carcinogens -- toxicity KW - Leukemia, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76643364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Leukemia+induced+in+rats+but+not+mice+by+dimethyl+morpholinophosphoramidate%2C+a+simulant+anticholinesterase+agent.&rft.au=Chan%2C+P%3BCardy%2C+R%3BHaseman%2C+J%3BMoe%2C+J%3BHuff%2C+J&rft.aulast=Chan&rft.aufirst=P&rft.date=1994-07-01&rft.volume=91&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of the safety and efficacy of topical nitroglycerin ointment to facilitate venous cannulation. AN - 76637160; 8047423 AB - The purpose of this study was to determine the safety and efficacy of 2% nitroglycerin ointment to facilitate venous cannulation. In a double-blind experimental design, 80 adult subjects were randomly assigned to receive a 2% nitroglycerin ointment or a placebo ointment prior to cannulation. Variables measured before and after ointment application included heart rate, electrocardiogram, vein size, and presence of headache. No statistically significant differences were found in vein size or adverse effects following nitroglycerin ointment application. JF - Nursing research AU - Griffith, P AU - James, B AU - Cropp, A AD - Critical Care/Heart, Lung and Blood Nursing Service, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD. PY - 1994 SP - 203 EP - 206 VL - 43 IS - 4 SN - 0029-6562, 0029-6562 KW - Ointments KW - 0 KW - Nitroglycerin KW - G59M7S0WS3 KW - Abridged Index Medicus KW - Index Medicus KW - Nursing KW - Hemodynamics -- drug effects KW - Headache -- chemically induced KW - Humans KW - Safety KW - Adult KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Administration, Topical KW - Nitroglycerin -- blood KW - Bloodletting -- instrumentation KW - Nitroglycerin -- adverse effects KW - Nitroglycerin -- administration & dosage KW - Bloodletting -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76637160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nursing+research&rft.atitle=Evaluation+of+the+safety+and+efficacy+of+topical+nitroglycerin+ointment+to+facilitate+venous+cannulation.&rft.au=Griffith%2C+P%3BJames%2C+B%3BCropp%2C+A&rft.aulast=Griffith&rft.aufirst=P&rft.date=1994-07-01&rft.volume=43&rft.issue=4&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Nursing+research&rft.issn=00296562&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-30 N1 - Date created - 1994-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recoverin is highly uveitogenic in Lewis rats. AN - 76635288; 8045724 AB - Recoverin, a calcium-binding protein that selectively localizes to the retina and pineal gland, has been identified as the target for the putative pathogenic autoimmune process of cancer-associated retinopathy (CAR). The present study was aimed at testing the capacity of recoverin to induce experimental autoimmune uveoretinitis and pinealitis in Lewis rats. Lewis rats were immunized against recombinant myristoylated recoverin by a single footpad injection of the protein, at various doses, emulsified in complete Freund's adjuvant. Development of uveoretinitis was monitored by clinical and histologic examinations, whereas pinealitis was detected by histologic examination. Immunization with recoverin induced severe panuveitic changes that closely resemble those induced by S-antigen (arrestin). The effect was dose-dependent, with 10 micrograms/rat the lowest immunopathogenic dose. Rats immunized with recoverin also developed pineal inflammation. Recoverin is highly immunopathogenic in Lewis rats. Although the ocular changes induced in rats differ from those seen in CAR, the data recorded here are in line with the concept that recoverin can initiate pathogenic autoimmune processes in the eye. JF - Investigative ophthalmology & visual science AU - Gery, I AU - Chanaud, N P AU - Anglade, E AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 3342 EP - 3345 VL - 35 IS - 8 SN - 0146-0404, 0146-0404 KW - Calcium-Binding Proteins KW - 0 KW - Eye Proteins KW - Lipoproteins KW - Nerve Tissue Proteins KW - Rcvrn protein, rat KW - Recoverin KW - 135844-11-0 KW - Hippocalcin KW - 149223-81-4 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Pineal Gland -- pathology KW - Dose-Response Relationship, Drug KW - Male KW - Female KW - Eye Proteins -- toxicity KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Retinitis -- immunology KW - Autoimmune Diseases -- pathology KW - Uveitis -- immunology KW - Calcium-Binding Proteins -- toxicity KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76635288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Recoverin+is+highly+uveitogenic+in+Lewis+rats.&rft.au=Gery%2C+I%3BChanaud%2C+N+P%3BAnglade%2C+E&rft.aulast=Gery&rft.aufirst=I&rft.date=1994-07-01&rft.volume=35&rft.issue=8&rft.spage=3342&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-26 N1 - Date created - 1994-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester. AN - 76630423; 7913712 AB - Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung diseases. JF - The Journal of clinical investigation AU - Maruyama, M AU - Hay, J G AU - Yoshimura, K AU - Chu, C S AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 368 EP - 375 VL - 94 IS - 1 SN - 0021-9738, 0021-9738 KW - Proteinase Inhibitory Proteins, Secretory KW - 0 KW - Proteins KW - SLPI protein, human KW - Secretory Leukocyte Peptidase Inhibitor KW - Serine Proteinase Inhibitors KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Promoter Regions, Genetic KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Moloney murine leukemia virus -- genetics KW - Epithelium -- metabolism KW - Cell Line KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Bronchi -- metabolism KW - Serine Proteinase Inhibitors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76630423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Modulation+of+secretory+leukoprotease+inhibitor+gene+expression+in+human+bronchial+epithelial+cells+by+phorbol+ester.&rft.au=Maruyama%2C+M%3BHay%2C+J+G%3BYoshimura%2C+K%3BChu%2C+C+S%3BCrystal%2C+R+G&rft.aulast=Maruyama&rft.aufirst=M&rft.date=1994-07-01&rft.volume=94&rft.issue=1&rft.spage=368&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-19 N1 - Date created - 1994-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1986 Sep;83(18):6692-6 [3462719] Immunology. 1992 Nov;77(3):330-7 [1478679] Nucleic Acids Res. 1986 Oct 24;14(20):7883-96 [3640338] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Cell. 1987 Jun 19;49(6):729-39 [3034432] Cell. 1987 Jun 19;49(6):741-52 [3034433] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] Cell. 1987 Oct 23;51(2):251-60 [2822255] FEBS Lett. 1987 Nov 16;224(1):14-8 [3678487] Nucleic Acids Res. 1987 Dec 23;15(24):10145-58 [3320962] Cancer Res. 1988 Apr 1;48(7):1904-9 [2450641] J Biol Chem. 1988 Oct 25;263(30):15335-41 [3170585] Biol Chem Hoppe Seyler. 1988 May;369 Suppl:79-82 [3060147] N Engl J Med. 1989 Feb 9;320(6):365-76 [2536474] Eur Respir J. 1988 Oct;1(9):792-800 [3229477] J Histochem Cytochem. 1989 Apr;37(4):493-8 [2926127] Mol Cell Biol. 1989 Feb;9(2):769-75 [2523515] J Cell Physiol. 1989 Jun;139(3):610-6 [2500449] J Clin Invest. 1989 Jul;84(1):138-44 [2472425] J Clin Invest. 1989 Oct;84(4):1302-13 [2507578] J Virol. 1990 Feb;64(2):543-50 [2104942] Trends Genet. 1989 Dec;5(12):411-7 [2696185] J Clin Invest. 1990 May;85(5):1343-52 [2185272] J Clin Invest. 1990 Jul;86(1):300-8 [2164045] Science. 1990 Jul 13;249(4965):178-81 [2371565] J Biol Chem. 1990 Dec 5;265(34):21128-33 [2250017] J Appl Physiol (1985). 1990 Nov;69(5):1843-8 [2272977] J Clin Invest. 1991 Feb;87(2):482-8 [1671391] Lancet. 1991 Feb 16;337(8738):392-4 [1671425] J Biol Chem. 1991 Mar 15;266(8):5177-81 [1848242] Scand J Clin Lab Invest Suppl. 1972;124:127-36 [5041008] Clin Chim Acta. 1974 Aug 20;54(3):381-5 [4547155] Anal Biochem. 1976 May 7;72:248-54 [942051] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Biochim Biophys Acta. 1982 Jan 18;700(2):178-83 [6915782] Ann Otol Rhinol Laryngol. 1982 May-Jun;91(3 Pt 1):268-71 [7046595] Virology. 1991 May;182(1):361-4 [2024472] J Biol Chem. 1991 May 15;266(14):9140-4 [1709163] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Thorax. 1983 Mar;38(3):180-3 [6857581] Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Eur J Respir Dis. 1984 Apr;65(3):201-9 [6202540] Nature. 1984 Oct 4-10;311(5985):433-8 [6090941] Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5 [6438633] Cell. 1986 Aug 29;46(5):659-67 [3488815] Mol Cell Biol. 1991 Jun;11(6):3355-64 [1903842] J Clin Invest. 1991 Jun;87(6):2207-15 [1674946] EMBO J. 1991 Jul;10(7):1817-25 [2050119] J Biol Chem. 1991 Oct 15;266(29):19611-7 [1918068] J Cell Physiol. 1991 Nov;149(2):260-8 [1660901] EMBO J. 1992 Jan;11(1):205-13 [1740106] J Clin Invest. 1992 May;89(5):1478-84 [1569186] Anal Biochem. 1992 Jan;200(1):81-8 [1595905] J Biol Chem. 1992 Jun 15;267(17):12030-5 [1351055] J Biol Chem. 1992 Aug 15;267(23):16056-60 [1379589] J Clin Invest. 1992 Oct;90(4):1296-301 [1357002] Acta Paediatr. 1992 Oct;81(10):757-9 [1384826] J Biol Chem. 1992 Nov 5;267(31):22506-11 [1331059] Am Rev Respir Dis. 1992 Dec;146(6):1426-9 [1360778] J Clin Invest. 1986 Nov;78(5):1349-54 [2429991] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Palliative and prophylactic benefits of continuously administered dopaminomimetics in Parkinson's disease. AN - 76626677; 7519334 AB - Motor response complications that ultimately affect most parkinsonian patients appear related to altered dopaminergic mechanisms at both the presynaptic and postsynaptic levels. "Wearing-off" phenomena reflect a shortened duration of the antiparkinsonian action of levodopa, caused initially by the reduced capacity of the degenerating nigrostriatal system to store dopamine. Later, secondary changes in postsynaptic structures contribute substantially to these complications as well as to the changes in levodopa dose-antiparkinsonian response relation and the threshold for levodopa-induced dyskinesias that underlie "on-off" fluctuations and "peak-dose" dyskinesias. In parkinsonian rats, levodopa treatment not only fails to normalize striatal systems modified by the loss of dopaminergic afferents, but actually tends to exacerbate these alterations. Moreover, the vulnerability of these downstream systems to levodopa-induced change appears closely related to the severity of dopamine terminal loss and the intermittence of levodopa administration. In parkinsonian patients, switching from a standard intermittent levodopa regimen to a continuously infused dopaminomimetic alleviates motor fluctuations and widens the therapeutic window for levodopa. Taken together, currently available data support the view that continuous dopaminomimetic therapy has both immediate and delayed palliative value for advanced parkinsonian patients and potentially could confer prophylactic benefit to those at earlier stages of their disorder. JF - Neurology AU - Chase, T N AU - Engber, T M AU - Mouradian, M M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - S15 EP - S18 VL - 44 IS - 7 Suppl 6 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agents KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Humans KW - Palliative Care KW - Antiparkinson Agents -- adverse effects KW - Dopamine Agents -- therapeutic use KW - Dyskinesia, Drug-Induced -- drug therapy KW - Dyskinesia, Drug-Induced -- prevention & control KW - Dyskinesia, Drug-Induced -- etiology KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy KW - Dopamine Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76626677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Palliative+and+prophylactic+benefits+of+continuously+administered+dopaminomimetics+in+Parkinson%27s+disease.&rft.au=Chase%2C+T+N%3BEngber%2C+T+M%3BMouradian%2C+M+M&rft.aulast=Chase&rft.aufirst=T&rft.date=1994-07-01&rft.volume=44&rft.issue=7+Suppl+6&rft.spage=S15&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-26 N1 - Date created - 1994-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro. AN - 76626331; 7518879 AB - Zidovudine (AZT) as used in the treatment of AIDS, causes a mitochondrial myopathy characterized by depletion of mitochondrial DNA, enzymatic defects in the respiratory chain system, and accumulation of lipid droplets. Most of these changes are also seen in normal human myotubes treated with AZT. Because L-carnitine plays a major role in the transport of long chain fatty acids across the inner mitochondrial membrane and facilitates the beta-oxidation of fatty acids, we examined the effect of L-carnitine in preventing the destructive effect of AZT on the mitochondria and the myotubes of human muscle in tissue culture. Myotubes, prepared from human muscle biopsies, were exposed to various concentrations of AZT for up to 3 weeks. One-third of the flasks were treated with AZT alone, another third with AZT plus L-carnitine and another third were untreated. The cultures were evaluated with: (a) immunocytochemistry counting the number of myotubes stained with antibodies to Leu-19; (b) enzyme histochemistry for NADH reaction and oil-red-O stain to assess mitochondrial enzymatic activity and lipid droplet accumulation; and (c) electron microscopy counting all the organelles within representative sections of the myotubes, at x24,000, and calculating the volumetric density of each organelle/unit volume of tissue. AZT, at concentrations 250 microM and above, caused depopulation of the Leu-19-positive myotubes, destructive changes in the mitochondria consisting of swelling, lamellar inclusions and multiple concentric cristae, accumulation of lipid droplets, and increase lysosomes. L-Carnitine increased the number of Leu-19-positive myotubes from 3.4 +/- 0.6 to 9.4 +/- 1.2, preserved the morphology of the mitochondria, increased their volumetric density from 2.5 +/- 0.4 to 6.0 +/- 0.7, and reduced the volumetric density of the lipid droplets from 12.2 +/- 4.9 to 1.4 +/- 0.7 and of the lysosomes from 15.6 +/- 3.6 to 3.9 +/- 1.4 (p < 0.001). L-Carnitine, used concurrently with AZT, prevents the human myotubes from the AZT-associated destruction, preserves the structure and volume of mitochondria and prevents the accumulation of lipids. The findings may have potential clinical implications in preventing the myotoxicity of AZT in patients with AIDS. JF - Laboratory investigation; a journal of technical methods and pathology AU - Semino-Mora, M C AU - Leon-Monzon, M E AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institutes of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 102 EP - 112 VL - 71 IS - 1 SN - 0023-6837, 0023-6837 KW - Zidovudine KW - 4B9XT59T7S KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - AIDS/HIV KW - Culture Techniques KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Humans KW - Mitochondrial Myopathies -- chemically induced KW - Histocytochemistry KW - Staining and Labeling KW - Immunohistochemistry KW - Zidovudine -- adverse effects KW - Mitochondria, Muscle -- ultrastructure KW - Carnitine -- pharmacology KW - Mitochondria, Muscle -- drug effects KW - Muscles -- ultrastructure KW - Muscles -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76626331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Effect+of+L-carnitine+on+the+zidovudine-induced+destruction+of+human+myotubes.+Part+I%3A+L-carnitine+prevents+the+myotoxicity+of+AZT+in+vitro.&rft.au=Semino-Mora%2C+M+C%3BLeon-Monzon%2C+M+E%3BDalakas%2C+M+C&rft.aulast=Semino-Mora&rft.aufirst=M&rft.date=1994-07-01&rft.volume=71&rft.issue=1&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-19 N1 - Date created - 1994-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Eighth Aspen Cancer Conference: molecular mechanisms of toxicity in relation to the genetics of animal and human neoplasia. AN - 76624828; 8043194 JF - Molecular carcinogenesis AU - Tennant, R W AU - Prescott, D M AU - Puck, T T AU - Slaga, T J AU - Saffiotti, U AU - Wogan, G N AU - Nesnow, S AU - McClain, R M Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 117 EP - 124 VL - 10 IS - 3 KW - Cyclins KW - 0 KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Cyclins -- physiology KW - Animals KW - Protein Kinases -- physiology KW - Oncogenes KW - Risk Factors KW - Humans KW - Species Specificity KW - Mutagenesis KW - Cell Survival KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76624828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Eighth+Aspen+Cancer+Conference%3A+molecular+mechanisms+of+toxicity+in+relation+to+the+genetics+of+animal+and+human+neoplasia.&rft.au=Tennant%2C+R+W%3BPrescott%2C+D+M%3BPuck%2C+T+T%3BSlaga%2C+T+J%3BSaffiotti%2C+U%3BWogan%2C+G+N%3BNesnow%2C+S%3BMcClain%2C+R+M&rft.aulast=Tennant&rft.aufirst=R&rft.date=1994-07-01&rft.volume=10&rft.issue=3&rft.spage=117&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 - 1994-08-30 N1 - Date created - 1994-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Managing occupational risks in the dental office: HIV and the dental professional. AN - 76622328; 8040535 AB - Despite universal precautions, work behavior modifications and technological advances, health care workers continue to experience occupational exposures to HIV and other bloodborne pathogens. Although the risk for infection is low when compared with other bloodborne pathogens, 39 documented cases of HIV seroconversion have been recorded. Recent attention has focused on secondary prevention of HIV infection through post-exposure chemoprophylaxis. JF - Journal of the American Dental Association (1939) AU - Beekmann, S E AU - Henderson, D K AD - Hospital Epidemiology Service, National Institutes of Health, Bethesda, Md. 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 847 EP - 852 VL - 125 IS - 7 SN - 0002-8177, 0002-8177 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Dentistry KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - HIV Seropositivity KW - Risk Factors KW - Needlestick Injuries -- prevention & control KW - Humans KW - Blood-Borne Pathogens KW - Universal Precautions KW - Occupational Exposure KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Dental Staff UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76622328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Dental+Association+%281939%29&rft.atitle=Managing+occupational+risks+in+the+dental+office%3A+HIV+and+the+dental+professional.&rft.au=Beekmann%2C+S+E%3BHenderson%2C+D+K&rft.aulast=Beekmann&rft.aufirst=S&rft.date=1994-07-01&rft.volume=125&rft.issue=7&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Dental+Association+%281939%29&rft.issn=00028177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-25 N1 - Date created - 1994-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 1 increases thymidine labeling index of normal tissues of mice but not the tumor. AN - 76622124; 8040027 AB - This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for different mouse normal cells other than bone marrow cells. Semi-continuous injections of tritiated thymidine were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14 days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1 administered 24 h prior to the first radiation. The thymidine labeling index of normal tissues was higher following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all normal tissues tested, including the lip and tongue mucosal basal cell layers, crypt cells of the duodenum, alveolar cells of the lung, hepatocytes, and basal skin cells. The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation. The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine labeling index declined after the first day following the completion of fractionated irradiation. Recombinant human interleukin 1 increased the 24 h thymidine labeling index in normal tissues in mice, but not in RIF-1 tumor. Fractionated irradiation could maintain the effect of a single dose of interleukin 1, administered 24 h prior to the first fraction, up to 24 h after the end of radiation. JF - International journal of radiation oncology, biology, physics AU - Zaghloul, M S AU - Dorie, M J AU - Kallman, R F AD - Radiotherapy Department, National Cancer Institute, Fom El Khalig, Cairo, Egypt. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 805 EP - 811 VL - 29 IS - 4 SN - 0360-3016, 0360-3016 KW - Interleukin-1 KW - 0 KW - Radiation-Protective Agents KW - Recombinant Proteins KW - Tritium KW - 10028-17-8 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Animals KW - Skin -- metabolism KW - Duodenum -- metabolism KW - Radiotherapy Dosage KW - Mice, Inbred C3H KW - Pulmonary Alveoli -- radiation effects KW - Tongue -- drug effects KW - Time Factors KW - Lip -- metabolism KW - Recombinant Proteins -- pharmacology KW - Lip -- radiation effects KW - Lip -- drug effects KW - Mouth Mucosa -- radiation effects KW - Mice KW - Dose-Response Relationship, Radiation KW - Epithelium -- drug effects KW - Mouth Mucosa -- drug effects KW - Duodenum -- drug effects KW - Skin -- radiation effects KW - Skin -- drug effects KW - Pulmonary Alveoli -- metabolism KW - Pulmonary Alveoli -- drug effects KW - Tongue -- radiation effects KW - Epithelium -- metabolism KW - Epithelium -- radiation effects KW - Duodenum -- radiation effects KW - Tongue -- metabolism KW - Female KW - Mouth Mucosa -- metabolism KW - Thymidine -- metabolism KW - Sarcoma, Experimental -- radiotherapy KW - Interleukin-1 -- pharmacology KW - Sarcoma, Experimental -- metabolism KW - Radiation-Protective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76622124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Interleukin+1+increases+thymidine+labeling+index+of+normal+tissues+of+mice+but+not+the+tumor.&rft.au=Zaghloul%2C+M+S%3BDorie%2C+M+J%3BKallman%2C+R+F&rft.aulast=Zaghloul&rft.aufirst=M&rft.date=1994-07-01&rft.volume=29&rft.issue=4&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-23 N1 - Date created - 1994-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model. AN - 76617721; 8040025 AB - The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 x 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses > or = 30 Gy. Radiation changes were present in the aorta and vena cava at doses > or = 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed a few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. JF - International journal of radiation oncology, biology, physics AU - Sindelar, W F AU - Tepper, J E AU - Kinsella, T J AU - Barnes, M AU - DeLuca, A M AU - Terrill, R AU - Matthews, D AU - Anderson, W J AU - Bollinger, B K AU - Johnstone, P A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 781 EP - 788 VL - 29 IS - 4 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Laparotomy KW - Animals KW - Retroperitoneal Space -- radiation effects KW - Retroperitoneal Fibrosis -- etiology KW - Anastomosis, Surgical KW - Vena Cava, Inferior -- radiation effects KW - Combined Modality Therapy KW - Dogs KW - Aorta, Abdominal -- radiation effects KW - Radiation Injuries, Experimental -- etiology KW - Dose-Response Relationship, Radiation KW - Aorta, Abdominal -- surgery KW - Bile Ducts, Extrahepatic -- radiation effects KW - Intraoperative Care KW - Radiotherapy -- methods KW - Ureter -- radiation effects KW - Models, Biological KW - Intestine, Small -- radiation effects KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76617721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Late+effects+of+intraoperative+radiation+therapy+on+retroperitoneal+tissues%2C+intestine%2C+and+bile+duct+in+a+large+animal+model.&rft.au=Sindelar%2C+W+F%3BTepper%2C+J+E%3BKinsella%2C+T+J%3BBarnes%2C+M%3BDeLuca%2C+A+M%3BTerrill%2C+R%3BMatthews%2C+D%3BAnderson%2C+W+J%3BBollinger%2C+B+K%3BJohnstone%2C+P+A&rft.aulast=Sindelar&rft.aufirst=W&rft.date=1994-07-01&rft.volume=29&rft.issue=4&rft.spage=781&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-23 N1 - Date created - 1994-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1987: Delivery of intraoperative radiation therapy after pneumonectomy: experimental observations and early clinical results. Updated in 1994. AN - 76607109; 8037548 JF - The Annals of thoracic surgery AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute/National Institutes of Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 269 EP - 270 VL - 58 IS - 1 SN - 0003-4975, 0003-4975 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Radiotherapy, High-Energy -- adverse effects KW - Postoperative Complications KW - Combined Modality Therapy KW - Humans KW - Esophagitis -- etiology KW - Dogs KW - Radiotherapy, High-Energy -- methods KW - Intraoperative Care -- methods KW - Intraoperative Care -- adverse effects KW - Pneumonectomy KW - Lung Neoplasms -- radiotherapy KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - Lung Neoplasms -- surgery KW - Carcinoma, Non-Small-Cell Lung -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76607109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Annals+of+thoracic+surgery&rft.atitle=1987%3A+Delivery+of+intraoperative+radiation+therapy+after+pneumonectomy%3A+experimental+observations+and+early+clinical+results.+Updated+in+1994.&rft.au=Pass%2C+H+I&rft.aulast=Pass&rft.aufirst=H&rft.date=1994-07-01&rft.volume=58&rft.issue=1&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+thoracic+surgery&rft.issn=00034975&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-18 N1 - Date created - 1994-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of 12 cDNA-expressed human, rodent, and rabbit cytochromes P450 in the metabolism of benzo[a]pyrene and benzo[a]pyrene trans-7,8-dihydrodiol. AN - 76603473; 8043197 AB - The potent carcinogen benzo[a]pyrene (B[a]P) and its metabolite B[a]P trans-7,8-dihydrodiol (7,8-diol) require metabolic activation by the microsomal cytochrome P450s (P450s) to exert several adverse biological effects, including binding to DNA, toxicity, mutagenicity, and carcinogenicity. In the study reported here, we defined the role of each of 12 individual cDNA-expressed cytochrome P450s in the metabolism of B[a]P and 7,8-diol. Human P450s 1A1 and 1A2 were expressed in the absence or presence of epoxide hydrolase (EH) in a human lymphoblastoid cell line, and six human and five rodent and rabbit P450s were expressed from cDNA with vaccinia virus vectors in the hepatoma cell line Hep G2. B[a]P metabolism resulted in nine metabolites (three diols, three quinones, and three phenols), which were separated, identified, and quantitated by high-pressure liquid chromatography. In the human lymphoblastoid cells, human 1A1 metabolized B[a]P at a rate 4.5 times greater than that for 1A2. EH was shown to be directly involved in B[a]P activation, since increasing the amount of EH resulted in less 7-hydroxybenzo[a]pyrene and more 7,8-diol formation. Of the human P450s expressed with the vaccinia virus vectors in Hep G2 cells, 1A2 and 2C9 showed the highest activity and 2B6 showed moderate activity for B[a]P metabolism. Mouse 1A1 had activity 40 times higher than any human, rabbit, or rodent P450s, indicating the potential pitfalls of extrapolating P450 activity across species. Metabolism of the 7,8-diol resulted in six metabolites (four tetrols and two triols). In the lymphoblastoid cells, human 1A1 was shown to be 4.2 times more active than 1A2 for 7,8-diol metabolism. Among human P450s expressed from vaccinia virus, 1A2, 2E1, and 2C9 gave the highest activity, and 2C8 and 3A4 showed moderate activity for 7,8-diol metabolism to the diol epoxides. Again, mouse 1A1 was much more active than any other P450. These studies, in which we determined the capacity of individual P450 in the metabolism and activation of B[a]P and 7,8-diol, may thus lead to a better understanding of how P450s control the detoxification and activation of polycyclic aromatic hydrocarbons. JF - Molecular carcinogenesis AU - Shou, M AU - Korzekwa, K R AU - Crespi, C L AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 159 EP - 168 VL - 10 IS - 3 SN - 0899-1987, 0899-1987 KW - DNA, Complementary KW - 0 KW - Dihydroxydihydrobenzopyrenes KW - Recombinant Proteins KW - benzo(a)pyrene 7,8-dihydrodiol KW - 13345-25-0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Epoxide Hydrolases -- metabolism KW - Animals KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Vaccinia virus KW - DNA, Complementary -- genetics KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Humans KW - Rabbits KW - Cytochrome P-450 Enzyme System -- metabolism KW - Dihydroxydihydrobenzopyrenes -- metabolism KW - Benzo(a)pyrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76603473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+role+of+12+cDNA-expressed+human%2C+rodent%2C+and+rabbit+cytochromes+P450+in+the+metabolism+of+benzo%5Ba%5Dpyrene+and+benzo%5Ba%5Dpyrene+trans-7%2C8-dihydrodiol.&rft.au=Shou%2C+M%3BKorzekwa%2C+K+R%3BCrespi%2C+C+L%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Shou&rft.aufirst=M&rft.date=1994-07-01&rft.volume=10&rft.issue=3&rft.spage=159&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 - 1994-08-30 N1 - Date created - 1994-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Experimental melanin-protein-induced uveitis in the Lewis rat. Immunopathologic processes. AN - 76602887; 7913541 AB - To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class II and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 micrograms of lipopolysaccharide confirmed by histopathology. Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans. JF - Ophthalmology AU - Chan, C C AU - Hikita, N AU - Dastgheib, K AU - Whitcup, S M AU - Gery, I AU - Nussenblatt, R B AD - Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 1275 EP - 1280 VL - 101 IS - 7 SN - 0161-6420, 0161-6420 KW - Cell Adhesion Molecules KW - 0 KW - Eye Proteins KW - Histocompatibility Antigens Class II KW - Melanins KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - CD4-Positive T-Lymphocytes -- immunology KW - Disease Models, Animal KW - Cell Adhesion Molecules -- analysis KW - Histocompatibility Antigens Class II -- analysis KW - Recurrence KW - Hypersensitivity, Delayed -- immunology KW - Rats KW - Lymphocyte Activation KW - Monocytes -- immunology KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- chemically induced KW - Female KW - Autoimmune Diseases -- immunology KW - Uveitis -- pathology KW - Uveitis -- immunology KW - Uveitis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76602887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=Experimental+melanin-protein-induced+uveitis+in+the+Lewis+rat.+Immunopathologic+processes.&rft.au=Chan%2C+C+C%3BHikita%2C+N%3BDastgheib%2C+K%3BWhitcup%2C+S+M%3BGery%2C+I%3BNussenblatt%2C+R+B&rft.aulast=Chan&rft.aufirst=C&rft.date=1994-07-01&rft.volume=101&rft.issue=7&rft.spage=1275&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-18 N1 - Date created - 1994-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of chronic cocaine administration on [3H]dopamine uptake in the nucleus accumbens, striatum and frontal cortex of rats. AN - 76598480; 8035309 AB - The uptake of [3H]dopamine into synaptosomes obtained from the nucleus accumbens, striatum and frontal cortex was evaluated after chronic treatment with cocaine. Cocaine was administered in a concentration of 10 mg/kg, twice a day for 7 days. Fourteen days after the last injection, locomotor activity and [3H] dopamine uptake were evaluated. Base-line locomotor activity was significantly lower (29%) in rats treated chronically with cocaine compared with saline-treated rats. A challenge dose of cocaine (2.5 mg/kg or 5.0 mg/kg) or d-amphetamine (1 mg/kg) produced similar increases in locomotor activity above the corresponding base-line values in both saline- and cocaine-treated rats, indicating that behavioral sensitization had not occurred. Chronic cocaine administration produced a significant decrease in the uptake of [3H]dopamine into the frontal cortex (49%) with no significant differences in the nucleus accumbens or striatum. The decrease in [3H]dopamine uptake in the frontal cortex was due to a decrease in the Vmax with no change in the affinity of [3H]dopamine for the dopamine transporter. No differences were produced in the IC50 values of GBR 12909 or cocaine for [3H] dopamine uptake after chronic cocaine treatment. However, in all three brain regions, the IC50 values for cocaine were significantly greater than the values for GBR 12909. In addition, the IC50 values for GBR 12909 and cocaine in the frontal cortex were significantly greater than values for either compound in the nucleus accumbens or striatum. The administration of methamphetamine, using a similar treatment schedule, produced no changes in [3H]dopamine uptake in any of the three brain areas. These data indicate an inhibition effect of repeated cocaine administration on [3H]dopamine uptake in the frontal cortex of rats. JF - The Journal of pharmacology and experimental therapeutics AU - Masserano, J M AU - Venable, D AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health Neurosciences Center at St. Elizabeths, Washington, District of Columbia. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 133 EP - 141 VL - 270 IS - 1 SN - 0022-3565, 0022-3565 KW - Neurotransmitter Uptake Inhibitors KW - 0 KW - Piperazines KW - Tritium KW - 10028-17-8 KW - Methamphetamine KW - 44RAL3456C KW - vanoxerine KW - 90X28IKH43 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Drug Interactions KW - Synaptosomes -- drug effects KW - Cerebral Cortex -- metabolism KW - Corpus Striatum -- metabolism KW - Piperazines -- pharmacology KW - Depression, Chemical KW - Rats KW - Rats, Sprague-Dawley KW - Frontal Lobe -- metabolism KW - Methamphetamine -- pharmacology KW - Nucleus Accumbens -- metabolism KW - Motor Activity -- drug effects KW - Time Factors KW - Synaptosomes -- metabolism KW - Male KW - Neurotransmitter Uptake Inhibitors -- pharmacology KW - Brain -- drug effects KW - Dopamine -- pharmacokinetics KW - Brain -- metabolism KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76598480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+chronic+cocaine+administration+on+%5B3H%5Ddopamine+uptake+in+the+nucleus+accumbens%2C+striatum+and+frontal+cortex+of+rats.&rft.au=Masserano%2C+J+M%3BVenable%2C+D%3BWyatt%2C+R+J&rft.aulast=Masserano&rft.aufirst=J&rft.date=1994-07-01&rft.volume=270&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of hepatic transcription factors during liver development and oval cell differentiation. AN - 76597730; 8027180 AB - The oval cells are thought to be the progeny of a liver stem cell compartment and strong evidence now exists indicating that these cells can participate in liver regeneration by differentiating into different hepatic lineages. To better understand the regulation of this process we have studied the expression of liver-enriched transcriptional factors (HNF1 alpha and HNF1 beta, HNF3 alpha, HNF3 beta, and HNF3 gamma, HNF4, C/EBP, C/EBP beta, and DBP) in an experimental model of oval cell proliferation and differentiation and compared the expression of these factors to that observed during late stages of hepatic ontogenesis. The steady-state mRNA levels of four (HNF1 alpha, HNF3 alpha, HNF4, and C/EBP beta) "liver-enriched" transcriptional factors gradually decrease during the late period of embryonic liver development while three factors (HNF1 beta, HNF3 beta, and DBP) increase. In the normal adult rat liver the expression of all the transcription factors are restricted to the hepatocytes. However, during early stages of oval cell proliferation both small and large bile ducts start to express HNF1 alpha and HNF1 beta, HNF3 gamma, C/EBP, and DBP but not HNF4. At the later stages all of these factors are also highly expressed in the proliferating oval cells. Expression of HNF4 is first observed when the oval cells differentiate morphologically and functionally into hepatocytes and form basophilic foci. At that time the expression of some of the other factors is also further increased. Based on these data we suggest that the upregulation of the "establishment" factors (HNF1 and -3) may be an important step in oval cell activation. The high levels of these factors in the oval cells and embryonic hepatoblasts further substantiates the similarity between the two cell compartments. Furthermore, the data suggest that HNF4 may be responsible for the final commitment of a small portion of the oval cells to differentiate into hepatocytes which form the basophilic foci and eventually regenerate the liver parenchyma. JF - The Journal of cell biology AU - Nagy, P AU - Bisgaard, H C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-0037. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 223 EP - 233 VL - 126 IS - 1 SN - 0021-9525, 0021-9525 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DBP protein, rat KW - DNA-Binding Proteins KW - Foxa1 protein, rat KW - Foxa2 protein, rat KW - Foxa3 protein, rat KW - Hepatocyte Nuclear Factor 1-alpha KW - Hepatocyte Nuclear Factor 3-alpha KW - Hepatocyte Nuclear Factor 4 KW - Hnf1a protein, rat KW - Nuclear Proteins KW - Phosphoproteins KW - Transcription Factors KW - Hepatocyte Nuclear Factor 1 KW - 126548-29-6 KW - Hepatocyte Nuclear Factor 3-gamma KW - 135845-91-9 KW - Hepatocyte Nuclear Factor 3-beta KW - 135845-92-0 KW - Hepatocyte Nuclear Factor 1-beta KW - 138674-15-4 KW - Index Medicus KW - Nuclear Proteins -- isolation & purification KW - Animals KW - Nuclear Proteins -- genetics KW - Blotting, Northern KW - DNA-Binding Proteins -- genetics KW - Cell Differentiation KW - Liver Regeneration KW - Rats KW - In Situ Hybridization KW - Up-Regulation KW - DNA-Binding Proteins -- isolation & purification KW - Cell Division KW - Liver -- anatomy & histology KW - Stem Cells -- cytology KW - Liver -- growth & development KW - Transcription Factors -- isolation & purification KW - Stem Cells -- physiology KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Liver -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76597730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+of+hepatic+transcription+factors+during+liver+development+and+oval+cell+differentiation.&rft.au=Nagy%2C+P%3BBisgaard%2C+H+C%3BThorgeirsson%2C+S+S&rft.aulast=Nagy&rft.aufirst=P&rft.date=1994-07-01&rft.volume=126&rft.issue=1&rft.spage=223&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 - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Arch Environ Health. 1972 Nov;25(5):354-64 [4346789] Development. 1991 Oct;113(2):589-99 [1685988] Lab Invest. 1985 Apr;52(4):354-62 [2858600] EMBO J. 1985 Oct;4(10):2487-91 [4054095] J Histochem Cytochem. 1986 Feb;34(2):197-201 [2418098] Cancer Res. 1987 Oct 15;47(20):5469-75 [2443240] Carcinogenesis. 1987 Nov;8(11):1737-40 [3664968] Lab Invest. 1988 Jul;59(1):52-9 [2455831] Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937-41 [2460858] EMBO J. 1988 Aug;7(8):2485-93 [2847919] J Biol Chem. 1989 Jan 5;264(1):266-71 [2462558] Genes Dev. 1988 Jul;2(7):786-800 [2850264] Cancer Res. 1989 Mar 15;49(6):1541-7 [2466557] Science. 1989 Mar 31;243(4899):1681-8 [2494700] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4117-21 [2726767] Cell. 1989 Jun 30;57(7):1179-87 [2736625] Cell. 1989 Oct 6;59(1):145-57 [2571419] Genes Dev. 1989 Aug;3(8):1146-56 [2792758] Cell. 1990 Apr 20;61(2):279-91 [2331750] Cancer Res. 1990 Jun 1;50(11):3439-44 [1692260] Genes Dev. 1990 Mar;4(3):372-9 [1970973] EMBO J. 1990 Jul;9(7):2257-63 [2357969] Development. 1990 Jun;109(2):473-81 [2401206] Cell. 1990 Nov 2;63(3):643-53 [2171780] Genes Dev. 1990 Aug;4(8):1427-36 [2227418] Nucleic Acids Res. 1990 Nov 11;18(21):6277-82 [1700853] Genes Dev. 1990 Sep;4(9):1541-51 [2253878] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9838-42 [2263635] Mol Cell Biol. 1991 Feb;11(2):773-84 [1990282] Genes Dev. 1990 Dec;4(12B):2353-65 [2279702] J Pathol. 1990 Dec;162(4):279-84 [2290113] Genes Dev. 1991 Mar;5(3):416-27 [1672118] Cell Growth Differ. 1990 Jan;1(1):47-52 [2078499] Cancer Res. 1991 May 15;51(10):2611-20 [1708696] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3807-11 [2023930] Genes Dev. 1991 Jun;5(6):1042-56 [2044952] Mol Cell Biol. 1991 Sep;11(9):4405-14 [1875930] New Biol. 1991 Mar;3(3):289-96 [1878351] FEBS Lett. 1991 Aug 19;288(1-2):133-7 [1879546] Genes Dev. 1991 Sep;5(9):1553-67 [1884998] Am J Pathol. 1991 Sep;139(3):535-52 [1716045] EMBO J. 1991 Nov;10(11):3177-82 [1717262] Genes Dev. 1992 Mar;6(3):439-53 [1547942] Science. 1992 Apr 17;256(5055):370-3 [1314426] Mol Cell Biol. 1992 Jul;12(7):3023-31 [1620113] Am J Physiol. 1992 Aug;263(2 Pt 1):G139-48 [1325126] Biochim Biophys Acta. 1992 Sep 24;1132(2):119-26 [1390883] Mol Carcinog. 1992;6(3):190-8 [1359897] J Cell Sci Suppl. 1992;16:123-7 [1297647] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3948-52 [7683413] J Cell Biol. 1993 May;121(4):887-98 [8491780] Int J Dev Biol. 1993 Mar;37(1):189-201 [8389577] Cell Growth Differ. 1993 Jul;4(7):555-61 [7691152] Cell. 1991 Nov 1;67(3):569-79 [1934061] Genes Dev. 1991 Dec;5(12A):2225-34 [1748280] Science. 1991 Dec 20;254(5039):1762-7 [1763325] Nature. 1992 Jan 30;355(6359):457-61 [1734282] Trends Biochem Sci. 1991 Nov;16(11):427-30 [1776173] J Cancer Res Clin Oncol. 1992;118(2):87-115 [1346535] Mech Dev. 1991 Dec;36(1-2):47-58 [1685890] Eur J Biochem. 1980 Nov;112(2):243-9 [6161811] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane-induced hypophagia and hyperthermia in rats is mediated by serotonin-2A receptors. AN - 76595373; 8035308 AB - The administration of various doses of the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) to rats produced dose-related decreases in 1-hr food intake in a food-restricted paradigm and in locomotor activity. DOM also produced dose-related increases in temperature. Pretreatment with propranolol [a beta adrenoceptor antagonist that also has high binding affinity for serotonin (5-HT) 5-HT1A, 5-HT1B and 5-HT2C sites], bemesetron or ondansetron (5-HT3 antagonists) did not attenuate either DOM-induced hypophagia or hyperthermia. In contrast, pretreatment with metergoline (a 5-HT1/5-HT2 antagonist) and ritanserin (a 5-HT2A/5-HT2C antagonist) significantly attenuated both DOM-induced hypophagia and hyperthermia. However, pretreatment with mesulergine (a 5-HT2C/5-HT2A antagonist) significantly attenuated DOM-induced hyperthermia but not hypophagia. On the other hand, spiperone (5-HT1A/5-HT2A/D2 antagonist) pretreatment significantly attenuated DOM-induced hyperthermia but accentuated DOM-induced hypophagia. Daily administration of DOM (1.0 mg kg-1 day-1) produced complete tolerance to its hypophagic effect by day 4 but did not produce cross-tolerance to m-chlorophenylpiperazine-induced hypophagia. In contrast, daily administration of DOM for 7 days did not produce either tolerance to its hyperthermic effect or modify m-chlorophenylpiperazine-induced hyperthermia in rats. These findings suggest that DOM-induced hypophagia and hyperthermia in rats are mediated by stimulation of 5-HT2a receptors. JF - The Journal of pharmacology and experimental therapeutics AU - Aulakh, C S AU - Mazzola-Pomietto, P AU - Wozniak, K M AU - Hill, J L AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 127 EP - 132 VL - 270 IS - 1 SN - 0022-3565, 0022-3565 KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin Antagonists KW - 2,5-Dimethoxy-4-Methylamphetamine KW - 15588-95-1 KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Index Medicus KW - Stimulation, Chemical KW - Rats KW - Drug Tolerance KW - Animals KW - Body Temperature KW - Dose-Response Relationship, Drug KW - Rats, Wistar KW - Motor Activity -- drug effects KW - Piperazines -- pharmacology KW - Time Factors KW - Male KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Fever -- chemically induced KW - Eating -- drug effects KW - 2,5-Dimethoxy-4-Methylamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76595373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Evidence+that+1-%282%2C5-dimethoxy-4-methylphenyl%29-2-aminopropane-induced+hypophagia+and+hyperthermia+in+rats+is+mediated+by+serotonin-2A+receptors.&rft.au=Aulakh%2C+C+S%3BMazzola-Pomietto%2C+P%3BWozniak%2C+K+M%3BHill%2C+J+L%3BMurphy%2C+D+L&rft.aulast=Aulakh&rft.aufirst=C&rft.date=1994-07-01&rft.volume=270&rft.issue=1&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potential laboratory test for dysplastic nevus syndrome: ultraviolet hypermutability of a shuttle vector plasmid. AN - 76590500; 8027583 AB - The diagnosis of the melanoma-prone disorder dysplastic nevus syndrome (DNS) is based currently on a combination of clinical and histopathologic examinations of patients. To develop a potential laboratory test for DNS, we utilized the observation that an ultraviolet light (UV)-treated mutagenesis plasmid shuttle vector has an abnormally increased frequency of mutations after transfection into lymphoblastoid cells from a patient with familial DNS. pSP189 (containing the bacterial suppressor tRNA gene supF as a marker for mutations and a gene for ampicillin resistance for selection) was treated with UV and transfected into familial DNS, xeroderma pigmentosum complementation group A (XP-A), and normal lymphoblastoid cells by electroporation or diethylaminoethyl (DEAE) dextran. Untreated plasmid pZ189K (containing a gene for kanamycin resistance) was co-transfected as an internal standard to reduce the variability of plasmid survival measurements. After 2 d, plasmids were extracted, used to transform an indicator strain of Escherichia coli, and assayed on plates containing ampicillin or kanamycin. Counting light blue or white colonies (containing mutated supF in the plasmid) and blue colonies (with wild type supF) permitted measurement of the plasmid survival and mutation frequency. Transfection by electroporation or DEAE dextran resulted in abnormally reduced survival of UV-treated plasmid after passage through the XP-A but normal survival in the three DNS lines. Transfection of UV-treated plasmid by DEAE dextran yielded a greater hypermutability with the familial DNS lines than by electroporation. These results suggest that pSP189 UV hypermutability with normal UV survival using DEAE dextran transfection may form the basis of a potential laboratory assay for familial DNS. JF - The Journal of investigative dermatology AU - Moriwaki, S AU - Tarone, R E AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 7 EP - 12 VL - 103 IS - 1 SN - 0022-202X, 0022-202X KW - supF KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Ultraviolet Rays KW - RNA, Transfer -- genetics KW - Diagnostic Tests, Routine KW - Humans KW - Genetic Vectors KW - Plasmids KW - Genes, Suppressor KW - Dysplastic Nevus Syndrome -- diagnosis KW - Dysplastic Nevus Syndrome -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=A+potential+laboratory+test+for+dysplastic+nevus+syndrome%3A+ultraviolet+hypermutability+of+a+shuttle+vector+plasmid.&rft.au=Moriwaki%2C+S%3BTarone%2C+R+E%3BKraemer%2C+K+H&rft.aulast=Moriwaki&rft.aufirst=S&rft.date=1994-07-01&rft.volume=103&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative pharmacodynamics of hepatic cytochrome P450 2B induction by 5,5-diphenyl- and 5,5-diethyl-substituted barbiturates and hydantoins in the male F344/NCr rat. AN - 76590333; 8035330 AB - To explore further the structural requirements for ligand interaction with the putative phenobarbital receptor, the pharmacodynamics of CYP2B induction by 5,5-diphenylbarbituric acid, phenytoin (5,5-diphenylhydantoin), barbital (5,5-diethylbarbituric acid) and 5,5-diethylhydantoin were investigated in the male F344/NCr rat. Steady-state total (free plus protein-bound) serum drug concentration, measured after 14 days of administration of the compounds in the diet, was used as an approximation of intrahepatocellular drug concentration. The serum concentrations associated with half-maximal hepatic CYP2B induction (EC50 values) were 6 to 11 microM and 15 to 18 microM for the diphenyl-substituted barbiturate and hydantoin, respectively, based on measurement of pentoxy- or benzyloxyresorufin O-dealkylation activities, or immunoreactive CYP2B1 protein. The corresponding potency values for the diethyl-substituted barbiturate and hydantoin were 16 to 20 microM and > or = 500 microM, respectively. The magnitudes of the maximal CYP2B induction responses elicited by the diphenyl-substituted congeners and by barbital were 94 to 122% of the responses resulting from phenobarbital itself. In contrast, the maximum induction responses elicited by 5,5-diethylhydantoin were only 24% as great as those elicited by phenobarbital. The finding of a CYP2B inducer with a potency value 2 to 3 orders of magnitude lower than those for certain other prototype CYP2B inducers is suggestive but not proof of receptor mediation in the induction process. JF - The Journal of pharmacology and experimental therapeutics AU - Nims, R W AU - McClain, R M AU - Manchand, P S AU - Belica, P S AU - Thomas, P E AU - Mellini, D W AU - Utermahlen, W E AU - Lubet, R A AD - Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 348 EP - 355 VL - 270 IS - 1 SN - 0022-3565, 0022-3565 KW - Hydantoins KW - 0 KW - Oxazines KW - 5,5-diphenylbarbituric acid KW - 21914-07-8 KW - 5,5-diethylhydantoin KW - 5455-34-5 KW - Barbital KW - 5WZ53ENE2P KW - Phenytoin KW - 6158TKW0C5 KW - benzyloxyresorufin KW - 87687-02-3 KW - pentoxyresorufin KW - 87687-03-4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Enzyme Induction -- drug effects KW - Oxazines -- metabolism KW - Male KW - Organ Size -- drug effects KW - Alkylation KW - Liver -- anatomy & histology KW - Phenytoin -- pharmacokinetics KW - Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- drug effects KW - Hydantoins -- pharmacology KW - Barbital -- pharmacokinetics KW - Phenytoin -- pharmacology KW - Phenobarbital -- pharmacology KW - Phenobarbital -- analogs & derivatives KW - Liver -- drug effects KW - Hydantoins -- pharmacokinetics KW - Phenobarbital -- pharmacokinetics KW - Barbital -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Comparative+pharmacodynamics+of+hepatic+cytochrome+P450+2B+induction+by+5%2C5-diphenyl-+and+5%2C5-diethyl-substituted+barbiturates+and+hydantoins+in+the+male+F344%2FNCr+rat.&rft.au=Nims%2C+R+W%3BMcClain%2C+R+M%3BManchand%2C+P+S%3BBelica%2C+P+S%3BThomas%2C+P+E%3BMellini%2C+D+W%3BUtermahlen%2C+W+E%3BLubet%2C+R+A&rft.aulast=Nims&rft.aufirst=R&rft.date=1994-07-01&rft.volume=270&rft.issue=1&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetic evaluation of the combination of zidovudine and didanosine in children with human immunodeficiency virus infection. AN - 76587550; 8021765 AB - As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents. JF - The Journal of pediatrics AU - Mueller, B U AU - Pizzo, P A AU - Farley, M AU - Husson, R N AU - Goldsmith, J AU - Kovacs, A AU - Woods, L AU - Ono, J AU - Church, J A AU - Brouwers, P AD - Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 142 EP - 146 VL - 125 IS - 1 SN - 0022-3476, 0022-3476 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Drug Therapy, Combination KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Humans KW - Drug Monitoring KW - Adult KW - Child KW - Adolescent KW - Male KW - Female KW - Child, Preschool KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - Zidovudine -- pharmacokinetics KW - HIV Infections -- blood KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - Zidovudine -- administration & dosage KW - Didanosine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76587550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics&rft.atitle=Pharmacokinetic+evaluation+of+the+combination+of+zidovudine+and+didanosine+in+children+with+human+immunodeficiency+virus+infection.&rft.au=Mueller%2C+B+U%3BPizzo%2C+P+A%3BFarley%2C+M%3BHusson%2C+R+N%3BGoldsmith%2C+J%3BKovacs%2C+A%3BWoods%2C+L%3BOno%2C+J%3BChurch%2C+J+A%3BBrouwers%2C+P&rft.aulast=Mueller&rft.aufirst=B&rft.date=1994-07-01&rft.volume=125&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading. AN - 76585049; 8026023 AB - Studies have shown that the rise in intracellular ionized calcium, [Ca2+]i, in hypoxic myocardium is driven by an increase in sodium, [Na+]i, but the source of Na+ is not known. Inhibitors of the voltage-gated Na+ channel were used to investigate the effect of Na+ channel blockade on hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated adult rat cardiac myocytes. Single electrically stimulated (0.2 Hz) cells were loaded with either SBFI (to index [Na+]i) or indo-1 (to index [Ca2+]i) and exposed to glucose-free hypoxia (PO2 < 0.02 mm Hg). Both [Na+]i and [Ca2+]i increased during hypoxia when cells became inexcitable following ATP-depletion contracture. The hypoxic rise in [Na+]i and [Ca2+]i was significantly attenuated by 1 mumol/L R 56865. Tetrodotoxin (60 mumol/L), a selective Na(+)-channel blocker, also markedly reduced the rise in [Ca2+]i during hypoxia and reoxygenation. Reoxygenation-induced cellular hypercontracture was reduced from 83% (45 of 54 cells) under control conditions to 12% (4 of 32) in the presence of R 56865 (P < .05). Lidocaine reduced hypercontracture dose dependently with 13% of cells hypercontracting in 100 mumol/L lidocaine, 42% in 50 mumol/L lidocaine, and 93% in 25 mumol/L lidocaine. The Na(+)-H+ exchange blocker, ethylisopropylamiloride (10 mumol/L) was also effective, limiting hypercontracture to 12%. R 56865, lidocaine, and ethylisopropylamiloride were also effective in preventing hypercontracture in normoxic myocytes induced by 75 mumol/L veratridine, an agent that impairs Na+ channel inactivation. Ethylisopropylamiloride prevented the veratridine-induced rise in [Ca2+]i without affecting Na(+)-Ca2+ exchange, suggesting that amiloride derivatives can reduce Ca2+ loading by blocking Na+ entry through Na+ channels, an action that may in part underlie their ability to prevent hypoxic Na+ and Ca2+ loading. Na+ influx through the voltage-gated Na+ channel is an important route of hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated rat cardiac myocytes. Importantly, the Na+ channel appears to serve as a route for hypoxic Na+ influx after myocytes become inexcitable. JF - Circulation AU - Haigney, M C AU - Lakatta, E G AU - Stern, M D AU - Silverman, H S AD - Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, MD. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 391 EP - 399 VL - 90 IS - 1 SN - 0009-7322, 0009-7322 KW - Benzofurans KW - 0 KW - Benzothiazoles KW - Calcium Channel Blockers KW - Ethers, Cyclic KW - Fluorescent Dyes KW - Piperidines KW - Sodium Channel Blockers KW - Sodium-Hydrogen Antiporter KW - Thiazoles KW - sodium-binding benzofuran isophthalate KW - 124549-08-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Amiloride KW - 7DZO8EB0Z3 KW - R 56865 KW - 8MUQ2U7UV6 KW - Lidocaine KW - 98PI200987 KW - Sodium KW - 9NEZ333N27 KW - Calcium KW - SY7Q814VUP KW - ethylisopropylamiloride KW - VW50CE070T KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Sodium-Hydrogen Antiporter -- metabolism KW - Myocardial Contraction -- drug effects KW - Amiloride -- pharmacology KW - Cell Separation KW - Amiloride -- analogs & derivatives KW - Thiazoles -- pharmacology KW - Rats KW - Piperidines -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - Lidocaine -- pharmacology KW - Tetrodotoxin -- pharmacology KW - Calcium -- metabolism KW - Myocardium -- cytology KW - Hypoxia -- metabolism KW - Myocardium -- metabolism KW - Sodium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76585049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Sodium+channel+blockade+reduces+hypoxic+sodium+loading+and+sodium-dependent+calcium+loading.&rft.au=Haigney%2C+M+C%3BLakatta%2C+E+G%3BStern%2C+M+D%3BSilverman%2C+H+S&rft.aulast=Haigney&rft.aufirst=M&rft.date=1994-07-01&rft.volume=90&rft.issue=1&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The economic impact of treatment of severe lupus nephritis with prednisone and intravenous cyclophosphamide. AN - 76584010; 8024609 AB - It has been reported that outcomes are improved in patients with severe lupus nephritis treated with combined prednisone and intravenous cyclophosphamide, compared with those treated with prednisone alone. These findings motivated this analysis of the economic impact of the combined therapy. The annual expected incidence of severe lupus nephritis in the year 1988 in the US was estimated to be 1,130. A hypothetical patient cohort of this size was used as the model for the present analysis; the costs of treatment with prednisone alone and with combined prednisone and intravenous cyclophosphamide were calculated and compared. The analysis took into account the expected rate of renal failure with each therapeutic approach, as well as age, sex, and the economic value of working years gained. Although the treatment costs are higher for the combination therapy, the analysis revealed overall savings due to a reduced need for kidney dialysis or transplantation, and the economic value of working capacity gained. Savings attributable to patient care costs were $50.8 million; those attributable to working capacity gained were $42.3 million. This analysis indicates that over a 10-year period, as much as $93.1 million per annual cohort is saved by the use of combination therapy for the treatment of severe lupus nephritis. JF - Arthritis and rheumatism AU - McInnes, P M AU - Schuttinga, J AU - Sanslone, W R AU - Stark, S P AU - Klippel, J H AD - National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 1000 EP - 1006 VL - 37 IS - 7 SN - 0004-3591, 0004-3591 KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Drug Therapy, Combination KW - Kidney Failure, Chronic -- economics KW - Costs and Cost Analysis KW - Injections, Intravenous KW - Kidney Failure, Chronic -- drug therapy KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Cyclophosphamide -- administration & dosage KW - Lupus Nephritis -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - Prednisone -- therapeutic use KW - Lupus Nephritis -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76584010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=The+economic+impact+of+treatment+of+severe+lupus+nephritis+with+prednisone+and+intravenous+cyclophosphamide.&rft.au=McInnes%2C+P+M%3BSchuttinga%2C+J%3BSanslone%2C+W+R%3BStark%2C+S+P%3BKlippel%2C+J+H&rft.aulast=McInnes&rft.aufirst=P&rft.date=1994-07-01&rft.volume=37&rft.issue=7&rft.spage=1000&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postoperative complications in patients receiving suramin therapy. AN - 76578980; 8023275 AB - Suramin is an antiparasitic agent that is currently being evaluated for antineoplastic activity. Documented toxicities of suramin include adrenal and renal insufficiency, coagulation factor abnormalities, immunosuppression, and polyneuropathy. These adverse effects have potential for contributing to postoperative morbidity in surgical patients. Because no experience with suramin has been reported in the surgical literature, this 5-year retrospective review of postoperative complications in patients receiving suramin was performed. From a review of 171 charts, 14 patients were identified who had undergone a major surgical procedure either while receiving intravenous suramin or within 1 year after its administration. Primary diagnoses included prostate cancer (six), lymphoma (four), ovarian cancer (two), colon cancer (one), and glioblastoma (one). All patients received replacement dose hydrocortisone at the initiation of suramin therapy and thereafter. Eighteen major surgical procedures were performed with 18 complications occurring in five patients. The predominant complications encountered were hemorrhage (five), impaired wound healing (three), and bowel dysmotility (two). A highly significant relationship existed between the incidence of complications and interval from completion of suramin therapy to the time of operation (p < 0.0005), with 17 of the 18 morbidities occurring within the first month. The length of operation (p < 0.05) and amount of blood transfused during the procedure were related to postoperative morbidity (p < 0.05). No other factors evaluated were correlated to complications. This experience suggests the avoidance of elective procedures during the first month after suramin therapy and a heightened awareness of the potential for bleeding and wound healing problems in patients receiving suramin who do require an emergent procedure. JF - Surgery AU - Cole, D J AU - Ettinghausen, S E AU - Pass, H I AU - Danforth, D N AU - Linehan, M W AU - Myers, C W AU - Cooper, M R AU - Sindelar, W F AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 90 EP - 95 VL - 116 IS - 1 SN - 0039-6060, 0039-6060 KW - Suramin KW - 6032D45BEM KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasms -- drug therapy KW - Drug Evaluation KW - Infusions, Intravenous KW - Hemorrhage -- chemically induced KW - Aged, 80 and over KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Suramin -- adverse effects KW - Postoperative Complications -- chemically induced KW - Suramin -- administration & dosage KW - Suramin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76578980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgery&rft.atitle=Postoperative+complications+in+patients+receiving+suramin+therapy.&rft.au=Cole%2C+D+J%3BEttinghausen%2C+S+E%3BPass%2C+H+I%3BDanforth%2C+D+N%3BLinehan%2C+M+W%3BMyers%2C+C+W%3BCooper%2C+M+R%3BSindelar%2C+W+F&rft.aulast=Cole&rft.aufirst=D&rft.date=1994-07-01&rft.volume=116&rft.issue=1&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Surgery&rft.issn=00396060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Wearing-off fluctuations in Parkinson's disease: contribution of postsynaptic mechanisms. AN - 76574829; 8024257 AB - Wearing-off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady-state optimal-dose infusion of apomorphine. Although the plasma half-life of this dopamine receptor agonist remained constant, its mean efficacy half-time declined from 66 minutes in early, levodopa-naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing-off fluctuations. JF - Annals of neurology AU - Bravi, D AU - Mouradian, M M AU - Roberts, J W AU - Davis, T L AU - Sohn, Y H AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 27 EP - 31 VL - 36 IS - 1 SN - 0364-5134, 0364-5134 KW - Receptors, Dopamine KW - 0 KW - Levodopa KW - 46627O600J KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Severity of Illness Index KW - Receptors, Dopamine -- drug effects KW - Receptors, Dopamine -- physiology KW - Corpus Striatum -- physiopathology KW - Half-Life KW - Dose-Response Relationship, Drug KW - Humans KW - Middle Aged KW - Neuronal Plasticity KW - Drug Synergism KW - Movement -- drug effects KW - Levodopa -- pharmacology KW - Apomorphine -- pharmacokinetics KW - Apomorphine -- therapeutic use KW - Apomorphine -- pharmacology KW - Dopamine -- physiology KW - Levodopa -- therapeutic use KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy KW - Parkinson Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76574829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Wearing-off+fluctuations+in+Parkinson%27s+disease%3A+contribution+of+postsynaptic+mechanisms.&rft.au=Bravi%2C+D%3BMouradian%2C+M+M%3BRoberts%2C+J+W%3BDavis%2C+T+L%3BSohn%2C+Y+H%3BChase%2C+T+N&rft.aulast=Bravi&rft.aufirst=D&rft.date=1994-07-01&rft.volume=36&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner. AN - 76574110; 7517401 AB - To identify novel proteins capable of associating with the Raf-1 serine/threonine kinase, we investigated whether Raf-1 could interact with the Src homology 2 (SH2) domains of various signal-transducing molecules. In this report, we demonstrate that Raf-1 associated with the SH2 domain of Fyn (a member of the Src tyrosine kinase family) but not with the SH2 domains of phospholipase C-gamma 1, the p85 alpha subunit of phosphatidylinositol 3-kinase, and SH2-containing protein tyrosine phosphatase 2. Unlike most SH2 domain interactions that require tyrosine-phosphorylated residues, the Raf-1/Fyn SH2 domain association was dependent on the serine phosphorylation of Raf-1. Our results also demonstrate that Raf-1 interacted with the SH2 domain of Src and that this interaction was destabilized by mutation of Arg175 found within the conserved SH2 domain FLVRES sequence. In addition, we show that inclusion of additional Src sequences containing the SH3 domain increased the association of Raf-1 with the Src SH2 domain. Finally, using the baculovirus/Sf9 cell system, we show that coexpression of Raf-1 with full-length Fyn/Src resulted in the coimmunoprecipitation of Raf-1 with Fyn/Src, the tyrosine phosphorylation of Raf-1, and the stimulation of Raf-1 kinase activity. These results suggest that Raf-1 may form a functional complex with Fyn/Src mediated in part by SH2 domains and the serine phosphorylation of Raf-1. JF - The Journal of biological chemistry AU - Cleghon, V AU - Morrison, D K AD - Molecular Mechanisms of Carcinogenesis Laboratory, ABL-Basic Research Program National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 17749 EP - 17755 VL - 269 IS - 26 SN - 0021-9258, 0021-9258 KW - Proto-Oncogene Proteins KW - 0 KW - Recombinant Fusion Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - FYN protein, human KW - EC 2.7.10.2 KW - Fyn protein, mouse KW - Proto-Oncogene Proteins c-fyn KW - Proto-Oncogene Proteins pp60(c-src) KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Moths KW - Type C Phospholipases -- metabolism KW - Binding Sites KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Baculoviridae -- genetics KW - Phosphorylation KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins pp60(c-src) -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins pp60(c-src) -- genetics KW - Protein-Serine-Threonine Kinases -- genetics KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76574110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Raf-1+interacts+with+Fyn+and+Src+in+a+non-phosphotyrosine-dependent+manner.&rft.au=Cleghon%2C+V%3BMorrison%2C+D+K&rft.aulast=Cleghon&rft.aufirst=V&rft.date=1994-07-01&rft.volume=269&rft.issue=26&rft.spage=17749&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 - 1994-07-29 N1 - Date created - 1994-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydroxyrubicin, a deaminated derivative of doxorubicin, inhibits mammalian DNA topoisomerase II and partially circumvents multidrug resistance. AN - 76571819; 8014019 AB - In vivo effectiveness of doxorubicin remains restricted due to toxicity and drug resistance. Hydroxyrubicin is a synthetic analog of doxorubicin in which the basic amino group at the C-3' has been replaced by a hydroxyl group in order to overcome recognition by the multidrug resistant (MDR) P-glycoprotein and limit cardiotoxicity. The present study shows that hydroxyrubicin is a less potent intercalator than doxorubicin. Induction of topoisomerase II-mediated DNA cleavage in the human c-myc origin by the two drugs was similar, reaching a maximum at 0.5 microM. Results from the NCI Cell Screening program indicate a relatively good correlation between the cytotoxicity of the 2 drugs on 55 cell lines of various origins (r = 0.723). Using a clonogenic assay, we observed that hydroxyrubicin was 20-fold more cytotoxic against the MDR KB-V1 cell line than doxorubicin and was slightly more cytotoxic than doxorubicin in the sensitive KB3.1 cell line. Uptake studies showed that doxorubicin was retained up to 1 hr in KB3.1 cells and rapidly eliminated from resistant KB-V1 cells. In contrast, hydroxyrubicin was rapidly eliminated from both sensitive KB3.1 and MDR-positive KB-V1 cells. Both drugs induced protein-linked DNA single-strand breaks (SSBs) in both KB3.1 and KB-V1 cells, which is consistent with topoisomerase inhibition. However, the kinetics of DNA SSBs induced by both drugs was very different. DNA breaks disappeared quickly in both KB3.1 and KB-V1 cell lines after hydroxyrubicin removal while DNA breaks induced by doxorubicin disappeared very slowly in KB3.1 cells and rapidly in KB-V1 cells. We conclude that removal of the basic amino group at the C-3' of doxorubicin modifies drug transport and partially circumvents MDR without changing topoisomerase II inhibition when compared with doxorubicin. JF - International journal of cancer AU - Solary, E AU - Ling, Y H AU - Perez-Soler, R AU - Priebe, W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 85 EP - 94 VL - 58 IS - 1 SN - 0020-7136, 0020-7136 KW - c-myc KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents KW - DNA, Neoplasm KW - Topoisomerase II Inhibitors KW - Epirubicin KW - 3Z8479ZZ5X KW - 3'-deamino-3'-hydroxydoxorubicin KW - 73113-90-3 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - DNA, Neoplasm -- drug effects KW - KB Cells KW - Drug Screening Assays, Antitumor KW - Doxorubicin -- pharmacokinetics KW - Doxorubicin -- analogs & derivatives KW - Doxorubicin -- pharmacology KW - DNA Damage KW - Antibiotics, Antineoplastic -- pharmacology KW - Humans KW - DNA, Neoplasm -- metabolism KW - Epirubicin -- pharmacokinetics KW - Drug Resistance -- physiology KW - Epirubicin -- pharmacology KW - Antineoplastic Agents -- pharmacokinetics KW - Epirubicin -- analogs & derivatives KW - Antineoplastic Agents -- toxicity KW - Epirubicin -- toxicity KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76571819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hydroxyrubicin%2C+a+deaminated+derivative+of+doxorubicin%2C+inhibits+mammalian+DNA+topoisomerase+II+and+partially+circumvents+multidrug+resistance.&rft.au=Solary%2C+E%3BLing%2C+Y+H%3BPerez-Soler%2C+R%3BPriebe%2C+W%3BPommier%2C+Y&rft.aulast=Solary&rft.aufirst=E&rft.date=1994-07-01&rft.volume=58&rft.issue=1&rft.spage=85&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 - 1994-07-26 N1 - Date created - 1994-07-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease. AN - 76571567; 8016306 AB - Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received. JF - Radiation research AU - Kleinerman, R A AU - Littlefield, L G AU - Tarone, R E AU - Sayer, A M AU - Cookfair, D L AU - Wactawski-Wende, J AU - Inskip, P D AU - Block, A AU - Ramesh, K H AU - Boice, J D AD - Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 40 EP - 46 VL - 139 IS - 1 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Reference Values KW - Cells, Cultured KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Aged KW - Follow-Up Studies KW - Bone Marrow -- radiation effects KW - Time Factors KW - Female KW - Uterine Diseases -- radiotherapy KW - Neoplasms, Radiation-Induced -- etiology KW - Leukemia, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Leukemia, Radiation-Induced -- etiology KW - Lymphocytes -- radiation effects KW - Chromosome Aberrations KW - Uterine Cervical Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76571567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Chromosome+aberrations+in+lymphocytes+from+women+irradiated+for+benign+and+malignant+gynecological+disease.&rft.au=Kleinerman%2C+R+A%3BLittlefield%2C+L+G%3BTarone%2C+R+E%3BSayer%2C+A+M%3BCookfair%2C+D+L%3BWactawski-Wende%2C+J%3BInskip%2C+P+D%3BBlock%2C+A%3BRamesh%2C+K+H%3BBoice%2C+J+D&rft.aulast=Kleinerman&rft.aufirst=R&rft.date=1994-07-01&rft.volume=139&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxic and antitumor activity of a recombinant immunotoxin composed of disulfide-stabilized anti-Tac Fv fragment and truncated Pseudomonas exotoxin. AN - 76569898; 8014011 AB - Disulfide-stabilized Fv (dsFv)-immunotoxins are recombinant immunotoxins in which the inherently unstable Fv moiety, composed of the VH-VL heterodimer, is stabilized by a disulfide bond engineered between structurally conserved framework positions of VH and VL. Anti-Tac(dsFv)-PE38KDEL is composed of such a dsFv, directed to the alpha subunit of the IL2 receptor (IL2R), and containing a truncated form of Pseudomonas exotoxin (PE38KDEL). We have found this new type of immunotoxin to be indistinguishable in its in vitro activity and specificity from its single-chain immunotoxin counterpart, anti-Tac(Fv)-PE38KDEL. We have now examined the therapeutically relevant factors, including stability, pharmacokinetics, and antitumor activity of this new disulfide-stabilized Fv-immunotoxin. We found that anti-Tac(dsFv)-PE38KDEL was specifically cytotoxic to human activated T-lymphocytes in addition to IL2R bearing cell lines. Anti-Tac(dsFv)-PE38KDEL was considerably more stable at 37 degrees C in human serum and in buffered saline than the single-chain immunotoxin, anti-Tac(Fv)-PE38KDEL. The half-life in blood was similar for both immunotoxins (approx. 20 min). The therapeutic potential of the disulfide-stabilized immunotoxin was evaluated using an animal model of immunodeficient mice bearing subcutaneous tumor xenografts of human IL2R-bearing cells. Anti-Tac(dsFv)-PE38KDEL caused complete regression of tumors with no toxic effects in mice. Because dsFv-immunotoxins are more stable and can be produced with significantly improved yields compared to scFv-immunotoxins, dsFv-immunotoxin may be more useful for therapeutic applications. JF - International journal of cancer AU - Reiter, Y AU - Kreitman, R J AU - Brinkmann, U AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 142 EP - 149 VL - 58 IS - 1 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Peptide Fragments KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Drug Stability KW - Peptide Fragments -- toxicity KW - Immunoglobulin Variable Region -- toxicity KW - Humans KW - Mice KW - Mice, Nude KW - Plasmids KW - Mice, Inbred BALB C KW - Peptide Fragments -- immunology KW - Recombinant Proteins -- toxicity KW - Neoplasm Transplantation KW - Neoplasms, Experimental -- immunology KW - Neoplasms, Experimental -- drug therapy KW - Peptide Fragments -- pharmacokinetics KW - Immunoglobulin Fragments -- immunology KW - Female KW - Immunotoxins -- toxicity KW - Disulfides -- pharmacology KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Exotoxins -- toxicity KW - Immunotoxins -- metabolism KW - Receptors, Interleukin-2 -- immunology KW - Exotoxins -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76569898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytotoxic+and+antitumor+activity+of+a+recombinant+immunotoxin+composed+of+disulfide-stabilized+anti-Tac+Fv+fragment+and+truncated+Pseudomonas+exotoxin.&rft.au=Reiter%2C+Y%3BKreitman%2C+R+J%3BBrinkmann%2C+U%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1994-07-01&rft.volume=58&rft.issue=1&rft.spage=142&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 - 1994-07-26 N1 - Date created - 1994-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - B3(Fab)-PE38M: a recombinant immunotoxin in which a mutant form of Pseudomonas exotoxin is fused to the Fab fragment of monoclonal antibody B3. AN - 76566913; 8012967 AB - Recombinant immunotoxins were made by fusing the Fab domain of monoclonal antibody (MAb) B3 to PE38M, a truncated mutant form of Pseudomonas exotoxin (PE). The recombinant toxins were made in Escherichia coli by fusing genes encoding the antibody domains to a gene encoding the mutant form of PE. MAb B3 binds to a carbohydrate antigen found on many kinds of carcinomas. Immunotoxins in which MAb B3 has been chemically coupled to recombinant forms of PE have been shown to be very active cytotoxic agents. PE has also been targeted to tumor cells by replacing the cell-binding domain of PE (domain I) with a single-chain antibody to make a single-chain immunotoxin. In the current study, PE38M, a mutant form of PE, with a deletion of the cell-binding domain (amino acids 1-252) as well as mutations in domain III and some nonessential sequences in domain Ib (amino acids 365-380), was fused to the light chain of MAb B3. This protein was renatured in the presence of the Fd fragment of MAb B3 to produce a Fab-toxin fusion protein. Alternatively, the Fd fragment of MAb B3 was fused to PE38M and combined with the light chain. Both types of B3(Fab)-PE38M were just as active on target cells as previously described single-chain immunotoxins. Furthermore, the B3(Fab)-PE38M produced complete remissions of human tumor xenografts growing in nude mice. B3(Fab)-PE38M has two advantages over single-chain immunotoxins. One is that the yield of recombinant Fab-toxin is very high, with 10-22% of the starting protein recovered as cytotoxically active immunotoxin after chromatographic purification. The second is that the B3(Fab)-PE38M has a much longer survival in the circulation of mice with a t1/2 beta of approximately 5 h. JF - Cancer research AU - Choe, M AU - Webber, K O AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 3460 EP - 3467 VL - 54 IS - 13 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Fab Fragments KW - Immunotoxins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Base Sequence KW - Half-Life KW - Molecular Sequence Data KW - Escherichia coli -- chemistry KW - Mice KW - Mice, Inbred BALB C KW - Molecular Weight KW - Immunotoxins -- chemistry KW - Immunoglobulin Fab Fragments -- chemistry KW - Exotoxins -- genetics KW - Immunoglobulin Fab Fragments -- genetics KW - Immunotoxins -- genetics KW - Exotoxins -- chemistry KW - Immunotoxins -- metabolism KW - Antibodies, Monoclonal -- chemistry KW - Immunotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76566913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=B3%28Fab%29-PE38M%3A+a+recombinant+immunotoxin+in+which+a+mutant+form+of+Pseudomonas+exotoxin+is+fused+to+the+Fab+fragment+of+monoclonal+antibody+B3.&rft.au=Choe%2C+M%3BWebber%2C+K+O%3BPastan%2C+I&rft.aulast=Choe&rft.aufirst=M&rft.date=1994-07-01&rft.volume=54&rft.issue=13&rft.spage=3460&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 - 1994-07-27 N1 - Date created - 1994-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simultaneous measurement of cocaine, cocaethylene, their metabolites, and "crack" pyrolysis products by gas chromatography-mass spectrometry. AN - 76564912; 8013103 AB - We developed a sensitive and specific assay for the simultaneous measurement of cocaine, cocaethylene, six of their metabolites, and anhydroecgonine methyl ester, a pyrolysis product, in biological fluids. The assay involves solid-phase extraction columns containing a copolymeric bonded phase for isolation of cocaine analytes, derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide and 10 g/L trimethylchlorosilane, and measurement with gas chromatography-mass spectrometry operating in the selected-ion monitoring mode. Detector responses for analytes were linear over a concentration range of 3.1-1000 micrograms/L. The limits of detection were approximately 1 microgram/L for cocaine, ecgonine methyl ester, and benzoylecgonine and 3-6 micrograms/L for the remaining analytes. Hydrolysis of cocaine and artifact formation of anhydroecogonine methyl ester during extraction and assay was < 1%. Cocaine and its derivatives appear in different proportions in plasma, saliva, and urine according to the biological fluid and time of measurement. Each biological fluid provides unique information on the disposition of cocaine in human subjects. JF - Clinical chemistry AU - Cone, E J AU - Hillsgrove, M AU - Darwin, W D AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 1299 EP - 1305 VL - 40 IS - 7 Pt 1 SN - 0009-9147, 0009-9147 KW - anhydroecgonine methyl ester KW - 43021-26-7 KW - cocaethylene KW - FJO3071W5Y KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Sensitivity and Specificity KW - Smoking KW - Injections, Intravenous KW - Saliva -- chemistry KW - Kinetics KW - Humans KW - Administration, Intranasal KW - Substance-Related Disorders -- metabolism KW - Hydrolysis KW - Male KW - Cocaine -- analysis KW - Gas Chromatography-Mass Spectrometry -- methods KW - Cocaine -- analogs & derivatives KW - Cocaine -- urine KW - Gas Chromatography-Mass Spectrometry -- statistics & numerical data KW - Cocaine -- pharmacokinetics KW - Body Fluids -- chemistry KW - Cocaine -- blood KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76564912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+chemistry&rft.atitle=Simultaneous+measurement+of+cocaine%2C+cocaethylene%2C+their+metabolites%2C+and+%22crack%22+pyrolysis+products+by+gas+chromatography-mass+spectrometry.&rft.au=Cone%2C+E+J%3BHillsgrove%2C+M%3BDarwin%2C+W+D&rft.aulast=Cone&rft.aufirst=E&rft.date=1994-07-01&rft.volume=40&rft.issue=7+Pt+1&rft.spage=1299&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of connexins during differentiation of oval cells into hepatocytes. AN - 76563630; 7517369 AB - The connexins are a family of related gap-junction proteins, implicated in embryonic development, cell growth control, and cellular differentiation. To identify connexins involved in liver cell differentiation, both in vivo and in vitro systems were employed to study expression of connexins 26, 32, and 43. Northern blot analysis and in situ hybridization were used to measure the levels of connexin expression and cellular localization of the transcripts, respectively. Normal liver expressed high connexin 32, low connexin 26, and barely detectable connexin 43. In vivo proliferation and differentiation of oval cells was at first accompanied by increased connexin 43 and decreased connexin 32 expression; later as the oval cells differentiated into hepatocytes, connexin 43 disappeared and connexin 32 increased to control levels. In situ hybridization showed that both oval cells and bile duct epithelial cells, but not hepatocytes, expressed connexin 43. A switch from connexin 43 to connexin 32 expression was observed following in vitro transformation and differentiation of rat liver epithelial cells toward the hepatocytic lineage. These results suggest that early progenitor cells in the liver express connexin 43 and a switch from connexin 43 to connexin 32 may signal commitment to hepatocytic differentiation. JF - Experimental cell research AU - Zhang, M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 37 EP - 42 VL - 213 IS - 1 SN - 0014-4827, 0014-4827 KW - Connexin 43 KW - 0 KW - Connexins KW - Gjb2 protein, rat KW - RNA, Messenger KW - connexin 32 KW - Connexin 26 KW - 127120-53-0 KW - Keratins KW - 68238-35-7 KW - Index Medicus KW - Clone Cells KW - Animals KW - Fetus KW - Blotting, Northern KW - Humans KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - RNA, Messenger -- biosynthesis KW - Keratins -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - Embryonic and Fetal Development KW - Epithelial Cells KW - Connexin 43 -- biosynthesis KW - Epithelium -- metabolism KW - Cell Line, Transformed KW - Immunohistochemistry KW - Fluorescent Antibody Technique KW - Male KW - Liver -- cytology KW - Connexins -- biosynthesis KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76563630?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Modulation+of+connexins+during+differentiation+of+oval+cells+into+hepatocytes.&rft.au=Zhang%2C+M%3BThorgeirsson%2C+S+S&rft.aulast=Zhang&rft.aufirst=M&rft.date=1994-07-01&rft.volume=213&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tributyrin: a prodrug of butyric acid for potential clinical application in differentiation therapy. AN - 76561636; 8012972 AB - Butyric acid (BA) induces cytodifferentiation in vitro of a wide variety of neoplastic cells. The potential clinical utility of BA is limited by the apparent difficulty of achieving effective concentrations because of its rapid metabolism and short plasma half-life. In this study we addressed two approaches that may achieve effective concentrations of BA in vivo. One strategy is to use BA derivatives as prodrugs that can be metabolized to yield effective BA concentrations in vivo over a sustained period of time. Another strategy is to define agents that are synergistic with BA so that the desired effect can be achieved at lower concentrations of BA. In this study monobutyrin (MB) and tributyrin (TB) were studied in vitro for their effects on inducing differentiation of human myeloid leukemia HL60 cells and murine erythroleukemia cells. On a molar basis TB was about 4-fold more potent than either BA or MB for inducing differentiation of HL60 cells. BA, MB, or TB induced erythroid differentiation of murine erythroleukemia cells. On a molar basis TB was 3- to 4-fold more potent than BA, whereas MB was much less potent than BA. Combinations of all-trans-retinoic acid with either BA, MB, or TB induced myeloid differentiation of HL60 cells synergistically. We saw marked reductions in the doses of each agent that were needed in combination to achieve the same effect as single agents. For example, 130 microM TB, 110 nM all-trans-retinoic acid, and a combination of 13 microM TB plus 13 nM all-trans-retinoic acid all induced half-maximal differentiation of HL60 cells. Our results suggest that the readily available TB may be an effective prodrug of BA and may be useful either as a sole agent or in combination with other agents for cytodifferentiation therapy of human malignancies. JF - Cancer research AU - Chen, Z X AU - Breitman, T R AD - Laboratory of Biological Chemistry, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 3494 EP - 3499 VL - 54 IS - 13 SN - 0008-5472, 0008-5472 KW - Butyrates KW - 0 KW - Glycerides KW - Prodrugs KW - Triglycerides KW - Butyric Acid KW - 107-92-6 KW - 1-butyrylglycerol KW - 26999-06-4 KW - tributyrin KW - S05LZ624MF KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Drug Interactions KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Friend murine leukemia virus KW - Cell Differentiation -- drug effects KW - Cell Line KW - Triglycerides -- administration & dosage KW - Triglycerides -- pharmacology KW - Leukemia, Myeloid -- drug therapy KW - Butyrates -- administration & dosage KW - Prodrugs -- pharmacology KW - Butyrates -- pharmacology KW - Leukemia, Erythroblastic, Acute -- drug therapy KW - Leukemia, Erythroblastic, Acute -- pathology KW - Leukemia, Myeloid -- pathology KW - Glycerides -- pharmacology KW - Prodrugs -- administration & dosage KW - Glycerides -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76561636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tributyrin%3A+a+prodrug+of+butyric+acid+for+potential+clinical+application+in+differentiation+therapy.&rft.au=Chen%2C+Z+X%3BBreitman%2C+T+R&rft.aulast=Chen&rft.aufirst=Z&rft.date=1994-07-01&rft.volume=54&rft.issue=13&rft.spage=3494&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 - 1994-07-27 N1 - Date created - 1994-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development and characterization of nontumorigenic and tumorigenic epithelial cell lines from rat dorsal-lateral prostate. AN - 76558559; 8012960 AB - We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirements for optimal growth. Growth of NRP-154 cells is stimulated by dexamethasone and insulin, inhibited by transforming growth factor beta 1, but not significantly altered by epidermal growth factor, cholera toxin, dihydrotestosterone, retinoic acid, or 1 alpha,25-dihydroxyvitamin D3. Our data suggest that the NRP-152 and NRP-154 cell lines are suitable systems for analysis of normal prostate growth and prostatic carcinogenesis. JF - Cancer research AU - Danielpour, D AU - Kadomatsu, K AU - Anzano, M A AU - Smith, J M AU - Sporn, M B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 3413 EP - 3421 VL - 54 IS - 13 SN - 0008-5472, 0008-5472 KW - Receptors, Androgen KW - 0 KW - Transforming Growth Factor beta KW - Dihydrotestosterone KW - 08J2K08A3Y KW - Tretinoin KW - 5688UTC01R KW - Methylnitrosourea KW - 684-93-5 KW - Acid Phosphatase KW - EC 3.1.3.2 KW - Calcitriol KW - FXC9231JVH KW - Index Medicus KW - Karyotyping KW - Tretinoin -- pharmacology KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Receptors, Androgen -- analysis KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Calcitriol -- pharmacology KW - Rats KW - Acid Phosphatase -- analysis KW - Tumor Cells, Cultured KW - Dihydrotestosterone -- pharmacology KW - Rats, Wistar KW - Epithelium KW - Cell Line KW - Male KW - Prostatic Neoplasms -- chemistry KW - Prostatic Neoplasms -- pathology KW - Prostate -- drug effects KW - Prostate -- chemistry KW - Prostatic Neoplasms -- chemically induced KW - Prostate -- enzymology KW - Prostatic Neoplasms -- enzymology KW - Prostate -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76558559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+and+characterization+of+nontumorigenic+and+tumorigenic+epithelial+cell+lines+from+rat+dorsal-lateral+prostate.&rft.au=Danielpour%2C+D%3BKadomatsu%2C+K%3BAnzano%2C+M+A%3BSmith%2C+J+M%3BSporn%2C+M+B&rft.aulast=Danielpour&rft.aufirst=D&rft.date=1994-07-01&rft.volume=54&rft.issue=13&rft.spage=3413&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 - 1994-07-27 N1 - Date created - 1994-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo radiation protection by nitric oxide modulation. AN - 76558170; 7516820 AB - Drugs that affect blood flow have been shown to be whole body radiation protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. NG-Nitro-L-arginine given to mice between 15 and 60 min prior to radiation afforded significant protection from whole body irradiation, e.g., the estimated whole body irradiation dose required to kill 50% of mice by 30 days after radiation (LD50/30) in mice treated with NG-nitro-L-arginine 60 min before irradiation was 1051 cGy compared with a whole body radiation LD50/30 of 822 cGy in control mice (P < 0.00001). Treatment of mice with DEA/NO prior to whole body irradiation also significantly reduced toxicity; the estimated whole body radiation LD50/30 was 1063 and 945 cGy in mice treated with DEA/NO 10 or 30 min before irradiation, respectively (P < 0.00001 for radiation LD50/30 of either DEA/NO-treated group compared with control). Measurement of [14C]etanidazole binding to bone marrow demonstrated that DEA/NO and NG-nitro-L-arginine exacerbated bone marrow hypoxia. Perturbations of NO levels have profound effects on in vivo radiosensitivity of normal tissues. We hypothesize that alterations in regional blood flow may underlie the changes in radiosensitivity that we have observed. JF - Cancer research AU - Liebmann, J AU - DeLuca, A M AU - Coffin, D AU - Keefer, L K AU - Venzon, D AU - Wink, D A AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 3365 EP - 3368 VL - 54 IS - 13 SN - 0008-5472, 0008-5472 KW - Nitroarginine KW - 2149-70-4 KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Index Medicus KW - Radiation Dosage KW - Animals KW - Whole-Body Irradiation KW - Mice, Inbred C3H KW - Mice KW - Female KW - Amino Acid Oxidoreductases -- antagonists & inhibitors KW - Nitric Oxide -- physiology KW - Radiation Tolerance -- physiology KW - Nitric Oxide -- biosynthesis KW - Arginine -- analogs & derivatives KW - Arginine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76558170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+protection+by+nitric+oxide+modulation.&rft.au=Liebmann%2C+J%3BDeLuca%2C+A+M%3BCoffin%2C+D%3BKeefer%2C+L+K%3BVenzon%2C+D%3BWink%2C+D+A%3BMitchell%2C+J+B&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1994-07-01&rft.volume=54&rft.issue=13&rft.spage=3365&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 - 1994-07-27 N1 - Date created - 1994-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fewer dopamine transporter receptors in the prefrontal cortex of cocaine users. AN - 76546396; 8010366 AB - The authors investigated dopamine transporter receptor binding in the post-mortem prefrontal cortex of 13 subjects with histories of cocaine use who had positive blood screens for cocaine at autopsy and 13 comparison subjects with no history of cocaine use and negative blood screens for cocaine at autopsy. Synaptosomes from pulverized prefrontal cortex were assayed with [3H]GBR 12935 for dopamine transporter receptor. There was a 38% decrease in number of binding sites but no change in affinity constants in the cocaine users. JF - The American journal of psychiatry AU - Hitri, A AU - Casanova, M F AU - Kleinman, J E AU - Wyatt, R J AD - Neuropsychiatry Branch, NIMH Neuroscience Center, St. Elizabeths Hospital, Washington, D.C. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 1074 EP - 1076 VL - 151 IS - 7 SN - 0002-953X, 0002-953X KW - Ligands KW - 0 KW - Piperazines KW - Receptors, Dopamine KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Cocaine KW - I5Y540LHVR KW - Abridged Index Medicus KW - Index Medicus KW - Down-Regulation KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Piperazines -- metabolism KW - Male KW - Female KW - Frontal Lobe -- metabolism KW - Receptors, Dopamine -- analysis KW - Substance-Related Disorders -- metabolism KW - Cocaine -- metabolism KW - Frontal Lobe -- chemistry KW - Receptors, Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76546396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Fewer+dopamine+transporter+receptors+in+the+prefrontal+cortex+of+cocaine+users.&rft.au=Hitri%2C+A%3BCasanova%2C+M+F%3BKleinman%2C+J+E%3BWyatt%2C+R+J&rft.aulast=Hitri&rft.aufirst=A&rft.date=1994-07-01&rft.volume=151&rft.issue=7&rft.spage=1074&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-15 N1 - Date created - 1994-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette smoking, premature rupture of membranes, and vertical transmission of HIV-1 among women with low CD4+ levels. AN - 76542946; 7911527 AB - To examine the possible influence of obstetric factors, substance use during pregnancy, and other maternal factors on the relationship between a low maternal CD4+ level and vertical transmission of human immunodeficiency virus type 1 (HIV-1), data were analyzed from the Mothers and Infants Cohort Study, a prospective cohort followed for up to 4 years between 1986 and 1992 in Brooklyn and the Bronx, New York. The overall transmission rate for the cohort was 25.1% (95% confidence interval (CI) = 19.0-31.3). Prenatal CD4+ lymphocyte measurements were available for 162 HIV-seropositive mothers of infants with known infection outcomes. Among mothers who smoked cigarettes after the first trimester, those whose mean prenatal CD4+ level was < 20% had more than a threefold increased risk of transmitting their infection to their infants [relative risk (RR) = 3.30; 95% CI = 1.46-7.44; p = 0.004]. Among mothers who developed premature rupture of membranes, those with a low CD4+ level had a similarly increased risk of vertical transmission (RR = 4.33; 95% CI = 1.78-10.5; p = 0.003). These relative risks were much higher than those for mothers who did not smoke after the first trimester (RR = 1.14; 95% CI = 0.48-2.70; p = 0.76) or have premature rupture of membranes (RR = 1.29; 95% CI = 0.61-2.74; p = 0.50), indicating that these factors modified the effect of CD4+ level on transmission. Among all mothers without regard to CD4+ level, those who experienced preterm premature rupture of membranes were also at greater risk of transmission (RR = 2.24; 95% CI = 1.07-4.69; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Journal of acquired immune deficiency syndromes AU - Burns, D N AU - Landesman, S AU - Muenz, L R AU - Nugent, R P AU - Goedert, J J AU - Minkoff, H AU - Walsh, J H AU - Mendez, H AU - Rubinstein, A AU - Willoughby, A AD - Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Rockville, MD 20852. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 718 EP - 726 VL - 7 IS - 7 SN - 0894-9255, 0894-9255 KW - HIV Antibodies KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - HIV Antibodies -- blood KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Infant, Newborn KW - Follow-Up Studies KW - Substance Abuse, Intravenous -- complications KW - Alcohol Drinking KW - Female KW - Pregnancy KW - Pregnancy Complications, Infectious -- immunology KW - Fetal Membranes, Premature Rupture -- complications KW - HIV Infections -- transmission KW - Fetal Membranes, Premature Rupture -- immunology KW - HIV Infections -- immunology KW - Smoking -- immunology KW - HIV-1 KW - CD4-Positive T-Lymphocytes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76542946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes&rft.atitle=Cigarette+smoking%2C+premature+rupture+of+membranes%2C+and+vertical+transmission+of+HIV-1+among+women+with+low+CD4%2B+levels.&rft.au=Burns%2C+D+N%3BLandesman%2C+S%3BMuenz%2C+L+R%3BNugent%2C+R+P%3BGoedert%2C+J+J%3BMinkoff%2C+H%3BWalsh%2C+J+H%3BMendez%2C+H%3BRubinstein%2C+A%3BWilloughby%2C+A&rft.aulast=Burns&rft.aufirst=D&rft.date=1994-07-01&rft.volume=7&rft.issue=7&rft.spage=718&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes&rft.issn=08949255&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-12 N1 - Date created - 1994-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV, drug-use paraphernalia, and bleach. AN - 76533665; 8207656 JF - Journal of acquired immune deficiency syndromes AU - Haverkos, H W AU - Jones, T S AD - National Institute on Drug Abuse, Rockville, Maryland 20857. Y1 - 1994/07// PY - 1994 DA - July 1994 SP - 741 EP - 742 VL - 7 IS - 7 SN - 0894-9255, 0894-9255 KW - Sodium Hypochlorite KW - DY38VHM5OD KW - Index Medicus KW - AIDS/HIV KW - Needles KW - Humans KW - Syringes KW - Disinfection KW - HIV Infections -- prevention & control KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76533665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes&rft.atitle=HIV%2C+drug-use+paraphernalia%2C+and+bleach.&rft.au=Haverkos%2C+H+W%3BJones%2C+T+S&rft.aulast=Haverkos&rft.aufirst=H&rft.date=1994-07-01&rft.volume=7&rft.issue=7&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes&rft.issn=08949255&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-12 N1 - Date created - 1994-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the TCA3 gene in mast cells after Fc epsilon RI cross-linking. AN - 76530223; 8207245 AB - TCA3 is a pro-inflammatory cytokine expressed in mast cells after activation. To examine how this gene is regulated, TCA3 mRNA levels were examined and nuclear run-on experiments and promoter analysis were performed. Northern blot analysis showed that TCA3 message appeared in mast cells within 2 h after induction, with a t1/2 of 30 min. Nuclear run-on experiments revealed that the appearance of TCA3 mRNA occurred in large part because of an increase in the level of de novo transcription. Analysis of the promoter region demonstrated that inducible gene expression was directed by a region extending between 1.324 kb and 0.082 kb upstream from the transcription start site. There was a 60- to 80-fold induction with TCA3 CAT constructs extending between 1.324 kb and 0.324 kb upstream from the transcription start site after treatment with PMA/A23187 and a 30- to 40-fold induction with Fc epsilon RI cross-linking. There was a seven- to eightfold induction with the region extending between 0.136 kb and 0.082 kb upstream from the transcription start site. TCA3 CAT constructs containing regions encompassing either the 0.042 kb or 2.0 kb sequence from the transcription start site were not able to direct CAT-protein synthesis. The TCA3 5' flanking sequence contained negative regulatory activity. Electrophoretic mobility shift assays revealed that protein in nuclear extracts of activated mast cells bound to an NF-kappa B element of the TCA3 gene. These findings demonstrate that the TCA3 gene is regulated transcriptionally in mast cells, with minimal promoter sequences contained within the 0.082 kb upstream region of the TCA3 gene; a putative enhancer NF-kappa B element is contained between 0.324 kb and 0.136 kb and a putative inhibitory element is contained between 1.324 kb and 2.0 kb upstream from the transcription start site. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Oh, C K AU - Metcalfe, D D AD - Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/07/01/ PY - 1994 DA - 1994 Jul 01 SP - 325 EP - 332 VL - 153 IS - 1 SN - 0022-1767, 0022-1767 KW - CCL1 protein, human KW - 0 KW - Chemokine CCL1 KW - Chemokines, CC KW - Cytokines KW - NF-kappa B KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Receptors, IgE KW - Calcimycin KW - 37H9VM9WZL KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Sequence Homology, Nucleic Acid KW - Receptor Aggregation KW - Calcimycin -- pharmacology KW - RNA, Messenger -- genetics KW - Promoter Regions, Genetic KW - Base Sequence KW - Genes KW - Sequence Alignment KW - Oligodeoxyribonucleotides -- chemistry KW - Calcium -- physiology KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Consensus Sequence KW - Signal Transduction KW - Cell Line KW - Sequence Deletion KW - NF-kappa B -- metabolism KW - Cytokines -- genetics KW - Mast Cells -- physiology KW - Receptors, IgE -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76530223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Transcriptional+regulation+of+the+TCA3+gene+in+mast+cells+after+Fc+epsilon+RI+cross-linking.&rft.au=Oh%2C+C+K%3BMetcalfe%2C+D+D&rft.aulast=Oh&rft.aufirst=C&rft.date=1994-07-01&rft.volume=153&rft.issue=1&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-13 N1 - Date created - 1994-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-la Reduces the Severity of the Vascular Leak Syndrome Produced by Interleukin-2 and Interleukin-2 Plus Interferon-a AN - 762277927; 13645561 AB - Histological and ultrastructural changes were investigated in lung, liver, and heart of mice given interleukin-2 (IL-2), either alone or in combination with other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree with infiltration of lymphoid cells, moderate endothelial damage. mild hepatic parenchymal damage, and minimal myocardial alterations. Interferon-a (IFN-a) produced infiltration mainly of monocytes/macrophages in liver and heart; endothelial cell damage was absent in lung and heart and minimal in liver. Interleukin-1a (IL-1a) caused an increased number of neutrophils in liver and lung; VLS and parenchymal cell and endothelial damage were not found. The VLS and the cellular damage caused by the combination of IL-2 and IFN were much more severe than those produced by IL-2 alone. In animals treated with IL-2, IFN-a, and IL-1a, VLS was minimal and parenchymal and endothelial cell damage were less severe than after IL-2 alone or IL-2 plus IFN-a. Taken together, these observations show that IL-1a reduces ultrastructural changes produced by IL-2 and IFN-a. This reduction may be clinically useful in the treatment of neoplasms. JF - Toxicologic Pathology AU - Fujita, Shinsuke AU - Puri, Raj AU - Yu, Zu-Xi AU - Travis, William AU - Yamaguchi, Maria AU - Ferrans, Victor J AD - Pathology Branch, National Heart Lung and Blood Institute, National Institutes of Health Y1 - 1994/07// PY - 1994 DA - Jul 1994 SP - 381 EP - 397 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 22 IS - 4 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts; Immunology Abstracts KW - Macrophages KW - Lymphoid cells KW - Heart KW - vascular leak syndrome KW - Interleukin 2 KW - Interleukin 1 KW - Leukocytes (neutrophilic) KW - Endothelial cells KW - Interferon KW - Lung KW - Liver KW - Monocytes KW - a-Interferon KW - F 06955:Immunomodulation & Immunopharmacology KW - X 24490:Other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762277927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Interleukin-la+Reduces+the+Severity+of+the+Vascular+Leak+Syndrome+Produced+by+Interleukin-2+and+Interleukin-2+Plus+Interferon-a&rft.au=Fujita%2C+Shinsuke%3BPuri%2C+Raj%3BYu%2C+Zu-Xi%3BTravis%2C+William%3BYamaguchi%2C+Maria%3BFerrans%2C+Victor+J&rft.aulast=Fujita&rft.aufirst=Shinsuke&rft.date=1994-07-01&rft.volume=22&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339402200404 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-10-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Heart; Lymphoid cells; Macrophages; Interleukin 2; vascular leak syndrome; Interleukin 1; Leukocytes (neutrophilic); Endothelial cells; Interferon; Lung; Liver; Monocytes; a-Interferon DO - http://dx.doi.org/10.1177/019262339402200404 ER - TY - JOUR T1 - New pharmacological strategies for cognitive enhancement using a rat model of age-related memory impairment. AN - 76589402; 8030831 AB - We have developed the Stone maze paradigm for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Evidence produced thus far clearly implicates both the cholinergic and glutamatergic systems in acquisition performance in this complex maze task. Although results have been very inconsistent regarding the cognitive enhancing abilities of cholinomimetics for use in Alzheimer's disease, new classes of cholinesterase inhibitors may offer greater therapeutic efficacy. The use of glycine and polyamine agonists appears to be a viable strategy for positive modulation of the NMDA receptor. In addition, an approach that combines stimulation both of cholinergic and glutamatergic systems may have greater potential than agonism of either separately. Manipulation of signal transduction events might also have potential for cognitive enhancement. The influx of Ca2+ through the NMDA receptor stimulates production of NO via the action of NOS. By using NARG to block NOS activity, we have demonstrated in rats that NO production appears to influence learning in the Stone maze. We are currently exploring the age-related changes in NOS activity in specific brain regions of rats to determine if loss in the NO generating system is related to age-related memory impairment observed in the Stone maze. In addition, we are exploring pharmacological strategies for inducing NO production; however, because of the potential neurotoxicity for NO overstimulation, this strategy will present some obstacles. The identification of NO as a simple molecule serving vital physiological functions but representing potential for neurotoxicity presents an important unifying area for neurobiological investigations searching for mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease. JF - Annals of the New York Academy of Sciences AU - Ingram, D K AU - Spangler, E L AU - Iijima, S AU - Kuo, H AU - Bresnahan, E L AU - Greig, N H AU - London, E D AD - Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224. Y1 - 1994/06/30/ PY - 1994 DA - 1994 Jun 30 SP - 16 EP - 32 VL - 717 SN - 0077-8923, 0077-8923 KW - Parasympathomimetics KW - 0 KW - Receptors, Cholinergic KW - Receptors, N-Methyl-D-Aspartate KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Rats KW - Aging -- physiology KW - Animals KW - Parasympathomimetics -- pharmacology KW - Receptors, Cholinergic -- drug effects KW - Humans KW - Alzheimer Disease -- physiopathology KW - Alzheimer Disease -- drug therapy KW - Nitric Oxide -- metabolism KW - Disease Models, Animal KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, Cholinergic -- metabolism KW - Neuropsychological Tests KW - Cognition -- physiology KW - Cognition -- drug effects KW - Memory Disorders -- physiopathology KW - Memory Disorders -- drug therapy KW - Memory Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76589402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+pharmacological+strategies+for+cognitive+enhancement+using+a+rat+model+of+age-related+memory+impairment.&rft.au=Ingram%2C+D+K%3BSpangler%2C+E+L%3BIijima%2C+S%3BKuo%2C+H%3BBresnahan%2C+E+L%3BGreig%2C+N+H%3BLondon%2C+E+D&rft.aulast=Ingram&rft.aufirst=D&rft.date=1994-06-30&rft.volume=717&rft.issue=&rft.spage=16&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 - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between cytochrome P450 2B1 and cytochrome bs: inhibition by synthetic peptides indicates a role for P450 residues Lys-122 and Arg-125. AN - 76567855; 8024550 AB - Binding of cytochrome b5 to rat cytochrome P450 2B1 was inhibited (by 75%) by a synthetic peptide corresponding to P450 residues 116-134. The role of Lys-122 and Arg-125 were evaluated using peptides in which one or both of these basic residues were replaced with Glu. The Lys-122 substitution nearly abolished while the Arg-125 replacement decreased (by 20%) the inhibitory potential of the peptide. Substitution of both residues resulted in a peptide with no inhibitory activity. These results thus indicate a role for a specific P450 region as well as two basic residues within this region in the cytochrome P450-cytochrome b5 interaction. JF - Biochemical and biophysical research communications AU - Omata, Y AU - Sakamoto, H AU - Robinson, R C AU - Pincus, M R AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06/30/ PY - 1994 DA - 1994 Jun 30 SP - 1090 EP - 1095 VL - 201 IS - 3 SN - 0006-291X, 0006-291X KW - Peptides KW - 0 KW - Cytochromes b5 KW - 9035-39-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Arginine KW - 94ZLA3W45F KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - steroid 16-beta-hydroxylase KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Lysine -- chemistry KW - Arginine -- chemistry KW - Microsomes, Liver -- metabolism KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Amino Acid Sequence KW - Protein Binding KW - Male KW - Cytochromes b5 -- metabolism KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- metabolism KW - Steroid Hydroxylases -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76567855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+between+cytochrome+P450+2B1+and+cytochrome+bs%3A+inhibition+by+synthetic+peptides+indicates+a+role+for+P450+residues+Lys-122+and+Arg-125.&rft.au=Omata%2C+Y%3BSakamoto%2C+H%3BRobinson%2C+R+C%3BPincus%2C+M+R%3BFriedman%2C+F+K&rft.aulast=Omata&rft.aufirst=Y&rft.date=1994-06-30&rft.volume=201&rft.issue=3&rft.spage=1090&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 - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for molecular genetics in biological conservation. AN - 76564872; 7912434 AB - The recognition of recent accelerated depletion of species as a consequence of human industrial development has spawned a wide interest in identifying threats to endangered species. In addition to ecological and demographic perils, it has become clear that small populations that narrowly survive demographic contraction may undergo close inbreeding, genetic drift, and loss of overall genomic variation due to allelic loss or reduction to homozygosity. I review here the consequences of such genetic depletion revealed by applying molecular population genetic analysis to four endangered mammals: African cheetah, lion, Florida panther, and humpback whale. The accumulated genetic results, combined with physiological, ecological, and ethological data, provide a multifaceted perspective of the process of species diminution. An emerging role of population genetics, phylogenetics, and phylogeography as indicators of a population's natural history and its future prognosis provides valuable data of use in the development of conservation management plans for endangered species. JF - Proceedings of the National Academy of Sciences of the United States of America AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201. Y1 - 1994/06/21/ PY - 1994 DA - 1994 Jun 21 SP - 5748 EP - 5755 VL - 91 IS - 13 SN - 0027-8424, 0027-8424 KW - DNA, Mitochondrial KW - 0 KW - Index Medicus KW - Animals KW - Fertility KW - Polymorphism, Restriction Fragment Length KW - Whales -- genetics KW - Lions -- genetics KW - Africa KW - Inbreeding KW - Florida KW - Male KW - Female KW - DNA, Mitochondrial -- genetics KW - Animals, Wild KW - Phylogeny KW - Carnivora -- genetics KW - Molecular Biology KW - Conservation of Natural Resources UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76564872?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+role+for+molecular+genetics+in+biological+conservation.&rft.au=O%27Brien%2C+S+J&rft.aulast=O%27Brien&rft.aufirst=S&rft.date=1994-06-21&rft.volume=91&rft.issue=13&rft.spage=5748&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 - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1992 Oct;66(10):6008-18 [1382145] Nature. 1992 May 28;357(6376):274-6 [1589032] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3172-6 [8475057] J Hered. 1993 Jul-Aug;84(4):281-90 [8340617] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8239-43 [8367488] J Hered. 1993 Nov-Dec;84(6):443-9 [7505788] Genetics. 1966 Aug;54(2):595-609 [5968643] Science. 1974 May 24;184(4139):908-9 [4825892] J Mol Evol. 1973 Nov 27;2(4):323-8 [4807198] Science. 1979 Nov 30;206(4422):1101-3 [493997] Nature. 1983 Oct 27-Nov 2;305(5937):771-5 [6355856] Biol Reprod. 1983 Nov;29(4):1019-25 [6640033] Science. 1985 Mar 22;227(4693):1428-34 [2983425] Nature. 1987 Jan 1-7;325(6099):31-6 [3025745] Biol Reprod. 1987 Mar;36(2):351-60 [3580457] N Engl J Med. 1988 Mar 24;318(12):727-32 [3347221] Science. 1988 Sep 16;241(4872):1455-60 [3420403] Mol Biol Evol. 1988 Sep;5(5):584-99 [3193879] Science. 1989 Mar 24;243(4898):1549-51 [2928790] Proc Natl Acad Sci U S A. 1989 Dec;86(23):9350-4 [2594772] Proc Natl Acad Sci U S A. 1990 Jan;87(2):836-40 [1967831] Nature. 1990 Mar 15;344(6263):238-40 [1969116] J Virol. 1990 May;64(5):1964-72 [2157864] J Hered. 1991 Sep-Oct;82(5):378-86 [1940281] Science. 1992 Feb 21;255(5047):940 [1546290] Science. 1992 Dec 11;258(5089):1739-40 [1465610] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RNase inhibition of human immunodeficiency virus infection of H9 cells. AN - 76561307; 8016107 AB - Onconase and bovine seminal RNase, two members of the RNase A superfamily, inhibit human immunodeficiency virus type 1 replication in H9 leukemia cells 90-99.9% over a 4-day incubation at concentrations not toxic to uninfected H9 cells. Two other members of the same protein family, bovine pancreatic RNase A and human eosinophil-derived neurotoxin, have no detectable antiviral activity, demonstrating a strikingly selective antiviral activity among homologous ribonucleases. The antiviral RNases do not appear to affect viral particles directly but inhibit replication in host cell cultures. Onconase, already in clinical trials for cancer therapy, and bovine seminal RNase have potential as antiviral therapeutics. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Youle, R J AU - Wu, Y N AU - Mikulski, S M AU - Shogen, K AU - Hamilton, R S AU - Newton, D AU - D'Alessio, G AU - Gravell, M AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06/21/ PY - 1994 DA - 1994 Jun 21 SP - 6012 EP - 6016 VL - 91 IS - 13 SN - 0027-8424, 0027-8424 KW - Antineoplastic Agents KW - 0 KW - Antiviral Agents KW - Egg Proteins KW - Ribonucleases KW - EC 3.1.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Semen -- enzymology KW - Dose-Response Relationship, Drug KW - Humans KW - Leukemia KW - Cattle KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Kinetics KW - Antineoplastic Agents -- toxicity KW - Time Factors KW - Cell Line KW - Male KW - Ribonucleases -- toxicity KW - Virus Replication -- drug effects KW - Ribonuclease, Pancreatic -- toxicity KW - HIV-1 -- physiology KW - Egg Proteins -- toxicity KW - HIV-1 -- drug effects KW - Antiviral Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76561307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=RNase+inhibition+of+human+immunodeficiency+virus+infection+of+H9+cells.&rft.au=Youle%2C+R+J%3BWu%2C+Y+N%3BMikulski%2C+S+M%3BShogen%2C+K%3BHamilton%2C+R+S%3BNewton%2C+D%3BD%27Alessio%2C+G%3BGravell%2C+M&rft.aulast=Youle&rft.aufirst=R&rft.date=1994-06-21&rft.volume=91&rft.issue=13&rft.spage=6012&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 - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: AIDS. 1990 Dec;4(12):1189-96 [2128454] Science. 1988 Nov 25;242(4882):1166-8 [2847316] Trends Biochem Sci. 1991 Mar;16(3):104-6 [2057997] Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6570-4 [1713684] J Biol Chem. 1991 Nov 5;266(31):21202-7 [1939162] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2844-8 [2704750] J Immunol. 1989 May 1;142(9):3070-5 [2540236] J Natl Cancer Inst. 1990 Jan 17;82(2):151-3 [2294226] J Immunol. 1990 Feb 15;144(4):1257-62 [2303707] Cell Tissue Kinet. 1990 May;23(3):237-46 [2357721] Nature. 1990 Sep 6;347(6288):92-5 [1975641] FEBS Lett. 1990 Oct 15;272(1-2):12-8 [1699801] J Clin Invest. 1990 Nov;86(5):1684-9 [2243139] J Biol Chem. 1991 Jan 5;266(1):245-51 [1985896] Antimicrob Agents Chemother. 1990 Oct;34(10):2034-7 [1963293] J Biol Chem. 1991 Nov 5;266(31):21208-14 [1939163] Biochem J. 1992 Jan 15;281 ( Pt 2):343-8 [1736883] J Biol Chem. 1992 Jul 25;267(21):14859-65 [1634526] J Biol Chem. 1992 Sep 25;267(27):19572-8 [1527074] Proteins. 1992 Nov;14(3):392-400 [1438177] Res Exp Med (Berl). 1993;193(1):1-12 [8446767] Cell. 1993 Mar 12;72(5):753-65 [7680958] Crit Rev Ther Drug Carrier Syst. 1993;10(1):1-28 [8472310] J Biol Chem. 1993 May 15;268(14):10686-93 [8486718] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7089-93 [8346221] J Neurosci. 1994 Feb;14(2):538-44 [8301353] Phytopathology. 1969 Dec;59(12):1787-94 [5377747] Eur J Biochem. 1972 Mar 27;26(2):153-61 [5046038] Nature. 1974 Feb 22;247(5442):577 [4818560] J Gen Virol. 1974 Feb;22(2):225-32 [4206833] Arch Biochem Biophys. 1975 Aug;169(2):522-8 [1180561] Virology. 1979 May;95(1):218-21 [220792] Cell. 1980 Jul;20(3):769-75 [6251972] J Biol Chem. 1980 Nov 25;255(22):10959-65 [6253494] Cancer Res. 1980 Oct;40(10):3740-4 [7438057] FEBS Lett. 1982 Nov 1;148(1):127-30 [6293872] Cell. 1983 Feb;32(2):607-17 [6130853] Adv Immunol. 1986;39:177-253 [3538819] Biol Chem Hoppe Seyler. 1987 Oct;368(10):1305-12 [3426801] Biochem Biophys Res Commun. 1988 Feb 15;150(3):1032-6 [3342056] Nature. 1988 Sep 22;335(6188):369-72 [2843774] AIDS. 1990 Dec;4(12):1197-204 [2088398] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of human immunodeficiency virus type 1 integrase by 3'-azido-3'-deoxythymidylate. AN - 76561054; 8016063 AB - The effects of 3'-azido-3'-deoxythymidine (AZT) and three of its intracellular metabolites, azido- thymidine mono-, di-, and triphosphates, on the human immunodeficiency virus type 1 integrase have been determined. AZT mono-, di-, and triphosphate have an IC50 for integration between 110 and 150 microM, whereas AZT does not inhibit the integrase. The inhibition by AZT monophosphate can be partially reversed by coincubation with either thymidine monophosphate or 2',3'-dideoxythymidine monophosphate, suggesting that either of these monophosphates can bind to the integrase but that the azido group at the 3' position could be responsible for the inhibition. Integrase inhibition is associated with reduced enzyme-DNA binding but does not appear to be competitive with respect to the DNA substrate. Inhibition of an integrase deletion mutant containing only amino acids 50-212 suggests that these nucleotides bind in the catalytic core. Concentrations up to 1 mM AZT monophosphate can accumulate in vivo, indicating that integrase inhibition may contribute to the antiviral effects of AZT. The increasing incidence of AZT-resistant virus strains may, therefore, be associated with mutations not only in the reverse transcriptase but also in the human immunodeficiency virus integrase. Finally, these observations suggest that additional strategies for antiviral drug development could be based upon nucleotide analogs as inhibitors of human immunodeficiency virus integrase. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Mazumder, A AU - Cooney, D AU - Agbaria, R AU - Gupta, M AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/06/21/ PY - 1994 DA - 1994 Jun 21 SP - 5771 EP - 5775 VL - 91 IS - 13 SN - 0027-8424, 0027-8424 KW - Dideoxynucleotides KW - 0 KW - Oligodeoxyribonucleotides KW - Recombinant Proteins KW - Thymine Nucleotides KW - 3'-azido-3'-deoxythymidine 5'phosphate KW - 29706-85-2 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - DNA Nucleotidyltransferases KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Oligodeoxyribonucleotides -- chemistry KW - Kinetics KW - DNA -- metabolism KW - Molecular Sequence Data KW - Substrate Specificity KW - Oligodeoxyribonucleotides -- metabolism KW - Virus Integration KW - Recombinant Proteins -- antagonists & inhibitors KW - Sequence Deletion KW - Mutagenesis KW - Zidovudine -- analogs & derivatives KW - HIV-1 -- genetics KW - Zidovudine -- pharmacology KW - Thymine Nucleotides -- pharmacology KW - DNA Nucleotidyltransferases -- antagonists & inhibitors KW - HIV-1 -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76561054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+human+immunodeficiency+virus+type+1+integrase+by+3%27-azido-3%27-deoxythymidylate.&rft.au=Mazumder%2C+A%3BCooney%2C+D%3BAgbaria%2C+R%3BGupta%2C+M%3BPommier%2C+Y&rft.aulast=Mazumder&rft.aufirst=A&rft.date=1994-06-21&rft.volume=91&rft.issue=13&rft.spage=5771&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 - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] Mol Pharmacol. 1990 May;37(5):665-70 [2338944] Nucleic Acids Res. 1991 May 25;19(10):2729-34 [2041748] Biochem Pharmacol. 1991 Jul 25;42(4):905-11 [1867645] Cell. 1991 Dec 20;67(6):1211-21 [1760846] Nucleic Acids Res. 1991 Dec 25;19(24):6691-8 [1662361] Science. 1992 Feb 7;255(5045):723-6 [1738845] J Med Virol. 1992 Feb;36(2):79-83 [1374791] Science. 1992 Jun 26;256(5065):1783-90 [1377403] J Biol Chem. 1992 Aug 5;267(22):15789-94 [1379238] Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6741-5 [1323118] J Acquir Immune Defic Syndr. 1992;5(8):749-59 [1381438] J Virol. 1993 Feb;67(2):1127-31 [8419642] Annu Rev Genet. 1992;26:527-44 [1482125] Mol Pharmacol. 1993 Jan;43(1):57-63 [8380884] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2399-403 [8460151] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3428-32 [8386373] Biochem Pharmacol. 1993 Apr 22;45(8):1571-6 [8387298] Science. 1993 May 28;260(5112):1286-93 [7684163] Antimicrob Agents Chemother. 1993 Apr;37(4):918-20 [8388206] Biochem Biophys Res Commun. 1993 May 14;192(3):1409-14 [8389550] Biochemistry. 1993 Jun 15;32(23):6002-10 [7685186] Cell. 1984 Jul;37(3):1043-52 [6204767] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6461-5 [6208550] Proc Natl Acad Sci U S A. 1984 Dec;81(24):7885-9 [6083562] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333-7 [2430286] Biochem Biophys Res Commun. 1988 Jul 15;154(1):124-9 [3164996] Science. 1989 Mar 31;243(4899):1731-4 [2467383] Mol Pharmacol. 1989 Jul;36(1):9-14 [2747633] Science. 1989 Dec 1;246(4934):1155-8 [2479983] Biochem Biophys Res Commun. 1990 Jan 15;166(1):273-9 [2405846] Biochemistry. 1991 May 21;30(20):4831-5 [1709809] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single amino acid change in Raf-1 inhibits Ras binding and alters Raf-1 function. AN - 76557407; 8016101 AB - Ras and Raf-1 are key proteins involved in the transmission of developmental and proliferative signals generated by receptor and nonreceptor tyrosine kinases. Genetic and biochemical studies demonstrate that Raf-1 functions downstream of Ras in many signaling pathways. Although Raf-1 directly associates with GTP-bound Ras, an effect of this interaction on Raf-1 activity in vivo has not been established. To examine the biological consequence of the Ras/Raf-1 interaction in vivo, we set out to identify key residues of Raf-1 required for Ras binding. In this report, we show that a single amino acid mutation in Raf-1 (Arg89 to Leu) disrupted the interaction with Ras in vitro and in the yeast two-hybrid system. This mutation prevented Ras-mediated but not tyrosine kinase-mediated enzymatic activation of Raf-1 in the baculovirus/Sf9 expression system. Furthermore, kinase-defective Raf-1 proteins containing the Arg89-->Leu mutation were no longer dominant-inhibitory or capable of blocking Ras-mediated signal transduction in Xenopus laevis oocytes. These results demonstrate that the association of Raf-1 and Ras modulates both the kinase activity and the biological function of Raf-1 and identify Arg89 as a critical residue involved in this interaction. In addition, the finding that tyrosine kinases can stimulate the enzymatic activity of Raf-1 proteins containing a mutation at the Ras-interaction site suggests that Raf-1 can be activated by Ras-independent pathways. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Fabian, J R AU - Vojtek, A B AU - Cooper, J A AU - Morrison, D K AD - Molecular Mechanisms of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/06/21/ PY - 1994 DA - 1994 Jun 21 SP - 5982 EP - 5986 VL - 91 IS - 13 SN - 0027-8424, 0027-8424 KW - Proto-Oncogene Proteins KW - 0 KW - Recombinant Fusion Proteins KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Arginine KW - 94ZLA3W45F KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Animals KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Oocytes -- physiology KW - Moths KW - Transcriptional Activation KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Xenopus laevis KW - Transfection KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Cell Line KW - Female KW - Signal Transduction KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Point Mutation KW - Protein-Serine-Threonine Kinases -- genetics KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76557407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+single+amino+acid+change+in+Raf-1+inhibits+Ras+binding+and+alters+Raf-1+function.&rft.au=Fabian%2C+J+R%3BVojtek%2C+A+B%3BCooper%2C+J+A%3BMorrison%2C+D+K&rft.aulast=Fabian&rft.aufirst=J&rft.date=1994-06-21&rft.volume=91&rft.issue=13&rft.spage=5982&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 - 1994-07-28 N1 - Date created - 1994-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1985 Dec;43(3 Pt 2):615-21 [2416466] J Biol Chem. 1994 Feb 11;269(6):3913-6 [8307946] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] Oncogene. 1990 Mar;5(3):345-51 [1690378] Mol Cell Biol. 1990 Oct;10(10):5324-32 [2118994] Nature. 1990 Nov 8;348(6297):125-32 [2122258] Nature. 1991 Jan 10;349(6305):117-27 [1898771] Cell. 1991 Jan 25;64(2):281-302 [1846320] Nature. 1991 Jan 31;349(6308):426-8 [1992343] Cancer Cells. 1990 Dec;2(12):377-82 [2150916] Oncogene. 1991 Apr;6(4):495-500 [2030909] Mol Cell Biol. 1991 Dec;11(12):5985-91 [1719375] Cell. 1992 Mar 20;68(6):1041-50 [1312393] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2922-6 [1372995] Genes Dev. 1992 Apr;6(4):545-56 [1313769] Oncogene. 1992 Sep;7(9):1867-73 [1386920] Nature. 1992 Dec 10;360(6404):534-5 [1334231] Nature. 1992 Dec 10;360(6404):600-3 [1461284] J Biol Chem. 1992 Dec 25;267(36):25628-31 [1281467] J Cell Biol. 1993 Mar;120(5):1197-202 [8436591] Nature. 1993 May 6;363(6424):15-6 [8479530] Nature. 1993 May 13;363(6425):133-40 [8483497] Cell. 1993 May 7;73(3):571-83 [7683975] Science. 1993 Jun 11;260(5114):1658-61 [8503013] Mol Cell Biol. 1993 Jul;13(7):4197-202 [8321223] Nature. 1993 Jul 15;364(6434):249-52 [8321321] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6213-7 [8327501] Nature. 1993 Jul 22;364(6435):308-13 [8332187] Nature. 1993 Jul 22;364(6435):352-5 [8332195] Cell. 1993 Jul 16;74(1):205-14 [8334704] J Cell Biol. 1993 Aug;122(3):645-52 [8335690] Nucleic Acids Res. 1984 Sep 25;12(18):7057-70 [6207484] Virology. 1985 Oct 15;146(1):78-89 [2994296] Cell. 1993 Jul 30;74(2):215-7 [8343948] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] Development. 1993 May;118(1):127-38 [8375330] J Biol Chem. 1993 Sep 25;268(27):20232-6 [8397201] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8683-6 [8378348] Mol Cell Biol. 1993 Nov;13(11):7133-43 [8413302] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10947-51 [8248196] Nature. 1986 Apr 10-16;320(6062):540-3 [2938016] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor. Identification of amino acid residues that determine binding of the antihypertensive drug losartan. AN - 76532351; 8206967 AB - The biphenylimidazole derivative losartan exemplifies a novel class of nonpeptide antagonists that selectively inhibit angiotensin II binding to the mammalian AT1 receptor and have potentially wide application as anti-hypertensive agents. In contrast to mammalian AT1 receptors, which have high affinity for both peptide antagonists and losartan, amphibian and avian angiotensin II receptors are pharmacologically distinct and recognize peptide but not nonpeptide antagonists. Mutant rat AT1 receptors in which non-conserved amino acids were replaced by the corresponding amphibian residues were constructed to identify specific sites in the AT1 receptor that determine losartan binding. Only minor changes in binding affinity for peptide antagonists were observed in COS-7 cells transiently expressing mutant receptors, indicating that the structural integrity of the receptor was maintained. However, analysis of receptors with single point and combined mutations revealed that specific residues in transmembrane domains III, IV, V, VI, and VII are involved in binding of the nonpeptide antagonist to the mammalian AT1 receptor. The most marked attenuation of losartan binding (IC50 > 50 microM) was observed in a mutant receptor containing amino acid substitutions at Val108, Ala163, Thr198, Ser252, Leu300, and Phe301. These results have demonstrated that the binding site of a potent nonpeptide antagonist of the AT1 receptor is defined by epitopes located within the membrane-spanning regions of the receptor and is distinct from the site at which peptide antagonists bind to the AT1 receptor. JF - The Journal of biological chemistry AU - Ji, H AU - Leung, M AU - Zhang, Y AU - Catt, K J AU - Sandberg, K AD - Endocrinology and Reproduction Research Branch, NICHHD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06/17/ PY - 1994 DA - 1994 Jun 17 SP - 16533 EP - 16536 VL - 269 IS - 24 SN - 0021-9258, 0021-9258 KW - Angiotensins KW - 0 KW - Biphenyl Compounds KW - Imidazoles KW - Receptors, Angiotensin KW - Recombinant Proteins KW - Tetrazoles KW - Angiotensin II KW - 11128-99-7 KW - Losartan KW - JMS50MPO89 KW - Index Medicus KW - Animals KW - Angiotensins -- pharmacology KW - Amino Acid Sequence KW - Angiotensins -- antagonists & inhibitors KW - Binding Sites KW - Cloning, Molecular KW - Rats KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Binding, Competitive KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Kidney KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Angiotensin II -- metabolism KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- metabolism KW - Tetrazoles -- metabolism KW - Imidazoles -- metabolism KW - Biphenyl Compounds -- metabolism KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76532351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+structural+requirements+for+specific+binding+of+nonpeptide+and+peptide+antagonists+to+the+AT1+angiotensin+receptor.+Identification+of+amino+acid+residues+that+determine+binding+of+the+antihypertensive+drug+losartan.&rft.au=Ji%2C+H%3BLeung%2C+M%3BZhang%2C+Y%3BCatt%2C+K+J%3BSandberg%2C+K&rft.aulast=Ji&rft.aufirst=H&rft.date=1994-06-17&rft.volume=269&rft.issue=24&rft.spage=16533&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 - 1994-07-14 N1 - Date created - 1994-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-Tac(Fab)-PE40, a recombinant double-chain immunotoxin which kills interleukin-2-receptor-bearing cells and induces complete remission in an in vivo tumor model. AN - 76535671; 8206679 AB - We have produced a single plasmid encoding both the heavy chain Fd domain (VH + CH1) of the anti-interleukin-2 receptor (IL2R) monoclonal antibody anti-Tac, and the anti-Tac light chain fused to PE40, a truncated derivative of Pseudomonas exotoxin. The active immunotoxin anti-Tac(Fab)-PE40 could be recovered from E. coli from either periplasm or renatured inclusion bodies. The double-chain immunotoxin was very cytotoxic toward IL2R-bearing cell lines, human activated T cells and fresh adult-T-cell-leukemia cells. The cytotoxicity was similar to that of anti-Tac(Fv)-PE40, the single-chain recombinant toxin containing only the variable domains of anti-Tac. IL2R-binding affinity was also equivalent to that of anti-Tac(Fv)-PE40, which is one-third that of anti-Tac. The serum half-life in mice was significantly prolonged as compared with anti-Tac(Fv)-PE40, with a beta phase of 430 vs. 57 minutes, but the LD50s were equivalent when the immunotoxins were administered in 3 daily doses. Anti-Tac(Fab)-PE40 was very cytotoxic in vitro toward transfected ATAC-4 carcinoma cells which express IL2Rs. In mice bearing ATAC-4 tumors, anti-Tac(Fab)-PE40 showed significant anti-tumor activity, inducing complete remissions in 80 and 100% of treated animals at approximately 7 and 14% respectively of the LD50. Anti-Tac(Fab)-PE40 was much more effective in vitro and in vivo than chemical conjugates between anti-Tac and truncated PE molecules. The recombinant Fab toxin should be studied further as potential treatment for IL2R-related malignancies, particularly if smaller recombinant immunotoxins have insufficient half-life in humans. JF - International journal of cancer AU - Kreitman, R J AU - Chang, C N AU - Hudson, D V AU - Queen, C AU - Bailon, P AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06/15/ PY - 1994 DA - 1994 Jun 15 SP - 856 EP - 864 VL - 57 IS - 6 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Oligodeoxyribonucleotides KW - Receptors, Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Recombinant Fusion Proteins -- pharmacokinetics KW - Base Sequence KW - Tumor Cells, Cultured -- drug effects KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - Molecular Sequence Data KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Recombinant Fusion Proteins -- chemistry KW - Immunotoxins -- chemistry KW - Exotoxins -- administration & dosage KW - Immunotoxins -- toxicity KW - Exotoxins -- toxicity KW - Exotoxins -- chemistry KW - Neoplasms, Experimental -- drug therapy KW - Receptors, Interleukin-2 -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76535671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Anti-Tac%28Fab%29-PE40%2C+a+recombinant+double-chain+immunotoxin+which+kills+interleukin-2-receptor-bearing+cells+and+induces+complete+remission+in+an+in+vivo+tumor+model.&rft.au=Kreitman%2C+R+J%3BChang%2C+C+N%3BHudson%2C+D+V%3BQueen%2C+C%3BBailon%2C+P%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1994-06-15&rft.volume=57&rft.issue=6&rft.spage=856&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 - 1994-07-12 N1 - Date created - 1994-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage. AN - 76525824; 7911340 AB - The cytokine interleukin-10 (IL-10) has been implicated in the pathogenesis of a number of disease states, including Epstein-Barr virus and human immunodeficiency virus (HIV-1) infections. In the acquired immunodeficiency syndrome (AIDS), it has been suggested that IL-10 may have a deleterious effect by suppressing cell-mediated immunity. However, there are few data on its direct effects on HIV-1 replication. In the present study, we have found that recombinant human IL-10 (rhIL-10), present during days 0 through 2, potently inhibits HIV production in elutriated monocyte/macrophage (M/M) cultures with a 50% inhibitory concentration (IC50) of approximately 0.03 U/mL. This effect did not appear to be caused by toxicity to M/M because there was no change in cell viability, ability to phagocytose latex beads, or protein synthesis as measured by [3H]-leucine incorporation, at doses of rhIL-10 that inhibit viral replication. In addition, lipopolysaccharide-induced production of IL-1 beta, IL-6, or tumor necrosis factor-alpha was not affected at these doses, nor were human mononuclear cell proliferative responses to phytohemagglutinin, OKT3 antibody, or tetanus toxoid. HIV-1 replication was similarly decreased by rhIL-10 in the monocytoid line U937 without signs of cellular toxicity. However, these effects required much higher concentrations of rhIL-10, and viral production was only partially suppressed. rhIL-10 also slightly inhibited HIV-induced cytopathicity in ATH-8, a tetanus toxoid-specific, retrovirally immortalized T-cell line, but had no effect on HIV replication in the H9 and MOLT-4 T cell lines. Thus, rhIL-10 appears to inhibit HIV replication predominantly in cells of the M/M lineage. This effect may serve to reduce viral production in patients with AIDS. However, additional studies will be needed to more precisely define its physiologic role in this disease. JF - Blood AU - Saville, M W AU - Taga, K AU - Foli, A AU - Broder, S AU - Tosato, G AU - Yarchoan, R AD - Retroviral Diseases Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/06/15/ PY - 1994 DA - 1994 Jun 15 SP - 3591 EP - 3599 VL - 83 IS - 12 SN - 0006-4971, 0006-4971 KW - Recombinant Proteins KW - 0 KW - Interleukin-10 KW - 130068-27-8 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Recombinant Proteins -- pharmacology KW - Macrophages -- microbiology KW - Cells, Cultured KW - Humans KW - Monocytes -- drug effects KW - Monocytes -- microbiology KW - CD4-Positive T-Lymphocytes -- microbiology KW - Macrophages -- drug effects KW - Virus Replication -- drug effects KW - Interleukin-10 -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76525824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin-10+suppresses+human+immunodeficiency+virus-1+replication+in+vitro+in+cells+of+the+monocyte%2Fmacrophage+lineage.&rft.au=Saville%2C+M+W%3BTaga%2C+K%3BFoli%2C+A%3BBroder%2C+S%3BTosato%2C+G%3BYarchoan%2C+R&rft.aulast=Saville&rft.aufirst=M&rft.date=1994-06-15&rft.volume=83&rft.issue=12&rft.spage=3591&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-12 N1 - Date created - 1994-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specificity of the cytochrome P-450 interaction with cytochrome b5. AN - 76574657; 8013641 AB - The specificity of the interaction of cytochrome b5 with different forms of cytochrome P-450 was examined. Immunopurification of cytochromes P-450 1A1, 2B1 and 2E1 from rat liver microsomes resulted in co-purification of cytochrome b5 with cytochrome P-450 forms 2B1 and 2E1 but not 1A1. This specificity was evaluated in conjunction with multiple sequence alignment of the three cytochrome P-450s and a molecular model of the cytochrome P-450-cytochrome b5 complex [(1989) Biochemistry 28, 8201-8205]. These analyses suggest two basic residues in the arginine cluster region of P-450, which are present in P-450s 2B1 and 2E1 but are absent in P-450 1A1, as potential binding sites for cytochrome b5. JF - FEBS letters AU - Omata, Y AU - Robinson, R C AU - Gelboin, H V AU - Pincus, M R AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06/13/ PY - 1994 DA - 1994 Jun 13 SP - 241 EP - 245 VL - 346 IS - 2-3 SN - 0014-5793, 0014-5793 KW - Cytochromes b5 KW - 9035-39-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP2B1 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Oxidoreductases -- isolation & purification KW - Animals KW - Models, Molecular KW - Oxidoreductases, N-Demethylating -- isolation & purification KW - Oxidoreductases -- chemistry KW - Amino Acid Sequence KW - Rats KW - Rats, Sprague-Dawley KW - Oxidoreductases, N-Demethylating -- chemistry KW - Sequence Alignment KW - Oxidoreductases -- metabolism KW - Microsomes, Liver -- enzymology KW - Molecular Sequence Data KW - Oxidoreductases, N-Demethylating -- metabolism KW - Male KW - Cytochromes b5 -- isolation & purification KW - Cytochromes b5 -- metabolism KW - Cytochrome P-450 Enzyme System -- isolation & purification KW - Cytochrome P-450 Enzyme System -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochromes b5 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76574657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Specificity+of+the+cytochrome+P-450+interaction+with+cytochrome+b5.&rft.au=Omata%2C+Y%3BRobinson%2C+R+C%3BGelboin%2C+H+V%3BPincus%2C+M+R%3BFriedman%2C+F+K&rft.aulast=Omata&rft.aufirst=Y&rft.date=1994-06-13&rft.volume=346&rft.issue=2-3&rft.spage=241&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 - 1994-07-25 N1 - Date created - 1994-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel RNA-binding motif in omnipotent suppressors of translation termination, ribosomal proteins and a ribosome modification enzyme? AN - 19800616; 8731068 AB - Using computer methods for database search, multiple alignment, protein sequence motif analysis and secondary structure prediction, a putative new RNA-binding motif was identified. The novel motif is conserved in yeast omnipotent translation termination suppressor SUP1, the related DOM34 protein and its pseudogene homologue; three groups of eukaryotic and archaeal ribosomal proteins, namely L30e, L7Ae/S6e and S12e; an uncharacterized Bacillus subtilis protein related to the L7A/S6e group; and Escherichia coli ribosomal protein modification enzyme RimK. We hypothesize that a new type of RNA-binding domain may be utilized to deliver additional activities to the ribosome. JF - Nucleic Acids Research AU - Koonin, E V AU - Bork, P AU - Sander, C AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894. Y1 - 1994/06/11/ PY - 1994 DA - 1994 Jun 11 SP - 2166 EP - 2167 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 22 IS - 11 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - Pseudogenes KW - Bacillus subtilis KW - Computers KW - Secondary structure KW - Enzymes KW - Ribosomes KW - Translation termination KW - Protein structure KW - Databases KW - Ribosomal proteins KW - Escherichia coli KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19800616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=A+novel+RNA-binding+motif+in+omnipotent+suppressors+of+translation+termination%2C+ribosomal+proteins+and+a+ribosome+modification+enzyme%3F&rft.au=Koonin%2C+E+V%3BBork%2C+P%3BSander%2C+C&rft.aulast=Koonin&rft.aufirst=E&rft.date=1994-06-11&rft.volume=22&rft.issue=11&rft.spage=2166&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 - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Protein structure; Pseudogenes; Databases; Ribosomal proteins; Computers; Secondary structure; Enzymes; Ribosomes; Amino acid sequence; Translation termination; Bacillus subtilis; Escherichia coli ER - TY - JOUR T1 - Anti-HIV michellamines from Ancistrocladus korupensis. AN - 76584690; 8021914 AB - Here we report details of the isolation and determination of the absolute configurations and comparative anti-HIV activities of novel, atropisomeric naphthylisoquinoline alkaloid dimers, michellamines A, B, and C, from a newly described species of Ancistrocladus from the Korup rainforest of Cameroon. We further provide a more extensive analysis of the range of anti-HIV activity of michellamine B, the most potent and abundant member of the series. Michellamine B inhibited HIV-induced cell killing and viral replication in a variety of human cell lines, as well as in cultures of human peripheral blood leukocytes and monocytes. Michellamine B was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6 and the pyridinone-resistant strain A17; the compound also inhibited several strains of HIV-2. JF - Journal of medicinal chemistry AU - Boyd, M R AU - Hallock, Y F AU - Cardellina, J H AU - Manfredi, K P AU - Blunt, J W AU - McMahon, J B AU - Buckheit, R W AU - Bringmann, G AU - Schäffer, M AU - Cragg, G M AD - Laboratory of Drug Discovery Research & Development, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702-1201. Y1 - 1994/06/10/ PY - 1994 DA - 1994 Jun 10 SP - 1740 EP - 1745 VL - 37 IS - 12 SN - 0022-2623, 0022-2623 KW - Antiviral Agents KW - 0 KW - Isoquinolines KW - Naphthalenes KW - michellamine A KW - 137793-81-8 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Drug Interactions KW - Virus Replication -- drug effects KW - Cells, Cultured KW - Humans KW - Zidovudine -- pharmacology KW - HIV-2 -- drug effects KW - Africa KW - Microbial Sensitivity Tests KW - HIV-1 -- drug effects KW - Naphthalenes -- pharmacology KW - Naphthalenes -- isolation & purification KW - Plants -- chemistry KW - Isoquinolines -- pharmacology KW - Isoquinolines -- chemistry KW - HIV -- drug effects KW - Naphthalenes -- chemistry KW - HIV -- physiology KW - Antiviral Agents -- pharmacology KW - Antiviral Agents -- chemistry KW - Antiviral Agents -- isolation & purification KW - Isoquinolines -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76584690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-HIV+michellamines+from+Ancistrocladus+korupensis.&rft.au=Boyd%2C+M+R%3BHallock%2C+Y+F%3BCardellina%2C+J+H%3BManfredi%2C+K+P%3BBlunt%2C+J+W%3BMcMahon%2C+J+B%3BBuckheit%2C+R+W%3BBringmann%2C+G%3BSch%C3%A4ffer%2C+M%3BCragg%2C+G+M&rft.aulast=Boyd&rft.aufirst=M&rft.date=1994-06-10&rft.volume=37&rft.issue=12&rft.spage=1740&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 - 1994-08-03 N1 - Date created - 1994-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine kinase-deficient mutant human insulin receptors (Met1153-->Ile) overexpressed in transfected rat adipose cells fail to mediate translocation of epitope-tagged GLUT4. AN - 76537147; 8202531 AB - Insulin regulates essential pathways for growth, differentiation, and metabolism in vivo. We report a physiologically relevant system for dissecting the molecular mechanisms of insulin signal transduction related to glucose transport. This is an extension of our recently reported method for transfection of DNA into rat adipose cells in primary culture. In the present work, cDNA coding for GLUT4 with an epitope tag (HA1) in the first exofacial loop is used as a reporter gene so that GLUT4 translocation can be studied exclusively in transfected cells. Insulin stimulates a 4.3-fold recruitment of transfected epitope-tagged GLUT4 to the cell surface. Cells cotransfected with the reporter gene and the human insulin receptor gene show an increase in cell surface GLUT4 in the basal state (no insulin) to levels comparable to those seen with maximal insulin stimulation of cells transfected with the reporter gene alone. In contrast, cells overexpressing a naturally occurring tyrosine kinase-deficient mutant insulin receptor (Met1153-->Ile) show no increase in the basal cell surface GLUT4 and no shift in the insulin dose-response curve relative to cells transfected with the reporter gene alone. These results demonstrate that insulin receptor tyrosine kinase activity is essential in insulin-stimulated glucose transport in adipose cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Quon, M J AU - Guerre-Millo, M AU - Zarnowski, M J AU - Butte, A J AU - Em, M AU - Cushman, S W AU - Taylor, S I AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06/07/ PY - 1994 DA - 1994 Jun 07 SP - 5587 EP - 5591 VL - 91 IS - 12 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Glucose Transporter Type 4 KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - SLC2A4 protein, human KW - Slc2a4 protein, rat KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Animals KW - Glucose -- metabolism KW - Humans KW - Biological Transport KW - Structure-Activity Relationship KW - Rats KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Adipose Tissue -- metabolism KW - Cell Compartmentation KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Signal Transduction KW - DNA Primers -- chemistry KW - Monosaccharide Transport Proteins -- metabolism KW - Receptor, Insulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76537147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tyrosine+kinase-deficient+mutant+human+insulin+receptors+%28Met1153--%26gt%3BIle%29+overexpressed+in+transfected+rat+adipose+cells+fail+to+mediate+translocation+of+epitope-tagged+GLUT4.&rft.au=Quon%2C+M+J%3BGuerre-Millo%2C+M%3BZarnowski%2C+M+J%3BButte%2C+A+J%3BEm%2C+M%3BCushman%2C+S+W%3BTaylor%2C+S+I&rft.aulast=Quon&rft.aufirst=M&rft.date=1994-06-07&rft.volume=91&rft.issue=12&rft.spage=5587&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 - 1994-07-06 N1 - Date created - 1994-07-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1991 May 15;266(14):8814-9 [2026596] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):214-8 [1846039] J Biol Chem. 1991 Aug 25;266(24):15587-90 [1651915] J Clin Endocrinol Metab. 1991 Oct;73(4):894-901 [1890161] J Biol Chem. 1992 Apr 25;267(12):8383-9 [1314826] Biochemistry. 1992 Sep 1;31(34):8059-63 [1324726] Biochemistry. 1992 Oct 20;31(41):9947-54 [1390778] Endocr Rev. 1992 Aug;13(3):566-95 [1330507] Recent Prog Horm Res. 1993;48:291-339 [7680139] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4379-83 [8506276] J Biol Chem. 1993 Jul 5;268(19):14523-6 [7686158] Biochem Biophys Res Commun. 1993 Jul 15;194(1):338-46 [8392839] Biochem Biophys Res Commun. 1993 Sep 15;195(2):762-8 [8396927] J Cell Biol. 1993 Oct;123(1):127-35 [8408193] J Lipid Res. 1978 Feb;19(2):269-73 [632689] J Biol Chem. 1981 May 25;256(10):4772-7 [7014557] Biochim Biophys Acta. 1983 Dec 19;763(4):393-407 [6360220] Science. 1984 Mar 23;223(4642):1301-4 [6367041] Nature. 1985 Feb 28-Mar 6;313(6005):756-61 [2983222] Proc Natl Acad Sci U S A. 1987 Jan;84(1):41-5 [3540958] J Biol Chem. 1989 May 15;264(14):7776-9 [2656669] Diabetes Care. 1990 Mar;13(3):198-208 [2407475] Proc Natl Acad Sci U S A. 1990 May;87(9):3358-62 [2159147] J Biol Chem. 1990 Oct 5;265(28):16873-9 [1698770] J Biol Chem. 1990 Oct 25;265(30):18172-9 [2211693] Mol Cell Biol. 1991 Jun;11(6):3070-4 [2038318] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid treatment increases the ability of CRH to induce seizures. AN - 76836178; 7970144 AB - We examined whether glucocorticoids could enhance the ability of corticotropin-releasing hormone (CRH) to induce seizures. Rats were treated with systemic glucocorticoids (dexamethasone, 100 micrograms) or vehicle for either 3 days (chronic) or 2 h (acute) before intracerebroventricular CRH (3 or 10 micrograms) or saline injections and then monitored for 8 h following each injection. Our results suggest that chronic, but not acute, glucocorticoid pretreatment increases the likelihood of CRH-induced seizures. JF - Neuroscience letters AU - Rosen, J B AU - Pishevar, S K AU - Weiss, S R AU - Smith, M A AU - Kling, M A AU - Gold, P W AU - Schulkin, J AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/06/06/ PY - 1994 DA - 1994 Jun 06 SP - 113 EP - 116 VL - 174 IS - 1 SN - 0304-3940, 0304-3940 KW - Glucocorticoids KW - 0 KW - Dexamethasone KW - 7S5I7G3JQL KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Aggression -- drug effects KW - Rats, Sprague-Dawley KW - Dexamethasone -- pharmacology KW - Dexamethasone -- administration & dosage KW - Drug Synergism KW - Male KW - Injections, Intraventricular KW - Seizures -- chemically induced KW - Glucocorticoids -- administration & dosage KW - Corticotropin-Releasing Hormone -- administration & dosage KW - Corticotropin-Releasing Hormone -- pharmacology KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76836178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Glucocorticoid+treatment+increases+the+ability+of+CRH+to+induce+seizures.&rft.au=Rosen%2C+J+B%3BPishevar%2C+S+K%3BWeiss%2C+S+R%3BSmith%2C+M+A%3BKling%2C+M+A%3BGold%2C+P+W%3BSchulkin%2C+J&rft.aulast=Rosen&rft.aufirst=J&rft.date=1994-06-06&rft.volume=174&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-07 N1 - Date created - 1994-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of nickel(II) and tetraglycine on hydroxylation of the guanine moiety in 2'-deoxyguanosine, DNA, and nucleohistone by hydrogen peroxide. AN - 76564089; 8029697 AB - The purpose of this study was to determine whether the Ni(II)-tetraglycine complex system (NiG4) that is known to disproportionate H2O2 at pH > or = 8 can catalyze oxidation of the guanine residues in 2'-deoxyguanosine (dG), calf thymus DNA, and calf thymus nucleohistone (NH) by H2O2 at physiological pH. Incubation of dG with H2O2 in the presence of NiG4 at 37 degrees C, produced two effects: (a) formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and (b) decomposition of dG to 2,6-diamino-4-hydroxy-5-formamidopyrimidine and several low molecular weight unidentified products. The magnitude of both effects depended on incubation time (1-48 h), H2O2 concentration (7.5-40 mM), NiG4 concentration (0.1 or 1 mM), and pH (6.0-8.0). The effects were not detected below pH 6 and above pH 8.0. For 0.1 mM NiG4 and 7.5 mM H2O2, production of 8-OH-dG from dG (0.75 mM) during 24 h at 37 degrees C was significantly lower than from NH (1 mg/ml) or DNA (0.5 mg/ml), indicating possible specific effects that might be related to the strength of interaction of NiG4 with dG, NH, or DNA. The results indicate production of hydroxyl radical or other oxidizing species in the reaction of H2O2 with NiG4 at pH 7-8. Reactions like this may be relevant to the mechanisms of Ni(II)-mediated oxidative damage, observed in vitro and in vivo, which may contribute to the toxic and carcinogenic effects of this metal. JF - The Science of the total environment AU - Datta, A K AU - North, S L AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/06/06/ PY - 1994 DA - 1994 Jun 06 SP - 207 EP - 216 VL - 148 IS - 2-3 SN - 0048-9697, 0048-9697 KW - Histones KW - 0 KW - Oligopeptides KW - Guanine KW - 5Z93L87A1R KW - glycyl-glycyl-glycyl-glycine KW - 637-84-3 KW - Nickel KW - 7OV03QG267 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Animals KW - Cattle KW - Hydrogen-Ion Concentration KW - Hydroxylation -- drug effects KW - Time Factors KW - Guanine -- metabolism KW - Deoxyguanosine -- metabolism KW - Nickel -- pharmacology KW - Hydrogen Peroxide -- metabolism KW - Histones -- metabolism KW - DNA -- metabolism KW - Oligopeptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76564089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Science+of+the+total+environment&rft.atitle=Effect+of+nickel%28II%29+and+tetraglycine+on+hydroxylation+of+the+guanine+moiety+in+2%27-deoxyguanosine%2C+DNA%2C+and+nucleohistone+by+hydrogen+peroxide.&rft.au=Datta%2C+A+K%3BNorth%2C+S+L%3BKasprzak%2C+K+S&rft.aulast=Datta&rft.aufirst=A&rft.date=1994-06-06&rft.volume=148&rft.issue=2-3&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=00489697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-09 N1 - Date created - 1994-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional protein binding domains governing basal expression of the rat luteinizing hormone receptor gene. AN - 76507131; 8195242 AB - The functional importance of specific protein binding domains on transcription within the GC-rich 173-base pair promoter of the luteinizing hormone receptor gene was studied by mutagenesis and gel retardation analysis. Transcription was dependent on the presence of two Sp1 elements in the promoter domain of transfected expressing mouse Leydig tumor cells (mLTC) and nonexpressing Chinese hamster ovary cells. Mutation of two protein binding domains located downstream of the Sp1 elements (M1 and C-box) revealed tissue-specific regulation of promoter activity by each domain. Also, gel retardation studies indicated the presence of multiple trans factors that bind to the C-box and M1 domains. Removal of the AP-2 element from the C-box resulted in mLTC-specific transcriptional activation that may involve an M1/C-box interaction. In addition, competition by overlapping NF-1 and AP-2 elements was demonstrable in both the C-box and upstream R domain for separate trans factors that exhibit neutral or inhibitory functions, respectively. Competition between the inhibitory and neutral DNA binding factors within both upstream and promoter domains may be responsible for a mechanism that controls the on/off state of luteinizing hormone receptor gene expression in gonadal cells. These studies reveal a complex pattern of transcriptional regulation that may reflect targeted mechanisms for the control of luteinizing hormone receptor gene expression. JF - The Journal of biological chemistry AU - Tsai-Morris, C H AU - Geng, Y AU - Xie, X Z AU - Buczko, E AU - Dufau, M L AD - Section on Molecular Endocrinology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06/03/ PY - 1994 DA - 1994 Jun 03 SP - 15868 EP - 15875 VL - 269 IS - 22 SN - 0021-9258, 0021-9258 KW - Oligodeoxyribonucleotides KW - 0 KW - Receptors, LH KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - DNA -- metabolism KW - Binding Sites KW - Mutagenesis KW - Rats KW - DNA -- isolation & purification KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - CHO Cells KW - Consensus Sequence KW - Cricetinae KW - Regulatory Sequences, Nucleic Acid KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Receptors, LH -- biosynthesis KW - Receptors, LH -- genetics KW - Transcription, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76507131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+protein+binding+domains+governing+basal+expression+of+the+rat+luteinizing+hormone+receptor+gene.&rft.au=Tsai-Morris%2C+C+H%3BGeng%2C+Y%3BXie%2C+X+Z%3BBuczko%2C+E%3BDufau%2C+M+L&rft.aulast=Tsai-Morris&rft.aufirst=C&rft.date=1994-06-03&rft.volume=269&rft.issue=22&rft.spage=15868&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 - 1994-06-30 N1 - Date created - 1994-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of the GABA rho 1 receptor alters agonist affinity and channel gating. AN - 76730471; 7919166 AB - Seventeen site-directed mutations were constructed in the GABA rho 1 receptor with the aim of finding agonist binding domains common to rho 1 and rho 2 receptors but distinct from those identified in members of the family of homologous, ligand gated ion channels. Mutated cDNAs were expressed in Xenopus oocytes and tested by voltage clamp experiments. Five of the mutations abolished responsiveness to GABA. Mutation Q189H, in the conserved cysteine loop, diminished apparent GABA affinity to about 1/10 of wild type values in a manner consistent with decreased allosteric cooperativity among agonist recognition sites. Mutation R316A, located in the extracellular loop between transmembrane domains II and III, increased the Hill coefficient to 3.9 in a fashion consistent with enhanced open probability of a receptor multimer. JF - Neuroreport AU - Kusama, T AU - Wang, J B AU - Spivak, C E AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/06/02/ PY - 1994 DA - 1994 Jun 02 SP - 1209 EP - 1212 VL - 5 IS - 10 SN - 0959-4965, 0959-4965 KW - DNA, Complementary KW - 0 KW - GABA Agonists KW - Oligonucleotides KW - Receptors, GABA KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - DNA, Complementary -- genetics KW - Kinetics KW - DNA, Complementary -- metabolism KW - Molecular Sequence Data KW - Membrane Potentials -- physiology KW - Xenopus KW - Amino Acid Sequence KW - Oligonucleotides -- chemical synthesis KW - Female KW - Receptors, GABA -- drug effects KW - Receptors, GABA -- metabolism KW - GABA Agonists -- metabolism KW - Ion Channel Gating -- genetics KW - Receptors, GABA -- genetics KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76730471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Mutagenesis+of+the+GABA+rho+1+receptor+alters+agonist+affinity+and+channel+gating.&rft.au=Kusama%2C+T%3BWang%2C+J+B%3BSpivak%2C+C+E%3BUhl%2C+G+R&rft.aulast=Kusama&rft.aufirst=T&rft.date=1994-06-02&rft.volume=5&rft.issue=10&rft.spage=1209&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-10 N1 - Date created - 1994-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. AN - 76519727; 8196770 AB - Mitogen-activated protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors. In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellular proliferation. The tyrosine-kinase class of growth-factor receptors transmits signals to ERKs in a multistep process that involves Ras and a limited number of defined molecules. In contrast, ERK activation by G-protein-coupled receptors is poorly understood, as is the role of ras in this signalling pathway. We have explored in COS-7 cells the mechanism of ERKs activation by m1 and m2 muscarinic receptors, typical examples of receptors coupled through Gq proteins to induce phosphatidylinositol hydrolysis and to G(i) proteins to inhibit adenylyl cyclase, respectively. Here we present evidence that ERK activation is mediated by beta gamma subunits of heterotrimeric G proteins acting on a ras-dependent pathway. JF - Nature AU - Crespo, P AU - Xu, N AU - Simonds, W F AU - Gutkind, J S AD - Molecular Signalling Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06/02/ PY - 1994 DA - 1994 Jun 02 SP - 418 EP - 420 VL - 369 IS - 6479 SN - 0028-0836, 0028-0836 KW - Adenylate Cyclase Toxin KW - 0 KW - Phosphatidylinositols KW - Receptors, Muscarinic KW - Virulence Factors, Bordetella KW - Epidermal Growth Factor KW - 62229-50-9 KW - Carbachol KW - 8Y164V895Y KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Phosphatidylinositols -- metabolism KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Protein Kinase C -- metabolism KW - Virulence Factors, Bordetella -- pharmacology KW - Transfection KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Carbachol -- pharmacology KW - Cell Line KW - Receptors, Muscarinic -- genetics KW - Protein-Tyrosine Kinases -- genetics KW - Protein-Serine-Threonine Kinases -- metabolism KW - Oncogene Protein p21(ras) -- genetics KW - Oncogene Protein p21(ras) -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Protein-Tyrosine Kinases -- metabolism KW - GTP-Binding Proteins -- genetics KW - Signal Transduction KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76519727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Ras-dependent+activation+of+MAP+kinase+pathway+mediated+by+G-protein+beta+gamma+subunits.&rft.au=Crespo%2C+P%3BXu%2C+N%3BSimonds%2C+W+F%3BGutkind%2C+J+S&rft.aulast=Crespo&rft.aufirst=P&rft.date=1994-06-02&rft.volume=369&rft.issue=6479&rft.spage=418&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-24 N1 - Date created - 1994-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nature. 1994 Jun 2;369(6479):361-2 [8196762] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From the National Institute on Deafness and other Communication Disorders. AN - 85212498; pmid-8208584 JF - Otolaryngology--Head and Neck Surgery AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1994 SP - 607 EP - 609 VL - 110 IS - 6 SN - 0194-5998, 0194-5998 KW - United States KW - Human KW - Research KW - Otorhinolaryngologic Diseases KW - National Institutes of Health (U.S.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85212498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Otolaryngology--Head+and+Neck+Surgery&rft.atitle=From+the+National+Institute+on+Deafness+and+other+Communication+Disorders.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1994-06-01&rft.volume=110&rft.issue=6&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Otolaryngology--Head+and+Neck+Surgery&rft.issn=01945998&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Structural basis for mechanical transduction in the frog vestibular sensory apparatus: II. The role of microtubules in the organization of the cuticular plate. AN - 85158896; pmid-7928733 AB - The actin matrix of the cuticular plate, which supports the sensory stereocilia bundle, is coupled to the axial cytoskeleton of the hair cell through a well defined microtubule columnar framework. A collection of axial microtubules in a columnar organization penetrate deep into the dense actin matrix of the cuticular plate. Each microtubule displays at the end a 300-500 nm long fuzzy cap that enmeshes with the actin matrix of the cuticular plate. The microtubule associated proteins MAP-1A and MAP-1B were localized by confocal immunofluorescence to the point of microtubule insertion in the cuticular plate. These proteins are likely components of the microtubule capping structure and may mediate the interaction of the microtubules with the actin matrix. The structural interaction of the microtubules with the cuticular plate provides important mechanical coupling of the transduction apparatus to the axial cytoskeleton of the hair cell. JF - Hearing Research AU - Jaeger, R G AU - Fex, J AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, MD 20850. PY - 1994 SP - 207 EP - 215 VL - 77 IS - 1-2 SN - 0378-5955, 0378-5955 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85158896?accountid=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=Structural+basis+for+mechanical+transduction+in+the+frog+vestibular+sensory+apparatus%3A+II.+The+role+of+microtubules+in+the+organization+of+the+cuticular+plate.&rft.au=Jaeger%2C+R+G%3BFex%2C+J%3BKachar%2C+B&rft.aulast=Jaeger&rft.aufirst=R&rft.date=1994-06-01&rft.volume=77&rft.issue=1-2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Transdermal nicotine: reduction of smoking with minimal abuse liability. AN - 77748793; 7862918 AB - Cigarette consumption as well as the physiologic, performance and subjective effects of the nicotine patch were evaluated in ten subjects who smoked ad libitum while residing on a residential research ward for 30 days. Nicotine transdermal systems ("patches") delivering a total of 0, 22 or 44 mg per 24 h were applied daily at a constant dose during each 7-day condition; the order of dosing conditions was varied according to a randomized, double-blind, crossover design. Nicotine patches significantly but modestly reduced spontaneous smoking and significantly increased venous plasma nicotine levels. Self ratings of patch liking, satisfaction with cigarettes and the ability to identify the patch condition did not change as a function of the nicotine dose, indicating minimal abuse liability. There were no consistent changes in the puffing pattern measures; however, in all patch conditions, subjects with extensive histories of illicit drug use smoked cigarettes faster than subjects with histories of occasional drug use. Small changes in resting heart rate, pulse and blood pressure occurred when the nicotine patch was worn. Thus large changes in venous plasma nicotine levels engender only modest changes in ad libitum cigarette consumption, measures of abuse liability and cardiovascular effects. These findings are consistent with the notion that the addictive and toxic effects of nicotine are partially determined by the rate of drug administration. JF - Psychopharmacology AU - Pickworth, W B AU - Bunker, E B AU - Henningfield, J E AD - National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 9 EP - 14 VL - 115 IS - 1-2 SN - 0033-3158, 0033-3158 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Heart Rate -- drug effects KW - Administration, Cutaneous KW - Double-Blind Method KW - Body Temperature -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Blood Pressure -- drug effects KW - Skin Diseases -- chemically induced KW - Male KW - Nicotine -- therapeutic use KW - Nicotine -- adverse effects KW - Nicotine -- administration & dosage KW - Substance-Related Disorders -- psychology KW - Smoking -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77748793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transdermal+nicotine%3A+reduction+of+smoking+with+minimal+abuse+liability.&rft.au=Pickworth%2C+W+B%3BBunker%2C+E+B%3BHenningfield%2C+J+E&rft.aulast=Pickworth&rft.aufirst=W&rft.date=1994-06-01&rft.volume=115&rft.issue=1-2&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-20 N1 - Date created - 1995-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow transplantation for acute lymphoblastic leukaemia. AN - 76907068; 7803908 AB - Allogeneic bone marrow transplantation (BMT) has been used in the treatment of poor risk acute lymphoblastic leukaemia (ALL) for over 20 years. Over this period results have improved and indications for treatment have become more clearly defined. Over 60% of adults and over 70% of children with poor risk ALL in first remission, and 30-40% of patients in second remissions can be expected to achieve long term leukaemia-free survival. Factors implicated in the cure of ALL by BMT are the myeloablative preparative regimen, a graft-versus-leukaemia effect, and post transplant chemotherapy. Improved results of chemotherapy have changed the perceived indications for BMT in ALL and have led to controversy over the best treatment approach. However there is good evidence to show that BMT offers a better chance of leukaemia free survival in certain very poor risk categories. These include Philadelphia chromosome positive ALL, remission induction failures, and children in second remission who relapse after adequate chemotherapy. Particular issues in the use of BMT in ALL are the prevention and management of extramedullary leukaemia, the treatment of relapse following BMT, and the prevention and monitoring of late effects. In the future the use of unrelated donors, and a continuing fall in transplant related morbidity and mortality will extend the use of BMT in poor risk ALL. JF - Bailliere's clinical haematology AU - Barrett, A J AD - Bone Marrow Transplant Unit, NHLBI, National Institute of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 377 EP - 401 VL - 7 IS - 2 SN - 0950-3536, 0950-3536 KW - Index Medicus KW - Multicenter Studies as Topic KW - Humans KW - Salvage Therapy KW - Child KW - Adult KW - Treatment Outcome KW - Forecasting KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adolescent KW - Male KW - Growth Disorders -- etiology KW - Neoplasms, Second Primary KW - Combined Modality Therapy KW - Whole-Body Irradiation -- adverse effects KW - Clinical Trials as Topic KW - Prognosis KW - Diseases in Twins KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Tissue Donors KW - Child, Preschool KW - Survival Rate KW - Twins, Monozygotic KW - Histocompatibility KW - Risk Factors KW - Graft vs Host Disease KW - Middle Aged KW - Female KW - Remission Induction KW - Bone Marrow Transplantation -- adverse effects KW - Bone Marrow Transplantation -- statistics & numerical data KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- therapy KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76907068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bailliere%27s+clinical+haematology&rft.atitle=Bone+marrow+transplantation+for+acute+lymphoblastic+leukaemia.&rft.au=Barrett%2C+A+J&rft.aulast=Barrett&rft.aufirst=A&rft.date=1994-06-01&rft.volume=7&rft.issue=2&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Bailliere%27s+clinical+haematology&rft.issn=09503536&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-30 N1 - Date created - 1995-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current techniques for measuring dental fluorosis: issues in data analysis. AN - 76891145; 7993561 AB - The currently popular scoring systems used to diagnosis fluorosis use different measurement units, evaluate variable numbers of sites per person, and involve non-comparable groupings of clinical symptoms. Although none of these factors is related to the level of fluoride exposure in the examined population, their combined effect produces fluorosis prevalence values for a population which vary considerably among and within these scoring systems. Intrinsic factors for a scoring system include the inclusion of a questionable category, the minimal level of fluorotic involvement, and the number of affected sites within a subject required for case definition. Thus, a case definition of fluorosis for each scoring system, although not mandatory, would certainly be desirable so that dental epidemiologists and clinical investigators can interpret fluorosis scores relative to risk assessment. On the other hand, ratios of fluorosis prevalence magnitudes, as evidenced by odds ratios, can be more stable between scoring systems when groups with different fluoride exposure levels are compared. There is a strong correlation between extent and specific measures of fluorosis severity for Dean's Index (DI) and the Tooth Surface Index of Fluorosis (TSIF) scoring system, as well as within each scoring system separately. Parallel patterns in fluorosis severity were found among groups with different fluoride exposure on severity levels of fluorosis may be better understood by using relative measures rather than by using differences in severity levels. JF - Advances in dental research AU - Kingman, A AD - Epidemiology & Oral Diseases Prevention Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20816. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 56 EP - 65 VL - 8 IS - 1 SN - 0895-9374, 0895-9374 KW - Fluorides KW - Q80VPU408O KW - Dentistry KW - Severity of Illness Index KW - Odds Ratio KW - Analysis of Variance KW - Humans KW - Data Interpretation, Statistical KW - Statistics, Nonparametric KW - Fluorides -- adverse effects KW - Prevalence KW - Fluorosis, Dental -- diagnosis KW - Fluorosis, Dental -- epidemiology KW - Fluorosis, Dental -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76891145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+dental+research&rft.atitle=Current+techniques+for+measuring+dental+fluorosis%3A+issues+in+data+analysis.&rft.au=Kingman%2C+A&rft.aulast=Kingman&rft.aufirst=A&rft.date=1994-06-01&rft.volume=8&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Advances+in+dental+research&rft.issn=08959374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Strategies for improving methods of assessing fluoride accumulation in body fluids and tissues. AN - 76880000; 7993554 JF - Advances in dental research AU - Selwitz, R H Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 111 EP - 112 VL - 8 IS - 1 KW - Biomarkers KW - 0 KW - Fluorides KW - Q80VPU408O KW - Dentistry KW - Fluorosis, Dental -- diagnosis KW - Dentin -- chemistry KW - Bone and Bones -- chemistry KW - Humans KW - Body Burden KW - Tissue Distribution KW - Environmental Exposure KW - Body Fluids -- chemistry KW - Fluorides -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76880000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Advances+in+dental+research&rft.atitle=Strategies+for+improving+methods+of+assessing+fluoride+accumulation+in+body+fluids+and+tissues.&rft.au=Selwitz%2C+R+H&rft.aulast=Selwitz&rft.aufirst=R&rft.date=1994-06-01&rft.volume=8&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Advances+in+dental+research&rft.issn=08959374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-19 N1 - Date created - 1995-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroimmunotherapy: a practical approach to the treatment of immune-mediated neurologic diseases. AN - 76869822; 7984835 AB - Immunosuppressive drugs and immunomodulating procedures can improve the quality of life in patients with immune-related neurologic diseases, or even be life saving, if properly used to avoid deleterious or irreversible adverse effects. For the successful use of these drugs or procedures, the treating physician must be familiar and comfortable with the drugs' mode of action and consider some important principles: 1. The diagnosis must be secure before starting therapy. 2. It is essential to have a basic understanding of the immunologic dysfunction that is amenable to immunotherapy. 3. The goals and the expectations of therapy must be defined, and the risk/benefit ratio of the drugs or procedures must be well understood. 4. Improvement must be based on objective measurements of muscle strength and a beneficial change in activities of daily living, and not solely on a change in the laboratory test values. 5. The limitations of therapy and the time suitable for starting or stopping a drug should be clear to both the therapist and the patient. 6. The selection of a drug or procedure should be guided on the basis of current knowledge, preferably established in controlled trials. 7. Every effort must be made to prevent the development of adverse effects and to determine the lowest dose of a medication that controls the disease. 8. Drug interactions that can cause adverse effects and conditions that can worsen a disease must be avoided. JF - Seminars in neurology AU - Dalakas, M C AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 97 EP - 105 VL - 14 IS - 2 SN - 0271-8235, 0271-8235 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - Drug Interactions KW - Humans KW - Autoimmune Diseases -- drug therapy KW - Nervous System Diseases -- drug therapy KW - Nervous System Diseases -- immunology KW - Neuroimmunomodulation KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76869822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurology&rft.atitle=Neuroimmunotherapy%3A+a+practical+approach+to+the+treatment+of+immune-mediated+neurologic+diseases.&rft.au=Dalakas%2C+M+C&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1994-06-01&rft.volume=14&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Seminars+in+neurology&rft.issn=02718235&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-05 N1 - Date created - 1995-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicokinetics of pentachlorophenol in the F344 rat. Gavage and dosed feed studies. AN - 76841479; 7975721 AB - 1. The toxicokinetics of pentachlorophenol (PCP) were studied in the Fischer 344 rat using i.v. and oral (gavage, dosed feed) routes of exposure. 2. Only minor sex differences were observed in the elimination kinetics of PCP after i.v. administration at 5 mg/kg. 3. Absorption of PCP from the gastrointestinal tract after gavage doses of 9.5 and 38 mg/kg in aqueous methylcellulose vehicles was first order with an absorption half-life of about 1.3 h. 4. The absorption rate constant of PCP from doses feed was comparable with that obtained from aqueous methylcellulose gavage formulations. 5. Bioavailability of PCP administered in dosed feed was significantly lower than the bioavailability of PCP administered by gavage. 6. Dose proportionality was established to a dosage of at least 38 mg/kg. 7. Daily fluctuation of PCP plasma concentrations was observed during the dosed feed study with peak and trough concentrations occurring in early morning and late afternoon, respectively. 8. The time course of PCP plasma concentrations during the dosed feed study were simulated using a computer model based on linear theory. The simulations were comparable with the experimentally determined concentrations. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Yuan, J H AU - Goehl, T J AU - Murrill, E AU - Moore, R AU - Clark, J AU - Hong, H L AU - Irwin, R D AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 553 EP - 560 VL - 24 IS - 6 SN - 0049-8254, 0049-8254 KW - Pentachlorophenol KW - D9BSU0SE4T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Computer Simulation KW - Injections, Intravenous KW - Half-Life KW - Sex Characteristics KW - Intubation, Gastrointestinal KW - Intestinal Absorption KW - Male KW - Female KW - Pentachlorophenol -- pharmacokinetics KW - Pentachlorophenol -- administration & dosage KW - Pentachlorophenol -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76841479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.atitle=Toxicokinetics+of+pentachlorophenol+in+the+F344+rat.+Gavage+and+dosed+feed+studies.&rft.au=Yuan%2C+J+H%3BGoehl%2C+T+J%3BMurrill%2C+E%3BMoore%2C+R%3BClark%2C+J%3BHong%2C+H+L%3BIrwin%2C+R+D&rft.aulast=Yuan&rft.aufirst=J&rft.date=1994-06-01&rft.volume=24&rft.issue=6&rft.spage=553&rft.isbn=&rft.btitle=&rft.title=Xenobiotica%3B+the+fate+of+foreign+compounds+in+biological+systems&rft.issn=00498254&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-08 N1 - Date created - 1994-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arachidonic acid and diacylglycerol ACT synergistically through protein kinase C to persistently enhance synaptic transmission in the hippocampus. AN - 76782120; 7936199 AB - In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically induce a membrane-inserted, constitutively active form of protein kinase C. We have investigated the effects of these lipid protein kinase C activators on synaptic efficacy in the Schaffer collateral input to CA1 hippocampal pyramidal cells. Arachidonic acid (5 microM) perfusion combined with repetitive afferent stimulation had no consistent effect on field excitatory postsynaptic potentials recorded in stratum radiatum, while treatment with a cell-permeable diglyceride, oleoyl-acetylglycerol (5 micrograms/ml), followed by stimulation, led to a short-term potentiation. By contrast, the combination of oleoyl-acetylglycerol and arachidonic acid gave rise to a long-lasting non-decremental potentiation of field excitatory postsynaptic potentials. The induction of potentiation was "activity dependent", as there was either no significant effect or there was a measurable depression when repetitive synaptic stimulation was omitted. Furthermore, consistent with a protein kinase C-dependent process, the potentiation was blocked by the kinase inhibitors H-7 and staurosporine. The results suggest that relatively low concentrations of arachidonic acid and diacylglycerol work synergistically through protein kinase C to persistently enhance synaptic transmission. This synergy has the makings of an associative (Hebbian) device for long-term potentiation induction operating at the second messenger level. JF - Neuroscience AU - Bramham, C R AU - Alkon, D L AU - Lester, D S AD - Laboratory of Adaptive Systems, NINDS, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 737 EP - 743 VL - 60 IS - 3 SN - 0306-4522, 0306-4522 KW - 1,2-diacylglycerol KW - 0 KW - Diglycerides KW - Nerve Tissue Proteins KW - Arachidonic Acid KW - 27YG812J1I KW - 1-oleoyl-2-acetylglycerol KW - 86390-77-4 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats KW - Animals KW - Second Messenger Systems KW - Rats, Sprague-Dawley KW - Long-Term Potentiation -- physiology KW - Enzyme Activation -- drug effects KW - Drug Synergism KW - Male KW - Protein Kinase C -- metabolism KW - Diglycerides -- pharmacology KW - Synaptic Transmission -- drug effects KW - Arachidonic Acid -- pharmacology KW - Nerve Tissue Proteins -- metabolism KW - Hippocampus -- enzymology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76782120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arachidonic+acid+and+diacylglycerol+ACT+synergistically+through+protein+kinase+C+to+persistently+enhance+synaptic+transmission+in+the+hippocampus.&rft.au=Bramham%2C+C+R%3BAlkon%2C+D+L%3BLester%2C+D+S&rft.aulast=Bramham&rft.aufirst=C&rft.date=1994-06-01&rft.volume=60&rft.issue=3&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-17 N1 - Date created - 1994-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abstinent alcoholics exhibit an exaggerated stress response to 2-deoxy-D-glucose challenge. AN - 76781289; 7943676 AB - Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism; however, the mechanism and clinical significance of this disturbance are poorly understood. We used 2-deoxy-D-glucose (2-DG), which produces intracellular glucoprivation, to compare neurochemical, physiological, and behavioral responses to glucoprivic stress between alcoholics abstinent for 3 weeks and healthy volunteers. Twenty-six male alcoholics and 15 male healthy volunteers received intravenous infusions of placebo, 12.5 mg/kg, and 25.0 mg/kg of body weight of 2-DG over 30 min on three separate days, following a random-ordered, double-blind procedure. Minimal effects were observed following administration of the 12.5 mg/kg of body weight dose of 2-DG. Following 25.0 mg/kg, alcoholics showed both exaggerated ACTH and cortisol responses and greater increases in caloric intake when compared with controls. Although anxiety, desire to consume alcohol, plasma progesterone, and sympathetic and adrenal medullary activity all increased following 2-DG, these responses did not differ between alcoholics and controls. The present findings suggest certain specificity for the exaggerated hypothalamic and adrenocortical responses to mild glucoprivic stress in 3-week-abstinent alcoholics. JF - Alcoholism, clinical and experimental research AU - George, D T AU - Lindquist, T AU - Alim, T AU - Flood, M AU - Eckardt, M J AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 685 EP - 691 VL - 18 IS - 3 SN - 0145-6008, 0145-6008 KW - Blood Glucose KW - 0 KW - Insulin KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Double-Blind Method KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Feeding Behavior -- physiology KW - Insulin -- blood KW - Energy Intake -- physiology KW - Humans KW - Arousal -- physiology KW - Energy Intake -- drug effects KW - Hydrocortisone -- blood KW - Arousal -- drug effects KW - Adult KW - Male KW - Adrenocorticotropic Hormone -- blood KW - Alcoholism -- rehabilitation KW - Blood Glucose -- metabolism KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Pituitary-Adrenal System -- physiopathology KW - Temperance KW - Alcoholism -- physiopathology KW - Stress, Physiological -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76781289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Abstinent+alcoholics+exhibit+an+exaggerated+stress+response+to+2-deoxy-D-glucose+challenge.&rft.au=George%2C+D+T%3BLindquist%2C+T%3BAlim%2C+T%3BFlood%2C+M%3BEckardt%2C+M+J%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1994-06-01&rft.volume=18&rft.issue=3&rft.spage=685&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-24 N1 - Date created - 1994-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An uptake system for dietary alkaloids in poison frogs (Dendrobatidae). AN - 76779820; 7940573 AB - The skin of poison frogs (Dendrobatidae) contains a wide variety of alkaloids that presumably serve a defensive role. These alkaloids persist for years in captivity, but are not present in captive-raised frogs. Alkaloids fed to poison frogs (Dendrobates, Phyllobates, Epipedobates) are readily accumulated into skin, where they remain for months. The process can be selective; an ant indolizidine is accumulated, while an ant pyrrolidine is not. Frogs (Colostethus) of the same family, which do not normally contain alkaloids, do not accumulate alkaloids. Such an alkaloid uptake system provides a means of maintaining skin alkaloids and suggests that some if not all such 'dendrobatid alkaloids' may have a dietary origin. JF - Toxicon : official journal of the International Society on Toxinology AU - Daly, J W AU - Secunda, S I AU - Garraffo, H M AU - Spande, T F AU - Wisnieski, A AU - Cover, J F AD - Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 657 EP - 663 VL - 32 IS - 6 SN - 0041-0101, 0041-0101 KW - Alkaloids KW - 0 KW - Poisons KW - Index Medicus KW - Animals KW - Chromatography, Gas KW - Diet KW - Poisons -- metabolism KW - Ranidae -- metabolism KW - Alkaloids -- metabolism KW - Skin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76779820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.atitle=An+uptake+system+for+dietary+alkaloids+in+poison+frogs+%28Dendrobatidae%29.&rft.au=Daly%2C+J+W%3BSecunda%2C+S+I%3BGarraffo%2C+H+M%3BSpande%2C+T+F%3BWisnieski%2C+A%3BCover%2C+J+F&rft.aulast=Daly&rft.aufirst=J&rft.date=1994-06-01&rft.volume=32&rft.issue=6&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Toxicon+%3A+official+journal+of+the+International+Society+on+Toxinology&rft.issn=00410101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-25 N1 - Date created - 1994-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in the brain: implications for the study of human alcoholism. AN - 76775862; 7943685 AB - Gender differences in alcohol intake and response to alcohol may be influenced by basic variations in the organization and modulation of male and female brains. Although a number of genetic, social, environmental, and metabolic factors have been proposed to explain the gender differences observed in risk for alcoholism, alcohol intake, and medical consequences of excessive alcohol intake, very little attention has been given to the role of gender differences in the brain regarding alcohol use. Recent evidence documents the influence of neurosteroids on neurotransmitter activity in the brain and the impact of alcohol on neurosteroid levels. Neurosteroids are found in different levels in males and females during development and throughout life, depending on factors such as age, stage of development, estrous and menstrual cycles, and stress. This study discusses the hypothesis that many of the gender differences observed concerning alcohol use and misuse are determined by gender differences in the brain, which in turn differentially influence the behavioral and neurochemical responses of males and females to alcohol. JF - Alcoholism, clinical and experimental research AU - Lancaster, F E AD - Division of Basic Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 740 EP - 746 VL - 18 IS - 3 SN - 0145-6008, 0145-6008 KW - Gonadal Steroid Hormones KW - 0 KW - Receptors, Neurotransmitter KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Receptors, Neurotransmitter -- physiology KW - Ethanol -- pharmacokinetics KW - Humans KW - Metabolic Clearance Rate -- physiology KW - Neurons -- physiology KW - Gonadal Steroid Hormones -- physiology KW - Neuroglia -- physiology KW - Male KW - Female KW - Brain -- physiopathology KW - Sex Characteristics KW - Alcoholism -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76775862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Gender+differences+in+the+brain%3A+implications+for+the+study+of+human+alcoholism.&rft.au=Lancaster%2C+F+E&rft.aulast=Lancaster&rft.aufirst=F&rft.date=1994-06-01&rft.volume=18&rft.issue=3&rft.spage=740&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-24 N1 - Date created - 1994-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of cis-elements mediating the stimulation of rat insulin-like growth factor-binding protein-1 promoter activity by dexamethasone, cyclic adenosine 3',5'-monophosphate, and phorbol esters, and inhibition by insulin. AN - 76761871; 7523864 AB - Insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the action of IGFs on target cells. IGFBP-1 transcription is highly regulated by hormonal and metabolic factors. In rat H4-II-E hepatoma cells, IGFBP-1 messenger RNA is stimulated by dexamethasone, cAMP, and phorbol esters, and dominantly inhibited by insulin. To identify the cis-elements that determine transcriptional regulation by these agents, we have coupled rat IGFBP-1 promoter fragments to a luciferase reporter gene and transfected H4-II-E cells using the cationic liposome procedure. Promoter fragments whose 5'-end was at nucleotide (nt) -925 or -327 (with respect to the transcription initiation site, 1) conferred positive regulation of promoter activity by dexamethasone, cAMP, and phorbol esters. Insulin inhibited promoter activity in the presence of any of the three stimulatory agents. Stimulation by cAMP or phorbol esters was abolished when the region between nt -327 and -235 was deleted. Although this region contains potential activating protein-2 and activating protein-1 sites, the sites responsible for this regulation have not yet been identified. By contrast, stimulation by dexamethasone was retained in deletion constructs whose 5'-end was at nt -92, but was abolished by site mutagenesis of either the left or right half-sites of a potential glucocorticoid response element (GRE) located between nt -91 and -77. Surprisingly, substitution mutations in an up-stream region, -108 to -99 (M4), also decreased dexamethasone-stimulated promoter activity despite the presence of an intact GRE. We postulate that a positive factor that binds to the wild-type M4 region neutralizes factors that inhibit interaction of the glucocorticoid receptor with the GRE. The M4 region also is involved in inhibition by insulin. Insulin inhibition of dexamethasone-stimulated promoter activity was lost after deletion of nt -135 to -92 or mutation of the region between nt -108 and -99. This insulin response element is conserved in the human IGFBP-1 promoter and is homologous to the insulin response element of the phosphoenolpyruvate carboxykinase gene, which also is rapidly inhibited by insulin in H4-II-E cells. The rat IGFBP-1 promoter provides a valuable model system for studying the multihormonal regulation of transcription. JF - Molecular endocrinology (Baltimore, Md.) AU - Suh, D S AU - Ooi, G T AU - Rechler, M M AD - Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 794 EP - 805 VL - 8 IS - 6 SN - 0888-8809, 0888-8809 KW - Carrier Proteins KW - 0 KW - Glucocorticoids KW - Insulin KW - Insulin-Like Growth Factor Binding Protein 1 KW - Nucleotides KW - Phorbol Esters KW - RNA, Messenger KW - Dexamethasone KW - 7S5I7G3JQL KW - DNA KW - 9007-49-2 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Promoter Regions, Genetic -- physiology KW - Animals KW - Liver Neoplasms, Experimental -- metabolism KW - RNA, Messenger -- analysis KW - DNA -- analysis KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Glucocorticoids -- pharmacology KW - Gene Deletion KW - Rats KW - Base Sequence KW - Tumor Cells, Cultured KW - Liver Neoplasms, Experimental -- pathology KW - DNA -- genetics KW - Molecular Sequence Data KW - Genes, Reporter KW - Liver Neoplasms, Experimental -- physiopathology KW - Promoter Regions, Genetic -- genetics KW - Gene Expression Regulation -- drug effects KW - Nucleotides -- physiology KW - Mutation KW - Nucleotides -- analysis KW - Phorbol Esters -- pharmacology KW - Enhancer Elements, Genetic -- physiology KW - Carrier Proteins -- antagonists & inhibitors KW - Dexamethasone -- pharmacology KW - Carrier Proteins -- genetics KW - Cyclic AMP -- pharmacology KW - Enhancer Elements, Genetic -- genetics KW - Carrier Proteins -- physiology KW - Insulin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76761871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Identification+of+cis-elements+mediating+the+stimulation+of+rat+insulin-like+growth+factor-binding+protein-1+promoter+activity+by+dexamethasone%2C+cyclic+adenosine+3%27%2C5%27-monophosphate%2C+and+phorbol+esters%2C+and+inhibition+by+insulin.&rft.au=Suh%2C+D+S%3BOoi%2C+G+T%3BRechler%2C+M+M&rft.aulast=Suh&rft.aufirst=D&rft.date=1994-06-01&rft.volume=8&rft.issue=6&rft.spage=794&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measurement of relative cerebral blood volume changes with visual stimulation by 'double-dose' gadopentetate-dimeglumine-enhanced dynamic magnetic resonance imaging. AN - 76749333; 7928216 JF - Investigative radiology AU - Frank, J A AU - Mattay, V S AU - Duyn, J AU - Sobering, G AU - Barrios, F A AU - Zigun, J AU - Sexton, R AU - Kwok, P AU - Woo, J AU - Moonen, C AD - Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - S157 EP - S160 VL - 29 Suppl 2 SN - 0020-9996, 0020-9996 KW - Contrast Media KW - 0 KW - Organometallic Compounds KW - Pentetic Acid KW - 7A314HQM0I KW - Gadolinium DTPA KW - K2I13DR72L KW - Index Medicus KW - Cerebral Cortex -- blood supply KW - Injections, Intravenous KW - Humans KW - Geniculate Bodies -- blood supply KW - Magnetic Resonance Imaging KW - Contrast Media -- adverse effects KW - Photic Stimulation KW - Organometallic Compounds -- administration & dosage KW - Blood Volume KW - Pentetic Acid -- analogs & derivatives KW - Pentetic Acid -- adverse effects KW - Pentetic Acid -- administration & dosage KW - Contrast Media -- administration & dosage KW - Organometallic Compounds -- adverse effects KW - Cerebrovascular Circulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76749333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+radiology&rft.atitle=Measurement+of+relative+cerebral+blood+volume+changes+with+visual+stimulation+by+%27double-dose%27+gadopentetate-dimeglumine-enhanced+dynamic+magnetic+resonance+imaging.&rft.au=Frank%2C+J+A%3BMattay%2C+V+S%3BDuyn%2C+J%3BSobering%2C+G%3BBarrios%2C+F+A%3BZigun%2C+J%3BSexton%2C+R%3BKwok%2C+P%3BWoo%2C+J%3BMoonen%2C+C&rft.aulast=Frank&rft.aufirst=J&rft.date=1994-06-01&rft.volume=29+Suppl+2&rft.issue=&rft.spage=S157&rft.isbn=&rft.btitle=&rft.title=Investigative+radiology&rft.issn=00209996&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-01 N1 - Date created - 1994-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excitatory amino acid receptors in glial progenitor cells: molecular and functional properties. AN - 76747908; 7927651 AB - We have analyzed the molecular and biophysical properties of glutamate-gated channels in cells of the oligodendrocyte lineage, using both the CG-4 primary cell line (Louis et al: J. Neurosci. Res. 31:193-204, 1992a) and oligodendrocyte progenitors purified from the rat cerebral cortex. CG-4 progenitor cells, as well as primary progenitors, were stained with a specific anti-GABA antibody. In whole-cell patch-clamp recordings, rapid perfusion of the agonists L-glutamate, kainate, and AMPA produced rapidly desensitizing currents in CG-4 cells. NMDA was ineffective. Both rapidly desensitizing and steady-state components of responses to kainate were inhibited by the kainate/AMPA receptor antagonist CNQX. Northern blot analysis of total mRNA isolated from CG-4 cells revealed co-expression of both AMPA- and kainate-preferring glutamate receptor subunits. The activation of glutamate receptors in CG-4 cells caused a rapid and transient elevation of mRNAs for the immediate early gene NGFI-A. JF - Glia AU - Gallo, V AU - Patneau, D K AU - Mayer, M L AU - Vaccarino, F M AD - Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 94 EP - 101 VL - 11 IS - 2 SN - 0894-1491, 0894-1491 KW - Egr-1 KW - zif/268 KW - DNA-Binding Proteins KW - 0 KW - Early Growth Response Protein 1 KW - Egr1 protein, rat KW - Immediate-Early Proteins KW - Nerve Tissue Proteins KW - Neurotoxins KW - Receptors, Glutamate KW - Transcription Factors KW - Glutamic Acid KW - 3KX376GY7L KW - N-Methylaspartate KW - 6384-92-5 KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Animals KW - Cerebral Cortex -- cytology KW - Kainic Acid -- pharmacology KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - DNA-Binding Proteins -- biosynthesis KW - Transcription Factors -- biosynthesis KW - Rats KW - Genes, Immediate-Early -- drug effects KW - Cells, Cultured KW - N-Methylaspartate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Membrane Potentials -- drug effects KW - Stem Cells -- drug effects KW - Nerve Tissue Proteins -- physiology KW - Oligodendroglia -- drug effects KW - Receptors, Glutamate -- drug effects KW - Receptors, Glutamate -- physiology KW - Neurotoxins -- pharmacology KW - Stem Cells -- physiology KW - Glutamic Acid -- pharmacology KW - Oligodendroglia -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76747908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glia&rft.atitle=Excitatory+amino+acid+receptors+in+glial+progenitor+cells%3A+molecular+and+functional+properties.&rft.au=Gallo%2C+V%3BPatneau%2C+D+K%3BMayer%2C+M+L%3BVaccarino%2C+F+M&rft.aulast=Gallo&rft.aufirst=V&rft.date=1994-06-01&rft.volume=11&rft.issue=2&rft.spage=94&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=08941491&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-18 N1 - Date created - 1994-11-18 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Egr-1; zif/268 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Summary of the National Toxicology Program benzidine dye initiative. AN - 76740212; 7925189 AB - The benzidine dye initiative is a research program established by the National Toxicology Program to generate an integrated body of scientific information regarding the potential health risks associated with exposure to benzidine- and benzidine-congener-derived dyes. Because an in-depth evaluation of each of the hundreds of benzidine-congener-derived dyes was considered impractical, the research program was designed to study the metabolism and disposition, genetic toxicity, and in vivo toxicity and carcinogenicity of two primary benzidine congeners, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, and a select group of prototypical dyes derived from those amines. It was anticipated that by applying the basic information generated in these extensive studies, it would be possible to make regulatory decisions about other dyes after conducting only a minimal number of experiments such as studies of disposition and metabolism, and in vitro mutagenicity. This paper summarizes the results of studies conducted to evaluate the metabolism, disposition, mutagenicity, toxicity, and carcinogenicity of representative benzidine congeners and derived dyes. JF - Environmental health perspectives AU - Morgan, D L AU - Dunnick, J K AU - Goehl, T AU - Jokinen, M P AU - Matthews, H B AU - Zeiger, E AU - Mennear, J H AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 63 EP - 78 VL - 102 Suppl 2 SN - 0091-6765, 0091-6765 KW - Benzidines KW - 0 KW - Carcinogens KW - Coloring Agents KW - Mutagens KW - Index Medicus KW - Animals KW - Environmental Exposure KW - Carcinogenicity Tests KW - Mutagens -- toxicity KW - Research Design KW - Toxicology KW - Benzidines -- metabolism KW - Carcinogens -- metabolism KW - Coloring Agents -- toxicity KW - Carcinogens -- chemistry KW - Carcinogens -- toxicity KW - Coloring Agents -- metabolism KW - Coloring Agents -- chemistry KW - Benzidines -- toxicity KW - Benzidines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76740212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Summary+of+the+National+Toxicology+Program+benzidine+dye+initiative.&rft.au=Morgan%2C+D+L%3BDunnick%2C+J+K%3BGoehl%2C+T%3BJokinen%2C+M+P%3BMatthews%2C+H+B%3BZeiger%2C+E%3BMennear%2C+J+H&rft.aulast=Morgan&rft.aufirst=D&rft.date=1994-06-01&rft.volume=102+Suppl+2&rft.issue=&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-23 N1 - Date created - 1994-11-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1968 Oct;41(4):985-1036 [5686039] Acta Unio Int Contra Cancrum. 1963;19:499-501 [14050592] J Natl Cancer Inst. 1975 Jul;55(1):181-2 [808635] J Toxicol Environ Health. 1976 Jan;1(3):421-32 [1550] Cancer Res. 1979 Aug;39(8):3107-13 [455295] Toxicol Appl Pharmacol. 1979 Apr;48(2):237-48 [473173] Toxicol Appl Pharmacol. 1980 Jul;54(3):431-42 [7394798] Toxicol Appl Pharmacol. 1980 Nov;56(2):248-58 [7466824] Vet Pathol. 1981 Mar;18(2):228-38 [7467083] Toxicol Lett. 1980 Nov;7(1):29-36 [7292513] Mutat Res. 1982 Apr;97(2):103-16 [7043259] Cancer Res. 1982 Jul;42(7):2678-86 [7083160] Biochem Biophys Res Commun. 1982 Aug 31;107(4):1224-9 [6814437] Environ Health Perspect. 1983 Mar;49:101-6 [6832087] Environ Health Perspect. 1983 Mar;49:125-34 [6339219] Drug Metab Dispos. 1983 Mar-Apr;11(2):109-14 [6133713] Drug Metab Dispos. 1983 Jul-Aug;11(4):293-300 [6137333] Environ Mutagen. 1984;6(2):145-51 [6368218] Toxicol Appl Pharmacol. 1984 Jan;72(1):1-14 [6710475] Cancer Res. 1984 May;44(5):1893-7 [6424934] Mutat Res. 1984 Apr;136(1):33-47 [6371512] Nature. 1984 May 31-Jun 6;309(5967):464-6 [6328318] Environ Mutagen. 1984;6(5):705-17 [6383795] Fundam Appl Toxicol. 1984 Dec;4(6):949-59 [6519375] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3849-53 [2987950] Carcinogenesis. 1985 Jul;6(7):959-65 [4017176] Adv Exp Med Biol. 1986;197:537-49 [3766280] Environ Mutagen. 1987;9 Suppl 9:1-109 [3552650] Environ Health Perspect. 1988 Apr;77:33-6 [3383821] Cancer Res. 1989 Apr 15;49(8):1977-82 [2495173] Toxicol Pathol. 1989;17(1 Pt 1):50-6 [2749136] Cancer Res. 1990 Jan 15;50(2):266-72 [2403837] Food Chem Toxicol. 1989 Dec;27(12):801-6 [2558063] Toxicology. 1989 Dec 15;59(3):297-309 [2631298] Carcinogenesis. 1992 Jul;13(7):1235-40 [1638692] Cancer. 1950 Sep;3(5):789-804 [14772711] J Pharmacol Exp Ther. 1957 Jul;120(3):291-300 [13476352] Arch Environ Health. 1961 Apr;2:423-8 [13749285] Clin Toxicol. 1975;8(1):13-42 [805682] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hematopoietic malignancies and related disorders among benzene-exposed workers in China. AN - 76739669; 7920231 AB - Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7--myelodysplastic syndrome (MDS), 9--chronic granulocytic leukemia (CGL), 20--malignant lymphoma or related disorder (ML), 9--aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2--CGL, 3--ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also indicate that a greater diversity of hematologic neoplasms is evident among benzene-exposed workers than previously described. JF - Leukemia & lymphoma AU - Travis, L B AU - Li, C Y AU - Zhang, Z N AU - Li, D G AU - Yin, S N AU - Chow, W H AU - Li, G L AU - Dosemeci, M AU - Blot, W AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 91 EP - 102 VL - 14 IS - 1-2 SN - 1042-8194, 1042-8194 KW - Air Pollutants, Occupational KW - 0 KW - Benzene KW - J64922108F KW - Index Medicus KW - Anemia, Aplastic -- epidemiology KW - Medical Records KW - Anemia, Aplastic -- chemically induced KW - Anemia, Aplastic -- pathology KW - Humans KW - Air Pollutants, Occupational -- adverse effects KW - Retrospective Studies KW - Myelodysplastic Syndromes -- chemically induced KW - Myelodysplastic Syndromes -- pathology KW - China -- epidemiology KW - Adult KW - Cohort Studies KW - Incidence KW - Myelodysplastic Syndromes -- epidemiology KW - Middle Aged KW - Female KW - Male KW - Leukemia -- pathology KW - Lymphoma -- epidemiology KW - Leukemia -- chemically induced KW - Leukemia -- epidemiology KW - Occupational Diseases -- pathology KW - Lymphoma -- chemically induced KW - Occupational Diseases -- epidemiology KW - Lymphoma -- pathology KW - Occupational Diseases -- chemically induced KW - Benzene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76739669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=Hematopoietic+malignancies+and+related+disorders+among+benzene-exposed+workers+in+China.&rft.au=Travis%2C+L+B%3BLi%2C+C+Y%3BZhang%2C+Z+N%3BLi%2C+D+G%3BYin%2C+S+N%3BChow%2C+W+H%3BLi%2C+G+L%3BDosemeci%2C+M%3BBlot%2C+W%3BFraumeni%2C+J+F&rft.aulast=Travis&rft.aufirst=L&rft.date=1994-06-01&rft.volume=14&rft.issue=1-2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=10428194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-14 N1 - Date created - 1994-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cycloheximide inhibits the cytotoxicity of paclitaxel (Taxol). AN - 76733706; 7919452 AB - Treatment of human breast (MCF-7) and lung (A549) adenocarcinoma cell lines with 10 micrograms/ml cycloheximide provided substantial protection from paclitaxel-induced cytotoxicity. Addition of cycloheximide to cells at 0, 6, 12 or 18 h into a 24 h exposure to paclitaxel resulted in cytotoxicity similar to that found in cells treated with paclitaxel alone for only 0, 6, 12 or 18 h, respectively. DNA flow cytometry showed that paclitaxel blocked cells in G2/M. Mitotic index studies demonstrated that paclitaxel arrested cells in mitosis and that prolonged exposure to paclitaxel resulted in the development of multiple micronuclei. Concurrent incubation of cells in cycloheximide prevented the development of a G2/M block, mitotic arrest and micronuclei formation. The addition of cycloheximide to cells at 6 or 12 h into a 24 h exposure to paclitaxel reduced the degree of G2/M block to that produced by incubation of cells in paclitaxel alone for only 6 or 12 h. Mitotic index studies confirmed that cells treated with cycloheximide during paclitaxel exposure had a marked reduction in the percentage of cells in mitosis. However, the percentage of paclitaxel-treated cells which had multiple micronuclei was increased in cells treated with cycloheximide. These results indicate that entry into mitosis is a prerequisite for paclitaxel-induced cytotoxicity and that cycloheximide reduces cytotoxicity due to paclitaxel by preventing cells from entering mitosis. However, once cells have entered mitosis in the presence of paclitaxel, protein synthesis is not required for the development of multiple micronuclei and cytotoxicity. JF - Anti-cancer drugs AU - Liebmann, J AU - Cook, J A AU - Teague, D AU - Fisher, J AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 287 EP - 292 VL - 5 IS - 3 SN - 0959-4973, 0959-4973 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Cycloheximide KW - 98600C0908 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Neoplasm Proteins -- biosynthesis KW - Adenocarcinoma -- metabolism KW - Drug Interactions KW - Tumor Cells, Cultured -- drug effects KW - Mitotic Index -- drug effects KW - Humans KW - Lung Neoplasms -- drug therapy KW - Breast Neoplasms -- metabolism KW - DNA, Neoplasm -- analysis KW - Cell Death -- drug effects KW - Adenocarcinoma -- pathology KW - DNA, Neoplasm -- drug effects KW - Breast Neoplasms -- pathology KW - Flow Cytometry KW - Adenocarcinoma -- drug therapy KW - Cell Cycle -- drug effects KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism KW - Paclitaxel -- antagonists & inhibitors KW - Paclitaxel -- toxicity KW - Cycloheximide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76733706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Cycloheximide+inhibits+the+cytotoxicity+of+paclitaxel+%28Taxol%29.&rft.au=Liebmann%2C+J%3BCook%2C+J+A%3BTeague%2C+D%3BFisher%2C+J%3BMitchell%2C+J+B&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1994-06-01&rft.volume=5&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro antitumor effect of hydroxyurea on hormone-refractory prostate cancer cells and its potentiation by phenylbutyrate. AN - 76733699; 7919459 AB - Previous clinical trials have suggested that hydroxyurea may possess some activity against prostate cancer. The in vitro antiproliferative activity of hydroxyurea was evaluated in three hormone-refractory prostate cancer cell lines, PC-3, DU-145 and PC-3M. Fifty-percent inhibition of growth in all three cell lines required prolonged (120 h) exposure to hydroxyurea at a concentration of approximately 100 microM. Using pharmacokinetic data obtained during the course of a clinical trial of hydroxyurea, we simulated a dosing regimen that would sustain plasma drug concentrations above 100 microM for 120 h (1 g loading dose, followed by 500 mg every 6 h for 5 days in a 70 kg man). Since this dosing regimen is likely to generate an unacceptable degree of myelosuppression, in vitro combination studies were conducted with hydroxyurea and phenylbutyrate, a new differentiating agent with no myelosuppressive effects. These studies resulted in a reduction of the hydroxyurea concentration necessary for 50% growth inhibition (50 microM of hydroxyurea plus 0.5 mM of phenylbutyrate). A regimen designed to achieve that hydroxyurea concentration (400 mg loading dose, followed by 200 mg every 6 h for 5 days) should be clinically achievable. Based on these results, this combination deserves further evaluation in patients with stage D prostate cancer. JF - Anti-cancer drugs AU - Figg, W D AU - Walls, R G AU - Cooper, M R AU - Thibault, A AU - Sartor, O AU - McCall, N A AU - Myers, C E AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 336 EP - 342 VL - 5 IS - 3 SN - 0959-4973, 0959-4973 KW - Hormones KW - 0 KW - Phenylbutyrates KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Cell Survival -- drug effects KW - Tumor Cells, Cultured -- drug effects KW - Kinetics KW - Humans KW - Cell Division -- drug effects KW - Drug Synergism KW - Models, Biological KW - Male KW - Prostatic Neoplasms -- pathology KW - Hormones -- pharmacology KW - Phenylbutyrates -- pharmacology KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Neoplasms, Hormone-Dependent -- pathology KW - Hydroxyurea -- pharmacology KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76733699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=In+vitro+antitumor+effect+of+hydroxyurea+on+hormone-refractory+prostate+cancer+cells+and+its+potentiation+by+phenylbutyrate.&rft.au=Figg%2C+W+D%3BWalls%2C+R+G%3BCooper%2C+M+R%3BThibault%2C+A%3BSartor%2C+O%3BMcCall%2C+N+A%3BMyers%2C+C+E%3BSamid%2C+D&rft.aulast=Figg&rft.aufirst=W&rft.date=1994-06-01&rft.volume=5&rft.issue=3&rft.spage=336&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis: death as a "vital" biological function. AN - 76721346; 7917871 JF - Pediatric nephrology (Berlin, Germany) AU - Schnaper, H W AD - Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 377 EP - 382 VL - 8 IS - 3 SN - 0931-041X, 0931-041X KW - Oxidants KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Index Medicus KW - Animals KW - Humans KW - Cell Death KW - Immune System -- physiology KW - Proto-Oncogene Proteins -- physiology KW - Apoptosis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+nephrology+%28Berlin%2C+Germany%29&rft.atitle=Apoptosis%3A+death+as+a+%22vital%22+biological+function.&rft.au=Schnaper%2C+H+W&rft.aulast=Schnaper&rft.aufirst=H&rft.date=1994-06-01&rft.volume=8&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Pediatric+nephrology+%28Berlin%2C+Germany%29&rft.issn=0931041X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-24 N1 - Date created - 1994-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma. AN - 76717875; 8092829 AB - Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls. At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log10 CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 micrograms/ml; range, < 0.5 to 16.8 micrograms/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A. fumigatus. This model demonstrated that levels in plasma of greater than 6 micrograms/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 micrograms/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis. JF - Antimicrobial agents and chemotherapy AU - Berenguer, J AU - Ali, N M AU - Allende, M C AU - Lee, J AU - Garrett, K AU - Battaglia, S AU - Piscitelli, S C AU - Rinaldi, M G AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1303 EP - 1308 VL - 38 IS - 6 SN - 0066-4804, 0066-4804 KW - Itraconazole KW - 304NUG5GF4 KW - Amphotericin B KW - 7XU7A7DROE KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Animals KW - Drug Interactions KW - Kidney -- drug effects KW - Rabbits KW - Female KW - Cyclosporine -- blood KW - Lung Diseases, Fungal -- drug therapy KW - Itraconazole -- therapeutic use KW - Aspergillosis -- drug therapy KW - Itraconazole -- toxicity KW - Amphotericin B -- therapeutic use KW - Itraconazole -- blood KW - Amphotericin B -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76717875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Itraconazole+for+experimental+pulmonary+aspergillosis%3A+comparison+with+amphotericin+B%2C+interaction+with+cyclosporin+A%2C+and+correlation+between+therapeutic+response+and+itraconazole+concentrations+in+plasma.&rft.au=Berenguer%2C+J%3BAli%2C+N+M%3BAllende%2C+M+C%3BLee%2C+J%3BGarrett%2C+K%3BBattaglia%2C+S%3BPiscitelli%2C+S+C%3BRinaldi%2C+M+G%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Berenguer&rft.aufirst=J&rft.date=1994-06-01&rft.volume=38&rft.issue=6&rft.spage=1303&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-17 N1 - Date created - 1994-10-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):424-9 [1310577] J Clin Pathol. 1991 Jun;44(6):452-4 [2066421] Chemotherapy. 1992;38(2):118-26 [1317280] Antimicrob Agents Chemother. 1992 Feb;36(2):477-80 [1605615] Eur J Cancer. 1992;28A(4-5):838-41 [1326309] J Pharm Pharmacol. 1992 Jul;44(7):618-9 [1357148] Medicine (Baltimore). 1975 Nov;54(6):499-507 [1186493] Clin Pharmacol Ther. 1977 Jul;22(1):42-57 [872495] Transplantation. 1983 Mar;35(3):211-5 [6340275] Antimicrob Agents Chemother. 1983 Dec;24(6):921-4 [6660859] Sabouraudia. 1985 Jun;23(3):219-23 [2992106] Rev Infect Dis. 1987 Jan-Feb;9 Suppl 1:S15-32 [3027843] Rev Infect Dis. 1987 Jan-Feb;9 Suppl 1:S94-9 [3027853] Lancet. 1987 Aug 1;2(8553):282 [2886752] Lancet. 1987 Oct 17;2(8564):920-1 [2889119] J Clin Oncol. 1987 Dec;5(12):1985-93 [3681380] Lancet. 1987 Dec 5;2(8571):1335-6 [2890938] Am J Med. 1989 Jun;86(6 Pt 2):791-800 [2543220] Drugs. 1989 Mar;37(3):310-44 [2540949] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Arch Intern Med. 1989 Oct;149(10):2301-8 [2552949] Mycoses. 1989;32 Suppl 1:67-87 [2561187] Antimicrob Agents Chemother. 1990 Mar;34(3):448-54 [2159257] Ann Intern Med. 1990 Aug 15;113(4):327-9 [2165371] J Am Acad Dermatol. 1990 Sep;23(3 Pt 2):587-93 [2170478] J Am Acad Dermatol. 1990 Sep;23(3 Pt 2):607-14 [2170481] Semin Respir Infect. 1990 Jun;5(2):111-22 [2247706] Rev Infect Dis. 1990 Nov-Dec;12(6):1147-201 [2267490] N Engl J Med. 1991 Mar 7;324(10):654-62 [1994248] Clin Infect Dis. 1992 Jan;14(1):165-74 [1315160] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Satisfactorily attenuated and protective mutants derived from a partially attenuated cold-passaged respiratory syncytial virus mutant by introduction of additional attenuating mutations during chemical mutagenesis. AN - 76716507; 8091846 AB - A cold-passaged RSV mutant, designated cp-RSV, which acquired host range mutations during 52 passages at low temperature in bovine tissue culture, was completely attenuated for seropositive adults and children but retained the capacity to cause upper respiratory disease in seronegative infants. We sought to introduce additional attenuating mutations, such as temperature-sensitive (ts) and small-plaque (sp) mutations, into the cp-RSV mutant, which is a ts+ virus, in order to generate a mutant which would be satisfactorily attenuated in seronegative infants and young children. Nine mutants of cp-RSV, which had acquired either the ts or small-plaque sp phenotype, were generated by chemical mutagenesis with 5-fluorouracil. The two ts mutants with the lowest in vitro shut-off temperature, namely the cpts-248 (38 degrees C) and cpts-530 (39 degrees C) mutants, were the most restricted of the nine cp-RSV mutant progeny tested for efficiency of replication in Balb/c mice. In seronegative chimpanzees, the cpts-248 mutant replicated fourfold less efficiently in the nasopharynx and caused significantly less rhinorrhoea than its cp-RSV parent. The cpts-248 mutant virus, like its cp-RSV parent, was 1000-fold restricted in replication in the trachea compared with wild-type RSV. Previously, another candidate RSV live attenuated vaccine strain, a mutant designated ts-1, exhibited some instability of its ts phenotype following replication in susceptible humans or chimpanzees. Hence, we sought cp-RSV ts progeny that exhibited a greater degree of stability of the ts phenotype than the prototype ts-1 mutant.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Vaccine AU - Crowe, J E AU - Bui, P T AU - London, W T AU - Davis, A R AU - Hung, P P AU - Chanock, R M AU - Murphy, B R AD - Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 691 EP - 699 VL - 12 IS - 8 SN - 0264-410X, 0264-410X KW - Vaccines, Attenuated KW - 0 KW - Viral Vaccines KW - Index Medicus KW - Virus Replication KW - Animals KW - Humans KW - Cold Temperature KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Mutagenesis KW - Pan troglodytes KW - Vaccines, Attenuated -- immunology KW - Serial Passage KW - Cercopithecus aethiops KW - Vaccines, Attenuated -- genetics KW - Vero Cells KW - Respiratory Syncytial Virus Infections -- prevention & control KW - Cell Line KW - Female KW - Male KW - Respiratory Syncytial Viruses -- immunology KW - Viral Vaccines -- genetics KW - Viral Vaccines -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76716507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Satisfactorily+attenuated+and+protective+mutants+derived+from+a+partially+attenuated+cold-passaged+respiratory+syncytial+virus+mutant+by+introduction+of+additional+attenuating+mutations+during+chemical+mutagenesis.&rft.au=Crowe%2C+J+E%3BBui%2C+P+T%3BLondon%2C+W+T%3BDavis%2C+A+R%3BHung%2C+P+P%3BChanock%2C+R+M%3BMurphy%2C+B+R&rft.aulast=Crowe&rft.aufirst=J&rft.date=1994-06-01&rft.volume=12&rft.issue=8&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes. AN - 76711153; 8086337 AB - Exposure to estrogens during critical periods of development induces teratogenic and carcinogenic lesions in the reproductive tracts of humans and experimental animals. It is important to determine the molecular and cellular targets of estrogenic chemicals and to establish the mechanisms by which interactions of estrogens with the developing genital tract results in permanent lesions of growth and differentiation. The experiments presented here were designed to examined the effects of neonatal estrogen exposure on the expression of two genes, lactoferrin and epidermal growth factor, that are subject to steroid hormone regulation. Using in situ and Northern RNA hybridization, immunoblotting, and immunohistochemistry, our data demonstrate that exposure to the synthetic estrogen, diethylstilbestrol, during a critical neonatal period results in the persistent ovary-independent induction of mRNA and protein encoded by these two genes in the mouse uterus and vagina. The constitutive expression of lactoferrin and EGF, and probably other estrogen-regulated genes, may contribute to the establishment of a permanently "estrogenized" phenotype which is then instrumental in the development of abnormal tissue morphogenesis, function, and neoplasia in the rodent reproductive tract. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Nelson, K G AU - Sakai, Y AU - Eitzman, B AU - Steed, T AU - McLachlan, J AD - National Institute of Environmental Health Sciences, Laboratory of Developmental and Reproductive Toxicology, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 595 EP - 606 VL - 5 IS - 6 SN - 1044-9523, 1044-9523 KW - RNA, Messenger KW - 0 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Mice, Inbred Strains KW - Animals, Newborn KW - Animals KW - In Situ Hybridization KW - Blotting, Western KW - Mice KW - Immunohistochemistry KW - RNA, Messenger -- biosynthesis KW - Female KW - Vagina -- drug effects KW - Uterus -- metabolism KW - Uterus -- growth & development KW - Lactoferrin -- genetics KW - Epidermal Growth Factor -- biosynthesis KW - Lactoferrin -- biosynthesis KW - Diethylstilbestrol -- toxicity KW - Epidermal Growth Factor -- genetics KW - Vagina -- growth & development KW - Vagina -- metabolism KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76711153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Exposure+to+diethylstilbestrol+during+a+critical+developmental+period+of+the+mouse+reproductive+tract+leads+to+persistent+induction+of+two+estrogen-regulated+genes.&rft.au=Nelson%2C+K+G%3BSakai%2C+Y%3BEitzman%2C+B%3BSteed%2C+T%3BMcLachlan%2C+J&rft.aulast=Nelson&rft.aufirst=K&rft.date=1994-06-01&rft.volume=5&rft.issue=6&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-20 N1 - Date created - 1994-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of centrifuging shell vials at 3,500 x g on detection of viruses in clinical specimens. AN - 76691704; 8077407 AB - An increase in shell vial centrifugation force to 3,500 x g and a concomitant reduction in spin time to 15 min did not decrease the sensitivity of detecting viruses in clinical specimens compared with the accepted practice of using 700 x g for 40 min. No damage to the cell monolayer (ML) at the higher g force was observed. Toxicity to the ML is decreased with the shorter spin, probably because of reduced time of contact between the specimen and the ML. JF - Journal of clinical microbiology AU - Engler, H D AU - Selepak, S T AD - Clinical Pathology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-0001. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1580 EP - 1582 VL - 32 IS - 6 SN - 0095-1137, 0095-1137 KW - Index Medicus KW - Sensitivity and Specificity KW - Evaluation Studies as Topic KW - Humans KW - Specimen Handling KW - Time Factors KW - Centrifugation KW - Virology -- instrumentation KW - Viruses -- isolation & purification KW - Virology -- methods KW - Virus Diseases -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76691704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+microbiology&rft.atitle=Effect+of+centrifuging+shell+vials+at+3%2C500+x+g+on+detection+of+viruses+in+clinical+specimens.&rft.au=Engler%2C+H+D%3BSelepak%2C+S+T&rft.aulast=Engler&rft.aufirst=H&rft.date=1994-06-01&rft.volume=32&rft.issue=6&rft.spage=1580&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-06 N1 - Date created - 1994-10-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Diagn Microbiol Infect Dis. 1989 Sep-Oct;12(5):407-11 [2558834] J Clin Microbiol. 1991 Mar;29(3):463-5 [2037662] J Clin Microbiol. 1992 Mar;30(3):540-4 [1372616] J Clin Microbiol. 1977 Oct;6(4):328-31 [562356] J Clin Microbiol. 1984 Jun;19(6):917-9 [6088574] J Clin Microbiol. 1989 Sep;27(9):2107-9 [2550519] Mayo Clin Proc. 1985 Sep;60(9):577-85 [2991672] J Clin Microbiol. 1986 Apr;23(4):683-6 [3009538] J Clin Microbiol. 1986 Oct;24(4):677-9 [3533980] J Clin Microbiol. 1987 May;25(5):755-7 [3034962] J Clin Microbiol. 1988 Sep;26(9):1623-5 [2846644] J Clin Microbiol. 1985 Jan;21(1):29-32 [2981901] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical applications of IL-2. AN - 76682153; 7521197 AB - Several years of clinical trials with IL-2, including modifications of dose and schedule and combinations with other biologic agents or chemotherapy, have shown much more limited anticancer activity for this agent than was anticipated from the preclinical studies. Even for its FDA-approved indication (metastatic renal cell carcinoma patients with good performance status), IL-2 probably benefits only a small subset of patients, and no prognostic factors have yet been identified to pinpoint these patients. In addition, clinical activity in patients with renal cell carcinoma treated with high-dose IL-2 is achieved at the expense of substantial acute toxicity. Nonetheless, the durable complete responses observed in a small percentage of patients with metastatic renal cell carcinoma and metastatic melanoma, and the potent immunomodulatory effects of IL-2, suggest that it may yet become an important anticancer agent, perhaps in association with active and adoptive immunotherapy. The agent also has shown potential for the treatment of infectious diseases and immunodeficiency states. JF - Oncology (Williston Park, N.Y.) AU - Sznol, M AU - Parkinson, D R AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 61 EP - 7; discussion 67, 71, 74-5 VL - 8 IS - 6 SN - 0890-9091, 0890-9091 KW - Antineoplastic Agents KW - 0 KW - Interleukin-2 KW - Interferons KW - 9008-11-1 KW - Index Medicus KW - Drug Therapy, Combination KW - Killer Cells, Lymphokine-Activated -- physiology KW - Antineoplastic Agents -- administration & dosage KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials as Topic KW - Interferons -- administration & dosage KW - Kidney Neoplasms -- therapy KW - Interleukin-2 -- administration & dosage KW - Carcinoma, Renal Cell -- therapy KW - Interleukin-2 -- therapeutic use KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76682153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Clinical+applications+of+IL-2.&rft.au=Sznol%2C+M%3BParkinson%2C+D+R&rft.aulast=Sznol&rft.aufirst=M&rft.date=1994-06-01&rft.volume=8&rft.issue=6&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-06 N1 - Date created - 1994-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Models relating the timing of intercourse to the probability of conception and the sex of the baby. AN - 76679500; 8068836 AB - The probability that conception will result from intercourse on particular days of the menstrual cycle is of biological, demographic, and personal interest to many. We describe an existing model for conception as related to the timing of intercourse, and develop a method for fitting it by means of the expectation-maximization (EM) algorithm, using widely available software (GLIM). We then generalize the model to allow for effects on its parameters due to reproductively toxic exposures. A further extension allows one to address the question of whether the pattern of intercourse in a conception cycle has an influence on the sex of the resulting baby. We illustrate the methods by application to data from a prospective study of couples trying to begin a pregnancy. JF - Biometrics AU - Weinberg, C R AU - Gladen, B C AU - Wilcox, A J AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 358 EP - 367 VL - 50 IS - 2 SN - 0006-341X, 0006-341X KW - Estrogens KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Luteinizing Hormone KW - 9002-67-9 KW - Index Medicus KW - Probability KW - Estrogens -- urine KW - Humans KW - Progesterone -- urine KW - Algorithms KW - Infant, Newborn KW - Pregnancy KW - Spermatozoa -- physiology KW - Ovulation KW - Pregnancy Trimester, First KW - Luteinizing Hormone -- blood KW - Female KW - Male KW - Ejaculation KW - Fertilization KW - Sex Characteristics KW - Menstrual Cycle KW - Abortion, Spontaneous -- epidemiology KW - Coitus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76679500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Models+relating+the+timing+of+intercourse+to+the+probability+of+conception+and+the+sex+of+the+baby.&rft.au=Weinberg%2C+C+R%3BGladen%2C+B+C%3BWilcox%2C+A+J&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1994-06-01&rft.volume=50&rft.issue=2&rft.spage=358&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-27 N1 - Date created - 1994-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disposal of ethidium bromide. AN - 76679210; 8073504 JF - Trends in biochemical sciences AU - Hengen, P N AD - National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 257 EP - 258 VL - 19 IS - 6 SN - 0968-0004, 0968-0004 KW - Hazardous Waste KW - 0 KW - Medical Waste Disposal KW - Ethidium KW - EN464416SI KW - Index Medicus KW - Medical Waste Disposal -- methods KW - Waste Disposal, Fluid -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76679210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+biochemical+sciences&rft.atitle=Disposal+of+ethidium+bromide.&rft.au=Hengen%2C+P+N&rft.aulast=Hengen&rft.aufirst=P&rft.date=1994-06-01&rft.volume=19&rft.issue=6&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Trends+in+biochemical+sciences&rft.issn=09680004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational risks for colon cancer in Sweden. AN - 76678058; 8071728 AB - Using the Cancer-Environment Registry of Sweden, which links census information (1960) with cancer incidence data (1961 to 1979), we conducted a systematic, population-based assessment of colon cancer incidence among cohorts defined by industry and occupation for all employed persons in Sweden. Small but statistically significant excesses of colon cancer were observed among white-collar occupations, including administrators, professionals, and clerical and sales workers, whereas a reduction in incidence was found among workers in agricultural and related jobs, such as farmers, fishermen, and hunters. Analysis by subsite within the colon revealed little difference in results. The observed risk patterns are consistent with previous reports on colon cancer risk and occupational physical activity levels, ie, elevated risk among sedentary white-collar workers and reduced risk among agricultural workers. Few craftsman and production processing jobs were linked to colon cancer, although statistically significant excesses were observed among shoe and leather workers, metal smiths, and foundry workers in the metal manufacturing industry. The findings indicate that occupation in general is likely to play a relatively small role in colon cancer etiology, with perhaps its major contribution an indirect one via physical activity. JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Chow, W H AU - Malker, H S AU - Hsing, A W AU - McLaughlin, J K AU - Weiner, J A AU - Stone, B J AU - Ericsson, J L AU - Blot, W J AD - National Cancer Institute, Division of Cancer Etiology, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 647 EP - 651 VL - 36 IS - 6 SN - 0096-1736, 0096-1736 KW - Index Medicus KW - Registries KW - Risk Factors KW - Humans KW - Cohort Studies KW - Sweden -- epidemiology KW - Incidence KW - Occupations -- statistics & numerical data KW - Poisson Distribution KW - Colonic Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76678058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.atitle=Occupational+risks+for+colon+cancer+in+Sweden.&rft.au=Chow%2C+W+H%3BMalker%2C+H+S%3BHsing%2C+A+W%3BMcLaughlin%2C+J+K%3BWeiner%2C+J+A%3BStone%2C+B+J%3BEricsson%2C+J+L%3BBlot%2C+W+J&rft.aulast=Chow&rft.aufirst=W&rft.date=1994-06-01&rft.volume=36&rft.issue=6&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+medicine.+%3A+official+publication+of+the+Industrial+Medical+Association&rft.issn=00961736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flexible maximum likelihood methods for assessing joint effects in case-control studies with complex sampling. AN - 76667359; 8068835 AB - Case-control studies can often be made more efficient by using frequency matching, randomized recruitment, stratified sampling, or two-stage sampling. These designs share two common features: (1) some "first-stage" variables are ascertained for all study subjects, while complete variable ascertainment is carried out for only a selected subsample, and (2) the subsampling of subjects for "second-stage" variable ascertainment depends jointly on their disease status and their observed first-stage variables. Because first-stage variables alter the subsampling fractions, standard analyses require a multiplicative specification of any joint effects of a second- and a first-stage variable. We show that by making use of missing data methods, maximum likelihood estimates can be obtained for risk parameters of interest, even those characterizing interactions between first- and second-stage variables. Joint effects can thus be modelled flexibly, with allowance for both additive and multiplicative models. Preliminary data from a case-control study of lung cancer as related to age, sex, and smoking provide an example, leading to the suggestion that the combined effect of age and smoking is multiplicative. JF - Biometrics AU - Wacholder, S AU - Weinberg, C R AD - Biostatistics Branch, National Cancer Institute, Rockville, Maryland 20852. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 350 EP - 357 VL - 50 IS - 2 SN - 0006-341X, 0006-341X KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Probability KW - Age Factors KW - Sex Factors KW - Random Allocation KW - Humans KW - Utah -- epidemiology KW - Aged KW - Risk Factors KW - Adult KW - Connecticut -- epidemiology KW - Idaho -- epidemiology KW - Middle Aged KW - Female KW - Male KW - Smoking KW - Lung Neoplasms -- etiology KW - Biometry KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Case-Control Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76667359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Flexible+maximum+likelihood+methods+for+assessing+joint+effects+in+case-control+studies+with+complex+sampling.&rft.au=Wacholder%2C+S%3BWeinberg%2C+C+R&rft.aulast=Wacholder&rft.aufirst=S&rft.date=1994-06-01&rft.volume=50&rft.issue=2&rft.spage=350&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-27 N1 - Date created - 1994-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An open trial of clozapine in 11 adolescents with childhood-onset schizophrenia. AN - 76649068; 8056728 AB - To review the response of 11 adolescents with childhood-onset schizophrenia to a 6-week open clozapine trial. Eleven children meeting DSM-III-R criteria for schizophrenia had a 6-week open trial of clozapine (mean sixth week daily dose 370 mg). Behavioral ratings included the Brief Psychiatric Rating Scale and Children's Global Assessment Scale. More than half showed marked improvement in Brief Psychiatric Rating Scale ratings by 6 weeks of clozapine therapy compared to admission drug rating and compared to a systematic 6-week trial of haloperidol. This open trial indicates that clozapine may be a promising treatment for children and adolescents with schizophrenia who do not respond well to typical neuroleptics. A double-blind placebo-controlled study is ongoing. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Frazier, J A AU - Gordon, C T AU - McKenna, K AU - Lenane, M C AU - Jih, D AU - Rapoport, J L AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 658 EP - 663 VL - 33 IS - 5 SN - 0890-8567, 0890-8567 KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - Haloperidol -- adverse effects KW - Haloperidol -- therapeutic use KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Clozapine -- therapeutic use KW - Schizophrenia, Childhood -- psychology KW - Schizophrenia, Childhood -- drug therapy KW - Clozapine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76649068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=An+open+trial+of+clozapine+in+11+adolescents+with+childhood-onset+schizophrenia.&rft.au=Frazier%2C+J+A%3BGordon%2C+C+T%3BMcKenna%2C+K%3BLenane%2C+M+C%3BJih%2C+D%3BRapoport%2C+J+L&rft.aulast=Frazier&rft.aufirst=J&rft.date=1994-06-01&rft.volume=33&rft.issue=5&rft.spage=658&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-12 N1 - Date created - 1994-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ras mutations in methylclofenapate-induced B6C3F1 and C57BL/10J mouse liver tumours. AN - 76584814; 8020144 AB - The majority of genotoxic carcinogen-induced liver tumours of the sensitive B6C3F1 mouse contain activated H-ras oncogenes. Such mutations also occur in hepatocarcinogenesis-resistant strains. In order to determine whether this is true of non-genotoxic carcinogen-induced tumours, liver tumours induced in B6C3F1 and C57BL/10J mice by methylclofenapate (MCP) were compared. Polymerase chain reaction (PCR) analysis revealed H-ras codon 61 mutations in 11/46 B6C3F1 and 4/31 C57BL/10J liver tumours. The nude mouse tumorigenicity (NMT) assay was used to analyse tumours without codon 61 mutations. Of the 12 B6C3F1 liver tumour DNAs subjected to this assay, one contained a H-ras codon 117 mutation. Further PCR analysis on frozen tumour samples (46 B6C3F1 and 15 C57BL/10J) revealed no codon 12 mutations; one additional codon 117 mutation was identified in a B6C3F1 tumour. Overall, then, H-ras codon 61 mutations were detected in MCP-induced B6C3F1 tumours less frequently than in genotoxin-induced tumours. Two B6C3F1 tumours contained codon 117 mutations similar to those previously found in tumours induced by ciprofibrate, furan and furfural, and in at least one spontaneous tumour. Ras mutations were also detected in some C57BL/10J tumours, providing further evidence that ras oncogenes can participate in hepatocarcinogenesis in resistant mice. JF - Carcinogenesis AU - Stanley, L A AU - Blackburn, D R AU - Devereaux, S AU - Foley, J AU - Lord, P G AU - Maronpot, R R AU - Orton, T C AU - Anderson, M W AD - NIEHS, Research Triangle Park, NC 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1125 EP - 1131 VL - 15 IS - 6 SN - 0143-3334, 0143-3334 KW - H-ras KW - Codon KW - 0 KW - Clofenapate KW - 21340-68-1 KW - Index Medicus KW - Animals KW - Alleles KW - DNA Damage KW - Mice, Inbred C57BL KW - Mice, Nude KW - Mice KW - Mutation KW - Genes, ras KW - Liver Neoplasms, Experimental -- genetics KW - Clofenapate -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76584814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ras+mutations+in+methylclofenapate-induced+B6C3F1+and+C57BL%2F10J+mouse+liver+tumours.&rft.au=Stanley%2C+L+A%3BBlackburn%2C+D+R%3BDevereaux%2C+S%3BFoley%2C+J%3BLord%2C+P+G%3BMaronpot%2C+R+R%3BOrton%2C+T+C%3BAnderson%2C+M+W&rft.aulast=Stanley&rft.aufirst=L&rft.date=1994-06-01&rft.volume=15&rft.issue=6&rft.spage=1125&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-03 N1 - Date created - 1994-08-03 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic analysis of murine cell lines from diethylstilbestrol-induced uterine endometrial adenocarcinomas. AN - 76579695; 8019968 AB - Treatment of female CD-1 mice with the synthetic estrogen diethylstilbestrol (DES) on days 1 through 5 after birth results in a 90% incidence of endometrial adenocarcinomas by 18 months of age Three cell lines were established from DES-induced uterine carcinomas and studied for specific chromosomal changes. Each cell line exhibited numerical decreases in chromosomes 9, 11, 13, and X as common abnormalities. Structural alterations involving chromosomes 3, 6, 11, and 19 occurred nonrandomly among the three cell lines. Every cell line showed a rearrangement in the long arm of chromosome 3 (3q+), a translocation between chromosomes 3 and 19 [t(3;19)], isochromosome of chromosome 11 [i(11)], and a marker chromosome (M2) either as common abnormalities or recurrent abnormalities. t(3;19), i(11), and M2 were observed also in the primary colonies from which the cell lines arose. The changes were not observed in a cell line derived from the uterus of one untreated control mouse, suggesting that these chromosomal alterations may have occurred during DES-induced neoplastic transformation. The chromosomal alterations found in the present study may prove useful in investigating the genetic changes involved in DES carcinogenesis. JF - Cancer genetics and cytogenetics AU - Endo, S AU - Kodama, S AU - Newbold, R AU - McLachlan, J AU - Barrett, J C AD - Laboratory of Reproductive and Development Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 99 EP - 103 VL - 74 IS - 2 SN - 0165-4608, 0165-4608 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Karyotyping KW - Animals, Newborn KW - Animals KW - Aneuploidy KW - Mice KW - Translocation, Genetic KW - Female KW - Cell Line KW - Uterine Neoplasms -- genetics KW - Diethylstilbestrol -- adverse effects KW - Adenocarcinoma -- chemically induced KW - Uterine Neoplasms -- chemically induced KW - Chromosome Aberrations KW - Adenocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76579695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+genetics+and+cytogenetics&rft.atitle=Cytogenetic+analysis+of+murine+cell+lines+from+diethylstilbestrol-induced+uterine+endometrial+adenocarcinomas.&rft.au=Endo%2C+S%3BKodama%2C+S%3BNewbold%2C+R%3BMcLachlan%2C+J%3BBarrett%2C+J+C&rft.aulast=Endo&rft.aufirst=S&rft.date=1994-06-01&rft.volume=74&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Cancer+genetics+and+cytogenetics&rft.issn=01654608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A binding site model and structure-activity relationships for the rat A3 adenosine receptor. AN - 76570658; 8022403 AB - A novel adenosine receptor, the A3 receptor, has recently been cloned. We have systematically investigated the hitherto largely unexplored structure-activity relationships (SARs) for binding at A3 receptors, using 125I-N6-2-(4-aminophenyl)ethyladenosine as a radioligand and membranes from Chinese hamster ovary cells stably transfected with the rat A3-cDNA. As is the case for A1 and A2a receptors, substitutions at the N6 and 5' positions of adenosine, the prototypic agonist ligand, may yield fairly potent compounds. However, the highest affinity and A3 selectivity is found for N6,5'-disubstituted compounds, in contrast to A1 and A2a receptors. Thus, N6-benzyladenosine-5'-N-ethylcarboxamide is highly potent (Ki, 6.8 nM) and moderately selective (13- and 14-fold versus A1 and A2a). The N6 region of the A3 receptor also appears to tolerate hydrophilic substitutions, in sharp contrast to the other subtypes. Potencies of N6,5'-disubstituted compounds in inhibition of adenylate cyclase via A3 receptors parallel their high affinity in the binding assay. None of the typical xanthine or nonxanthine (A1/A2) antagonists tested show any appreciable affinity for rat A3 receptors. 1,3-Dialkylxanthines did not antagonize the A3 agonist-induced inhibition of adenylate cyclase. A His residue in helix 6 that is absent in A3 receptors but present in A1/A2 receptors may be causal in this respect. In a molecular model for the rat A3 receptor, this mutation, together with an increased bulkiness of residues surrounding the ligand, make antagonist binding unfavorable when compared with a previously developed A1 receptor model. Second, this A3 receptor model predicted similarities with A1 and A2 receptors in the binding requirements for the ribose moiety and that xanthine-7-ribosides would bind to rat A3 receptors. This hypothesis was supported experimentally by the moderate affinity (Ki 6 microM) of 7-riboside of 1,3-dibutylxanthine, which appears to be a partial agonist at rat A3 receptors. The model presented here, which is consistent with the detailed SAR found in this study, may serve to suggest future chemical modification, site-directed mutagenesis, and SAR studies to further define essential characteristics of the ligand-receptor interaction and to develop even more potent and selective A3 receptor ligands. JF - Molecular pharmacology AU - van Galen, P J AU - van Bergen, A H AU - Gallo-Rodriguez, C AU - Melman, N AU - Olah, M E AU - IJzerman, A P AU - Stiles, G L AU - Jacobson, K A AD - Molecular Recognition Section, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1101 EP - 1111 VL - 45 IS - 6 SN - 0026-895X, 0026-895X KW - Adenylyl Cyclase Inhibitors KW - 0 KW - Receptors, Purinergic P1 KW - Index Medicus KW - Rats KW - Animals KW - Models, Molecular KW - CHO Cells KW - Radioligand Assay KW - Structure-Activity Relationship KW - Cricetinae KW - Binding Sites KW - Receptors, Purinergic P1 -- chemistry KW - Receptors, Purinergic P1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76570658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+binding+site+model+and+structure-activity+relationships+for+the+rat+A3+adenosine+receptor.&rft.au=van+Galen%2C+P+J%3Bvan+Bergen%2C+A+H%3BGallo-Rodriguez%2C+C%3BMelman%2C+N%3BOlah%2C+M+E%3BIJzerman%2C+A+P%3BStiles%2C+G+L%3BJacobson%2C+K+A&rft.aulast=van+Galen&rft.aufirst=P&rft.date=1994-06-01&rft.volume=45&rft.issue=6&rft.spage=1101&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 - 1994-08-01 N1 - Date created - 1994-08-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1985 Sep 5;260(19):10806-11 [2993290] FEBS Lett. 1991 Jun 24;284(2):155-60 [1647979] J Med Chem. 1990 Oct;33(10):2818-21 [2213834] FASEB J. 1991 Sep;5(12):2668-76 [1916091] J Recept Res. 1991;11(6):891-907 [1661335] J Med Chem. 1991 Dec;34(12):3388-90 [1766003] J Med Chem. 1992 Feb 7;35(3):407-22 [1738138] J Med Chem. 1992 Feb 21;35(4):629-35 [1542091] Biochem Pharmacol. 1992 Mar 3;43(5):1089-93 [1554381] J Biol Chem. 1992 May 25;267(15):10764-70 [1587851] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7432-6 [1323836] Med Res Rev. 1992 Sep;12(5):423-71 [1513184] J Med Chem. 1992 Oct 30;35(22):4143-9 [1433217] Drug Des Discov. 1992;9(1):49-67 [1457698] Trends Pharmacol Sci. 1993 Jan;14(1):7-12 [8095116] Br J Pharmacol. 1993 May;109(1):3-5 [8495245] J Med Chem. 1993 May 14;36(10):1333-42 [8496902] J Biol Chem. 1993 Aug 15;268(23):16887-90 [8349579] J Med Chem. 1993 Sep 3;36(18):2639-44 [8410976] J Med Chem. 1991 Mar;34(3):1202-6 [2002461] J Med Chem. 1990 Aug;33(8):2240-54 [2374150] J Mol Biol. 1990 Jun 20;213(4):899-929 [2359127] J Med Chem. 1989 Oct;32(10):2247-54 [2795597] J Med Chem. 1989 Jun;32(6):1231-7 [2724296] Eur J Pharmacol. 1988 Oct 26;156(1):157-60 [3208837] J Biol Chem. 1988 Nov 25;263(33):17522-6 [3182861] J Med Chem. 1988 Jun;31(6):1179-83 [3373486] J Med Chem. 1988 May;31(5):1014-20 [3361572] J Med Chem. 1987 Oct;30(10):1709-11 [2888894] J Med Chem. 1986 Jul;29(7):1305-8 [3806581] J Med Chem. 1986 Sep;29(9):1683-9 [3018244] Mol Pharmacol. 1986 Apr;29(4):331-46 [3010074] Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21 [2997628] J Med Chem. 1985 Sep;28(9):1334-40 [2993622] J Med Chem. 1991 Aug;34(8):2570-9 [1875349] J Med Chem. 1991 Sep;34(9):2877-82 [1895305] Biochem Pharmacol. 1973 Dec 1;22(23):3099-108 [4202581] Can J Physiol Pharmacol. 1980 Jun;58(6):673-91 [6253037] Cell Mol Neurobiol. 1983 Mar;3(1):69-80 [6309393] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Withdrawal of repeated intravenous infusions of cocaine persistently reduces binding to dopamine transporters in the nucleus accumbens of Lewis rats. AN - 76563169; 7912283 AB - Male, Lewis rats were administered cocaine or saline i.v. in an intermittent fashion for 5, 10 or 20 days and killed at various times afterwards. Dopamine transporter binding was then measured in dorsal striatum and nucleus accumbens. Transporter binding was not changed in dorsal striatum under any conditions tested. In the nucleus accumbens, however, binding was decreased in animals given cocaine (10 mg/kg total) for 10 days and withdrawn for 10, 30 or 60 days, but not in animals withdrawn for 0, 1, 3 and 6 days. There were no changes in animals given cocaine for 5 days and withdrawn for 10, or in animals given drug for 20 days and withdrawn for 1 day. Animals given only 1/10 of the cocaine dose had no changes in nucleus accumbens after 10 days of administration and 10 days of withdrawal. Scatchard analysis in control animals indicated that there were significant differences in both Kd and Bmax when comparing nucleus accumbens with dorsal striatum. Within the nucleus accumbens, decreases in binding after a cessation of cocaine administration were associated with a change in Bmax and not in Kd. These data indicate that long-lasting changes in the mesolimbic dopaminergic system can occur during the withdrawal period, and may contribute to behavioral effects during this period. JF - The Journal of pharmacology and experimental therapeutics AU - Pilotte, N S AU - Sharpe, L G AU - Kuhar, M J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 963 EP - 969 VL - 269 IS - 3 SN - 0022-3565, 0022-3565 KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Tyrosine 3-Monooxygenase -- analysis KW - Animals KW - Rats, Inbred Lew KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Carrier Proteins -- metabolism KW - Nucleus Accumbens -- metabolism KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76563169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Withdrawal+of+repeated+intravenous+infusions+of+cocaine+persistently+reduces+binding+to+dopamine+transporters+in+the+nucleus+accumbens+of+Lewis+rats.&rft.au=Pilotte%2C+N+S%3BSharpe%2C+L+G%3BKuhar%2C+M+J&rft.aulast=Pilotte&rft.aufirst=N&rft.date=1994-06-01&rft.volume=269&rft.issue=3&rft.spage=963&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-26 N1 - Date created - 1994-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis and chemical carcinogenesis. AN - 76563119; 8029504 AB - Long recognized as a normal component of organogenesis during development, apoptosis (programmed cell death) has recently been implicated in alterations of cell growth and differentiation. Tissue homeostasis is normally maintained by a balance between cell division and cell death, with apoptosis often functioning in complement to cell growth. Thus, antithetical parallels in chemical carcinogenesis can be drawn between apoptosis and the proliferative events more commonly addressed. While enhanced cell replication may contribute to an increased frequency of mutation, apoptosis within a tissue may counteract chemical carcinogenesis through loss of mutated cells. Many strong carcinogens act as tumor promoters, selectively expanding an initiated cell population advantageously over surrounding cells. Similarly, chemicals with a selective inhibition of apoptosis within an initiated population would offer a growth advantage. In contrast, chemicals causing selective apoptosis of initiated cells would be expected to have an anticarcinogenic effect. Selective apoptosis, in concert with cell-specific replication, may explain the unique promoting effects of different carcinogens such as the peroxisome-proliferating chemicals, phenobarbital, and 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin (TCDD). Cell turnover, both cell growth and cell death, is central to the process of chemically induced carcinogenesis in animals and understanding its impact is a critical determinant of the relevance of chemically induced effects to man. JF - Risk analysis : an official publication of the Society for Risk Analysis AU - Marsman, D S AU - Barrett, J C AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 321 EP - 326 VL - 14 IS - 3 SN - 0272-4332, 0272-4332 KW - Carcinogens KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Homeostasis -- physiology KW - Apoptosis -- drug effects KW - Liver Neoplasms, Experimental -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76563119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.atitle=Apoptosis+and+chemical+carcinogenesis.&rft.au=Marsman%2C+D+S%3BBarrett%2C+J+C&rft.aulast=Marsman&rft.aufirst=D&rft.date=1994-06-01&rft.volume=14&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Risk+analysis+%3A+an+official+publication+of+the+Society+for+Risk+Analysis&rft.issn=02724332&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated lung perfusion with tumor necrosis factor: a swine model in preparation of human trials. AN - 76547378; 8010790 AB - Isolated lung perfusion with tumor necrosis factor (TNF) potentially could deliver high doses of drug and avoid systemic toxicity in patients with unresectable lung cancer or metastases. We investigated the feasibility of isolated lung perfusion with TNF in a pig model. Eleven animals had left-sided isolated lung perfusion with no TNF (n = 3), 40 micrograms/kg TNF (n = 2), 80 micrograms/kg TNF (n = 3), and 40 micrograms/kg TNF at moderate (39.5 degrees C) hyperthermia (n = 3). Hemodynamic monitoring and measurement of systemic and pulmonary circuit TNF levels were performed. Surviving animals were electively sacrificed a minimum of 6 months after isolated lung perfusion. All sham-perfused pigs survived. Isolated lung perfusion elevated pulmonary artery pressure, decreased cardiac output, and had minimal effects on mean pressure (15 +/- 0 versus 32 +/- 8 mm Hg, 4.5 +/- 1.1 versus 3.03 +/- 0.03 L/min, 67 +/- 11 versus 61 +/- 2 mm Hg; before versus after 90 minutes of isolated lung perfusion). Both 40 micrograms/kg animals and 2 of the 3 hyperthermic perfusion pigs survived, with 1 requiring pneumonectomy. Of the three 80 micrograms/kg animals, 1 survived, 1 died, and 1 required pneumonectomy. Survivors, compared with dying animals, had lower systemic/pulmonary TNF ratios and lower peak systemic TNF levels. All surviving pigs were electively sacrificed. These data justify phase I human protocols of isolated lung perfusion with TNF and hyperthermia; however, intraoperative leak rates must be monitored to ensure pulmonary isolation because systemic TNF levels may dictate treatment morbidity/mortality. JF - The Annals of thoracic surgery AU - Pogrebniak, H W AU - Witt, C J AU - Terrill, R AU - Kranda, K AU - Travis, W D AU - Rosenberg, S A AU - Pass, H I AD - Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1477 EP - 1483 VL - 57 IS - 6 SN - 0003-4975, 0003-4975 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Oxygen KW - S88TT14065 KW - Abridged Index Medicus KW - Index Medicus KW - Swine KW - Hypotension -- chemically induced KW - Animals KW - Injections, Intravenous KW - Humans KW - Disease Models, Animal KW - Vascular Resistance -- drug effects KW - Cardiac Output -- drug effects KW - Drug Tolerance KW - Pulmonary Artery KW - Heart Rate -- drug effects KW - Survival Rate KW - Oxygen -- blood KW - Hyperthermia, Induced KW - Pulmonary Edema -- chemically induced KW - Radiography KW - Blood Pressure -- drug effects KW - Pulmonary Edema -- pathology KW - Bradycardia -- chemically induced KW - Female KW - Tumor Necrosis Factor-alpha -- toxicity KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Lung -- diagnostic imaging KW - Chemotherapy, Cancer, Regional Perfusion KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Tumor Necrosis Factor-alpha -- analysis KW - Lung -- drug effects KW - Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76547378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Annals+of+thoracic+surgery&rft.atitle=Isolated+lung+perfusion+with+tumor+necrosis+factor%3A+a+swine+model+in+preparation+of+human+trials.&rft.au=Pogrebniak%2C+H+W%3BWitt%2C+C+J%3BTerrill%2C+R%3BKranda%2C+K%3BTravis%2C+W+D%3BRosenberg%2C+S+A%3BPass%2C+H+I&rft.aulast=Pogrebniak&rft.aufirst=H&rft.date=1994-06-01&rft.volume=57&rft.issue=6&rft.spage=1477&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+thoracic+surgery&rft.issn=00034975&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-15 N1 - Date created - 1994-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin. AN - 76547080; 8006454 AB - In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical-specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at non-cytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor alpha production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation. JF - The Journal of investigative dermatology AU - Wilmer, J L AU - Burleson, F G AU - Kayama, F AU - Kanno, J AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 915 EP - 922 VL - 102 IS - 6 SN - 0022-202X, 0022-202X KW - Cytokines KW - 0 KW - Interleukin-1 KW - Interleukin-8 KW - Phenols KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Oxazolone KW - 15646-46-5 KW - Croton Oil KW - 8001-28-3 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Interleukin-1 -- physiology KW - Animals KW - Interleukin-8 -- analysis KW - Humans KW - Granulocyte-Macrophage Colony-Stimulating Factor -- physiology KW - RNA, Messenger -- analysis KW - Gene Expression KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Interleukin-1 -- analysis KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Tumor Necrosis Factor-alpha -- genetics KW - Interleukin-8 -- physiology KW - Cells, Cultured KW - Granulocyte-Macrophage Colony-Stimulating Factor -- analysis KW - Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - Tumor Necrosis Factor-alpha -- analysis KW - Interleukin-8 -- genetics KW - Interleukin-1 -- genetics KW - Time Factors KW - Female KW - Cytokines -- genetics KW - Keratinocytes -- chemistry KW - Skin -- physiopathology KW - Skin -- pathology KW - Cytokines -- metabolism KW - Dermatitis, Contact -- etiology KW - Dermatitis, Contact -- pathology KW - Phenols -- adverse effects KW - Skin -- drug effects KW - Oxazolone -- adverse effects KW - Croton Oil -- adverse effects KW - Keratinocytes -- metabolism KW - Keratinocytes -- pathology KW - Dermatitis, Contact -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76547080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Cytokine+induction+in+human+epidermal+keratinocytes+exposed+to+contact+irritants+and+its+relation+to+chemical-induced+inflammation+in+mouse+skin.&rft.au=Wilmer%2C+J+L%3BBurleson%2C+F+G%3BKayama%2C+F%3BKanno%2C+J%3BLuster%2C+M+I&rft.aulast=Wilmer&rft.aufirst=J&rft.date=1994-06-01&rft.volume=102&rft.issue=6&rft.spage=915&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-19 N1 - Date created - 1994-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative hyaline droplet nephropathy in male F344/NCr rats induced by sodium barbital and diethylacetylurea, a breakdown product of sodium barbital. AN - 76543303; 7516096 AB - Hyaline droplet nephropathy in male rats due to alpha 2u-globulin accumulation in proximal tubules is caused by chemicals from several chemical classes. We have previously shown that the well-known sedative/hypnotic barbiturate, sodium barbital, and its breakdown product, diethylacetylurea, are renal toxins and renal tumor promoters. To determine comparative induction of hyaline droplets in renal tubules by sodium barbital and diethylacetylurea, male F344/NCr rats, 6 weeks of age, were given diets containing 0, 170, 341, 500, or 1000 ppm of diethylacetylurea or containing 500, 1000, or 4000 ppm of sodium barbital for periods of 2 or 10 weeks. Rats were terminated at 2 or 10 weeks and the histology of the kidney was evaluated using light microscopy with hematoxylin and eosin staining and staining by the Heidenhain method. Quantitative analysis showed dose responses for the degree of droplet accumulation in the P2 and P3 segments of the proximal tubules. Diethylacetylurea was more potent. Immunohistochemistry and ultrastructural evaluation revealed the nature of the droplets. Western blotting confirmed the presence of alpha 2u-globulin. Renal tubular necrosis, regeneration, and increased levels of cell proliferation using proliferating cell nuclear antigen immunohistochemistry were also found. Female rats similarly exposed to each chemical did not show tubule droplet accumulations nor renal lesions. We confirm for the first time that these two chemicals can be added to the enlarging list of nephrotoxic chemicals inducing alpha 2u-globulin nephropathy and possessing tumor promoting and renal carcinogenic properties. JF - Toxicology and applied pharmacology AU - Kurata, Y AU - Diwan, B A AU - Lehman-McKeeman, L AU - Rice, J M AU - Ward, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 224 EP - 232 VL - 126 IS - 2 SN - 0041-008X, 0041-008X KW - Nuclear Proteins KW - 0 KW - Proliferating Cell Nuclear Antigen KW - diethylacetylurea KW - 2274-01-3 KW - Barbital KW - 5WZ53ENE2P KW - Urea KW - 8W8T17847W KW - Index Medicus KW - Rats KW - Immunoblotting KW - Animals KW - Rats, Inbred F344 KW - Kidney Tubules, Proximal -- ultrastructure KW - Microscopy, Electron KW - Kidney Tubules, Proximal -- pathology KW - Nuclear Proteins -- metabolism KW - Immunohistochemistry KW - Male KW - Female KW - Hyalin -- metabolism KW - Diabetic Nephropathies -- chemically induced KW - Barbital -- antagonists & inhibitors KW - Diabetic Nephropathies -- pathology KW - Barbital -- toxicity KW - Urea -- toxicity KW - Urea -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76543303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Comparative+hyaline+droplet+nephropathy+in+male+F344%2FNCr+rats+induced+by+sodium+barbital+and+diethylacetylurea%2C+a+breakdown+product+of+sodium+barbital.&rft.au=Kurata%2C+Y%3BDiwan%2C+B+A%3BLehman-McKeeman%2C+L%3BRice%2C+J+M%3BWard%2C+J+M&rft.aulast=Kurata&rft.aufirst=Y&rft.date=1994-06-01&rft.volume=126&rft.issue=2&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-12 N1 - Date created - 1994-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys. AN - 76533950; 8210225 AB - Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause an acute chemical toxicity resulting in a parkinsonian state in humans and nonhuman primates. We wished to assess whether the toxicity from MPTP is associated with changes on magnetic resonance images of brain structures containing dopamine neuronal processes or with disrupture of the blood-brain barrier. Normal rhesus monkeys and monkeys at various times after being subjected to unilateral intracarotid injection of MPTP (0.4 mg/kg) were studied with magnetic resonance imaging using T1- and T2-weighted spin-echo and gradient-echo sequences. Disrupture of the blood-brain barrier was assessed also with magnetic resonance imaging after administration of gadolinium-diethylenetriamine pentaacetic acid. Parkinsonian symptoms contralateral to the infused carotid usually appeared within 1 day after MPTP exposure, reaching their peak severity by 7 days, when all monkeys showed clear clinical abnormalities. Magnetic resonance imaging changes developed in concomitance with the clinical signs and were characterized by increased signal intensity on T2-weighted images as well as decreased intensity on T1-weighted images of the ipsilateral caudate and putamen. T2 hyperintensity was also present just dorsal to the pars compacta of the substantia nigra, in the region of the proximal nigrostriatal tract. All magnetic resonance imaging changes dissipated in the next 2 weeks. There were no abnormalities at any time in the globus pallidus, nucleus accumbens, and other structures innervated by the mesocorticolimbic dopamine system. After MPTP exposure, there was no evidence of blood-brain barrier disrupture, suggesting that vasogenic edema was an unlikely factor in the production of the observed abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Annals of neurology AU - Miletich, R S AU - Bankiewicz, K S AU - Quarantelli, M AU - Plunkett, R J AU - Frank, J AU - Kopin, I J AU - Di Chiro, G AD - Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 689 EP - 697 VL - 35 IS - 6 SN - 0364-5134, 0364-5134 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Carotid Arteries KW - Animals KW - Reference Values KW - Infusions, Intra-Arterial KW - Analysis of Variance KW - Putamen -- pathology KW - Caudate Nucleus -- pathology KW - Macaca mulatta KW - Nucleus Accumbens -- pathology KW - Time Factors KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- administration & dosage KW - Parkinson Disease, Secondary -- chemically induced KW - Parkinson Disease, Secondary -- pathology KW - Corpus Striatum -- metabolism KW - Dopamine -- metabolism KW - Substantia Nigra -- drug effects KW - Substantia Nigra -- metabolism KW - Blood-Brain Barrier -- drug effects KW - Nerve Degeneration KW - Parkinson Disease, Secondary -- metabolism KW - Magnetic Resonance Imaging -- methods KW - Substantia Nigra -- pathology KW - MPTP Poisoning KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76533950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=MRI+detects+acute+degeneration+of+the+nigrostriatal+dopamine+system+after+MPTP+exposure+in+hemiparkinsonian+monkeys.&rft.au=Miletich%2C+R+S%3BBankiewicz%2C+K+S%3BQuarantelli%2C+M%3BPlunkett%2C+R+J%3BFrank%2C+J%3BKopin%2C+I+J%3BDi+Chiro%2C+G&rft.aulast=Miletich&rft.aufirst=R&rft.date=1994-06-01&rft.volume=35&rft.issue=6&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-08 N1 - Date created - 1994-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multistage carcinogenesis utilizing human genital cells and human papillomaviruses. AN - 76533585; 8202958 AB - The preponderance of evidence indicates that a subset of human papillomaviruses are important etiological agents for cervical cancer. However, the necessity of other agents as well as cellular events is recognized because not all women with papillomaviruses develop cancer. Therefore, the exact role of papillomaviruses in the multistage carcinogenesis process is unclear. Regulation of specific viral genes is important to the malignant process. The current study demonstrates that human herpesvirus-6, another ubiquitous virus, can infect genital epithelial cells and upregulate the expression of relevant papillomavirus genes. Thus, it can be considered a cofactor for cancer. JF - Toxicology letters AU - Di Paolo, J A AU - Popescu, N C AU - Ablashi, D V AU - Lusso, P AU - Zimonjic, D B AU - Woodworth, C D AD - National Cancer Institute, Laboratory of Biology, Bethesda, MD 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 7 EP - 11 VL - 72 IS - 1-3 SN - 0378-4274, 0378-4274 KW - HPV-16 KW - HPV-18 KW - Antibodies, Monoclonal KW - 0 KW - DNA, Viral KW - Index Medicus KW - AIDS/HIV KW - HIV-1 -- genetics KW - Humans KW - Gene Expression KW - Herpesvirus 6, Human -- genetics KW - Herpesviridae Infections -- complications KW - Transcriptional Activation KW - Polymerase Chain Reaction KW - In Situ Hybridization KW - Epithelium -- virology KW - DNA, Viral -- analysis KW - Keratinocytes -- virology KW - DNA, Viral -- genetics KW - Cell Line KW - Female KW - Cocarcinogenesis KW - Papillomavirus Infections -- complications KW - Papillomaviridae -- physiology KW - Cervix Uteri -- virology KW - Papillomaviridae -- genetics KW - Uterine Cervical Neoplasms -- virology KW - Tumor Virus Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76533585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multistage+carcinogenesis+utilizing+human+genital+cells+and+human+papillomaviruses.&rft.au=Di+Paolo%2C+J+A%3BPopescu%2C+N+C%3BAblashi%2C+D+V%3BLusso%2C+P%3BZimonjic%2C+D+B%3BWoodworth%2C+C+D&rft.aulast=Di+Paolo&rft.aufirst=J&rft.date=1994-06-01&rft.volume=72&rft.issue=1-3&rft.spage=7&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 - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - HPV-16; HPV-18 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of chlorpromazine pretreatment on cadmium toxicity in the male Wistar (WF/NCr) rat. AN - 76531132; 8207755 AB - A recent report has indicated that cadmium-induced testicular damage in CF-1 mice can be prevented by pretreatment with calmodulin inhibitors such as chlorpromazine (CPZ), trifluoperazine, or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7). However, the basis of this tolerance to cadmium is unclear and has not been demonstrated in any species other than mice. Thus, we examined the effects of the calmodulin inhibitor CPZ on cadmium toxicity in male Wistar (WF/NCr) rats. A single sc injection of 25 mumol CdCl2/kg proved nonlethal over 24 h but caused the typical spectrum of testicular lesions and increases in hemoglobin content (as assessed by hemoglobin absorbance in testicular supernatant). Pretreatment with 40 mumol CPZ/kg had no effect on cadmium-induced testicular lesions but did reduce testicular hemoglobin content, while 120 mumol CPZ/kg moderately reduced the severity of testicular lesions and hemoglobin contents. CPZ pretreatment in some cases increased cadmium content in liver and reduced testicular content but had no effect on renal levels. Cadmium treatment markedly increased hepatic and renal metallothionein (MT), a metal-binding protein often associated with tolerance to cadmium. CPZ alone likewise increased hepatic MT and MT mRNA, but did not modify renal MT, renal MT mRNA, or testicular MT mRNA. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) decreased in rats exposed only to cadmium or to CPZ, while CPZ pretreatment had no further effect on cadmium-induced reductions in TCBP levels. These results indicate that, like mice, CPZ in rats can reduce the testicular toxicity of cadmium as indicated by CPZ-induced reductions in testicular vascular lesions and hemoglobin contents. However, in rats CPZ has a less dramatic effect on such cadmium-induced lesions than in mice. The CPZ-induced stimulation of hepatic MT gene expression or modification of toxicokinetics may both play roles in this acquired tolerance to cadmium. JF - Journal of toxicology and environmental health AU - Shiraishi, N AU - Rehm, S AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 193 EP - 208 VL - 42 IS - 2 SN - 0098-4108, 0098-4108 KW - Blood Glucose KW - 0 KW - Hemoglobins KW - Oligonucleotide Probes KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Creatinine KW - AYI8EX34EU KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Zinc KW - J41CSQ7QDS KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Hemoglobins -- drug effects KW - Animals KW - Liver -- metabolism KW - Metallothionein -- genetics KW - Blood Urea Nitrogen KW - Tissue Distribution KW - Creatinine -- blood KW - Rats KW - Liver -- drug effects KW - Molecular Sequence Data KW - Oligonucleotide Probes -- chemistry KW - Gene Expression Regulation -- drug effects KW - Male KW - Kidney -- metabolism KW - Liver -- pathology KW - Kidney -- pathology KW - Dose-Response Relationship, Drug KW - Blood Glucose -- drug effects KW - Zinc -- metabolism KW - Kidney -- drug effects KW - Base Sequence KW - L-Lactate Dehydrogenase -- blood KW - Premedication KW - Rats, Wistar KW - Metallothionein -- metabolism KW - Testis -- metabolism KW - Testis -- drug effects KW - Testis -- pathology KW - Cadmium -- toxicity KW - Chlorpromazine -- therapeutic use KW - Chlorpromazine -- administration & dosage KW - Cadmium -- pharmacokinetics KW - Chlorpromazine -- toxicity KW - Cadmium -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76531132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Effect+of+chlorpromazine+pretreatment+on+cadmium+toxicity+in+the+male+Wistar+%28WF%2FNCr%29+rat.&rft.au=Shiraishi%2C+N%3BRehm%2C+S%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1994-06-01&rft.volume=42&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-14 N1 - Date created - 1994-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 6-[Fluorine-18]fluorodopamine pharmacokinetics and dosimetry in humans. AN - 76510704; 8195883 AB - PET scanning after injection of 6-[18F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[18F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[18F]fluorodopamine into 10 normal volunteers. The main target organs for 6-[18F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [18F]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. At administered doses required to visualize the left ventricular myocardium in humans, a 6-[18F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Goldstein, D S AU - Coronado, L AU - Kopin, I J AD - Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 964 EP - 973 VL - 35 IS - 6 SN - 0161-5505, 0161-5505 KW - Fluorine Radioisotopes KW - 0 KW - 6-fluorodopamine KW - 59043-70-8 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Radiation Dosage KW - Reference Values KW - Heart -- diagnostic imaging KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Tissue Distribution KW - Male KW - Dopamine -- analogs & derivatives KW - Fluorine Radioisotopes -- pharmacokinetics KW - Dopamine -- pharmacokinetics KW - Tomography, Emission-Computed UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76510704?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=6-%5BFluorine-18%5Dfluorodopamine+pharmacokinetics+and+dosimetry+in+humans.&rft.au=Goldstein%2C+D+S%3BCoronado%2C+L%3BKopin%2C+I+J&rft.aulast=Goldstein&rft.aufirst=D&rft.date=1994-06-01&rft.volume=35&rft.issue=6&rft.spage=964&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-30 N1 - Date created - 1994-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleosomal location of the STE6 TATA box and Mat alpha 2p-mediated repression. AN - 76509256; 8196639 AB - It has been proposed that yeast MATa cell-specific genes are repressed in MAT alpha cells by the Mat alpha 2p repressor-directed placement of a nucleosome in a position that incorporates the TATA box of the MATa-specific gene close to the nucleosomal pseudodyad. In this study, we address this proposal directly with a series of plasmids designed to place the MATa-specific STE6 TATA box at different locations in a nucleosome and in the internucleosomal linker. These plasmids contain different lengths of synthetic random DNA between the Mat alpha 2p operator and the TATA box of the STE6 promoter, which is located upstream of a lacZ reporter gene in a multicopy plasmid. We show that in MAT alpha cells, a nucleosome is retained in an identical translational frame relative to the Mat alpha 2p operator in all the constructs investigated, irrespective of the sequence of the DNA wrapped onto the histone octamer. This result shows that the nucleosomal organization of the STE6 promoter in MAT alpha cells is not conferred by the sequence of the promoter itself. No expression of the lacZ reporter gene was detectable in MAT alpha cells in any of the constructs, even with the TATA box located in a short internucleosomal linker. These data indicate that repression of MATa-specific genes in MAT alpha cells does not require the precise translational placement of the TATA box close to the nucleosomal pseudodyad; the gene remains repressed when the TATA box is located within the investigated 250-bp region in the organized chromatin domain abutting the Mat alpha 2p operator in MAT alpha cells and may remain repressed with the TATA box located anywhere within this organized repression domain. JF - Molecular and cellular biology AU - Patterton, H G AU - Simpson, R T AD - Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 4002 EP - 4010 VL - 14 IS - 6 SN - 0270-7306, 0270-7306 KW - MAT&agr; KW - MATa KW - STE6 KW - Fungal Proteins KW - 0 KW - Glycoproteins KW - Nucleosomes KW - Oligodeoxyribonucleotides KW - Peptides KW - Pheromones KW - Recombinant Fusion Proteins KW - STE6 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Mating Factor KW - 61194-02-3 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Peptide Biosynthesis KW - Nucleolus Organizer Region -- metabolism KW - Pheromones -- genetics KW - Plasmids KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - beta-Galactosidase -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - beta-Galactosidase -- biosynthesis KW - Nucleolus Organizer Region -- ultrastructure KW - Mutagenesis, Insertional KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Saccharomyces cerevisiae -- ultrastructure KW - Genes, Fungal KW - Nucleosomes -- ultrastructure KW - Nucleosomes -- metabolism KW - Fungal Proteins -- biosynthesis KW - ATP-Binding Cassette Transporters KW - Peptides -- genetics KW - Fungal Proteins -- genetics KW - TATA Box UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76509256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleosomal+location+of+the+STE6+TATA+box+and+Mat+alpha+2p-mediated+repression.&rft.au=Patterton%2C+H+G%3BSimpson%2C+R+T&rft.aulast=Patterton&rft.aufirst=H&rft.date=1994-06-01&rft.volume=14&rft.issue=6&rft.spage=4002&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 - 1994-06-24 N1 - Date created - 1994-06-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MAT&agr;; MATa; STE6 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1977;46:931-54 [332067] Annu Rev Cell Biol. 1990;6:643-78 [2275823] Prog Nucleic Acid Res Mol Biol. 1991;40:143-84 [2031082] Mol Cell Biol. 1991 Jun;11(6):3307-16 [2038333] Mol Cell Biol. 1991 Jul;11(7):3773-9 [1904546] Mol Gen Genet. 1991 Jun;227(2):197-204 [1905781] EMBO J. 1991 Oct;10(10):3033-41 [1915278] Nucleic Acids Res. 1991 Oct 25;19(20):5791 [1945859] Cell. 1991 Dec 20;67(6):1241-50 [1760848] Cell. 1992 Jan 10;68(1):133-42 [1732062] Cell. 1992 Feb 21;68(4):709-19 [1739976] Gene. 1992 Jan 2;110(1):119-22 [1544568] Genes Dev. 1992 Mar;6(3):411-25 [1547940] Nature. 1992 Nov 5;360(6399):40-6 [1436073] Trends Genet. 1992 Nov;8(11):387-91 [1332230] Cell. 1993 Jan 15;72(1):105-12 [8422672] Mol Cell Biol. 1993 Jul;13(7):4029-38 [8321210] Nucleic Acids Res. 1993 Jul 11;21(14):3295-300 [8341604] Nature. 1993 Oct 7;365(6446):512-20 [8413604] Nature. 1993 Oct 7;365(6446):520-7 [8413605] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1361-5 [8108416] Gene. 1980 Jul;10(2):157-66 [6248420] Annu Rev Biochem. 1980;49:1115-56 [6996562] EMBO J. 1983;2(4):593-7 [6313347] Mol Cell Biol. 1984 Nov;4(11):2420-7 [6096697] Nature. 1985 Apr 18-24;314(6012):598-603 [3887184] Cell. 1985 Aug;42(1):237-47 [3893743] Cell. 1985 Aug;42(1):3-4 [3893745] J Mol Biol. 1985 Dec 20;186(4):773-90 [3912515] Cell. 1986 Apr 11;45(1):95-104 [3955658] Proc Natl Acad Sci U S A. 1986 Apr;83(8):2536-40 [3517872] J Mol Biol. 1986 Aug 20;190(4):619-33 [3097328] Mol Cell Biol. 1986 May;6(5):1633-9 [3537708] Cell. 1987 Apr 24;49(2):203-10 [3568125] Mol Cell Biol. 1987 Apr;7(4):1401-8 [3600631] Cell. 1987 Jul 31;50(3):369-77 [3301002] Cell. 1987 Aug 28;50(5):801-8 [3621345] Mol Cell Biol. 1987 Oct;7(10):3637-45 [3316983] Nucleic Acids Res. 1987 Dec 23;15(24):10311-30 [3320966] Philos Trans R Soc Lond B Biol Sci. 1987 Dec 15;317(1187):537-61 [2894688] Cell. 1988 Jun 17;53(6):927-36 [3289753] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] EMBO J. 1988 Jul;7(7):2221-8 [3046934] Genes Dev. 1988 Jul;2(7):807-16 [3061876] Cell. 1989 Feb 24;56(4):549-61 [2917366] Nature. 1989 Aug 3;340(6232):400-4 [2569166] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5703-7 [2668945] Nature. 1989 Dec 14;342(6251):749-57 [2513489] Proc Natl Acad Sci U S A. 1989 Dec;86(24):9817-21 [2690074] Genes Dev. 1989 Sep;3(9):1349-61 [2558054] Nature. 1990 Jan 25;343(6256):387-9 [2405281] Mol Cell Biol. 1990 May;10(5):2247-60 [2183026] Nucleic Acids Res. 1990 Apr 11;18(7):1749-56 [2186365] Genes Dev. 1990 Feb;4(2):299-312 [2159934] Cell. 1987 Nov 20;51(4):613-22 [3677170] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Helicase-primase complex of herpes simplex virus type 1: a mutation in the UL52 subunit abolishes primase activity. AN - 76508679; 8189507 AB - The UL52 gene product of herpes simplex virus type 1 (HSV-1) comprises one subunit of a 3-protein helicase-primase complex that is essential for replication of viral DNA. The functions of the individual subunits of the complex are not known with certainty, although it is clear that the UL8 subunit is not required for either helicase or primase activity. Examination of the predicted amino acid sequence of the UL5 gene reveals the existence of conserved helicase motifs; it seems likely, therefore, that UL5 is responsible for the helicase activity of the complex. We have undertaken mutational analysis of UL52 in an attempt to understand the functional contribution of this protein to the helicase-primase complex. Amino acid substitution mutations were introduced into five regions of the UL52 gene that are highly conserved among HSV-1 and the related herpesviruses equine herpesvirus 1, human cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus. Of seven mutants analyzed by an in vivo replication assay, three mutants, in three different conserved regions of the protein, failed to support DNA replication. Within one of the conserved regions is a 6-amino-acid motif (IL)(VIM)(LF)DhD (where h is a hydrophobic residue), which is also conserved in mouse, yeast, and T7 primases. Mutagenesis of the first aspartate residue of the motif, located at position 628 of the UL52 protein, abolished the ability of the complex to support replication of an origin-containing plasmid in vivo and to synthesize oligoribonucleotide primers in vitro. The ATPase and helicase activities were unaffected, as was the ability of the mutant enzyme to support displacement synthesis on a preformed fork substrate. These results provide experimental support for the idea that UL52 is responsible for the primase activity of the HSV helicase-primase complex. JF - Journal of virology AU - Klinedinst, D K AU - Challberg, M D AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 3693 EP - 3701 VL - 68 IS - 6 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Viral Proteins KW - DNA Primase KW - EC 2.7.7.- KW - helicase-primase, Human herpesvirus 1 KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Virus Replication -- genetics KW - DNA Replication -- genetics KW - Base Sequence KW - Molecular Sequence Data KW - DNA Replication -- physiology KW - Amino Acid Sequence KW - Virus Replication -- physiology KW - DNA, Viral -- genetics KW - Cell Line KW - DNA Helicases -- metabolism KW - DNA Helicases -- genetics KW - Herpesvirus 1, Human -- genetics KW - Herpesvirus 1, Human -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76508679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Helicase-primase+complex+of+herpes+simplex+virus+type+1%3A+a+mutation+in+the+UL52+subunit+abolishes+primase+activity.&rft.au=Klinedinst%2C+D+K%3BChallberg%2C+M+D&rft.aulast=Klinedinst&rft.aufirst=D&rft.date=1994-06-01&rft.volume=68&rft.issue=6&rft.spage=3693&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 - 1994-06-20 N1 - Date created - 1994-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1989 Dec;63(12):5023-9 [2555539] J Virol. 1989 Jan;63(1):196-204 [2535726] J Biol Chem. 1990 Jul 5;265(19):11227-32 [2193033] Nucleic Acids Res. 1990 Jun 25;18(12):3573-8 [2163521] Gene. 1990 Sep 28;94(1):45-51 [2121621] J Virol. 1990 Dec;64(12):5883-90 [2173770] J Virol. 1990 Dec;64(12):5976-87 [2173776] Science. 1972 Apr 28;176(4033):367-76 [4554613] J Biol Chem. 1975 Jul 25;250(14):5523-9 [1095580] Eur J Biochem. 1977 Feb;72(3):543-58 [320003] Nature. 1977 Oct 13;269(5629):621-3 [199849] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4308-12 [228295] J Virol. 1989 Feb;63(2):591-9 [2536095] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2186-9 [2538835] Nucleic Acids Res. 1989 Jun 26;17(12):4713-30 [2546125] J Biol Chem. 1989 Nov 15;264(32):19266-70 [2553735] J Biol Chem. 1991 Feb 5;266(4):2669-74 [1846632] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1105-9 [1847509] J Biol Chem. 1991 Mar 5;266(7):4484-8 [1847923] Biochemistry. 1991 May 28;30(21):5286-92 [2036395] J Virol. 1991 Sep;65(9):4565-72 [1651402] J Biol Chem. 1991 Dec 5;266(34):23240-50 [1744119] J Virol. 1992 Jan;66(1):469-79 [1309257] J Gen Virol. 1992 Feb;73 ( Pt 2):313-21 [1311360] J Mol Evol. 1992 Apr;34(4):351-7 [1569588] J Virol. 1992 Jul;66(7):3986-95 [1318393] J Biol Chem. 1992 Jun 25;267(18):13062-72 [1618804] J Virol. 1992 Aug;66(8):4884-92 [1321275] J Virol. 1992 Nov;66(11):6735-46 [1328687] Virology. 1980 Jun;103(2):311-26 [6247818] J Gen Virol. 1981 May;54(Pt 1):219-22 [6270246] J Virol. 1981 Sep;39(3):894-902 [6270358] J Biol Chem. 1982 Oct 25;257(20):12426-34 [6288720] J Virol. 1983 Jan;45(1):354-66 [6296442] J Virol. 1984 Jan;49(1):236-47 [6317891] EMBO J. 1982;1(8):945-51 [6329717] J Biol Chem. 1986 Apr 5;261(10):4738-48 [3007474] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6322-6 [3018724] Proc Natl Acad Sci U S A. 1986 Dec;83(23):9094-8 [3024166] Virology. 1987 Nov;161(1):198-210 [2823462] J Virol. 1988 Jan;62(1):91-9 [2824860] J Virol. 1988 Feb;62(2):435-43 [2826806] J Virol. 1988 Feb;62(2):444-53 [2826807] J Virol. 1988 Mar;62(3):715-21 [2828666] J Virol. 1988 Mar;62(3):818-25 [2828677] Methods Enzymol. 1987;155:166-77 [2828863] Proc Natl Acad Sci U S A. 1988 Jan;85(2):396-400 [2829184] Nature. 1988 May 5;333(6168):22-3 [3362205] Proc Natl Acad Sci U S A. 1988 May;85(9):2959-63 [2834723] J Virol. 1988 Aug;62(8):2874-83 [2839706] J Virol. 1988 Aug;62(8):2970-7 [2839713] Nucleic Acids Res. 1988 Jul 25;16(14A):6585-96 [2840645] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5414-8 [2840659] Nucleic Acids Res. 1988 Nov 11;16(21):9909-16 [2461550] J Biol Chem. 1989 Dec 15;264(35):20835-8 [2556383] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defective proliferation and regulatory function of CD4+ T cells bearing Leu-8 homing receptor in primary biliary cirrhosis. Phorbol myristate acetate enhances T-cell function. AN - 76505968; 7515343 AB - The majority of circulating CD4+ T cells express the Leu-8 peripheral lymph node homing receptor, and these cells have previously been shown to have suppressor-inducer and suppressor function. In the present study, it was found that CD4+, Leu-8+ T cells from patients with primary biliary cirrhosis (PBC) have a significantly (P < 0.01) lower proliferative response when stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) compared to normal controls. The proliferative response of CD4+, Leu-8- T cells was similar in patients and controls. However, the proliferative responses of CD4+, Leu-8+ from patients with PBC was normal when cells were stimulated with PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with phorbol myristate acetate (PMA). CD4+ T cells from patients with PBC mediated normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B ratios and their regulatory function was similar to that of normal CD4+ T cells that had been irradiated to inactivate their suppressor activity. When CD4+ T cells from patients with PBC were precultured with the combination of Con A and PMA, they mediated potent inhibitory activity similar to that of normal CD4+ T cells. Thus, CD4+, Leu-8+ T cells from patients with PBC have a defect of proliferation and suppressor function that is reversed by coculture with PMA. This finding suggests that impairment of a PMA-inducible lymphocyte activation pathway contributes to abnormal lymphocyte function in PBC. JF - Digestive diseases and sciences AU - Moreno-Otero, R AU - Murakawa, Y AU - Kanof, M E AU - Civeira, M P AU - Jones, E A AU - James, S P AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1329 EP - 1336 VL - 39 IS - 6 SN - 0163-2116, 0163-2116 KW - Cell Adhesion Molecules KW - 0 KW - Membrane Glycoproteins KW - Receptors, Lymphocyte Homing KW - L-Selectin KW - 126880-86-2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - In Vitro Techniques KW - Adult KW - Enzyme-Linked Immunosorbent Assay KW - Aged KW - Middle Aged KW - Cell Separation KW - Male KW - Female KW - Lymphocyte Activation -- drug effects KW - Liver Cirrhosis, Biliary -- immunology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Receptors, Lymphocyte Homing -- analysis KW - Membrane Glycoproteins -- analysis KW - CD4-Positive T-Lymphocytes -- immunology KW - Cell Adhesion Molecules -- analysis KW - CD4-Positive T-Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76505968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+and+sciences&rft.atitle=Defective+proliferation+and+regulatory+function+of+CD4%2B+T+cells+bearing+Leu-8+homing+receptor+in+primary+biliary+cirrhosis.+Phorbol+myristate+acetate+enhances+T-cell+function.&rft.au=Moreno-Otero%2C+R%3BMurakawa%2C+Y%3BKanof%2C+M+E%3BCiveira%2C+M+P%3BJones%2C+E+A%3BJames%2C+S+P&rft.aulast=Moreno-Otero&rft.aufirst=R&rft.date=1994-06-01&rft.volume=39&rft.issue=6&rft.spage=1329&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+and+sciences&rft.issn=01632116&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-06 N1 - Date created - 1994-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of keratin 14 and alpha-fetoprotein expression during hepatic oval cell proliferation and liver regeneration. AN - 76493944; 7514611 AB - Keratin 14 (K14) expression has recently been demonstrated in cell lines of non-parenchymal hepatic origin (Bisgaard et al., 1993, Mol. Carcinog., 7:60-66; Bisgaard et al., 1991, J. Cell. Physiol., 147:333-343). These cell lines are thought to represent a progeny of a dormant stem cell compartment present in the adult rat liver, which may participate in the restoration of the liver mass after experimental liver injury. Utilizing a combination of 2-acetylaminofluorene (2-AAF) administration and partial hepatectomy to activate liver regeneration by proliferation of oval cells, we examined the modulation of K14 as well as alpha-fetoprotein (AFP) expression in proliferating oval cells and lineages hypothesized to be derived herefrom. We showed by Northern blot and in situ hybridization analyses that K14 and AFP transcripts were initially accumulating in epithelial cells located in subsets of ductal structures in the portal areas. As oval cells infiltrated the liver parenchyma, K14 transcripts were detected in oval cells, in foci of small basophilic hepatocytes, and in structures resembling glandular intestinal-type epithelium. AFP was expressed in oval cells, and at low but detectable levels in foci of basophilic hepatocytes, but not in glandular intestinal-type epithelium. Neither K14 nor AFP transcripts were detected in bile ducts or mature hepatocytes at any time during oval cell proliferation and reconstitution of the liver mass. To further study the modulation of K14 and AFP expression we utilized an in vitro model in which spontaneous transformation of rat liver epithelial (RLE) cells appeared to mimic the process of early differentiation along the hepatic lineage in vivo. We demonstrated that undifferentiated RLE cells at a late passage expressed K14 and vimentin, whereas transformation and differentiation to hepatoblast-like progeny resulted in an abrogation of K14 and vimentin expression and an induction of K18 and AFP. We propose that K14 and AFP are sequentially modulated in subpopulations of oval cells involved in the ongoing reconstitution of the liver mass. JF - Journal of cellular physiology AU - Bisgaard, H C AU - Nagy, P AU - Ton, P T AU - Hu, Z AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 475 EP - 484 VL - 159 IS - 3 SN - 0021-9541, 0021-9541 KW - RNA, Messenger KW - 0 KW - Vimentin KW - alpha-Fetoproteins KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - Keratins KW - 68238-35-7 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Poly A -- isolation & purification KW - Animals KW - 2-Acetylaminofluorene -- toxicity KW - Transcription, Genetic -- drug effects KW - Blotting, Northern KW - Vimentin -- biosynthesis KW - Poly A -- biosynthesis KW - RNA -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - In Situ Hybridization KW - Cells, Cultured KW - Hepatectomy KW - RNA -- isolation & purification KW - Cell Line KW - Female KW - Cell Division KW - Liver -- cytology KW - alpha-Fetoproteins -- biosynthesis KW - Liver -- drug effects KW - RNA, Messenger -- analysis KW - Gene Expression Regulation -- drug effects KW - Liver Regeneration KW - RNA, Messenger -- biosynthesis KW - Liver -- physiology KW - Keratins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76493944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Modulation+of+keratin+14+and+alpha-fetoprotein+expression+during+hepatic+oval+cell+proliferation+and+liver+regeneration.&rft.au=Bisgaard%2C+H+C%3BNagy%2C+P%3BTon%2C+P+T%3BHu%2C+Z%3BThorgeirsson%2C+S+S&rft.aulast=Bisgaard&rft.aufirst=H&rft.date=1994-06-01&rft.volume=159&rft.issue=3&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-21 N1 - Date created - 1994-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracellular ATP induces immediate-early gene expression but not cellular hypertrophy in neonatal cardiac myocytes. AN - 76492095; 8187273 AB - It is well-documented that norepinephrine (NE) induces the expression of immediate-early genes (IEGs), such as c-fos, c-jun, and jun-B, in cultured neonatal heart cells and leads to cell growth without cell division (ie, hypertrophy). Although purinergic receptors activated by ATP are present on cardiac myocytes and ATP is coreleased with NE from sympathetic nerve endings within the heart, the potential role of the purinergic system in the cascade of events that leads to cardiac hypertrophy is unknown. We report in the present study that stimulation of purinergic receptors by micromolar concentrations of extracellular ATP increased the levels of c-fos and jun-B mRNA as well as FOS and JUN-B proteins in neonatal cardiac myocytes. The magnitude of response to micromolar ATP was comparable to that elicited by NE. The increase in IEG expression induced by ATP was preceded by a rapid transient increase in cytosolic Ca2+. Pretreatment of myocytes with the intracellular Ca2+ chelator BAPTA-AM prevented the ATP-stimulated increase in cytosolic Ca2+ and attenuated the ATP-stimulated increase in c-fos expression. In contrast, NE did not increase cytosolic Ca2+ in quiescent myocytes, and pretreatment with BAPTA-AM did not inhibit the NE-stimulated increase in c-fos gene expression. Furthermore, although NE markedly increased [14C]phenylalanine incorporation into protein and myocyte hypertrophy measured by cell size, ATP did not. These results demonstrate that stimulation of purinergic receptors by ATP activates IEGs via a Ca(2+)-dependent pathway in cardiac myocytes that differs from the NE stimulated activation of these genes.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Circulation research AU - Zheng, J S AU - Boluyt, M O AU - O'Neill, L AU - Crow, M T AU - Lakatta, E G AD - Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1034 EP - 1041 VL - 74 IS - 6 SN - 0009-7330, 0009-7330 KW - Proto-Oncogene Proteins c-fos KW - 0 KW - RNA, Messenger KW - Phenylalanine KW - 47E5O17Y3R KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals, Newborn KW - Animals KW - Phenylalanine -- metabolism KW - Cells, Cultured KW - Proto-Oncogene Proteins c-fos -- analysis KW - Rats, Wistar KW - RNA, Messenger -- analysis KW - Genes, Immediate-Early -- drug effects KW - Cardiomegaly -- chemically induced KW - Genes, jun -- drug effects KW - Gene Expression Regulation -- drug effects KW - Genes, fos -- drug effects KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76492095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Extracellular+ATP+induces+immediate-early+gene+expression+but+not+cellular+hypertrophy+in+neonatal+cardiac+myocytes.&rft.au=Zheng%2C+J+S%3BBoluyt%2C+M+O%3BO%27Neill%2C+L%3BCrow%2C+M+T%3BLakatta%2C+E+G&rft.aulast=Zheng&rft.aufirst=J&rft.date=1994-06-01&rft.volume=74&rft.issue=6&rft.spage=1034&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=00097330&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenotypic modulation of keratins, vimentin, and alpha-fetoprotein in cultured rat liver epithelial cells after chemical, oncogene, and spontaneous transformation. AN - 76492073; 7514612 AB - Several lines of evidence have indicated that rat liver epithelial (RLE) cell lines may be related to a dormant stem cell compartment in the liver in vivo. We have demonstrated that keratin 14 (K14) is expressed together with vimentin in undifferentiated RLE cells. However, upon spontaneous transformation and differentiation to hepatoblast-like progeny the expression of these intermediate filaments (IF) is abrogated, while expression of another set of genes, among others keratin 18 (K18) and alpha-fetoprotein (AFP), is induced (Bisgaard et al., 1994, J. Cell. Physiol., in press). To better understand the mechanisms underlying IF expression during transformation and differentiation of RLE cells we examined the expression and regulation of IFs in clonal cell lines of chemically, oncogene, and spontaneously transformed RLE cells and their resulting tumors. These clonal lines provided a wide variety of tumor phenotypes including trabecular, solid and tubular adenocarcinomas, undifferentiated carcinomas, and spindle cell carcinomas. Northern blot analysis of the cell lines confirmed the differential expression of IF mRNAs. While keratin 8 (K8) was expressed at similar steady-state levels in all cell lines, K14 and vimentin but not K18 were expressed in the majority of cell lines chemically transformed with aflatoxin B1 or by transduction of oncogenes. In contrast, cell lines transformed spontaneously by prolonged passage in vitro expressed K18, while K14 and vimentin were absent. The keratin expression pattern in vitro was retained in the majority of the resulting tumors. However, the keratins expressed in vitro did not accurately predict the tumor phenotype in vivo. In particular, in tumors typed morphologically as adenocarcinomas, the keratin pair typically expressed in chemically transformed tumor cells was K8/K14, whereas K8/K18 was expressed in the tumors derived from spontaneously transformed cell lines. Finally we showed by nuclear run-on and in vitro translation analyses that the expression of K14, K18, and vimentin in transformed RLE cell lines was regulated at the transcriptional level, whereas that of K8 appeared to be posttranslational. These findings suggest that events controlling the differential expression of IF genes are involved in the processes leading to transformation and differentiation of the RLE cell lines. We conclude that the transformed RLE cell lines provide a valuable model to further examine the regulatory mechanisms involved in hepatic differentiation of undifferentiated "progenitor-like" RLE cells. JF - Journal of cellular physiology AU - Bisgaard, H C AU - Ton, P T AU - Nagy, P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 485 EP - 494 VL - 159 IS - 3 SN - 0021-9541, 0021-9541 KW - v-myc KW - v-raf KW - Retroviridae Proteins, Oncogenic KW - 0 KW - Vimentin KW - alpha-Fetoproteins KW - Keratins KW - 68238-35-7 KW - Oncogene Proteins v-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Genes, myc KW - Gene Expression KW - Transcription, Genetic KW - Mice KW - Mice, Nude KW - Cell Nucleus KW - Epithelium -- drug effects KW - Rats KW - Phenotype KW - Retroviridae Proteins, Oncogenic -- genetics KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Transfection KW - Cells, Cultured KW - Transplantation, Heterologous KW - Epithelium -- metabolism KW - Cell Line KW - Female KW - Oncogenes KW - Vimentin -- biosynthesis KW - alpha-Fetoproteins -- biosynthesis KW - Liver -- drug effects KW - Liver -- metabolism KW - Keratins -- biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76492073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Phenotypic+modulation+of+keratins%2C+vimentin%2C+and+alpha-fetoprotein+in+cultured+rat+liver+epithelial+cells+after+chemical%2C+oncogene%2C+and+spontaneous+transformation.&rft.au=Bisgaard%2C+H+C%3BTon%2C+P+T%3BNagy%2C+P%3BThorgeirsson%2C+S+S&rft.aulast=Bisgaard&rft.aufirst=H&rft.date=1994-06-01&rft.volume=159&rft.issue=3&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-21 N1 - Date created - 1994-06-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - v-myc; v-raf N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term effects of radiation therapy for a catecholamine-producing glomus jugulare tumor. Case report. AN - 76490095; 8189265 AB - A 42-year-old woman presented with otorrhea 22 years after extracranial resection of a norepinephrine-secreting glomus jugulare tumor with intravascular embolization and radiation therapy to the intracranial portion of the tumor. Tumor growth was arrested and was associated with a decrease in blood and urine norepinephrine levels. Extensive evaluation of the otorrhea, including computerized tomography-cisternography, gadolinium-enhanced magnetic resonance imaging, and arteriography showed marked diffuse necrosis of the temporal bone and skull base with limited tumor vascularity. Cerebrospinal fluid (CSF) collected from the right ear showed norepinephrine levels of 2975 pg/ml; plasma norepinephrine levels were normal. The precise site of CSF leakage could not be delineated. Exploration of the posterior fossa revealed a large dural defect at the anteromedial aspect of the petrous bone through which CSF flowed over the surface of the residual extradural glomus tumor. The defect was successfully sealed with a fascial patch. Postoperatively, CSF norepinephrine levels were normal and no further leakage was observed. JF - Journal of neurosurgery AU - Pluta, R M AU - Ram, Z AU - Patronas, N J AU - Keiser, H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1091 EP - 1094 VL - 80 IS - 6 SN - 0022-3085, 0022-3085 KW - Norepinephrine KW - X4W3ENH1CV KW - Abridged Index Medicus KW - Index Medicus KW - Cerebrospinal Fluid Otorrhea -- etiology KW - Temporal Bone -- radiation effects KW - Combined Modality Therapy KW - Humans KW - Cerebrospinal Fluid Otorrhea -- surgery KW - Adult KW - Osteoradionecrosis -- etiology KW - Follow-Up Studies KW - Female KW - Radiotherapy -- adverse effects KW - Norepinephrine -- urine KW - Glomus Jugulare Tumor -- secretion KW - Glomus Jugulare Tumor -- radiotherapy KW - Norepinephrine -- secretion KW - Norepinephrine -- cerebrospinal fluid KW - Glomus Jugulare Tumor -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76490095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Long-term+effects+of+radiation+therapy+for+a+catecholamine-producing+glomus+jugulare+tumor.+Case+report.&rft.au=Pluta%2C+R+M%3BRam%2C+Z%3BPatronas%2C+N+J%3BKeiser%2C+H&rft.aulast=Pluta&rft.aufirst=R&rft.date=1994-06-01&rft.volume=80&rft.issue=6&rft.spage=1091&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-20 N1 - Date created - 1994-06-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. AN - 76481706; 8182764 AB - Camptothecins belong to a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. Two camptothecin derivatives, topotecan (TPT) and CPT-11, are in clinical trials and their chemotherapeutic efficacy appears promising. Our aim was to compare simultaneously the molecular and cellular pharmacology of the various camptothecin derivatives that are presently in clinical trials. Cytotoxicity of drugs toward human colon carcinoma HT-29 cells was determined by colony-forming assays. DNA single-strand breaks (SSB) were measured by alkaline elution. Drug potency to induce topoisomerase 1-mediated DNA cleavage and the sequence selectivity of the breaks were determined by sequencing gel autoradiography. SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells. IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11. In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11. SN-38 remained the most potent compound in isolated nuclei, and CPT-11 was still inactive. The potency ranking was the same as in whole cells, and the C1000 values were 0.0025 microM for SN-38, 0.012 microM for CPT, 0.021 microM for 9-AC, 0.44 microM for TPT, and greater than 0.1 microM for CPT-11. Potency difference between SN-38 and the other compounds was greater in isolated nuclei than in whole cells. Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT. Cleavage patterns of CPT and 9-AC were similar but differed from those of TPT and SN-38. Although in vitro analyses do not necessarily reflect chemotherapeutic efficacy, this study found that SN-38 is the most potent compound and that 9-AC and TPT are less active than CPT in this system. The effect of CPT-11 is minimal. Therefore, the clinical activity of CPT-11 may strongly depend on its hydrolysis to SN-38. Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives. JF - Journal of the National Cancer Institute AU - Tanizawa, A AU - Fujimori, A AU - Fujimori, Y AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Md 20892. Y1 - 1994/06/01/ PY - 1994 DA - 1994 Jun 01 SP - 836 EP - 842 VL - 86 IS - 11 SN - 0027-8874, 0027-8874 KW - DNA, Neoplasm KW - 0 KW - Topoisomerase I Inhibitors KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Clinical Trials as Topic KW - DNA, Neoplasm -- drug effects KW - Camptothecin -- chemistry KW - Colonic Neoplasms -- genetics KW - Camptothecin -- pharmacology KW - Carcinoma -- drug therapy KW - Colonic Neoplasms -- drug therapy KW - Camptothecin -- analogs & derivatives KW - Carcinoma -- enzymology KW - Colonic Neoplasms -- enzymology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76481706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+topoisomerase+I+inhibition%2C+DNA+damage%2C+and+cytotoxicity+of+camptothecin+derivatives+presently+in+clinical+trials.&rft.au=Tanizawa%2C+A%3BFujimori%2C+A%3BFujimori%2C+Y%3BPommier%2C+Y&rft.aulast=Tanizawa&rft.aufirst=A&rft.date=1994-06-01&rft.volume=86&rft.issue=11&rft.spage=836&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 - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simian virus 40-like DNA sequences in human pleural mesothelioma. AN - 76475226; 8183577 AB - Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA virus-like sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications. JF - Oncogene AU - Carbone, M AU - Pass, H I AU - Rizzo, P AU - Marinetti, M AU - Di Muzio, M AU - Mew, D J AU - Levine, A S AU - Procopio, A AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/06// PY - 1994 DA - June 1994 SP - 1781 EP - 1790 VL - 9 IS - 6 SN - 0950-9232, 0950-9232 KW - Antigens, Polyomavirus Transforming KW - 0 KW - DNA, Viral KW - Viral Proteins KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Adult KW - Molecular Sequence Data KW - Viral Proteins -- analysis KW - Asbestos -- adverse effects KW - Aged KW - Middle Aged KW - Male KW - Female KW - Antigens, Polyomavirus Transforming -- analysis KW - Mesothelioma -- microbiology KW - Mesothelioma -- diagnosis KW - DNA, Viral -- chemistry KW - DNA, Viral -- analysis KW - Simian virus 40 -- genetics KW - Pleural Neoplasms -- microbiology KW - Mesothelioma -- etiology KW - Simian virus 40 -- immunology KW - Pleural Neoplasms -- etiology KW - Pleural Neoplasms -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76475226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Simian+virus+40-like+DNA+sequences+in+human+pleural+mesothelioma.&rft.au=Carbone%2C+M%3BPass%2C+H+I%3BRizzo%2C+P%3BMarinetti%2C+M%3BDi+Muzio%2C+M%3BMew%2C+D+J%3BLevine%2C+A+S%3BProcopio%2C+A&rft.aulast=Carbone&rft.aufirst=M&rft.date=1994-06-01&rft.volume=9&rft.issue=6&rft.spage=1781&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Iron accelerates while magnesium inhibits nickel-induced carcinogenesis in the rat kidney. AN - 76571480; 8023338 AB - Effects of magnesium basic carbonate (MgCarb) and metallic iron powder (Fe0) on nickel subsulfide (Ni3S2)-induced carcinogenesis were studied in kidneys of male F344/NCr rats. The rats, 20-40/group, received injections of Ni3S2 alone (62 mumol Ni) or with equimolar doses of MgCarb or Fe0 into the renal cortex of each pole of the right kidney. Control rats were given MgCarb, Fe0, or 0.1 ml of 50% aqueous glycerol, the injection vehicle. Final incidence of renal tumors 2 years after the injection of Ni3S2 alone or mixed with Fe0 was 60%. However, rats given Ni3S2 + Fe0 developed renal tumors much more rapidly. In contrast, the incidence of renal tumors in rats given Ni3S2 + MgCarb was only 20% (P < 0.01 vs. Ni3S2 alone). No kidney tumors were observed in the control rats. Between weeks 4 and 32 post injection, Ni3S2 alone caused erythrocytosis. This effect was attenuated by Fe0, but not by MgCarb. Hence, there is no firm correlation between carcinogenic activity of nickel and its ability to induce erythropoiesis. All kidney tumors were of mesenchymal cell origin and resembled the sarcomatous variant of the classic rat renal mesenchymal tumor. Some of them metastasized to the lungs and other organs. In 3-35 days post-injection, kidneys of rats treated with Ni3S2 alone showed moderate to extensive necrosis, inflammation, fibrosis, and degenerative and regenerative proliferative changes in the proximal tubular epithelium at the injection site. Similar, but more severe and multifocal changes were observed in the kidneys of Ni3S2 + Fe0-treated rats. The necrosis was less severe in kidneys injected with Ni3S2 + MgCarb, but fibrosis and degenerative and regenerative changes in proximal tubular epithelium were similar to those observed in other treatment groups. Ni3S2 deposits were seen inside macrophages and proximal tubular epithelial cells of Ni3S2 and Ni3S2+ Fe0-treated kidneys more frequently than in Ni3S2 + MgCarb-treated kidneys. Thus, magnesium antagonizes nickel carcinogenesis in the rat kidney while iron tends to enhance it. This result may be related to respectively attenuating or enhancing effects of magnesium and iron on the inflammatory response to Ni3S2. JF - Toxicology AU - Kasprzak, K S AU - Diwan, B A AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702. Y1 - 1994/05/31/ PY - 1994 DA - 1994 May 31 SP - 129 EP - 140 VL - 90 IS - 1-2 SN - 0300-483X, 0300-483X KW - Carcinogens KW - 0 KW - magnesium carbonate KW - 0E53J927NA KW - nickel subsulfide KW - 12035-72-2 KW - Nickel KW - 7OV03QG267 KW - Iron KW - E1UOL152H7 KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Drug Interactions KW - Lung Neoplasms -- secondary KW - Body Weight -- drug effects KW - Neoplasm Metastasis KW - Liver Neoplasms -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Liver Neoplasms -- secondary KW - Male KW - Kidney Neoplasms -- pathology KW - Nickel -- antagonists & inhibitors KW - Kidney Neoplasms -- chemically induced KW - Iron -- pharmacology KW - Kidney Neoplasms -- prevention & control KW - Magnesium -- pharmacology KW - Carcinogens -- toxicity KW - Nickel -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76571480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=Iron+accelerates+while+magnesium+inhibits+nickel-induced+carcinogenesis+in+the+rat+kidney.&rft.au=Kasprzak%2C+K+S%3BDiwan%2C+B+A%3BRice%2C+J+M&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=1994-05-31&rft.volume=90&rft.issue=1-2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene transfer of drug resistance genes. Implications for cancer therapy. AN - 76567450; 7912913 AB - Two general approaches to the gene therapy of cancer have been proposed: (1) strategies that use exogenous genes to modify cancer cells so that they are less malignant or more susceptible to host defenses or to killing by exogenous agents; and (2) approaches that modify host cells so that they are more effective in eliminating cancer cells or more resistant to agents that are used to treat cancer. In both cases, the development of vectors that encode in vivo selectable phenotypes, such as drug resistance, would be extremely valuable because of the inherent inefficiency of gene transfer and the potential of such vectors to protect normal tissues against toxic agents. To allow the selection of cells in vivo that have been transduced with vectors for gene therapy, we have utilized the human multidrug resistance (MDR1) gene. The product of this gene is a 170,000-dalton glycoprotein known as P-glycoprotein, which acts as an energy-dependent efflux pump for a great many cytotoxic anticancer drugs, including doxorubicin, daunorubicin, etoposide, teniposide, actinomycin D, and taxol. Vectors encoding an MDR1 cDNA are able to transduce many cell types, including bone marrow cells, with high efficiency to allow selection of drug resistance in vitro and in vivo in mouse models. Thus, it should be possible to protect the bone marrow of patients undergoing intensive chemotherapy by transduction of their bone marrow with MDR1 vectors. Furthermore, the ability to select for the presence of the MDR1 cDNA in vivo means that it can be used to introduce otherwise nonselectable genes into the bone marrow for therapy of cancer and other diseases. JF - Annals of the New York Academy of Sciences AU - Gottesman, M M AU - Germann, U A AU - Aksentijevich, I AU - Sugimoto, Y AU - Cardarelli, C O AU - Pastan, I AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/31/ PY - 1994 DA - 1994 May 31 SP - 126 EP - 38; discussion 138-43 VL - 716 SN - 0077-8923, 0077-8923 KW - MDR1 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - P-Glycoprotein KW - Recombinant Fusion Proteins KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Humans KW - Genetic Vectors KW - Bone Marrow -- metabolism KW - Mice KW - Forecasting KW - Retroviridae -- genetics KW - Structure-Activity Relationship KW - Membrane Glycoproteins -- chemistry KW - Gene Transfer Techniques KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- genetics KW - Drug Resistance KW - Genetic Therapy KW - Neoplasms -- therapy KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76567450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+transfer+of+drug+resistance+genes.+Implications+for+cancer+therapy.&rft.au=Gottesman%2C+M+M%3BGermann%2C+U+A%3BAksentijevich%2C+I%3BSugimoto%2C+Y%3BCardarelli%2C+C+O%3BPastan%2C+I&rft.aulast=Gottesman&rft.aufirst=M&rft.date=1994-05-31&rft.volume=716&rft.issue=&rft.spage=126&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 - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDR1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular and molecular mechanisms of impaired dopaminergic function during aging. AN - 76562325; 8010587 AB - One important cause of impaired motor function during aging is deterioration of the dopamine system. Such motor deficits in experimental animals can be closely related to loss of striatal dopamine receptors, and similar observations have now been made in humans. Two mechanisms account for the age-related decrease in striatal dopamine receptor levels: loss of receptor-containing neurons and reduced rates of receptor synthesis. The striatal neurons affected by aging appear to reside in a kainic-acid-sensitive population. Attempts to mimic those death mechanisms which occur in vivo using cultured neurons suggest that large D2-dopamine-receptor-containing cells may be the most vulnerable. Whether dopamine itself, the endogenous neurotransmitter for the cells, may ultimately be toxic to these neurons remains to be determined. The levels of D2-receptor mRNA in the surviving neurons is reduced during aging. This decrement is apparently due to a decreased rate of mRNA biosynthesis. Future experiments must therefore focus on the regulatory elements of this gene in order to determine why its transcription is selectively affected by aging. Finally, various interventions have been shown to delay or reverse the age changes characteristic of the dopaminergic system. Both dopamine receptors and motor function have been manipulated by diet and exercise as well as 6-OH-dopamine lesions and estrogen and prolactin administration. The possibility that such treatments might eventually be utilized therapeutically has become increasingly real as our knowledge of the affected cellular and molecular processes continues to expand. JF - Annals of the New York Academy of Sciences AU - Roth, G S AU - Joseph, J A AD - Molecular Physiology and Genetics Section, National Institute on Aging, Francis Scott Key Medical Center, Baltimore, Maryland 21224. Y1 - 1994/05/31/ PY - 1994 DA - 1994 May 31 SP - 129 EP - 135 VL - 719 SN - 0077-8923, 0077-8923 KW - RNA, Messenger KW - 0 KW - Receptors, Dopamine D2 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Corpus Striatum -- cytology KW - Animals KW - Motor Neurons -- physiology KW - Corpus Striatum -- physiology KW - RNA, Messenger -- metabolism KW - Molecular Biology KW - Humans KW - Neurons -- physiology KW - Motor Neuron Disease -- physiopathology KW - Gene Expression Regulation KW - Receptors, Dopamine D2 -- genetics KW - Receptors, Dopamine D2 -- metabolism KW - Aging -- physiology KW - Dopamine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76562325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+and+molecular+mechanisms+of+impaired+dopaminergic+function+during+aging.&rft.au=Roth%2C+G+S%3BJoseph%2C+J+A&rft.aulast=Roth&rft.aufirst=G&rft.date=1994-05-31&rft.volume=719&rft.issue=&rft.spage=129&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 - 1994-07-21 N1 - Date created - 1994-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. AN - 76526021; 8204577 AB - A unique characteristic of the CYP3A subfamily of cytochrome P450 enzymes is their ability to be activated by certain compounds. It is reported that CYP3A4-catalyzed phenanthrene metabolism is activated by 7,8-benzoflavone and that 7,8-benzoflavone serves as a substrate for CYP3A4. Kinetic analyses of these two substrates show that 7,8-benzoflavone increases the Vmax of phenanthrene metabolism without changing the Km and that phenanthrene decreases the Vmax of 7,8-benzoflavone metabolism without increasing the Km. These results suggest that both substrates (or substrate and activator) are simultaneously present in the active site. Both compounds must have access to the active oxygen, since neither phenanthrene nor 7,8-benzoflavone can competitively inhibit the other substrate. These data provide the first evidence that two different molecules can be simultaneously bound to the same P450 active site. Additionally, structure-activity relationship studies were performed with derivatives of 7,8-benzoflavone structure. The effects of 13 different compounds on the regioselectivity of phenanthrene, chrysene, and benzo[a]pyrene metabolism were determined. Of the 13 compounds studied, 6 were activators, 2 were partial activators, and 5 were inhibitors. Analyses of the data suggest that (1) naphthalene substituted with a ketone in the 2-position can activate 3A4 and (2) the presence of an activator results in a narrower effective substrate binding site. Since the CYP3A enzymes are very important in drug metabolism, the possibility of activation, and autoactivation, must be considered when in vitro-in vivo correlations are made and when possible drug interactions are considered. JF - Biochemistry AU - Shou, M AU - Grogan, J AU - Mancewicz, J A AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AU - Korzekwa, K R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/31/ PY - 1994 DA - 1994 May 31 SP - 6450 EP - 6455 VL - 33 IS - 21 SN - 0006-2960, 0006-2960 KW - Benzoflavones KW - 0 KW - Polycyclic Compounds KW - Recombinant Proteins KW - alpha-naphthoflavone KW - 604-59-1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Rats KW - Animals KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Enzyme Activation KW - Kinetics KW - Humans KW - Microsomes, Liver -- enzymology KW - Benzoflavones -- metabolism KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Binding Sites KW - Mixed Function Oxygenases -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Polycyclic Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76526021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+CYP3A4%3A+evidence+for+the+simultaneous+binding+of+two+substrates+in+a+cytochrome+P450+active+site.&rft.au=Shou%2C+M%3BGrogan%2C+J%3BMancewicz%2C+J+A%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V%3BKorzekwa%2C+K+R&rft.aulast=Shou&rft.aufirst=M&rft.date=1994-05-31&rft.volume=33&rft.issue=21&rft.spage=6450&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-08 N1 - Date created - 1994-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins against cancer. AN - 76514514; 8199194 JF - Biochimica et biophysica acta AU - Brinkmann, U AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/05/27/ PY - 1994 DA - 1994 May 27 SP - 27 EP - 45 VL - 1198 IS - 1 SN - 0006-3002, 0006-3002 KW - Antigens KW - 0 KW - Immunotoxins KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - Humans KW - Recombinant Proteins -- immunology KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Antigens -- immunology KW - Recombinant Proteins -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76514514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Immunotoxins+against+cancer.&rft.au=Brinkmann%2C+U%3BPastan%2C+I&rft.aulast=Brinkmann&rft.aufirst=U&rft.date=1994-05-27&rft.volume=1198&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. AN - 76510637; 8195116 AB - Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge, Jaspis johnstoni, has both fungicidal and antiproliferative activity. We now report that this peptide is a potent inducer of actin polymerization in vitro. The peptide has a much greater effect on Mg(2+)-actin than on Ca(2+)-actin. Competitive binding studies using rhodamine-phalloidin suggest that jasplakinolide binds to F-actin competitively with phalloidin with a dissociation constant of approximately 15 nM. This compares favorably to the previously reported IC50 of 35 nM for the antiproliferative effect of jasplakinolide on PC3 prostate carcinoma cells. The binding curve suggests that nearest neighbor positive cooperativity influences the binding of jasplakinolide (and perhaps also phalloidin) to F-actin. These results imply that jasplakinolide may exert its cytotoxic effect in vivo by inducing actin polymerization and/or stabilizing pre-existing actin filaments. JF - The Journal of biological chemistry AU - Bubb, M R AU - Senderowicz, A M AU - Sausville, E A AU - Duncan, K L AU - Korn, E D AD - Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/27/ PY - 1994 DA - 1994 May 27 SP - 14869 EP - 14871 VL - 269 IS - 21 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - Biopolymers KW - Cytotoxins KW - Depsipeptides KW - Peptides, Cyclic KW - jasplakinolide KW - 102396-24-7 KW - Phalloidine KW - 17466-45-4 KW - Index Medicus KW - Animals KW - Spectrometry, Fluorescence KW - Porifera KW - Kinetics KW - Binding, Competitive KW - Rabbits KW - Peptides, Cyclic -- pharmacology KW - Phalloidine -- metabolism KW - Actins -- metabolism KW - Cytotoxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76510637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Jasplakinolide%2C+a+cytotoxic+natural+product%2C+induces+actin+polymerization+and+competitively+inhibits+the+binding+of+phalloidin+to+F-actin.&rft.au=Bubb%2C+M+R%3BSenderowicz%2C+A+M%3BSausville%2C+E+A%3BDuncan%2C+K+L%3BKorn%2C+E+D&rft.aulast=Bubb&rft.aufirst=M&rft.date=1994-05-27&rft.volume=269&rft.issue=21&rft.spage=14869&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 - 1994-06-29 N1 - Date created - 1994-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - beta-Amyloid increases choline conductance of PC12 cells: possible mechanism of toxicity in Alzheimer's disease. AN - 76669946; 8069685 AB - When beta-amyloid-(1-40) is added to PC12 cells, there is an increase in choline conductance that is proportional to the beta-amyloid concentration. If a similar effect occurs in cholinergic brain cells of Alzheimer's disease patients, the intracellular choline concentration would be reduced, leading to a decrease in the production of acetylcholine. This could explain the reduced level of acetylcholine that has been found in post-mortem brain tissue of Alzheimer's disease patients. JF - Brain research AU - Galdzicki, Z AU - Fukuyama, R AU - Wadhwani, K C AU - Rapoport, S I AU - Ehrenstein, G AD - Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892. Y1 - 1994/05/23/ PY - 1994 DA - 1994 May 23 SP - 332 EP - 336 VL - 646 IS - 2 SN - 0006-8993, 0006-8993 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - amyloid beta-protein (1-40) KW - Choline KW - N91BDP6H0X KW - Index Medicus KW - Animals KW - Adrenal Gland Neoplasms KW - Kinetics KW - Humans KW - Time Factors KW - Pheochromocytoma KW - PC12 Cells KW - Electric Conductivity -- drug effects KW - Alzheimer Disease -- physiopathology KW - Peptide Fragments -- pharmacology KW - Amyloid beta-Peptides -- pharmacology KW - Membrane Potentials -- physiology KW - Choline -- metabolism KW - Membrane Potentials -- drug effects KW - Electric Conductivity -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76669946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=beta-Amyloid+increases+choline+conductance+of+PC12+cells%3A+possible+mechanism+of+toxicity+in+Alzheimer%27s+disease.&rft.au=Galdzicki%2C+Z%3BFukuyama%2C+R%3BWadhwani%2C+K+C%3BRapoport%2C+S+I%3BEhrenstein%2C+G&rft.aulast=Galdzicki&rft.aufirst=Z&rft.date=1994-05-23&rft.volume=646&rft.issue=2&rft.spage=332&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 - 1994-09-23 N1 - Date created - 1994-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative autoradiography of striatal dopamine D1, D2 and re-uptake sites in rats with vacuous chewing movements. AN - 76666002; 8069667 AB - Rats treated with haloperidol that developed vacuous chewing movements (VCM), a possible animal model of tardive dyskinesia, were studied with quantitative autoradiography for dopamine type-1 (D1) and type-2 (D2) receptors as well as dopamine re-uptake sites. Haloperidol increased striatal D2 receptors, but did not affect D1 receptors or the dopamine re-uptake site. D2 receptor increases occurred in rats with and without VCMs. In so far as VCM is a model for tardive dyskinesia, haloperidol induced increases in striatal D2 receptors do not appear to be etiologic for these abnormal movements. JF - Brain research AU - Knable, M B AU - Hyde, T M AU - Egan, M F AU - Tosayali, M AU - Wyatt, R J AU - Kleinman, J E AD - Clinical Brain Disorders Branch, National Institute of Mental Health, St. Elizabeths Hospital, Washington, DC 20032. Y1 - 1994/05/23/ PY - 1994 DA - 1994 May 23 SP - 217 EP - 222 VL - 646 IS - 2 SN - 0006-8993, 0006-8993 KW - Benzazepines KW - 0 KW - Dopamine D2 Receptor Antagonists KW - Ligands KW - Piperazines KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Salicylamides KW - Tritium KW - 10028-17-8 KW - Raclopride KW - 430K3SOZ7G KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Biological Transport KW - Mastication KW - Benzazepines -- metabolism KW - Piperazines -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Salicylamides -- metabolism KW - Autoradiography -- methods KW - Male KW - Dyskinesia, Drug-Induced -- metabolism KW - Corpus Striatum -- metabolism KW - Dopamine -- metabolism KW - Receptors, Dopamine D1 -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76666002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantitative+autoradiography+of+striatal+dopamine+D1%2C+D2+and+re-uptake+sites+in+rats+with+vacuous+chewing+movements.&rft.au=Knable%2C+M+B%3BHyde%2C+T+M%3BEgan%2C+M+F%3BTosayali%2C+M%3BWyatt%2C+R+J%3BKleinman%2C+J+E&rft.aulast=Knable&rft.aufirst=M&rft.date=1994-05-23&rft.volume=646&rft.issue=2&rft.spage=217&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 - 1994-09-23 N1 - Date created - 1994-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple, functional DBP sites on the promoter of the cholesterol 7 alpha-hydroxylase P450 gene, CYP7. Proposed role in diurnal regulation of liver gene expression. AN - 76479649; 8182075 AB - Hepatic cytochrome P450 cholesterol 7 alpha-hydroxylase, CYP7, is regulated in vivo at the protein and the mRNA level in response to multiple physiological factors, including liver cholesterol synthesis, bile acid feedback inhibition, and diurnal rhythm. In the present study we investigated whether the liver transcription factor DBP (albumin promoter D-site binding protein), which undergoes a striking diurnal rhythm in rat liver (DBP levels during evening/morning approximately 100:1), contributes to the diurnal regulation of CYP7 gene expression. DNase I footprinting analysis using bacterially expressed DBP and a cloned 5'-flanking DNA segment of the rat CYP7 gene revealed five distinct DBP-binding sites, designated A-E, distributed between nucleotides (nts) -41 and -295 relative to the CYP7 transcription start site. CYP7-directed gene transcription in HepG2 cells transfected with a 5'-CYP7 promoter-chloramphenicol acetyl-transferase reporter was activated up to 12-fold upon cotransfection of a DBP expression vector, whereas an HNF-1 alpha expression vector did not stimulate CYP7 gene activity. 5'-Deletion analyses and site-specific mutagenesis revealed that this stimulating effect of DBP can in part be ascribed to its functional interaction with DBP binding sites B (nts -115/-125), C (nts -172/-195), and D (nts -214/-230). C/EBP beta (LAP), another liver-enriched basic-leucine zipper transcription factor, bound to these same sites but effected a more modest increase in CYP7-directed gene transcription (up to 3-4-fold) when expressed in HepG2 cells. Competition for CYP7 promoter-binding sites between C/EBP, which undergoes < or = 2-fold diurnal change in rat liver, and the diurnally regulated DBP is proposed to determine the relative rates of basal versus diurnally regulated CYP7 gene transcription and thus may be a primary mechanism for setting the 3-6-fold amplitude that characterizes the circadian rhythm of liver CYP7 expression. Moreover, since DBP is first expressed in rat liver 3-4 weeks after birth, these findings may account for both the enhanced expression and the onset of the diurnal pattern of CYP7 enzyme levels at this stage of development. JF - The Journal of biological chemistry AU - Lee, Y H AU - Alberta, J A AU - Gonzalez, F J AU - Waxman, D J AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/20/ PY - 1994 DA - 1994 May 20 SP - 14681 EP - 14689 VL - 269 IS - 20 SN - 0021-9258, 0021-9258 KW - CYP7 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DBP protein, human KW - DBP protein, rat KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Cholesterol 7-alpha-Hydroxylase KW - EC 1.14.14.23 KW - Index Medicus KW - Animals KW - Carcinoma, Hepatocellular KW - Humans KW - Transcription, Genetic KW - Transcriptional Activation KW - Leucine Zippers KW - Binding Sites KW - Rats KW - Liver Neoplasms KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Transfection KW - Kinetics KW - Molecular Sequence Data KW - Feedback KW - Nuclear Proteins -- metabolism KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - Promoter Regions, Genetic KW - Liver -- enzymology KW - Gene Expression Regulation, Enzymologic KW - Circadian Rhythm KW - Transcription Factors -- metabolism KW - DNA -- metabolism KW - Cholesterol 7-alpha-Hydroxylase -- genetics KW - DNA -- genetics KW - Cholesterol 7-alpha-Hydroxylase -- biosynthesis KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76479649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multiple%2C+functional+DBP+sites+on+the+promoter+of+the+cholesterol+7+alpha-hydroxylase+P450+gene%2C+CYP7.+Proposed+role+in+diurnal+regulation+of+liver+gene+expression.&rft.au=Lee%2C+Y+H%3BAlberta%2C+J+A%3BGonzalez%2C+F+J%3BWaxman%2C+D+J&rft.aulast=Lee&rft.aufirst=Y&rft.date=1994-05-20&rft.volume=269&rft.issue=20&rft.spage=14681&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 - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP7 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A deletion in the second cytoplasmic loop of GluR3 produces a dominant negative mutant of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. AN - 76477037; 8182063 AB - We have characterized a GluR3 mutant (sGluR3) which has a 33-amino acid deletion in its second cytoplasmic loop (deficit from Tyr-715 to Gly-747 of GluR3-flop). Xenopus oocytes injected with cRNA transcribed from cDNA for this mutant did not respond to kainate and glutamate (each 100 microM) at a holding potential of -70 mV. In oocytes coinjected with cRNAs for this mutant and for normal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits, the current response to both kainate and glutamate was much weaker than that observed in oocytes injected with cRNA for the normal subunits alone. This inhibitory action was not accompanied by a significant change of ED50 value and shape of the I-V curve and was AMPA receptor-specific. A comparable deletion in GluR1 produced a mutant with properties similar to those of sGluR3, while a 33-amino acid deletion elsewhere in the second cytoplasmic loop of GluR3 (Met-674 to Phe-706) gave a mutant with a weaker effect. These results suggest that sGluR3 acts as a dominant negative mutant on the functional expression of normal AMPA receptors in oocytes by assembling with the normal subunits to produce an essentially nonfunctional receptor complex. JF - The Journal of biological chemistry AU - Sekiguchi, M AU - Doi, K AU - Zhu, W S AU - Watase, K AU - Yokotani, N AU - Wada, K AU - Wenthold, R J AD - Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/20/ PY - 1994 DA - 1994 May 20 SP - 14559 EP - 14565 VL - 269 IS - 20 SN - 0021-9258, 0021-9258 KW - Receptors, AMPA KW - 0 KW - Tyrosine KW - 42HK56048U KW - Kainic Acid KW - SIV03811UC KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Protein Biosynthesis KW - Protein Structure, Secondary KW - Amino Acid Sequence KW - Mutagenesis KW - Xenopus laevis KW - Evoked Potentials -- drug effects KW - Transfection KW - Cytoplasm -- metabolism KW - Restriction Mapping KW - Molecular Sequence Data KW - Cell Line KW - Female KW - Kainic Acid -- pharmacology KW - Oocytes -- metabolism KW - Receptors, AMPA -- biosynthesis KW - Oocytes -- drug effects KW - Receptors, AMPA -- physiology KW - Receptors, AMPA -- chemistry KW - Oocytes -- physiology KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76477037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+deletion+in+the+second+cytoplasmic+loop+of+GluR3+produces+a+dominant+negative+mutant+of+alpha-amino-3-hydroxy-5-methyl-4-isoxazole+propionic+acid+receptor.&rft.au=Sekiguchi%2C+M%3BDoi%2C+K%3BZhu%2C+W+S%3BWatase%2C+K%3BYokotani%2C+N%3BWada%2C+K%3BWenthold%2C+R+J&rft.aulast=Sekiguchi&rft.aufirst=M&rft.date=1994-05-20&rft.volume=269&rft.issue=20&rft.spage=14559&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 - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pandas, people and policy. AN - 76476878; 8183334 AB - Panda conservation in China has been plagued by controversy and cultural and political differences. But international cooperation, together with new studies identifying the main threats, offer renewed hope for the species' survival. JF - Nature AU - O'Brien, S J AU - Pan, W AU - Lu, Z AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1994/05/19/ PY - 1994 DA - 1994 May 19 SP - 179 EP - 180 VL - 369 IS - 6477 SN - 0028-0836, 0028-0836 KW - Index Medicus KW - Animals KW - International Cooperation KW - Breeding KW - Population KW - Animals, Zoo KW - China KW - Ursidae KW - Conservation of Natural Resources -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76476878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Pandas%2C+people+and+policy.&rft.au=O%27Brien%2C+S+J%3BPan%2C+W%3BLu%2C+Z&rft.aulast=O%27Brien&rft.aufirst=S&rft.date=1994-05-19&rft.volume=369&rft.issue=6477&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular uptake as a determinant of cytotoxicity of quaternized ellipticines to human brain tumor cells. AN - 76486679; 8185636 AB - The quaternized ellipticine derivative, 9-methoxy-N2-methylellipticinium acetate (MMEA), is representative of a group of ellipticinium compounds found preferentially cytotoxic to human brain tumor cell lines comprising a subpanel of the U.S. National Cancer Institute (NCI)'s in vitro "disease-oriented" anticancer drug discovery screen. The present studies indicate that the accumulation and cytotoxicity of MMEA in these susceptible cells are mediated in part by a cellular transport process having substrate and inhibitor specificities similar to those found in glial-derived cells which presumably comprise part of the structural (non-neuronal) elements of normal brain. JF - Biochemical and biophysical research communications AU - Vistica, D T AU - Kenney, S AU - Hursey, M L AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1994/05/16/ PY - 1994 DA - 1994 May 16 SP - 1762 EP - 1768 VL - 200 IS - 3 SN - 0006-291X, 0006-291X KW - Antineoplastic Agents KW - 0 KW - Ellipticines KW - Reserpine KW - 8B1QWR724A KW - Index Medicus KW - Cell Survival -- drug effects KW - Reserpine -- metabolism KW - Humans KW - In Vitro Techniques KW - Binding, Competitive KW - Biological Transport KW - Reserpine -- toxicity KW - Cell Line KW - Structure-Activity Relationship KW - Ellipticines -- metabolism KW - Ellipticines -- toxicity KW - Ellipticines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76486679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+uptake+as+a+determinant+of+cytotoxicity+of+quaternized+ellipticines+to+human+brain+tumor+cells.&rft.au=Vistica%2C+D+T%3BKenney%2C+S%3BHursey%2C+M+L%3BBoyd%2C+M+R&rft.aulast=Vistica&rft.aufirst=D&rft.date=1994-05-16&rft.volume=200&rft.issue=3&rft.spage=1762&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 - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Noninterfering synthetic peptides as internal controls for amino acid sequencing of sample unknowns. AN - 76655124; 8059958 AB - Noninterfering synthetic peptides have been designed that may be used as internal sequencing standards (ISS-1 and ISS-2) by placing them in an amino acid sequencer with the sample. The peptides are composed of four unnatural amino acids which all yield phenylthiohydantoin derivatives having unique retention times compared with those obtained from the commonly observed natural residues. These internal standards indicate how the entire sequencing system was functioning during the actual analysis of an unknown by providing an initial yield and numerous repetitive yields. Verifying proper operation is extremely important when cycles appear blank due to the presence of modified amino acids or a blocked N-terminus. In addition, the ISS peptides can detect and identify different types of sequencing errors. This sometimes eliminates the need to rerun a sample due to blank cycles caused by mechanical malfunctions which result in failure to cleave the N-terminal residues. ISS-1 or ISS-2 may also be utilized during method development to compare different sample supports and to normalize sequencing data from proteins or peptides that have been treated differently. JF - Analytical biochemistry AU - Parmelee, D C AU - Hoang, T N AU - Benjamin, T AU - Sechi, S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/15/ PY - 1994 DA - 1994 May 15 SP - 71 EP - 81 VL - 219 IS - 1 SN - 0003-2697, 0003-2697 KW - Amino Acids KW - 0 KW - Indicators and Reagents KW - Peptides KW - Index Medicus KW - Spectrometry, Mass, Fast Atom Bombardment -- methods KW - Reference Standards KW - Chromatography, High Pressure Liquid -- methods KW - Peptides -- chemical synthesis KW - Amino Acids -- analysis KW - Peptides -- chemistry KW - Amino Acid Sequence KW - Peptides -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76655124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=Noninterfering+synthetic+peptides+as+internal+controls+for+amino+acid+sequencing+of+sample+unknowns.&rft.au=Parmelee%2C+D+C%3BHoang%2C+T+N%3BBenjamin%2C+T%3BSechi%2C+S&rft.aulast=Parmelee&rft.aufirst=D&rft.date=1994-05-15&rft.volume=219&rft.issue=1&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-15 N1 - Date created - 1994-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The p53-dependent gamma-ray response of GADD45. AN - 76453645; 8168107 AB - Activation of the human GADD45 gene by ionizing radiation (IR) has previously been shown to be dependent on the tumor suppressor and transcription factor p53 (M. B. Kastan, et al., Cell 71: 587-597, 1992). Unlike GADD45, the response of other DNA damage-inducible genes to IR is not dependent on p53 based on the observation that induction in a panel of cell lines did not correlate with a normal p53 status; this included human GADD153, another member of the gadd (growth arrest and DNA damage inducible) group; MyD118, a gene related to GADD45; and the protooncogenes c-jun and c-fos. This p53-dependent response of GADD45 was further investigated in human cells with halogenated pyrimidines, which act as radiosensitizers when incorporated into cellular DNA. When cellular DNA contained halogenated pyrimidines such as iododeoxyuridine (IdUrd), GADD45 gamma-ray induction, as measured by increased mRNA, was enhanced. Rapid induction could be seen with doses as low as 0.5 Gy, and substitution with IdUrd resulted in an approximately 2-fold increase in induction over a wide dose range. This level of IdUrd substitution produced a similar fold increase in cellular radiosensitivity and has been shown previously (T. M. Kinsella et al., Int. J. Radiation Oncology Biol. Phys. 13: 733-739, 1987) to produce a similar fold increase in DNA strand breaks after IR. Considering that substitution with halogenated pyrimidines would be expected to have little effect on other cellular targets after IR, these experiments indicate that actual damage to DNA, primarily strand breaks, is a major signal for the activation of this p53-dependent pathway that is required for GADD45 induction and for activation of the G1 "checkpoint" cell cycle delay. JF - Cancer research AU - Zhan, Q AU - Bae, I AU - Kastan, M B AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/15/ PY - 1994 DA - 1994 May 15 SP - 2755 EP - 2760 VL - 54 IS - 10 SN - 0008-5472, 0008-5472 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DDIT3 protein, human KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - RNA, Messenger KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Transcription Factor CHOP KW - 147336-12-7 KW - Idoxuridine KW - LGP81V5245 KW - Index Medicus KW - Idoxuridine -- pharmacology KW - Gene Expression Regulation -- radiation effects KW - RNA, Messenger -- metabolism KW - Gamma Rays KW - DNA Damage KW - Humans KW - RNA, Messenger -- radiation effects KW - G1 Phase KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Cell Line KW - Tumor Suppressor Protein p53 -- metabolism KW - Proteins -- radiation effects KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76453645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+p53-dependent+gamma-ray+response+of+GADD45.&rft.au=Zhan%2C+Q%3BBae%2C+I%3BKastan%2C+M+B%3BFornace%2C+A+J&rft.aulast=Zhan&rft.aufirst=Q&rft.date=1994-05-15&rft.volume=54&rft.issue=10&rft.spage=2755&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 - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor activity and pharmacokinetics in mice of a recombinant immunotoxin containing a disulfide-stabilized Fv fragment. AN - 76449835; 8168102 AB - Disulfide-stabilized Fvs (dsFv) are recombinant Fv fragments of antibodies in which the inherently unstable VH-VL heterodimer is stabilized by a disulfide bond engineered between structurally conserved framework positions of VH and VL. We have recently described a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin (PE38KDEL). This disulfide-stabilized immunotoxin is indistinguishable in activity and specificity from its single-chain immunotoxin counterpart (Brinkmann et al., Proc. Natl. Acad. Sci. USA, 90: 7538-7542, 1993). We have now constructed and evaluated the stability, pharmacokinetics, and antitumor effect of a very similar disulfide-stabilized immunotoxin B3(dsFv)-PE38. This immunotoxin is specifically cytotoxic to human cancer cell lines such as A431 that express the B3 antigen on their surface. In addition, the dsFv-immunotoxin is more stable at 37 degrees C in human serum than the corresponding single-chain immunotoxin B3(Fv)-PE38. The survival of the disulfide-stabilized immunotoxin in the circulation of mice was determined by a bioassay on cultured A431 cells after administering the immunotoxin i.v. The half-life in blood was 23 min. To determine the therapeutic effects of the disulfide-stabilized immunotoxin, it was given i.v. to immunodeficient mice bearing s.c. human epidermoid carcinomas. The dsFv-immunotoxin caused complete regression of tumors with no toxic effect on mice. The antitumor effect was similar to that reported for the single-chain Fv-immunotoxin. Our data show that dsFv-immunotoxins retain full in vitro as well as in vivo activity when compared to scFv-immunotoxins. Because dsFv-immunotoxins have full activity, are more stable, and can be produced with significantly improved yields compared to scFv-immunotoxins, the dsFv-immunotoxins may be more useful for therapeutic applications than scFv-immunotoxins. JF - Cancer research AU - Reiter, Y AU - Pai, L H AU - Brinkmann, U AU - Wang, Q C AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/05/15/ PY - 1994 DA - 1994 May 15 SP - 2714 EP - 2718 VL - 54 IS - 10 SN - 0008-5472, 0008-5472 KW - Immunoglobulin Fragments KW - 0 KW - Immunotoxins KW - Recombinant Proteins KW - immunoglobulin Fv KW - Index Medicus KW - Animals KW - Plasmids -- metabolism KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured KW - Recombinant Proteins -- pharmacokinetics KW - Mice, Nude KW - Mice KW - Recombinant Proteins -- chemistry KW - Mice, Inbred BALB C KW - Female KW - Immunotoxins -- chemistry KW - Immunoglobulin Fragments -- pharmacology KW - Immunotoxins -- pharmacology KW - Immunoglobulin Fragments -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76449835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antitumor+activity+and+pharmacokinetics+in+mice+of+a+recombinant+immunotoxin+containing+a+disulfide-stabilized+Fv+fragment.&rft.au=Reiter%2C+Y%3BPai%2C+L+H%3BBrinkmann%2C+U%3BWang%2C+Q+C%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1994-05-15&rft.volume=54&rft.issue=10&rft.spage=2714&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 - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation-dependent ubiquitination of a T cell antigen receptor subunit on multiple intracellular lysines. AN - 76484394; 8188707 AB - The T cell antigen receptor zeta chain and other T cell antigen receptor components are ubiquitinated on receptor occupancy. A systematic mutagenesis of the zeta subunit was undertaken to determine the sites of ubiquitination. Ubiquitination was found to occur in the cytoplasmic domain of zeta with multiple lysines serving as sites for mono- and polyubiquitination. The mutation of all potential sites of ubiquitination did not inhibit receptor tyrosine phosphorylation or the ubiquitination of other T cell antigen receptor subunits. Lysines introduced into nonnative positions in the zeta molecule were also able to serve as sites for ubiquitination. These findings demonstrate that once a T cell antigen receptor is targeted for ubiquitination, there is little specificity with regard to the lysine residues that are modified. JF - The Journal of biological chemistry AU - Hou, D AU - Cenciarelli, C AU - Jensen, J P AU - Nguygen, H B AU - Weissman, A M AD - Laboratory of Immune Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/13/ PY - 1994 DA - 1994 May 13 SP - 14244 EP - 14247 VL - 269 IS - 19 SN - 0021-9258, 0021-9258 KW - Receptors, Antigen, T-Cell, gamma-delta KW - 0 KW - Ubiquitins KW - Tyrosine KW - 42HK56048U KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Electrophoresis, Gel, Two-Dimensional KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Tyrosine -- metabolism KW - Columbidae KW - Ubiquitins -- metabolism KW - Receptors, Antigen, T-Cell, gamma-delta -- metabolism KW - Receptors, Antigen, T-Cell, gamma-delta -- chemistry KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76484394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation-dependent+ubiquitination+of+a+T+cell+antigen+receptor+subunit+on+multiple+intracellular+lysines.&rft.au=Hou%2C+D%3BCenciarelli%2C+C%3BJensen%2C+J+P%3BNguygen%2C+H+B%3BWeissman%2C+A+M&rft.aulast=Hou&rft.aufirst=D&rft.date=1994-05-13&rft.volume=269&rft.issue=19&rft.spage=14244&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 - 1994-06-22 N1 - Date created - 1994-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis defines the individual roles of the glycosylation sites on follicle-stimulating hormone. AN - 76484170; 8188681 AB - To determine the specific role of each follicle-stimulating hormone (FSH) oligosaccharide, we mutated Asn to Gln at each glycosylation site (alpha Gln52, alpha Gln78, alpha Gln52-78, beta Gln7, beta Gln24, and beta Gln7-24) to selectively inhibit oligosaccharide attachment. For wild-type and mutant FSH, we determined the binding affinity to homogenized rat Sertoli cells and the signal-transducing activity in cultured rat granulosa cells. The binding affinity of FSH lacking any one of the oligosaccharides was increased over wild-type FSH, while the signal-transducing activity of FSH lacking the oligosaccharide at alpha Asn52 (alpha Gln52 FSH) was markedly reduced, and that of FSH lacking either beta oligosaccharide (beta Gln7 and beta Gln24 FSH) was slightly reduced. At each FSH beta glycosylation site, we made a second amino acid substitution to inhibit glycosylation (beta Tyr9 and beta Tyr26) and an amino acid substitution that preserved glycosylation (beta Ser9 and beta Ser26). The amino acid sequence of the second beta subunit glycosylation site was important for signal transduction, regardless of the presence or absence of the oligosaccharide. Thus, while each FSH oligosaccharide has a similar impact on binding affinity, the alpha 52 oligosaccharide has a disproportionate role in signal transduction, and the amino acid sequence at beta Asn24 functions in both binding and signal transduction. JF - The Journal of biological chemistry AU - Flack, M R AU - Froehlich, J AU - Bennet, A P AU - Anasti, J AU - Nisula, B C AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/13/ PY - 1994 DA - 1994 May 13 SP - 14015 EP - 14020 VL - 269 IS - 19 SN - 0021-9258, 0021-9258 KW - Receptors, FSH KW - 0 KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Sertoli Cells -- metabolism KW - Humans KW - Amino Acid Sequence KW - Glycosylation KW - Radioligand Assay KW - Binding Sites KW - Rats KW - Glycine -- genetics KW - Molecular Sequence Data KW - Receptors, FSH -- metabolism KW - Signal Transduction KW - Male KW - Mutagenesis, Site-Directed KW - Follicle Stimulating Hormone -- metabolism KW - Follicle Stimulating Hormone -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76484170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutagenesis+defines+the+individual+roles+of+the+glycosylation+sites+on+follicle-stimulating+hormone.&rft.au=Flack%2C+M+R%3BFroehlich%2C+J%3BBennet%2C+A+P%3BAnasti%2C+J%3BNisula%2C+B+C&rft.aulast=Flack&rft.aufirst=M&rft.date=1994-05-13&rft.volume=269&rft.issue=19&rft.spage=14015&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 - 1994-06-22 N1 - Date created - 1994-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Auxotrophs of Plasmodium falciparum dependent on p-aminobenzoic acid for growth. AN - 76491160; 8183896 AB - The isolation of auxotrophic strains of a parasite offers new opportunities for studying parasitology. We have isolated cloned lines of Plasmodium falciparum that, unlike the parent line from which they were derived, rely on exogenous p-aminobenzoic acid (PABA) for growth. Isolation involved random mutagenesis of a cloned line of P. falciparum and subsequent selection of PABA-dependent parasites. Both parent and PABA-dependent clones were analyzed for PABA uptake and synthesis. Each clone takes up comparable amounts of PABA from the medium. The parent line, clone 3D7, can synthesize PABA de novo, whereas the PABA-dependent clones cannot. The requirement of exogenous PABA for growth by the auxotrophic strains coupled with their inability to synthesize PABA indicates that normal parasite growth can be completely supported by either synthesis or salvage. This work further clarifies the relationship between the availability of PABA and success of the parasite, an issue of debate from classic studies showing reduced parasite load in individuals on milk-fed diets. JF - Proceedings of the National Academy of Sciences of the United States of America AU - McConkey, G A AU - Ittarat, I AU - Meshnick, S R AU - McCutchan, T F AD - Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/05/10/ PY - 1994 DA - 1994 May 10 SP - 4244 EP - 4248 VL - 91 IS - 10 SN - 0027-8424, 0027-8424 KW - Sulfamethoxazole KW - JE42381TNV KW - 4-Aminobenzoic Acid KW - TL2TJE8QTX KW - Index Medicus KW - Erythrocytes -- parasitology KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - In Vitro Techniques KW - Dose-Response Relationship, Radiation KW - Mutagenesis KW - Plasmodium falciparum -- growth & development KW - Sulfamethoxazole -- toxicity KW - Plasmodium falciparum -- radiation effects KW - Plasmodium falciparum -- drug effects KW - 4-Aminobenzoic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76491160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Auxotrophs+of+Plasmodium+falciparum+dependent+on+p-aminobenzoic+acid+for+growth.&rft.au=McConkey%2C+G+A%3BIttarat%2C+I%3BMeshnick%2C+S+R%3BMcCutchan%2C+T+F&rft.aulast=McConkey&rft.aufirst=G&rft.date=1994-05-10&rft.volume=91&rft.issue=10&rft.spage=4244&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 - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Parasitology. 1970 Dec;61(3):425-33 [4994294] Exp Parasitol. 1964 Jun;15:213-25 [14191322] Science. 1976 Aug 20;193(4254):673-5 [781840] Anal Biochem. 1976 May 7;72:248-54 [942051] J Parasitol. 1979 Jun;65(3):418-20 [383936] Nature. 1981 May 21;291(5812):238-9 [7015147] Antimicrob Agents Chemother. 1985 Apr;27(4):525-30 [3890727] Mol Biochem Parasitol. 1985 Jun;16(1):75-83 [3929085] Mol Biochem Parasitol. 1986 May;19(2):143-7 [2873508] Vaccine. 1988 Apr;6(2):141-5 [3291451] J Chromatogr. 1988 Dec 9;433:292-7 [3266217] Am J Trop Med Hyg. 1989 May;40(5):465-9 [2658635] Mol Biochem Parasitol. 1992 Jun;52(2):185-94 [1620158] Vaccine. 1993;11(2):126-35 [8382417] FEMS Immunol Med Microbiol. 1993 Jun;7(1):1-7 [8364518] Z Tropenmed Parasitol. 1973 Mar;24(1):51-9 [4200243] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stabilization of the Fv fragments in recombinant immunotoxins by disulfide bonds engineered into conserved framework regions. AN - 76489828; 7910034 AB - Disulfide-stabilized Fv's (dsFv's) are recombinant Fv fragments of antibodies in which the unstable variable heavy (VH) and variable light (VL) heterodimers are stabilized by disulfide bonds engineered at specific sites that lie between structurally conserved framework positions of VH and VL. We have recently described one example of a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin [Brinkmann, U., Reiter, Y., Jung, S.-H., Lee, B., & Pastan, I. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7538-7542]. This disulfide-stabilized immunotoxin has the same cytotoxic activity and specificity as its single-chain immunotoxin counterpart. To determine whether the stabilization of Fv's by disulfides at these positions is generally applicable, we made and analyzed two other dsFv-containing immunotoxins. One is made from the e23 antibody, which binds to the carcinoma-associated antigen erbB2; the other is made from the anti-Tac antibody, which binds to the p55 subunit of the IL-2 receptor. Comparison of the specificity and activity of these immunotoxins with those of their scFv counterparts revealed that e23(dsFv)-PE38KDEL was considerably more active than e23(Fv)-PE38KDEL, whereas anti-Tac(dsFv)-PE38KDEL was only somewhat more active than its single-chain counterpart. These results suggest that dsFv's have at least the same binding properties as scFv's, and in some cases they may have better binding. Thus, it should be feasible to use the positions we have identified in the conserved framework region to disulfide-stabilize many different Fv's.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Reiter, Y AU - Brinkmann, U AU - Kreitman, R J AU - Jung, S H AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/10/ PY - 1994 DA - 1994 May 10 SP - 5451 EP - 5459 VL - 33 IS - 18 SN - 0006-2960, 0006-2960 KW - Bacterial Toxins KW - 0 KW - Disulfides KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunotoxins KW - Oligodeoxyribonucleotides KW - Proto-Oncogene Proteins KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Receptor, Epidermal Growth Factor -- immunology KW - Amino Acid Sequence KW - Immunoglobulin Light Chains -- chemistry KW - Recombinant Proteins -- genetics KW - Plasmids KW - Receptors, Interleukin-2 -- immunology KW - Recombinant Proteins -- isolation & purification KW - Base Sequence KW - Cysteine -- chemistry KW - Immunoglobulin Heavy Chains -- chemistry KW - Molecular Sequence Data KW - Proto-Oncogene Proteins -- immunology KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Pseudomonas aeruginosa KW - Cell Line KW - Immunotoxins -- chemistry KW - Exotoxins -- genetics KW - Disulfides -- chemistry KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics KW - Exotoxins -- chemistry KW - Immunoglobulin Fragments -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76489828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stabilization+of+the+Fv+fragments+in+recombinant+immunotoxins+by+disulfide+bonds+engineered+into+conserved+framework+regions.&rft.au=Reiter%2C+Y%3BBrinkmann%2C+U%3BKreitman%2C+R+J%3BJung%2C+S+H%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1994-05-10&rft.volume=33&rft.issue=18&rft.spage=5451&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-10 N1 - Date created - 1994-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypothyroidism associated with aminoglutethimide in patients with prostate cancer. AN - 76486269; 8179445 AB - The administration of aminoglutethimide and hydrocortisone is a second-line hormonal maneuver commonly prescribed for the treatment of metastatic prostate cancer. We determine the incidence of aminoglutethimide-induced primary hypothyroidism in an elderly population who have prostate cancer. Prospective evaluation. Twenty-nine men with stage D2 prostate cancer who were treated at the National Cancer Institute, Bethesda, Md, in 1992. Clinical and biochemical evidence of hypothyroidism (thyrotropin levels greater than 10 mU/L) was noted in nine of 29 patients treated following the initiation of aminoglutethimide (250 mg four times daily). The elevation in thyrotropin and the clinical symptoms of hypothyroidism were reversed by the administration of levothyroxine (n = 4). Hypothyroidism should be included in the differential diagnosis of lethargy in elderly patients who are receiving aminoglutethimide for prostate cancer. Furthermore, patients who are receiving this agent at a dosage of 1000 mg/d or greater should have their serum thyrotropin levels monitored, and replacement therapy with levothyroxine should be initiated when abnormally elevated levels are noted. JF - Archives of internal medicine AU - Figg, W D AU - Thibault, A AU - Sartor, A O AU - Mays, D AU - Headlee, D AU - Calis, K A AU - Cooper, M R AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md. Y1 - 1994/05/09/ PY - 1994 DA - 1994 May 09 SP - 1023 EP - 1025 VL - 154 IS - 9 SN - 0003-9926, 0003-9926 KW - Aminoglutethimide KW - 0O54ZQ14I9 KW - Thyrotropin KW - 9002-71-5 KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Diagnosis, Differential KW - Thyrotropin -- blood KW - Humans KW - Aged KW - Male KW - Hypothyroidism -- blood KW - Prostatic Neoplasms -- blood KW - Aminoglutethimide -- therapeutic use KW - Aminoglutethimide -- adverse effects KW - Prostatic Neoplasms -- drug therapy KW - Hypothyroidism -- diagnosis KW - Hypothyroidism -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76486269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+internal+medicine&rft.atitle=Hypothyroidism+associated+with+aminoglutethimide+in+patients+with+prostate+cancer.&rft.au=Figg%2C+W+D%3BThibault%2C+A%3BSartor%2C+A+O%3BMays%2C+D%3BHeadlee%2C+D%3BCalis%2C+K+A%3BCooper%2C+M+R&rft.aulast=Figg&rft.aufirst=W&rft.date=1994-05-09&rft.volume=154&rft.issue=9&rft.spage=1023&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-07 N1 - Date created - 1994-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amiloride-sensitive channels in marginal cells in the stria vascularis of the guinea pig cochlea. AN - 85260305; pmid-8084526 AB - We examined marginal cells in stria vascularis for the presence of amiloride-sensitive Na+ channels, a possible pathway for maintaining a low Na+ concentration in the endolymph. Whole-cell voltage-clamp experiment shows that amiloride at 1 microM concentration reversibly reduces inward current more than outward current. Immunogold-labeling method shows that the luminal and lateral membrane have antigenic sites for these antibodies. These observations indicate the presence of amiloride-sensitive channels in the marginal cell. If amiloride-sensitive channels in the luminal membrane are highly selective to Na+, they could be an efficient pathway for Na+ uptake from the endolymph. In the basolateral membrane, amiloride-sensitive Na+ channels may make a relatively small contribution to the unusual resting potential. JF - Neuroscience Letters AU - Iwasa, Kuni H AU - Mizuta, K AU - Lim, D J AU - Benos, D J AU - Tachibana, M AD - National Institute on Deafness and Other Communication Disorders PY - 1994 SP - 163 EP - 166 VL - 172 IS - 1-2 SN - 0304-3940, 0304-3940 KW - Cochlea KW - Support, U.S. Gov't, P.H.S. KW - Guinea Pigs KW - Amiloride KW - Animal KW - Cell Membrane KW - Membrane Potentials KW - Electrophysiology KW - Immunohistochemistry KW - Sodium Channels UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85260305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+Letters&rft.atitle=Amiloride-sensitive+channels+in+marginal+cells+in+the+stria+vascularis+of+the+guinea+pig+cochlea.&rft.au=Iwasa%2C+Kuni+H%3BMizuta%2C+K%3BLim%2C+D+J%3BBenos%2C+D+J%3BTachibana%2C+M&rft.aulast=Iwasa&rft.aufirst=Kuni&rft.date=1994-05-01&rft.volume=172&rft.issue=1-2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Neuroscience+Letters&rft.issn=03043940&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Processing of frequency-modulated sounds in the cat's anterior auditory field. AN - 85237232; pmid-8064359 AB - 1. Single-neuron activity was recorded from the anterior auditory field (AAF) in the cortex of gas-anesthetized cats. 2. Tone bursts and broad-band complex sounds were used for auditory stimulation. Responses to frequency-modulated (FM) sounds, in particular, were studied systematically. 3. Linear FM sweeps were centered around the best frequency (BF) of a neuron and had an excursion large enough to cover its whole frequency tuning range. Rate and direction of change of the FM sweeps were varied. 4. In 69% of the FM responses, a peak was found at an instantaneous frequency that corresponded to the BF in the pure-tone response. Thirty-three percent of the units had multiple maxima in their FM response. These secondary maxima were not always reflected in the pure-tone response of the same neurons. 5. The vast majority of AAF neurons showed one of two types of selectivity for FM rate. Depending on the criterion, almost half of the cells (46%) preferred fast changes of > 200 Hz/ms (high-pass) in both FM directions. Forty-eight percent of all neurons showed band-pass behavior with a clear preference in the middle range of FM rates in one or both directions. Low-pass or all-pass neurons made up only a small proportion (4 and 1%, respectively) of AAF neurons. 6. When both directions of an FM sweep (low-to-high and high-to-low-frequency) were tested, 66% of the neurons clearly were selective for one direction. This selectivity was not present necessarily at the preferred FM rate. In general, FM direction selectivity was most pronounced at slower FM rates. 7. The selectivity of AAF neurons for the rate and direction of FM sounds makes these neurons suitable for the detection and analysis of communication sounds, which often contain FM components with a particular sweep rate and direction. JF - Journal of Neurophysiology AU - Tian, B AU - Rauschecker, J P AD - Laboratory of Neurophysiology, National Institute of Mental Health, Poolesville, Maryland 20837. PY - 1994 SP - 1959 EP - 1975 VL - 71 IS - 5 SN - 0022-3077, 0022-3077 KW - Auditory Cortex KW - Sound Localization KW - Brain Mapping KW - Auditory Pathways KW - Neurons KW - Cats KW - Pitch Perception KW - Animal KW - Evoked Potentials, Auditory KW - Support, Non-U.S. Gov't UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Processing+of+frequency-modulated+sounds+in+the+cat%27s+anterior+auditory+field.&rft.au=Tian%2C+B%3BRauschecker%2C+J+P&rft.aulast=Tian&rft.aufirst=B&rft.date=1994-05-01&rft.volume=71&rft.issue=5&rft.spage=1959&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Gene manipulation and genetic toxicology. AN - 76765662; 7934954 AB - Transgenic mice with recoverable target genes, with genes modified in expression or with ablated gene function provide important tools for defining the biological effects of chemicals. In many cases studies can be conducted with fewer animals and in a shorter timeframe. They also provide important tools for studies of carcinogenesis mechanisms and processes, for early detection of carcinogens and for identification of potential cancer therapies. JF - Mutagenesis AU - Tennant, R W AU - Hansen, L AU - Spalding, J AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 171 EP - 174 VL - 9 IS - 3 SN - 0267-8357, 0267-8357 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Animals KW - Oncogenes -- drug effects KW - Skin Neoplasms -- chemically induced KW - Mice KW - Mice, Transgenic KW - Genetic Engineering KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76765662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Gene+manipulation+and+genetic+toxicology.&rft.au=Tennant%2C+R+W%3BHansen%2C+L%3BSpalding%2C+J&rft.aulast=Tennant&rft.aufirst=R&rft.date=1994-05-01&rft.volume=9&rft.issue=3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-28 N1 - Date created - 1994-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Mortality of workers employed at an asbestos cement manufacturing plant in Senigallia]. TT - Studio di mortalità degli addetti alla produzione di manufatti in cemento-amianto nello stabilimento di Senigallia. AN - 76760460; 7935144 AB - The mortality (1948-1990) was investigated in 561 workers employed in an asbestos cement plant in Senigallia (Central Italy). A significant increase in lung cancer was observed in male subjects (SMR: 276; 95% C.I.: 175.2-414.8, 23 observed). The excess mortality was a function of the induction-latency time. Five deaths were observed among women, one of which due to malignant pleural neoplasm. JF - La Medicina del lavoro AU - Pettinari, A AU - Mengucci, R AU - Belli, S AU - Comba, P AD - Servizio di Igiene e Sanità Pubblica, Settore di Igiene e Sicurezza nei Luoghi di Lavoro, Regione Marche, U.S.L. 7, Senigallia, AN. PY - 1994 SP - 223 EP - 230 VL - 85 IS - 3 SN - 0025-7818, 0025-7818 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Humans KW - Asbestos -- adverse effects KW - Follow-Up Studies KW - Male KW - Italy KW - Female KW - Asbestosis -- mortality KW - Pleural Neoplasms -- mortality KW - Lung Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76760460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BMortality+of+workers+employed+at+an+asbestos+cement+manufacturing+plant+in+Senigallia%5D.&rft.au=Pettinari%2C+A%3BMengucci%2C+R%3BBelli%2C+S%3BComba%2C+P&rft.aulast=Pettinari&rft.aufirst=A&rft.date=1994-05-01&rft.volume=85&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-21 N1 - Date created - 1994-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Separation and sequencing of familiar and novel murine proteins using preparative two-dimensional gel electrophoresis. AN - 76749242; 7523108 AB - Strategies are needed for rapid protein isolation in order to identify disease-related proteins and facilitate the design of oligonucleotides for further molecular inquiry. In our laboratory, C3H10T1/2 murine fibroblasts have been found to express a variety of proteins in various subcellular fractions which are relevant to experimental transformation and carcinogenesis. Preparative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) procedures were developed to identify major cytoplasmic proteins by electroblotting and microsequencing. Isoelectric focusing tube gels were enlarged to 6 mm ID to accommodate larger protein loads at 0.5 to 2 mg protein. Separated proteins were electrotransferred from 6 mm thick slab gels onto 0.22 mu polyvinylidene difluoride membranes. Nearly 100 prominent blotted proteins were stained with Coomassie Brilliant Blue between pI 4.5-7.0 and 18-106 kDa and, of these, 27 prominent and well-resolved proteins were selected for sequencing. Sequences of 14 to 24 amino acid residues in length were obtained from 11 proteins which were identified from computerized databases. Some of these identified proteins had structural or enzymatic functions while others had only recently been discovered, including a newly reported Hsp 70 class member and a novel calcium-binding protein, reticulocalbin. The new heat shock protein has a molecular mass of 75 kDa and has been designated as Grp75, PBP74, CSA or p66mot-1 in mice and humans with purported roles in transformation and antigen processing. Reticulocalbin is an endoplasmic reticular protein which contains six domains of the EF-hand motif associated with high-affinity calcium-binding proteins. It may be involved in protein transport and luminal protein processing. In addition, sequences of 5 to 11 residues in length were also obtained from six other unidentified proteins. Thus, we have found that preparative 2-D PAGE serves as a powerful one-step purification method for protein isolation and characterization from an important in vitro murine model for the study of carcinogenesis. JF - Electrophoresis AU - Merrick, B A AU - Patterson, R M AU - Witcher, L L AU - He, C AU - Selkirk, J K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 735 EP - 745 VL - 15 IS - 5 SN - 0173-0835, 0173-0835 KW - Membranes, Artificial KW - 0 KW - Polyvinyls KW - Proteins KW - polyvinylidene fluoride KW - 24937-79-9 KW - Index Medicus KW - Animals KW - Sequence Alignment KW - Fibroblasts -- chemistry KW - Molecular Sequence Data KW - Databases, Factual KW - Mice KW - Amino Acid Sequence KW - Staining and Labeling KW - Cell Line KW - Proteins -- isolation & purification KW - Electrophoresis, Gel, Two-Dimensional KW - Cytoplasm -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76749242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Separation+and+sequencing+of+familiar+and+novel+murine+proteins+using+preparative+two-dimensional+gel+electrophoresis.&rft.au=Merrick%2C+B+A%3BPatterson%2C+R+M%3BWitcher%2C+L+L%3BHe%2C+C%3BSelkirk%2C+J+K&rft.aulast=Merrick&rft.aufirst=B&rft.date=1994-05-01&rft.volume=15&rft.issue=5&rft.spage=735&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-26 N1 - Date created - 1994-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenotypic change and altered protein expression in X-ray and methylcholanthrene-transformed C3H10T1/2 fibroblasts. AN - 76736852; 7925252 AB - The morphology, growth properties and cellular protein patterns from parent and two transformed C3H10T1/2 cell lines were analyzed to associate the phenotypic and protein differences with cell transformation. Transformed 10T1/2 cells were obtained by colony isolation after exposure of parent 10T1/2 cells to methylcholanthrene (MCA-1 cell line) or X-ray irradiation (XR-III cell line). Compared to parent 10T1/2 and MCA-1 cells, XR-III cells were much smaller in size and exhibited the highest growth rate, greatest cell saturation density, increased plating efficiency and greater expression of proliferating cell nuclear antigen. MCA-1 cells showed intermediate characteristics between parent and XR-III cells. Among the three cell lines, only XR-III cells showed anchorage-independent growth in soft agar. When [35S]methionine-labeled whole cell lysate proteins were separated by two-dimensional polyacrylamide gel electrophoresis, computer comparison algorithms revealed a 97% similarity in protein profiles among almost 800 proteins detected from each cell line. However, comparison of proteins patterns of the transformed cell lines to that of parent 10T1/2 cells showed that 30 and 20 proteins were induced or repressed in XR-III cells and MCA-1 cells, respectively. Similarly, 81 and 24 proteins showed significant quantitative changes (threefold or greater) in XR-III and MCA-1 cells, respectively, as compared with parent 10T1/2 cell proteins. The anchorage-independent growth and increased proliferation properties of XR-III cells suggest a later stage of transformation compared to MCA-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Electrophoresis AU - He, C AU - Merrick, B A AU - Witcher, L L AU - Patterson, R M AU - Daluge, D R AU - Selkirk, J K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 726 EP - 734 VL - 15 IS - 5 SN - 0173-0835, 0173-0835 KW - Antigens, Neoplasm KW - 0 KW - Neoplasm Proteins KW - Proliferating Cell Nuclear Antigen KW - Methylcholanthrene KW - 56-49-5 KW - Agar KW - 9002-18-0 KW - Index Medicus KW - Animals KW - Antigens, Neoplasm -- analysis KW - Cell Division -- physiology KW - Mice KW - Proliferating Cell Nuclear Antigen -- analysis KW - Precipitin Tests KW - Fibroblasts -- metabolism KW - Phenotype KW - X-Rays KW - Fibroblasts -- pathology KW - Electrophoresis, Gel, Two-Dimensional KW - Neoplasm Proteins -- biosynthesis KW - Cell Line, Transformed -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76736852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Phenotypic+change+and+altered+protein+expression+in+X-ray+and+methylcholanthrene-transformed+C3H10T1%2F2+fibroblasts.&rft.au=He%2C+C%3BMerrick%2C+B+A%3BWitcher%2C+L+L%3BPatterson%2C+R+M%3BDaluge%2C+D+R%3BSelkirk%2C+J+K&rft.aulast=He&rft.aufirst=C&rft.date=1994-05-01&rft.volume=15&rft.issue=5&rft.spage=726&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-26 N1 - Date created - 1994-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A double FDG/PET study of the effects of scopolamine in older adults. AN - 76721565; 7916916 AB - Two consecutive positron emission scans were done in one session using a double injection method of [18F]2-fluoro-2-deoxyglucose administration to examine the effects of the antimuscarinic drug scopolamine on cerebral glucose metabolism in ten older adults. Scopolamine causes temporary memory impairment, and its effects have been used to model aspects of the cognitive impairment that occur in Alzheimer's disease (AD). Cortical metabolic rates of patients with AD have been reported to be depressed, especially in parietal, temporal, and frontal association areas. After scopolamine administration to the elderly volunteers, absolute and normalized glucose metabolic rates were depressed in prefrontal and occipital regions and increased in parietal-occipital cortical regions and a left middle temporal region. These changes in the older volunteers are generally not consistent with changes seen in AD. We conclude that deficits in muscarinic system function may contribute to some but not all of the hypometabolic changes seen in AD patients. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Molchan, S E AU - Matochik, J A AU - Zametkin, A J AU - Szymanski, H V AU - Cantillon, M AU - Cohen, R M AU - Sunderland, T AD - Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 191 EP - 198 VL - 10 IS - 3 SN - 0893-133X, 0893-133X KW - Muscarinic Antagonists KW - 0 KW - Receptors, Muscarinic KW - Fluorodeoxyglucose F18 KW - 0Z5B2CJX4D KW - Scopolamine Hydrobromide KW - 451IFR0GXB KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Humans KW - Brain -- anatomy & histology KW - Tomography, Emission-Computed KW - Receptors, Muscarinic -- drug effects KW - Middle Aged KW - Scopolamine Hydrobromide -- adverse effects KW - Scopolamine Hydrobromide -- pharmacology KW - Glucose -- metabolism KW - Brain Chemistry -- drug effects KW - Deoxyglucose -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721565?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+double+FDG%2FPET+study+of+the+effects+of+scopolamine+in+older+adults.&rft.au=Molchan%2C+S+E%3BMatochik%2C+J+A%3BZametkin%2C+A+J%3BSzymanski%2C+H+V%3BCantillon%2C+M%3BCohen%2C+R+M%3BSunderland%2C+T&rft.aulast=Molchan&rft.aufirst=S&rft.date=1994-05-01&rft.volume=10&rft.issue=3&rft.spage=191&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 - 1994-11-16 N1 - Date created - 1994-11-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neuropsychopharmacology. 1995 May;12(3):273-6 [7612162] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subchronic treatment with haloperidol and clozapine in rats with neonatal excitotoxic hippocampal damage. AN - 76720680; 7916917 AB - We have previously demonstrated that rats with neonatal excitotoxic hippocampal damage manifest abnormal dopamine (DA)-related behaviors after puberty, a phenomenon that has implications for an animal model of schizophrenia. In this study we investigated the effects of subchronic treatment with haloperidol and clozapine in these animals. The ventral hippocampus (VH) of rat pups was lesioned with ibotenic acid on postnatal day 7 (PD7). Starting at PD56, rats were treated for 21 days with either vehicle (VEH), haloperidol (HAL) (0.1 mg/kg, IP), or clozapine (CLOZ) (4 mg/kg, IP). Spontaneous locomotor activity was measured 0.5 hour after the last injection. Apomorphine (APO)-induced stereotypy and locomotion were evaluated five days later. The VH lesioned rats treated with VEH expressed enhanced novelty- and apomorphine-induced hyperlocomotion, as well as potentiated apomorphine-induced stereotypic behaviors as compared to sham-lesioned counterparts. Spontaneous locomotor activity was suppressed by haloperidol but not by clozapine in the sham-operated group, whereas both drugs were effective in suppressing hyperlocomotion in the VH lesioned rats. Withdrawal supersensitivity to apomorphine was seen in the haloperidol but not in the clozapine-treated lesioned rats, and none of the drugs produced significant supersensitivity in the sham-operated animals. These results indicate that the two neuroleptics exerted differential behavioral effects in neurologically intact and hippocampally lesioned animals, and that these effects were also drug-specific. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Lipska, B K AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Washington, DC 20032. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 199 EP - 205 VL - 10 IS - 3 SN - 0893-133X, 0893-133X KW - Neurotoxins KW - 0 KW - Receptors, Dopamine KW - Ibotenic Acid KW - 2552-55-8 KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Animals KW - Apomorphine -- pharmacology KW - Stereotyped Behavior -- drug effects KW - Ibotenic Acid -- pharmacology KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - Receptors, Dopamine -- physiology KW - Apomorphine -- antagonists & inhibitors KW - Substance Withdrawal Syndrome -- psychology KW - Motor Activity -- drug effects KW - Female KW - Haloperidol -- pharmacology KW - Clozapine -- pharmacology KW - Neurotoxins -- toxicity KW - Animals, Newborn -- physiology KW - Hippocampus -- drug effects KW - Hippocampus -- anatomy & histology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76720680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Subchronic+treatment+with+haloperidol+and+clozapine+in+rats+with+neonatal+excitotoxic+hippocampal+damage.&rft.au=Lipska%2C+B+K%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1994-05-01&rft.volume=10&rft.issue=3&rft.spage=199&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 - 1994-11-16 N1 - Date created - 1994-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations of the E-cadherin gene in human gynecologic cancers. AN - 76691271; 8075649 AB - Expression of the E-cadherin cell adhesion molecule is reduced in several types of human carcinomas, and the protein serves as an invasion suppressor in vitro. To determine if mutations of the E-cadherin gene (on chromosome 16q22) contribute to epithelial tumorigenesis, 135 carcinomas of the endometrium and ovary were examined for alterations in the E-cadherin coding region. Four mutations were identified: one somatic nonsense and one somatic missense mutation, both with retention of the wild-type alleles, and two missense mutations with somatic loss of heterozygosity in the tumour tissue. These data support the classification of E-cadherin as a human tumour suppressor gene. JF - Nature genetics AU - Risinger, J I AU - Berchuck, A AU - Kohler, M F AU - Boyd, J AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Triangle Park, North Carolina 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 98 EP - 102 VL - 7 IS - 1 SN - 1061-4036, 1061-4036 KW - Cadherins KW - 0 KW - Codon KW - DNA, Complementary KW - DNA, Neoplasm KW - Neoplasm Proteins KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Polymerase Chain Reaction KW - Base Sequence KW - Alleles KW - DNA, Complementary -- genetics KW - Codon -- genetics KW - Humans KW - DNA Mutational Analysis KW - Neoplasm Proteins -- genetics KW - Molecular Sequence Data KW - Female KW - Gene Deletion KW - Polymorphism, Genetic KW - Ovarian Neoplasms -- genetics KW - Point Mutation KW - DNA, Neoplasm -- genetics KW - Endometrial Neoplasms -- genetics KW - Cadherins -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76691271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+of+the+E-cadherin+gene+in+human+gynecologic+cancers.&rft.au=Risinger%2C+J+I%3BBerchuck%2C+A%3BKohler%2C+M+F%3BBoyd%2C+J&rft.aulast=Risinger&rft.aufirst=J&rft.date=1994-05-01&rft.volume=7&rft.issue=1&rft.spage=98&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 - 1994-10-04 N1 - Date created - 1994-10-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - Z13009; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adducts in human and patas monkey maternal and fetal tissues induced by platinum drug chemotherapy. AN - 76686219; 8075509 AB - Platinum-DNA adducts in placenta and blood from a woman exposed to 200 mg/m2 of cis-diamminedichloroplatinum(II) (cisplatin) and 300 mg/m2 diamminecyclobutanedicarboxylatoplatinum(II) (carboplatin) for ovarian cancer have been documented by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectrometry (AAS). A patas monkey model was used to investigate transplacentally induced cisplatin-DNA damage in fetal tissues. During the last trimester of gestation, 5 patas monkeys were given multiple doses of cisplatin to mimic human ovarian cancer treatment. In spite of careful choice of dose and treatment conditions, cumulative toxicity occurred in monkeys given doses comparable on a mg/m2 basis to those received by the human. A total dose of 12 mg/m2 (0.625 mg/kg body weight), given in the last trimester, supported fetal viability, and multiple tissues, taken by cesarean section, were examined in the fetal monkeys. By cisplatin-DNA ELISA and AAS, maternal tissues from the monkey receiving the highest dose contained approximately twice as much DNA damage as the fetal tissues. A similar relationship was observed when we compared DNA adduct formation in fetal liver and biopsies of liver taken from the monkey dams at cesarean delivery. In all of the monkey pairs studied there were very significant levels of DNA damage in the placenta, and high adduct levels in brains of fetuses that survived treatment. Thus, cisplatin does cross the placenta in the patas monkey. These observations imply that the human fetus, for which the total maternal dose was approximately 5.4 mg platinum drug/kg body weight, may also have sustained some DNA damage. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Shamkhani, H AU - Anderson, L M AU - Henderson, C E AU - Moskal, T J AU - Runowicz, C D AU - Dove, L F AU - Jones, A B AU - Chaney, S G AU - Rice, J M AU - Poirier, M C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892. PY - 1994 SP - 207 EP - 216 VL - 8 IS - 3 SN - 0890-6238, 0890-6238 KW - DNA Adducts KW - 0 KW - cisplatin-DNA adduct KW - DNA KW - 9007-49-2 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Humans KW - Spectrophotometry, Atomic KW - Ovarian Neoplasms -- drug therapy KW - Pregnancy KW - Infant KW - Amniotic Fluid -- metabolism KW - Cystadenocarcinoma, Serous -- drug therapy KW - Adult KW - Fetal Blood -- metabolism KW - Enzyme-Linked Immunosorbent Assay KW - Erythrocebus patas KW - Placenta -- metabolism KW - Female KW - Male KW - DNA -- metabolism KW - DNA -- blood KW - Pregnancy Complications, Neoplastic -- drug therapy KW - Cisplatin -- blood KW - Cisplatin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76686219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=DNA+adducts+in+human+and+patas+monkey+maternal+and+fetal+tissues+induced+by+platinum+drug+chemotherapy.&rft.au=Shamkhani%2C+H%3BAnderson%2C+L+M%3BHenderson%2C+C+E%3BMoskal%2C+T+J%3BRunowicz%2C+C+D%3BDove%2C+L+F%3BJones%2C+A+B%3BChaney%2C+S+G%3BRice%2C+J+M%3BPoirier%2C+M+C&rft.aulast=Shamkhani&rft.aufirst=H&rft.date=1994-05-01&rft.volume=8&rft.issue=3&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-06 N1 - Date created - 1994-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reaction with DNA and mutagenic specificity of syn-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide. AN - 76684270; 8075375 AB - The spectroscopic characterization of purine deoxyribonucleoside adducts derived from the fjord-region syn-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide and the mutagenic specificity of the latter compound for the supF gene in the pSP189 shuttle vector are described. This dihydrodiol epoxide preferentially forms adducts with deoxyadenosine residues in DNA and is preferentially opened trans in reactions with DNA or with deoxyribonucleotides. In common with other fjord-region syn-dihydrodiol epoxides, the most frequently observed mutational changes were A-->T and G-->T changes. This hydrocarbon dihydrodiol epoxide is structurally similar to syn-benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide but has an additional benzene ring annelated distant from the reaction center. As anticipated, there were some common features in the chemistry and mutagenicities of these two compounds, but there were also substantive differences which indicate factors of importance in controlling reactions of these kinds of compounds with DNA. JF - Chemical research in toxicology AU - Szeliga, J AU - Lee, H AU - Harvey, R G AU - Page, J E AU - Ross, H L AU - Routledge, M N AU - Hilton, B D AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, PRI, DynCorp, Inc., NCI-Frederick Cancer Research and Development Center, Maryland 21701. PY - 1994 SP - 420 EP - 427 VL - 7 IS - 3 SN - 0893-228X, 0893-228X KW - supF KW - Chrysenes KW - 0 KW - Mutagens KW - Nucleic Acid Synthesis Inhibitors KW - benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide KW - 132832-27-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Cattle KW - Base Sequence KW - Spectrophotometry, Ultraviolet KW - Molecular Sequence Data KW - Circular Dichroism KW - Autoradiography KW - Magnetic Resonance Spectroscopy KW - Chrysenes -- toxicity KW - Mutagens -- toxicity KW - DNA -- chemistry KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76684270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Reaction+with+DNA+and+mutagenic+specificity+of+syn-benzo%5Bg%5Dchrysene+11%2C12-dihydrodiol+13%2C14-epoxide.&rft.au=Szeliga%2C+J%3BLee%2C+H%3BHarvey%2C+R+G%3BPage%2C+J+E%3BRoss%2C+H+L%3BRoutledge%2C+M+N%3BHilton%2C+B+D%3BDipple%2C+A&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1994-05-01&rft.volume=7&rft.issue=3&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-04 N1 - Date created - 1994-10-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Engineering interchain disulfide bonds into conserved framework regions of Fv fragments: improved biochemical characteristics of recombinant immunotoxins containing disulfide-stabilized Fv. AN - 76680893; 8073039 AB - Using molecular modeling technology, we have recently identified two positions in conserved framework regions of antibody Fv fragments (Fvs) that are distant from CDRs, and potentially can be used to make recombinant Fv fragments in which the unstable VH and VL heterodimer is stabilized by an interchain disulfide bond inserted between structurally conserved framework positions. A disulfide bond has been introduced at one of these positions, VH44-VL105, and shown to stabilize various Fvs that retain full binding and specificity. Recombinant immunotoxins, e.g. B3(dsFv)-PE38KDEL in which this disulfide-stabilized Fv moiety is connected to a truncated form of Pseudomonas exotoxin (PE; PE38KDEL) which contains the translocation and ADP ribosylation domains, are indistinguishable in binding and specificity from its single-chain immunotoxin counterparts. We have now analyzed the alternative position, (VH111-VL48), predicted by the modeling methodology, for disulfide stabilization of mAb B3(Fv) by producing a recombinant immunotoxin with such disulfide-stabilized (ds) Fv. This immunotoxin was also very active and retained full specificity to B3 antigen-positive cells. However, it was 2- to 3-fold less active than the VH44-VL105 dsFv-molecule. We also tested various biochemical features of VH44-VL105 and VH111-VL48 dsFv immunotoxins and compared them with the corresponding single-chain immunotoxin. We found the dsFv immunotoxins were more stable in human serum and more resistant to thermal and chemical denaturation than the single chain (sc) Fv immunotoxin. Because dsFv immunotoxins and dsFvs have full activity and specificity and improved stability, they may be more useful than scFv immunotoxins as therapeutic and diagnostic agents. JF - Protein engineering AU - Reiter, Y AU - Brinkmann, U AU - Webber, K O AU - Jung, S H AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 697 EP - 704 VL - 7 IS - 5 SN - 0269-2139, 0269-2139 KW - Bacterial Toxins KW - 0 KW - Disulfides KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Macromolecular Substances KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Drug Stability KW - Base Sequence KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Exotoxins -- chemistry KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Immunotoxins -- chemistry KW - Immunoglobulin Variable Region -- genetics KW - Disulfides -- chemistry KW - Protein Engineering KW - Immunoglobulin Heavy Chains -- chemistry KW - Immunoglobulin Variable Region -- chemistry KW - Immunoglobulin Light Chains -- genetics KW - Immunoglobulin Light Chains -- chemistry KW - Immunoglobulin Heavy Chains -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76680893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Engineering+interchain+disulfide+bonds+into+conserved+framework+regions+of+Fv+fragments%3A+improved+biochemical+characteristics+of+recombinant+immunotoxins+containing+disulfide-stabilized+Fv.&rft.au=Reiter%2C+Y%3BBrinkmann%2C+U%3BWebber%2C+K+O%3BJung%2C+S+H%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Reiter&rft.aufirst=Y&rft.date=1994-05-01&rft.volume=7&rft.issue=5&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-28 N1 - Date created - 1994-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative DNA base damage in renal, hepatic, and pulmonary chromatin of rats after intraperitoneal injection of cobalt(II) acetate. AN - 76680399; 8075364 AB - DNA base damage was studied in renal, hepatic, and pulmonary chromatin of male and female F344/NCr rats that had been given either 50 or 100 mumol of Co(II) acetate/kg body wt in a single ip dose and killed 2 or 10 days later. Control rats received 200 mumol of sodium acetate/kg body wt. Chromatin was isolated from organs and analyzed by gas chromatography/mass spectrometry with selected ion monitoring. The following 11 products derived from purine and pyrimidine bases in DNA were quantified: 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin,5-(hydroxymethyl)uracil(5-OHMe-Ura),5- hyd roxycytosine(5-OH- Cyt),thymine glycol, 5,6-dihydroxycytosine,4,6-diamino-5-formamido-pyrimidine (FapyAde),2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua),7,8-dihydro-8-oxoadenine,2-oxoadenine, and 7,8-dihydro-8-oxoguanine. The response was organ-specific. Eight of the DNA base products in renal chromatin of Co(II)-treated rats (mostly 5-OH-Cyt and other pyrimidine products), five in hepatic chromatin (mostly FapyGua and other purine products), and two in pulmonary chromatin (5-OHMe-Ura > FapyAde) were increased by 30% to more than 200% over control levels with increasing Co(II) dose. The renal and hepatic, but not pulmonary, DNA base damage tended to increase with time. No significant differences in response were found between male and female rats. The bases determined were typical products of hydroxyl radical attack on DNA, suggesting a role for this radical in the mechanism(s) of DNA damage caused by Co(II) in vivo. Some of these bases have been shown previously to be promutagenic. The present results imply involvement of oxidative DNA base damage in Co(II)-induced genotoxic and carcinogenic effects. JF - Chemical research in toxicology AU - Kasprzak, K S AU - Zastawny, T H AU - North, S L AU - Riggs, C W AU - Diwan, B A AU - Rice, J M AU - Dizdaroglu, M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Maryland 21702. PY - 1994 SP - 329 EP - 335 VL - 7 IS - 3 SN - 0893-228X, 0893-228X KW - Acetates KW - 0 KW - Chromatin KW - Acetic Acid KW - Q40Q9N063P KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Kidney -- drug effects KW - Hydrolysis KW - Rats KW - Oxidation-Reduction KW - Liver -- ultrastructure KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Gas Chromatography-Mass Spectrometry KW - Lung -- drug effects KW - Lung -- ultrastructure KW - Kidney -- ultrastructure KW - Male KW - Female KW - DNA Damage KW - Chromatin -- chemistry KW - Acetates -- administration & dosage KW - Chromatin -- drug effects KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76680399?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Oxidative+DNA+base+damage+in+renal%2C+hepatic%2C+and+pulmonary+chromatin+of+rats+after+intraperitoneal+injection+of+cobalt%28II%29+acetate.&rft.au=Kasprzak%2C+K+S%3BZastawny%2C+T+H%3BNorth%2C+S+L%3BRiggs%2C+C+W%3BDiwan%2C+B+A%3BRice%2C+J+M%3BDizdaroglu%2C+M&rft.aulast=Kasprzak&rft.aufirst=K&rft.date=1994-05-01&rft.volume=7&rft.issue=3&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-04 N1 - Date created - 1994-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Design of interchain disulfide bonds in the framework region of the Fv fragment of the monoclonal antibody B3. AN - 76676333; 8066084 AB - The Fv fragments are the smallest units of antibodies that retain the specific antigen binding characteristics of the whole molecule and are being used for the diagnosis and therapy of human diseases. These are noncovalently associated heterodimers of the heavy (VH) and the light (VL) chain variable domains, which, without modification, tend to dissociate, unfold, and/or nonspecifically aggregate. The fragment is usually stabilized by producing it as a single chain recombinant molecule in which the two chains are linked by means of a short polypeptide linker. An alternative strategy is to connect the two chains by means of an interchain disulfide bond. We used molecular graphics and other modeling tools to identify two possible interchain disulfide bond sites in the framework region of the Fv fragment of the monoclonal mouse antibody (mAb) B3. The mAb B3 binds to many human cancer cells and is being used in the development of a new anticancer agent. The two sites identified are VH44-VL105 and VH111-VL48. (VH44-VL100 and VH105-VL43 in the numbering scheme of Kabat et al., "Sequence of Proteins of Immunological Interest," U.S. DHHS, NIH publication No. 91-3242, 1991). This design was recently tested using the chimeric protein composed of a truncated form of Pseudomonas exotoxin and the Fv fragment of mAb B3 with the engineered disulfide bond at VH44-VL105 (Brinkmann et al., Proc. Natl. Acad. Sci. U.S.A. 90:7538, 1993). The chimeric toxin was found to be just as active as the corresponding single chain counterpart and considerably more stable. Because these disulfide bond sites are in the framework region, they can be located from sequence alignment alone. We expect that the disulfide bond at these sites will stabilize the Fv fragment of most antibodies and the antigen-specific portion of the T-cell receptors, which are homologous. JF - Proteins AU - Jung, S H AU - Pastan, I AU - Lee, B AD - Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 35 EP - 47 VL - 19 IS - 1 SN - 0887-3585, 0887-3585 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Cystine KW - 48TCX9A1VT KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Thermodynamics KW - Models, Molecular KW - Amino Acid Sequence KW - Exotoxins -- chemistry KW - Immunoglobulin Light Chains -- chemistry KW - Mice KW - Antibodies, Neoplasm -- chemistry KW - Recombinant Fusion Proteins -- chemistry KW - Immunotoxins -- chemistry KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Immunoglobulin Heavy Chains -- chemistry KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Binding Sites, Antibody KW - Cystine -- chemistry KW - Immunoglobulin Variable Region -- chemistry KW - Antibodies, Monoclonal -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76676333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins&rft.atitle=Design+of+interchain+disulfide+bonds+in+the+framework+region+of+the+Fv+fragment+of+the+monoclonal+antibody+B3.&rft.au=Jung%2C+S+H%3BPastan%2C+I%3BLee%2C+B&rft.aulast=Jung&rft.aufirst=S&rft.date=1994-05-01&rft.volume=19&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Proteins&rft.issn=08873585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differences in a K current in Schwann cells from normal and neurofibromatosis-infected damselfish. AN - 76672631; 8070896 AB - Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K+ current (K current), with a strong dependence on the Nernst potential for K+. This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (Kd approximately 1 mM) and by dendrotoxin (15 microM) but were insensitive to extracellular tetraethyammonium (< or = 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of -40 mV, while in tumored cells this average was 12%, a significant difference. JF - Glia AU - Fieber, L A AU - Schmale, M C AD - University of Miami Rosenstiel School of Marine and Atmospheric Science, NIEHS Marine and Freshwater Biomedical Sciences Center, Florida 33149-1098. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 64 EP - 72 VL - 11 IS - 1 SN - 0894-1491, 0894-1491 KW - Elapid Venoms KW - 0 KW - Neurotoxins KW - Potassium Channels KW - dendrotoxin KW - 74811-93-1 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Elapid Venoms -- pharmacology KW - Animals KW - Cells, Cultured KW - 4-Aminopyridine -- pharmacology KW - Peripheral Nerves -- cytology KW - Membrane Potentials -- physiology KW - Neurotoxins -- pharmacology KW - Electrophysiology KW - Schwann Cells -- drug effects KW - Potassium Channels -- physiology KW - Neurofibromatoses -- metabolism KW - Fishes -- physiology KW - Schwann Cells -- metabolism KW - Potassium Channels -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76672631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Glia&rft.atitle=Differences+in+a+K+current+in+Schwann+cells+from+normal+and+neurofibromatosis-infected+damselfish.&rft.au=Fieber%2C+L+A%3BSchmale%2C+M+C&rft.aulast=Fieber&rft.aufirst=L&rft.date=1994-05-01&rft.volume=11&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Glia&rft.issn=08941491&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-29 N1 - Date created - 1994-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco use and prostate cancer in blacks and whites in the United States. AN - 76671124; 8061169 AB - Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR] = 1.1, 95 percent confidence interval [CI] = 0.7-1.5) and in Whites (OR = 1.2, CI = 0.9-1.6), or for current cigarette smokers, in Blacks (OR = 1.0, CI = 0.7-1.4) and in Whites (OR = 1.2, CI = 0.8-1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR = 1.4, CI = 1.0-1.5) and current (OR = 1.5, CI = 1.0-2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR = 1.5, CI = 1.0-2.3) and former (OR = 1.7, CI = 1.1-2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer causes & control : CCC AU - Hayes, R B AU - Pottern, L M AU - Swanson, G M AU - Liff, J M AU - Schoenberg, J B AU - Greenberg, R S AU - Schwartz, A G AU - Brown, L M AU - Silverman, D T AU - Hoover, R N AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 221 EP - 226 VL - 5 IS - 3 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Age Factors KW - Humans KW - African Americans KW - Aged KW - Population Surveillance KW - Tobacco, Smokeless KW - Plants, Toxic KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Prostatic Neoplasms -- epidemiology KW - European Continental Ancestry Group KW - African Continental Ancestry Group KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76671124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Tobacco+use+and+prostate+cancer+in+blacks+and+whites+in+the+United+States.&rft.au=Hayes%2C+R+B%3BPottern%2C+L+M%3BSwanson%2C+G+M%3BLiff%2C+J+M%3BSchoenberg%2C+J+B%3BGreenberg%2C+R+S%3BSchwartz%2C+A+G%3BBrown%2C+L+M%3BSilverman%2C+D+T%3BHoover%2C+R+N&rft.aulast=Hayes&rft.aufirst=R&rft.date=1994-05-01&rft.volume=5&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-16 N1 - Date created - 1994-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial of intravenous interleukin-6 in patients with advanced cancer. AN - 76670216; 7520334 AB - Eighteen patients were treated with escalating doses of recombinant, Escherichia coli-derived human interleukin-6 (IL-6) intravenously every 8 h. Therapy was given for two cycles of 7 days each separated by a week off therapy. Fevers and chills were observed in most patients. Mild renal and liver function abnormalities were noted at higher doses of IL-6. Dose-limiting toxicity was reached at 30 micrograms/kg i.v. every 8 h due to reversible neurotoxicity, but significant rapidly reversible anemia and hyperglycemia were seen at lower doses. Platelet counts, white blood cell counts, and acute phase reactant levels were substantially elevated. No antitumor responses were seen. A maximum tolerated dose of 10 micrograms/kg i.v. every 8 h for two 7-day cycles is recommended for future phase II trials. JF - Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy AU - Weber, J AU - Gunn, H AU - Yang, J AU - Parkinson, D AU - Topalian, S AU - Schwartzentruber, D AU - Ettinghausen, S AU - Levitt, D AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 292 EP - 302 VL - 15 IS - 4 SN - 1067-5582, 1067-5582 KW - Acute-Phase Proteins KW - 0 KW - Interleukin-6 KW - Index Medicus KW - Injections, Intravenous KW - Hyperglycemia -- chemically induced KW - Acute-Phase Proteins -- drug effects KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Male KW - Female KW - Blood Cell Count -- drug effects KW - Interleukin-6 -- pharmacokinetics KW - Interleukin-6 -- adverse effects KW - Interleukin-6 -- therapeutic use KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76670216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.atitle=A+phase+I+trial+of+intravenous+interleukin-6+in+patients+with+advanced+cancer.&rft.au=Weber%2C+J%3BGunn%2C+H%3BYang%2C+J%3BParkinson%2C+D%3BTopalian%2C+S%3BSchwartzentruber%2C+D%3BEttinghausen%2C+S%3BLevitt%2C+D%3BRosenberg%2C+S+A&rft.aulast=Weber&rft.aufirst=J&rft.date=1994-05-01&rft.volume=15&rft.issue=4&rft.spage=292&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+with+emphasis+on+tumor+immunology+%3A+official+journal+of+the+Society+for+Biological+Therapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-19 N1 - Date created - 1994-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of tetrahydrobiopterin on the in situ phosphorylation of tyrosine hydroxylase in rat striatal synaptosomes. AN - 76659245; 7915013 AB - Tetrahydrobiopterin (BH4), the obligatory cofactor of the aromatic amino acid hydroxylases, decreased the in situ 32P-phosphorylation of tyrosine hydroxylase (TH) in rat striatal synaptosomes. Incubation of pre-32P-labeled synaptosomes with BH4 in the presence of a permeant analogue of cAMP decreased the cAMP-stimulated level of 32P label incorporation into TH by about 50%, as determined by immunoprecipitation and autoradiography of SDS-polyacrylamide gels. The extent of inhibition mirrored changes in intrasynaptosomal BH4 levels and varied both as a function of BH4 concentration and length of incubation. A similar decrease in the amount of TH 32P-labeling was observed with the precursor of BH4, sepiapterin. This effect, in turn, was reversed by the inhibitor of sepiapterin reductase, N-acetyl-serotonin. Finally, exposure of pre-32P-labeled synaptosomes to the inhibitor of protein phosphatase 2A, okadaic acid, blocked the response to BH4. Collectively, the data suggest that BH4 stimulates the dephosphorylation of TH in situ and thus may play a dual role both as a cofactor for catalysis and a regulator of hydroxylase activity. JF - Neurochemical research AU - Ribeiro, P AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 541 EP - 548 VL - 19 IS - 5 SN - 0364-3190, 0364-3190 KW - Ethers, Cyclic KW - 0 KW - Phosphorus Radioisotopes KW - Pteridines KW - Pterins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Biopterin KW - 22150-76-1 KW - Bucladesine KW - 63X7MBT2LQ KW - sepiapterin KW - CJQ26KO7HP KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - sapropterin KW - EGX657432I KW - Index Medicus KW - Rats KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Pteridines -- pharmacology KW - Animals KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Ethers, Cyclic -- pharmacology KW - Bucladesine -- pharmacology KW - Male KW - Biopterin -- analogs & derivatives KW - Tyrosine 3-Monooxygenase -- metabolism KW - Synaptosomes -- drug effects KW - Corpus Striatum -- ultrastructure KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects KW - Tyrosine 3-Monooxygenase -- drug effects KW - Biopterin -- pharmacology KW - Synaptosomes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76659245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+tetrahydrobiopterin+on+the+in+situ+phosphorylation+of+tyrosine+hydroxylase+in+rat+striatal+synaptosomes.&rft.au=Ribeiro%2C+P%3BKaufman%2C+S&rft.aulast=Ribeiro&rft.aufirst=P&rft.date=1994-05-01&rft.volume=19&rft.issue=5&rft.spage=541&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 - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for extrahepatic bile duct cancers: Los Angeles County, California (USA). AN - 76655163; 8061176 AB - Extrahepatic bile duct (EBD) cancers are rare and their risk factors are poorly understood. Except for a history of gallbladder diseases, evidence for other potential risk factors, such as excess body weight and use of tobacco and alcohol, is scant. A case-control study was conducted to examine risk factors for EBD cancers, including ampulla of Vater tumors, among Los Angeles County (California, USA) residents. Included were 105 histologically confirmed cases diagnosed between 1 March 1985 and 31 October 1989, aged 30 to 84 years, and 255 population-based controls frequency-matched to cases by gender and age in five-year groups. Cases and controls were interviewed about their demographic background and potential risk factors, including tobacco, alcohol, and beverage consumption, diet, medical history, and reproductive factors among women. For deceased cases, their next-of-kin were interviewed. Risk of cancers of both subsites of extrahepatic duct and ampulla of Vater increased with smoking of cigars/pipes or cigarettes. For both men and women, risks increased twofold or more among those who smoked cigarettes for 50 or more pack-years. While a history of gallbladder diseases substantially increased the risk of cancers of both subsites, excess body mass index was associated only with cancer of extrahepatic duct subsite (odds ratio [OR] = 4.0, 95 percent confidence interval [CI] = 1.1-14.2 among men and OR = 2.7; CI = 0.8-9.4 among women in the highest quartile relative to those in the lowest quartile). Alcohol drinkers had lower risks compared with nondrinkers, but no consistent trend was observed with amount consumed.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cancer causes & control : CCC AU - Chow, W H AU - McLaughlin, J K AU - Menck, H R AU - Mack, T M AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 267 EP - 272 VL - 5 IS - 3 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Age Factors KW - Los Angeles -- epidemiology KW - Common Bile Duct Neoplasms -- epidemiology KW - Sex Factors KW - Reproductive History KW - Ampulla of Vater -- pathology KW - Humans KW - Aged KW - Body Mass Index KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Tobacco, Smokeless KW - Population Surveillance KW - Plants, Toxic KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Gallbladder Diseases -- epidemiology KW - Middle Aged KW - Male KW - Female KW - Bile Duct Neoplasms -- epidemiology KW - Bile Ducts, Extrahepatic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76655163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Risk+factors+for+extrahepatic+bile+duct+cancers%3A+Los+Angeles+County%2C+California+%28USA%29.&rft.au=Chow%2C+W+H%3BMcLaughlin%2C+J+K%3BMenck%2C+H+R%3BMack%2C+T+M&rft.aulast=Chow&rft.aufirst=W&rft.date=1994-05-01&rft.volume=5&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-16 N1 - Date created - 1994-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV risk factors among injecting drug users in five US cities. AN - 76653648; 8060548 AB - To examine factors associated with HIV infection in injecting drug users (IDU), the independent and interactive effects of potential risk factors, and geographic differences in risk factors. IDU entering methadone treatment in New York City, Asbury Park and Trenton in New Jersey, Baltimore and Chicago between February 1987 and December 1991 were interviewed using a standard questionnaire and tested for HIV antibodies (n = 4584). Associations of HIV serostatus with race/ethnicity, other demographic characteristics, and injecting and sexual risk behaviors were assessed by logistic regression analyses. African Americans were at increased risk for HIV in four of the five cities, and Puerto Ricans in two cities. Injection in shooting galleries and 'speedball' injection emerged as behavioral variables highly associated with HIV, although interaction of these variables indicates that each variable contributes to HIV risk only in the absence of the other behavior. Geographic differences in HIV risk factors and the interaction of 'speedball' and shooting gallery use suggest that multiple HIV risk models are needed that reflect seroprevalence rates, variation in risk behaviors, and the social context of risk behaviors. Increased risk among racial/ethnic minorities independent of risk behaviors, suggests the need to examine further potential social and environmental factors, such as the social networks in which injecting and sexual behaviors occur, HIV seroprevalence within these networks, and the locales in which risk behaviors occur. JF - AIDS (London, England) AU - Battjes, R J AU - Pickens, R W AU - Haverkos, H W AU - Sloboda, Z AD - National Institute on Drug Abuse, Rockville, MD 20857. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 681 EP - 687 VL - 8 IS - 5 SN - 0269-9370, 0269-9370 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - AIDS/HIV KW - Chicago -- epidemiology KW - Dangerous Behavior KW - Odds Ratio KW - Needle Sharing -- statistics & numerical data KW - Puerto Rico -- ethnology KW - Humans KW - African Americans -- statistics & numerical data KW - Mexican Americans -- statistics & numerical data KW - Baltimore -- epidemiology KW - Comorbidity KW - Multivariate Analysis KW - Hispanic Americans -- statistics & numerical data KW - New Jersey -- epidemiology KW - New York City -- epidemiology KW - Risk Factors KW - Adult KW - Urban Population KW - United States -- epidemiology KW - HIV Seropositivity -- epidemiology KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Sexual Behavior -- statistics & numerical data KW - HIV Infections -- transmission KW - HIV Infections -- ethnology KW - Substance Abuse, Intravenous -- epidemiology KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76653648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=HIV+risk+factors+among+injecting+drug+users+in+five+US+cities.&rft.au=Battjes%2C+R+J%3BPickens%2C+R+W%3BHaverkos%2C+H+W%3BSloboda%2C+Z&rft.aulast=Battjes&rft.aufirst=R&rft.date=1994-05-01&rft.volume=8&rft.issue=5&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-22 N1 - Date created - 1994-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential steroid hormone induction of transcription from the mouse mammary tumor virus promoter. AN - 76649989; 8058066 AB - The Mouse Mammary Tumor Virus (MMTV) contains sequences in its proximal promoter region to which both glucocorticoid and progesterone receptors can bind. In transient transfection experiments both hormones are able to stimulate transcription from reporter plasmids containing either native or consensus hormone response elements (glucocorticoid response element/progesterone response element). Previous experiments have demonstrated that the MMTV long terminal repeat is reproducibly assembled into a phased array of nucleosomes when stably introduced into cells. Stimulation by glucocorticoids of endogenous templates led to a rapid but transient increase in transcription initiation and mRNA accumulation that can be correlated with increased sensitivity to restriction enzymes. In contrast, experiments using progesterone or a truncated glucocorticoid receptor failed to elicit a similar increase in mRNA levels as dexamethasone from stable chromatin templates. In an attempt to understand this differential response, we have compared the responsiveness of the MMTV promoter to glucocorticoids and progesterone when it is organized in either stable chromatin or in transiently acquired plasmids. Our results demonstrate that the native chromatin structure prevents activation of this locus by progesterone, but permits stimulation by glucocorticoids. JF - Molecular endocrinology (Baltimore, Md.) AU - Archer, T K AU - Lee, H L AU - Cordingley, M G AU - Mymryk, J S AU - Fragoso, G AU - Berard, D S AU - Hager, G L AD - Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 568 EP - 576 VL - 8 IS - 5 SN - 0888-8809, 0888-8809 KW - Chromatin KW - 0 KW - DNA Primers KW - Receptors, Glucocorticoid KW - Receptors, Progesterone KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Cell Nucleus -- metabolism KW - Chromatin -- physiology KW - Cell Nucleus -- drug effects KW - Mice KW - Receptors, Glucocorticoid -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Receptors, Progesterone -- metabolism KW - Transfection KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Time Factors KW - Cell Line KW - Gene Expression -- drug effects KW - Promoter Regions, Genetic KW - Dexamethasone -- pharmacology KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76649989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Differential+steroid+hormone+induction+of+transcription+from+the+mouse+mammary+tumor+virus+promoter.&rft.au=Archer%2C+T+K%3BLee%2C+H+L%3BCordingley%2C+M+G%3BMymryk%2C+J+S%3BFragoso%2C+G%3BBerard%2C+D+S%3BHager%2C+G+L&rft.aulast=Archer&rft.aufirst=T&rft.date=1994-05-01&rft.volume=8&rft.issue=5&rft.spage=568&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-14 N1 - Date created - 1994-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of a 35 kDa fos-related antigen (FRA) in the long-term induction of striatal dynorphin expression in the 6-hydroxydopamine lesioned rat. AN - 76643626; 7914658 AB - D1 dopamine (DA) receptor agonists induce the expression of the opioid peptide dynorphin (DYN) in the striatum, an effect accentuated several fold by removing the dopaminergic innervation to the striatum (e.g., by lesioning the DA cell bodies in the substantia nigra [SN]). D1 receptor-mediated effects are thought to involve cAMP and/or phosphoinositides as second messengers. However, it is unclear what third messengers are involved in the regulation of DYN expression. The present experiments evaluated the possible role of two families of immediate-early gene (IEG) proteins, Fos and Jun, in the induction of DYN biosynthesis following repeated treatment with DA agonists. In addition, the role of N-methyl-D-aspartate (NMDA) receptors in modulating DA-induced changes in DYN and IEG protein expression was assessed. Adult male rats received unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the SN. Following a recovery period, animals were injected twice daily with the DA agonist, apomorphine (APO; 5 mg/kg), for 4 or 7 days. As expected, APO induced DYN biosynthesis, at both the peptide and mRNA level, several fold more in the striatum ipsilateral to the 6-OHDA lesion than in the contralateral control side (or a sham lesioned striatum). These effects appeared to be mediated by D1 receptors since the D1 agonist, SKF 38393 (5 mg/kg), caused the same changes in DYN expression as APO whereas a D2 agonist, quinpirole (1 mg/kg), had no effect. Paralleling the increase in DYN expression, APO also induced the expression of c-Fos and Fos-related antigens (FRA's), in particular a 35 kDa FRA, but had no effect on the expression of various Jun-related IEG proteins (i.e., c-Jun, Jun B, Jun D). Consistent with the notion that Fos and FRA proteins alter transcriptional activity by binding to AP-1 (or AP-1-like) DNA sequences in the promoter regions of target genes, we found that repeated APO treatment caused large increases in AP-1 binding activity in striata ipsilateral to 6-OHDA lesions. These data indicate that repeated activation of D1 receptors increases both the expression of a 35 kDa FRA and AP-1 binding, events which may mediate the large increases in DYN expression in the DA denervated striatum. While co-administration of the NMDA receptor antagonist, MK-801, inhibited APO-induced increases in DYN and Fos/FRA expression in the intact striatum, its only effect in the DA-denervated striatum was a partial (35%) inhibition of the APO-induced increase in DYN-ir concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Brain research. Molecular brain research AU - Bronstein, D M AU - Ye, H AU - Pennypacker, K R AU - Hudson, P M AU - Hong, J S AD - Laboratory of Integrative Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 191 EP - 203 VL - 23 IS - 3 SN - 0169-328X, 0169-328X KW - Ergolines KW - 0 KW - Immediate-Early Proteins KW - Nerve Tissue Proteins KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Receptors, Dopamine KW - Receptors, N-Methyl-D-Aspartate KW - fos-related antigen 1 KW - Quinpirole KW - 20OP60125T KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Dynorphins KW - 74913-18-1 KW - Atropine KW - 7C0697DR9I KW - Oxidopamine KW - 8HW4YBZ748 KW - Apomorphine KW - N21FAR7B4S KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Animals KW - Apomorphine -- pharmacology KW - Ergolines -- pharmacology KW - Dopamine -- physiology KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - RNA, Messenger -- genetics KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Genes, Immediate-Early KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Receptors, Dopamine -- physiology KW - Rats, Inbred F344 KW - Base Sequence KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Molecular Sequence Data KW - Proto-Oncogene Proteins c-jun -- genetics KW - Genes, fos KW - Atropine -- pharmacology KW - Male KW - Genes, jun KW - Nerve Tissue Proteins -- physiology KW - Immediate-Early Proteins -- biosynthesis KW - Immediate-Early Proteins -- genetics KW - Oxidopamine -- toxicity KW - Corpus Striatum -- metabolism KW - Proto-Oncogene Proteins c-fos -- physiology KW - Corpus Striatum -- drug effects KW - Gene Expression Regulation -- drug effects KW - Immediate-Early Proteins -- physiology KW - Dynorphins -- genetics KW - Dynorphins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76643626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+a+35+kDa+fos-related+antigen+%28FRA%29+in+the+long-term+induction+of+striatal+dynorphin+expression+in+the+6-hydroxydopamine+lesioned+rat.&rft.au=Bronstein%2C+D+M%3BYe%2C+H%3BPennypacker%2C+K+R%3BHudson%2C+P+M%3BHong%2C+J+S&rft.aulast=Bronstein&rft.aufirst=D&rft.date=1994-05-01&rft.volume=23&rft.issue=3&rft.spage=191&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 - 1994-09-12 N1 - Date created - 1994-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of the reproductive and developmental toxicity of pesticide/fertilizer mixtures based on confirmed pesticide contamination in California and Iowa groundwater. AN - 76636878; 8056207 AB - Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100 x the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-1 mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1x, 10x, and 100x) where 1x was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F0 or F1 mice at doses up to 100x the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F0 or the F1 generation mice exposed to either CAL or IOWA at up to 100x. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats). JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Heindel, J J AU - Chapin, R E AU - Gulati, D K AU - George, J D AU - Price, C J AU - Marr, M C AU - Myers, C B AU - Barnes, L H AU - Fail, P A AU - Grizzle, T B AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 605 EP - 621 VL - 22 IS - 4 SN - 0272-0590, 0272-0590 KW - Fertilizers KW - 0 KW - Pesticides KW - Water Pollutants, Chemical KW - Index Medicus KW - Rats KW - California KW - Litter Size -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Spermatozoa -- drug effects KW - Mice KW - Birth Weight -- drug effects KW - Iowa KW - Male KW - Female KW - Pregnancy KW - Reproduction -- drug effects KW - Water Pollutants, Chemical -- toxicity KW - Pesticides -- toxicity KW - Fertilizers -- toxicity KW - Embryonic and Fetal Development -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76636878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Assessment+of+the+reproductive+and+developmental+toxicity+of+pesticide%2Ffertilizer+mixtures+based+on+confirmed+pesticide+contamination+in+California+and+Iowa+groundwater.&rft.au=Heindel%2C+J+J%3BChapin%2C+R+E%3BGulati%2C+D+K%3BGeorge%2C+J+D%3BPrice%2C+C+J%3BMarr%2C+M+C%3BMyers%2C+C+B%3BBarnes%2C+L+H%3BFail%2C+P+A%3BGrizzle%2C+T+B&rft.aulast=Heindel&rft.aufirst=J&rft.date=1994-05-01&rft.volume=22&rft.issue=4&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-09 N1 - Date created - 1994-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatic regeneration in vitamin A-deficient rats: changes in the expression of transforming growth factor alpha/epidermal growth factor receptor and retinoic acid receptors alpha and beta. AN - 76627761; 7519440 AB - We have studied the effect of vitamin A deficiency on the expression of transforming growth factor alpha (TGF-alpha), hepatocyte growth factor, acidic fibroblast growth factor, and TGF-beta 1 after partial hepatectomy of vitamin A-supplemented and vitamin A-deficient rats. In addition, the expressions of epidermal growth factor receptor and retinoic acid receptors alpha (RAR alpha) and beta (RAR beta) were studied. Partial hepatectomy was performed on the animals from the vitamin A-supplemented and -deficient groups at the age of 10 weeks when the weights of the animals on the deficient diet had reached a plateau. Two animals from each group were sacrificed before the operation and also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy of the vitamin A-deficient rats leads to a focal necrosis of liver followed by a rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth factor receptor was highly elevated in the livers of deficient animals after partial hepatectomy. In the vitamin A-supplemented animals, the level of epidermal growth factor receptor was down-regulated following partial hepatectomy. Proliferation of oval cells in vitamin A-deficient livers following partial hepatectomy and subsequent increase in 2.1-kilobase alpha-fetoprotein mRNA was observed, suggesting an activation of the stem cell compartment. Another unexpected result was an inverse relationship between RAR beta and RAR alpha expression, the latter becoming the major species after partial hepatectomy in animals on the vitamin A-deficient regimen.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Hu, Z AU - Fujio, K AU - Marsden, E R AU - Thorgeirsson, S S AU - Evarts, R P AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-0037. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 503 EP - 508 VL - 5 IS - 5 SN - 1044-9523, 1044-9523 KW - RNA, Messenger KW - 0 KW - Rara protein, rat KW - Receptors, Retinoic Acid KW - Retinoic Acid Receptor alpha KW - Transforming Growth Factor alpha KW - Transforming Growth Factor beta KW - alpha-Fetoproteins KW - retinoic acid receptor beta KW - Fibroblast Growth Factor 1 KW - 104781-85-3 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Transforming Growth Factor beta -- biosynthesis KW - Animals KW - Liver -- cytology KW - Liver -- pathology KW - alpha-Fetoproteins -- biosynthesis KW - Hepatocyte Growth Factor -- genetics KW - Transcription, Genetic KW - Liver -- chemistry KW - Organ Size KW - RNA, Messenger -- biosynthesis KW - Rats KW - Hepatocyte Growth Factor -- biosynthesis KW - Diet KW - alpha-Fetoproteins -- genetics KW - Transforming Growth Factor beta -- genetics KW - Fibroblast Growth Factor 1 -- biosynthesis KW - Female KW - Fibroblast Growth Factor 1 -- genetics KW - Vitamin A Deficiency -- metabolism KW - Receptors, Retinoic Acid -- genetics KW - Receptors, Retinoic Acid -- biosynthesis KW - Transforming Growth Factor alpha -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Transforming Growth Factor alpha -- biosynthesis KW - Liver Regeneration -- physiology KW - Receptor, Epidermal Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76627761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Hepatic+regeneration+in+vitamin+A-deficient+rats%3A+changes+in+the+expression+of+transforming+growth+factor+alpha%2Fepidermal+growth+factor+receptor+and+retinoic+acid+receptors+alpha+and+beta.&rft.au=Hu%2C+Z%3BFujio%2C+K%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S%3BEvarts%2C+R+P&rft.aulast=Hu&rft.aufirst=Z&rft.date=1994-05-01&rft.volume=5&rft.issue=5&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acquired immunodeficiency syndrome in the elderly. AN - 76625974; 8043943 AB - Recent data from the US show that since 1990 the number of paediatric patients with AIDS is decreasing while the number of patients with AIDS over age 50 years is increasing. To date, little attention has been given to understanding AIDS risk-taking behaviours, clinical presentations, and therapeutic needs of middle-aged and older HIV-infected individuals. Older HIV-infected individuals deteriorate more rapidly than younger patients due to an accelerated loss of CD4+ helper T cells. Despite recognised age-related physiological differences between young and elderly individuals, scant information about drug optimisation for the treatment of AIDS in older individuals is available. More data need to be collected about this group of AIDS patients, and appropriate treatment strategies designed for their special needs. JF - Drugs & aging AU - Adler, W H AU - Nagel, J E AD - Clinical Immunology Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 410 EP - 416 VL - 4 IS - 5 SN - 1170-229X, 1170-229X KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Immunity, Cellular KW - Blood Transfusion -- adverse effects KW - Zidovudine -- adverse effects KW - Humans KW - Prognosis KW - Aged KW - Social Isolation KW - Aging -- physiology KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Aging -- immunology KW - Acquired Immunodeficiency Syndrome -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76625974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drugs+%26+aging&rft.atitle=Acquired+immunodeficiency+syndrome+in+the+elderly.&rft.au=Adler%2C+W+H%3BNagel%2C+J+E&rft.aulast=Adler&rft.aufirst=W&rft.date=1994-05-01&rft.volume=4&rft.issue=5&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=Drugs+%26+aging&rft.issn=1170229X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-30 N1 - Date created - 1994-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative effects of typical and atypical neuroleptics on smooth pursuit eye tracking in schizophrenia. AN - 76618878; 8043521 AB - Smooth pursuit eye movement (SPEM) gain, total saccades, and subtypes of saccades were quantified from the visual pursuit tracking of 26 fluphenazine-treated patients with schizophrenia and 42 normal controls. Tracking was repeated in 16 patients who underwent a placebo-controlled, double-blind crossover comparison of fluphenazine and clozapine. Fluphenazine-treated patients showed significant reduction in SPEM gain and significant increases in both total, intrusive, and anticipatory saccades and in saccadic amplitude, when compared to controls. Clozapine significantly reduced SPEM gain and significantly increased total and catch-up saccades, when compared to placebo or fluphenazine. High amplitude of intrusive saccades in drug-free patients predicted poor response to clozapine, suggesting that intact frontal cortical function may enable optimal clozapine response. JF - Schizophrenia research AU - Litman, R E AU - Hommer, D W AU - Radant, A AU - Clem, T AU - Pickar, D AD - Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 107 EP - 120 VL - 12 IS - 2 SN - 0920-9964, 0920-9964 KW - Clozapine KW - J60AR2IKIC KW - Fluphenazine KW - S79426A41Z KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Male KW - Female KW - Fluphenazine -- adverse effects KW - Fluphenazine -- therapeutic use KW - Clozapine -- adverse effects KW - Pursuit, Smooth -- drug effects KW - Schizophrenia -- physiopathology KW - Saccades -- physiology KW - Clozapine -- therapeutic use KW - Schizophrenic Psychology KW - Attention -- physiology KW - Pursuit, Smooth -- physiology KW - Schizophrenia -- drug therapy KW - Attention -- drug effects KW - Saccades -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76618878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Quantitative+effects+of+typical+and+atypical+neuroleptics+on+smooth+pursuit+eye+tracking+in+schizophrenia.&rft.au=Litman%2C+R+E%3BHommer%2C+D+W%3BRadant%2C+A%3BClem%2C+T%3BPickar%2C+D&rft.aulast=Litman&rft.aufirst=R&rft.date=1994-05-01&rft.volume=12&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-31 N1 - Date created - 1994-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects on operant learning and brain acetylcholine esterase activity in rats following chronic inorganic arsenic intake. AN - 76618369; 8043317 AB - 1. Very young and adult Wistar rats were given As5+, 5 mg arsenic kg-1 body weight day-1 (sodium arsenate). 2. Operant learning was tested in a Skinner box at the end of exposure and, in the case of developing animals, also after a recovery period. 3. Acetylcholine esterase (AChE) activity was estimated in discrete brain regions of these animals. 4. The animals exposed to arsenic took longer to acquire the learned behaviour and to extinguish the operant. AChE activity was inhibited in some regions of the brain. JF - Human & experimental toxicology AU - Nagaraja, T N AU - Desiraju, T AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 353 EP - 356 VL - 13 IS - 5 SN - 0960-3271, 0960-3271 KW - Arsenates KW - 0 KW - sodium arsenate KW - 7631-89-2 KW - Acetylcholinesterase KW - EC 3.1.1.7 KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Aging -- metabolism KW - Psychomotor Performance -- drug effects KW - Body Weight -- drug effects KW - Rats, Wistar KW - Male KW - Female KW - Organ Size -- drug effects KW - Conditioning, Operant -- drug effects KW - Brain -- enzymology KW - Brain -- drug effects KW - Acetylcholinesterase -- metabolism KW - Arsenates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76618369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Effects+on+operant+learning+and+brain+acetylcholine+esterase+activity+in+rats+following+chronic+inorganic+arsenic+intake.&rft.au=Nagaraja%2C+T+N%3BDesiraju%2C+T&rft.aulast=Nagaraja&rft.aufirst=T&rft.date=1994-05-01&rft.volume=13&rft.issue=5&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-26 N1 - Date created - 1994-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 gene mutation in hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline in nonhuman primates. AN - 76569621; 8014109 AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several heterocyclic amines formed during the cooking of proteinaceous foods. IQ is a potent carcinogen in rodent bioassays and causes a high incidence of hepatocellular carcinomas in nonhuman primates. We examined 20 hepatocellular carcinomas (HCCs) from nonhuman primates for mutations of the p53 gene using polymerase chain reaction-single strand conformational polymorphism analysis. Mutations in the p53 gene were detected in 4 of 20 HCCs (20%) with 3 showing G-to-T transversions and one a G-to-A transition. Three of these mutations were observed in codons 175 and 248 that are known mutational hot spots in human cancers. These data indicate that part of the IQ-induced HCCs in nonhuman primates may involve inactivation of the p53 gene and suggest that IQ and possibly other heterocyclic amines may participate in human carcinogenesis by a similar mechanism. JF - Japanese journal of cancer research : Gann AU - Fujimoto, Y AU - Hampton, L L AU - Snyderwine, E G AU - Nagao, M AU - Sugimura, T AU - Adamson, R H AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 506 EP - 509 VL - 85 IS - 5 SN - 0910-5050, 0910-5050 KW - Mutagens KW - 0 KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Index Medicus KW - Animals KW - Base Sequence KW - Macaca fascicularis KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Quinolines -- pharmacology KW - Genes, p53 KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- chemically induced KW - Mutation KW - Carcinoma, Hepatocellular -- chemically induced KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76569621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=p53+gene+mutation+in+hepatocellular+carcinoma+induced+by+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+in+nonhuman+primates.&rft.au=Fujimoto%2C+Y%3BHampton%2C+L+L%3BSnyderwine%2C+E+G%3BNagao%2C+M%3BSugimura%2C+T%3BAdamson%2C+R+H%3BThorgeirsson%2C+S+S&rft.aulast=Fujimoto&rft.aufirst=Y&rft.date=1994-05-01&rft.volume=85&rft.issue=5&rft.spage=506&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-22 N1 - Date created - 1994-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chief cells possess somatostatin receptors regulated by secretagogues acting through the calcium or cAMP pathway. AN - 76529663; 7911277 AB - Inhibition both in vivo and in vitro of pepsinogen secretion by somatostatin (SS) and the histological demonstration that fundic D-cells contain long cytoplasmic processes extending to chief cells suggest a possible direct effect of SS on chief cell function. The aim of the present study was to determine whether SS interacts directly with receptors on isolated gastric chief cells and, if so, how SS alters cell function. Binding of 125I-[Tyr11]SS14 to chief cells was saturable, time and temperature dependent, and was inhibited by both SS14 (Ki 1.6 nM) and SS28 (Ki 5.2 nM). SMS-201-995 was 1,300-fold less potent than SS14. Calcium-mobilizing secretagogues reduced binding of 125I-[Tyr11]SS14 with efficacies of cholecystokinin octapeptide (CCK-8) > carbachol > gastrin. Adenosine 3',5'-cyclic monophosphate (cAMP)-activating secretagogues also inhibited binding with efficacies of secretin > vasoactive intestinal polypeptide (VIP). 12-O-tetradecanoylphorbol 13-acetate (TPA) or A-23187 also decreased binding. Analyses demonstrated that CCK-8 and TPA were decreasing the affinity of SS receptors for 125I-[Tyr11]SS14 without affecting their binding capacity. Both SS14 and SS28 at a maximally effective concentration inhibited cAMP production caused by VIP or secretin (20-30%) but did not alter cytosolic calcium ([Ca2+]i), inositol phosphates, or pepsinogen release. We conclude that chief cells possess SS receptors with a high affinity for both SS14 and SS28 but low affinity for SMS-201-995 and thus resemble the SSB receptors described in the rat cerebral cortex. Although occupation of these receptors by SS has no effect on pepsinogen release induced by secretagogues acting through either the calcium or the cAMP pathway, SS receptor occupation is regulated by agents activating phospholipase C, adenylate cyclase, protein kinase C, and [Ca2]i. JF - The American journal of physiology AU - Felley, C P AU - O'Dorisio, T M AU - Howe, B AU - Coy, D H AU - Mantey, S A AU - Pradhan, T K AU - Sutliff, V E AU - Jensen, R T AD - National Institute of Diabetes and Digestive and Kidney Diseases, Digestive Diseases Branch, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - G789 EP - G798 VL - 266 IS - 5 Pt 1 SN - 0002-9513, 0002-9513 KW - Receptors, Somatostatin KW - 0 KW - Secretin KW - 1393-25-5 KW - Colforsin KW - 1F7A44V6OU KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Somatostatin KW - 51110-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Octreotide KW - RWM8CCW8GP KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Vasoactive Intestinal Peptide -- pharmacology KW - Animals KW - Second Messenger Systems KW - Thermodynamics KW - Octreotide -- pharmacology KW - Guinea Pigs KW - Cholera Toxin -- pharmacology KW - Epithelium -- drug effects KW - Colforsin -- pharmacology KW - Epithelial Cells KW - Cells, Cultured KW - Kinetics KW - Binding, Competitive KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Secretin -- pharmacology KW - Epithelium -- metabolism KW - Male KW - Somatostatin -- pharmacology KW - Receptors, Somatostatin -- metabolism KW - Calcium -- metabolism KW - Receptors, Somatostatin -- analysis KW - Cyclic AMP -- metabolism KW - Receptors, Somatostatin -- drug effects KW - Somatostatin -- metabolism KW - Gastric Mucosa -- drug effects KW - Somatostatin -- analogs & derivatives KW - Gastric Mucosa -- cytology KW - Gastric Mucosa -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76529663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Chief+cells+possess+somatostatin+receptors+regulated+by+secretagogues+acting+through+the+calcium+or+cAMP+pathway.&rft.au=Felley%2C+C+P%3BO%27Dorisio%2C+T+M%3BHowe%2C+B%3BCoy%2C+D+H%3BMantey%2C+S+A%3BPradhan%2C+T+K%3BSutliff%2C+V+E%3BJensen%2C+R+T&rft.aulast=Felley&rft.aufirst=C&rft.date=1994-05-01&rft.volume=266&rft.issue=5+Pt+1&rft.spage=G789&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet. AN - 76521325; 8200073 AB - Oxazepam has been the subject of recent toxicological and carcinogenesis studies because it is a commonly prescribed tranquilizer and has been shown to cause tumors in rodents. In this study, male and female B6C3F1 mice received 0, 125, 2500 or 5000 p.p.m. oxazepam in the diet for up to 2 years. Hepatocellular adenomas and carcinomas, as well as hepatoblastomas, which developed in these mice, were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 20 or more tumors from each exposure group and analyzed by oligonucleotide hybridization, single-stranded conformation polymorphism analysis and direct sequencing of PCR-amplified H-ras gene fragments for codon 61 mutations. Thirteen of 37 (35%) hepatocellular adenomas and carcinomas from the 125 p.p.m. exposure group had mutations in codon 61, while mutations were detected in only 2 of 25 or 8% of the liver tumors from the 2500 p.p.m. exposure group and none of the 22 tumors from the 5000 p.p.m. group. This compares to 63% of 126 historical control liver tumors and 55% of 20 liver tumors from unexposed B6C3F1 mice in this study. In addition, 12 hepatoblastomas from the two high dose groups were examined for H-ras mutations at codon 61, but none were detected. No tumor DNAs from any of the exposure groups tested had mutations in codons 12, 13 or 117 of the H-ras gene or codons 12 or 13 of the K-ras gene, the other known hotspots for ras activation in mouse liver tumors. These results, together with those from the National Toxicology Program study showing no evidence of cytotoxicity or genotoxicity by oxazepam, suggest that oxazepam preferentially promotes cells that have activating lesions other than ras. JF - Carcinogenesis AU - Devereux, T R AU - White, C M AU - Sills, R C AU - Bucher, J R AU - Maronpot, R R AU - Anderson, M W AD - Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 1083 EP - 1087 VL - 15 IS - 5 SN - 0143-3334, 0143-3334 KW - H-ras KW - Codon KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Mice KW - Diet KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Male KW - Female KW - Genes, ras KW - Liver Neoplasms, Experimental -- genetics KW - Oxazepam -- toxicity KW - Hepatoblastoma -- genetics KW - Adenoma -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Hepatoblastoma -- chemically induced KW - Adenoma -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76521325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Low+frequency+of+H-ras+mutations+in+hepatocellular+adenomas+and+carcinomas+and+in+hepatoblastomas+from+B6C3F1+mice+exposed+to+oxazepam+in+the+diet.&rft.au=Devereux%2C+T+R%3BWhite%2C+C+M%3BSills%2C+R+C%3BBucher%2C+J+R%3BMaronpot%2C+R+R%3BAnderson%2C+M+W&rft.aulast=Devereux&rft.aufirst=T&rft.date=1994-05-01&rft.volume=15&rft.issue=5&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-01 N1 - Date created - 1994-07-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of plasmid reporter gene expression in CHO cells by DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. AN - 76493938; 8185827 AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are two members of a family of carcinogenic heterocyclic amines (HAs) found in cooked meats that form DNA adducts after activation to N-acetoxy derivatives. The ability of IQ- and PhIP-DNA adducts to inhibit gene expression was investigated using a human growth hormone (hGH) reporter gene in a pUC12-based mammalian expression vector under the control of either the herpes simplex virus-1 thymidine kinase promoter or the human immunodeficiency virus-1 long terminal repeat. The plasmids were treated in vitro with 0, 5, 10, or 40 microM N-hydroxy-IQ or N-hydroxy-PhIP in the presence of a 10-fold molar excess of acetic anhydride to generate the N-acetoxy derivatives in situ. The adduct levels in the plasmids were quantitated by the 32P-postlabeling method. The adducted (and control) plasmids were each transfected into repair-deficient or -proficient Chinese hamster ovary cells, and expression of hGH was measured by immunoassay of growth hormone secreted into the cell medium. The results showed that IQ- and PhIP-DNA adducts inhibited gene expression in both plasmids and that the degree of inhibition of hGH production was proportional to the levels of IQ- and PhIP-DNA adducts. The degree of inhibition, however, was independent of the promoter, despite the differences in the strengths of the two promoters to drive hGH production. Repair capacity influenced the extent of inhibition of gene expression by HA adducts since, in general, fewer adducts were needed to inhibit reporter gene expression in repair-deficient cells than in repair-proficient cells. In both cell lines, DNA adducts of PhIP appeared to be more potent in inhibiting hGH expression than adducts of IQ. Whether alteration of gene expression by HA adducts plays a role in the carcinogenicity of these compounds deserves further study. JF - Molecular carcinogenesis AU - Fan, L AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0037. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 30 EP - 37 VL - 10 IS - 1 SN - 0899-1987, 0899-1987 KW - Imidazoles KW - 0 KW - Pyridines KW - Quinolines KW - 2-(phenylazoxy)-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 133763-19-6 KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Index Medicus KW - AIDS/HIV KW - Animals KW - DNA Repair KW - In Vitro Techniques KW - CHO Cells KW - Plasmids KW - Cricetinae KW - Gene Expression -- drug effects KW - Quinolines -- pharmacology KW - Imidazoles -- pharmacology KW - DNA Damage KW - Pyridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76493938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+plasmid+reporter+gene+expression+in+CHO+cells+by+DNA+adducts+of+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline+and+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine.&rft.au=Fan%2C+L%3BSnyderwine%2C+E+G&rft.aulast=Fan&rft.aufirst=L&rft.date=1994-05-01&rft.volume=10&rft.issue=1&rft.spage=30&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 - 1994-06-22 N1 - Date created - 1994-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid disrupts the Golgi apparatus and increases the cytosolic routing of specific protein toxins. AN - 76491520; 8188744 AB - All-trans retinoic acid can specifically increase receptor mediated intoxication of ricin A chain immunotoxins more than 10,000 times, whereas fluid phase endocytosis of ricin A chain alone or ricin A chain immunotoxins was not influenced by retinoic acid. The immunotoxin activation by retinoic acid does not require RNA or protein synthesis and is not a consequence of increased receptor binding of the immunotoxin. Vitamin D3 and thyroid hormone T3, that activate retinoic acid receptor (RAR) cognates, forming heterodimers with retinoid X receptor (RXR), do not affect the potency of immunotoxins. Among other retinoids tested, 13-cis retinoic acid, which binds neither RAR nor RXR, also increases the potency of the ricin A chain immunotoxin. Therefore, retinoic acid receptor activation does not appear to be necessary for immunotoxin activity. Retinoic acid potentiation of immunotoxins is prevented by brefeldin A (BFA) indicating that in the presence of retinoic acid, the immunotoxin is efficiently routed through the Golgi apparatus en route to the cytoplasm. Directly examining cells with a monoclonal antibody (Mab) against mannosidase II, a Golgi apparatus marker enzyme, demonstrates that the Golgi apparatus changes upon treatment with retinoic acid from a perinuclear network to a diffuse aggregate. Within 60 min after removal of retinoic acid the cell reassembles the perinuclear Golgi network indistinguishable with that of normal control cells. C6-NBD-ceramide, a vital stain for the Golgi apparatus, shows that retinoic acid prevents the fluorescent staining of the Golgi apparatus and eliminates fluorescence of C6-NBD-ceramide prestained Golgi apparatus. Electron microscopy of retinoic acid-treated cells demonstrates the specific absence of any normal looking Golgi apparatus and a perinuclear vacuolar structure very similar to that seen in monensin-treated cells. This vacuolization disappears after removal of the retinoic acid and a perinuclear Golgi stacking reappears. These results indicate that retinoic acid alters intracellular routing, probably through the Golgi apparatus, potentiating immunotoxin activity indepedently of new gene expression. Retinoic acid appears to be a new reagent to manipulate the Golgi apparatus and intracellular traffic. As retinoic acid and immunotoxins are both in clinical trials for cancer therapy, their combined activity in vivo would be interesting to examine. JF - The Journal of cell biology AU - Wu, Y N AU - Gadina, M AU - Tao-Cheng, J H AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 743 EP - 753 VL - 125 IS - 4 SN - 0021-9525, 0021-9525 KW - Antibodies, Monoclonal KW - 0 KW - Ceramides KW - Cyclopentanes KW - Fluorescent Dyes KW - Immunotoxins KW - Receptors, Retinoic Acid KW - Triiodothyronine KW - 06LU7C9H1V KW - Cholecalciferol KW - 1C6V77QF41 KW - Brefeldin A KW - 20350-15-6 KW - Tretinoin KW - 5688UTC01R KW - N-(7-(4-nitrobenzo-2-oxa-1,3-diazole))-6-aminocaproyl sphingosine KW - 86701-10-2 KW - Ricin KW - 9009-86-3 KW - Mannosidases KW - EC 3.2.1.- KW - mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase KW - EC 3.2.1.114 KW - 4-Chloro-7-nitrobenzofurazan KW - EQF2794IRE KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Animals KW - Triiodothyronine -- pharmacology KW - Humans KW - 4-Chloro-7-nitrobenzofurazan -- analogs & derivatives KW - Mannosidases -- immunology KW - Biological Transport -- drug effects KW - Rats KW - Cyclopentanes -- pharmacology KW - Tumor Cells, Cultured KW - Cholecalciferol -- pharmacology KW - Gene Expression Regulation KW - Cell Line KW - Tretinoin -- pharmacology KW - Cytosol -- metabolism KW - Ricin -- toxicity KW - Immunotoxins -- toxicity KW - Ricin -- metabolism KW - Golgi Apparatus -- ultrastructure KW - Golgi Apparatus -- drug effects KW - Tretinoin -- antagonists & inhibitors KW - Immunotoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76491520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retinoic+acid+disrupts+the+Golgi+apparatus+and+increases+the+cytosolic+routing+of+specific+protein+toxins.&rft.au=Wu%2C+Y+N%3BGadina%2C+M%3BTao-Cheng%2C+J+H%3BYoule%2C+R+J&rft.aulast=Wu&rft.aufirst=Y&rft.date=1994-05-01&rft.volume=125&rft.issue=4&rft.spage=743&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 - 1994-06-22 N1 - Date created - 1994-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1980 Dec;87(3 Pt 1):849-54 [7462326] Biochem J. 1981 Mar 15;194(3):821-7 [7306026] J Biol Chem. 1982 Feb 25;257(4):1598-601 [6120167] J Biol Chem. 1984 Aug 10;259(15):9359-64 [6746651] J Cell Biol. 1985 Jan;100(1):27-34 [3965473] Science. 1985 May 10;228(4700):745-7 [2581316] J Biol Response Mod. 1985 Jun;4(3):273-86 [4020386] Blood. 1986 Jun;67(6):1680-7 [3085747] J Biol Chem. 1987 Apr 5;262(10):4676-82 [3558362] J Biol Chem. 1987 Apr 25;262(12):5908-12 [3571242] J Immunol. 1987 Jun 15;138(12):4502-8 [3495593] J Biol Chem. 1988 Jan 25;263(3):1295-300 [3257214] Cell. 1989 Mar 10;56(5):801-13 [2647301] J Cell Biol. 1989 Jul;109(1):61-72 [2745557] Annu Rev Cell Biol. 1989;5:1-23 [2688704] Proc Natl Acad Sci U S A. 1990 Jan;87(1):308-12 [2104981] Nature. 1990 May 17;345(6272):224-9 [2159111] Exp Cell Res. 1991 Feb;192(2):389-95 [1899070] J Cell Biol. 1991 Feb;112(4):567-77 [1847146] J Cell Biol. 1991 Jun;113(5):1009-23 [1710224] J Biol Chem. 1991 Oct 5;266(28):18586-92 [1917980] Cell. 1991 Nov 1;67(3):449-51 [1934055] Cell. 1991 Nov 1;67(3):601-16 [1682055] J Cell Biol. 1991 Nov;115(4):971-81 [1955466] Nature. 1992 Jan 23;355(6358):359-61 [1309942] Blood. 1992 Feb 1;79(3):576-85 [1370636] Cell. 1992 Jan 24;68(2):397-406 [1310260] Nature. 1992 Jan 30;355(6359):441-6 [1310350] Nature. 1992 Jan 30;355(6359):446-9 [1310351] Annu Rev Nutr. 1992;12:443-71 [1323983] Exp Cell Res. 1992 Dec;203(2):321-8 [1459197] Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4 [8380496] J Biol Chem. 1993 May 15;268(14):10686-93 [8486718] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7293-7 [8394016] J Biol Chem. 1993 Nov 15;268(32):23986-90 [8226941] Biochemistry. 1973 Jul 31;12(16):3121-6 [4730499] Exp Cell Res. 1975 Sep;94(2):426-31 [1238268] J Biol Chem. 1976 Jul 10;251(13):3985-92 [932017] J Cell Biol. 1980 Dec;87(3 Pt 1):663-71 [7007394] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dexfenfluramine and serotonin neurotoxicity: further preclinical evidence that clinical caution is indicated. AN - 76489108; 7514223 AB - Dexfenfluramine, a drug used as an appetite suppressant in Europe, is currently under evaluation for approval in the United States. Studies in animals indicate that dexfenfluramine damages brain serotonin neurons, but have been challenged by some because of questions regarding their relevance to humans. The present studies were designed to address the three most salient questions regarding the applicability of preclinical dexfenfluramine neurotoxicity data to humans. Specifically, the present studies sought to determine: 1) whether dexfenfluramine's effects on brain serotonin neurons are transient and related to its therapeutic actions; 2) whether the p.o. route of administration affords protection against dexfenfluramine neurotoxicity; and 3) whether the mouse, an animal thought to best approximate the human with regard to dexfenfluramine metabolism, is sensitive to dexfenfluramine's neurotoxic action. Results from the present study indicate that monkeys continue to show large serotonergic deficits as long as 12 to 17 months after dexfenfluramine treatment, suggesting that dexfenfluramine's effects in nonhuman primates are persistent and unlikely to be related to its therapeutic actions. Furthermore, the present results indicate that the p.o. route of administration affords little or no protection against dexfenfluramine neurotoxicity. Finally, mice, like all other animals tested to date, were found to be susceptible to dexfenfluramine neurotoxicity. Taken together, these findings indicate that concern over possible dexfenfluramine neurotoxicity in humans is warranted, and that physicians and patients alike need to be aware of dexfenfluramine's toxic potential toward brain serotonin neurons. JF - The Journal of pharmacology and experimental therapeutics AU - McCann, U AU - Hatzidimitriou, G AU - Ridenour, A AU - Fischer, C AU - Yuan, J AU - Katz, J AU - Ricaurte, G AD - Section on Anxiety and Affective Disorders, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 792 EP - 798 VL - 269 IS - 2 SN - 0022-3565, 0022-3565 KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Index Medicus KW - Rats KW - Saimiri KW - Animals KW - Rats, Sprague-Dawley KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Hydroxyindoleacetic Acid -- metabolism KW - Mice KW - Species Specificity KW - Fenfluramine -- toxicity KW - Brain -- cytology KW - Brain -- drug effects KW - Brain -- metabolism KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76489108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Dexfenfluramine+and+serotonin+neurotoxicity%3A+further+preclinical+evidence+that+clinical+caution+is+indicated.&rft.au=McCann%2C+U%3BHatzidimitriou%2C+G%3BRidenour%2C+A%3BFischer%2C+C%3BYuan%2C+J%3BKatz%2C+J%3BRicaurte%2C+G&rft.aulast=McCann&rft.aufirst=U&rft.date=1994-05-01&rft.volume=269&rft.issue=2&rft.spage=792&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis of human leukemic HL-60 cells induced to differentiate by phorbol ester treatment. AN - 76485983; 8182936 AB - In the human leukemic HL-60 cell line, we have reported previously that monocytic/macrophage-like differentiation induced by TPA (12-O-tetradecanoylphorbol-13-acetate) was associated with a decreased sensitivity to various apoptosis-inducing stimuli (Solary, Bertrand, Pommier, Blood 1993; 81:1359-1368). In the present study, we studied further the effects of TPA alone on the induction of apoptosis in HL-60 cells. Based on morphology by electron microscopy, identification of internucleosomal DNA cleavage by gel electrophoresis and quantitation of DNA fragmentation by a filter binding assay, we observed that neither morphologic changes nor DNA damage were identified in TPA-differentiated HL-60 cells as long as they kept the adherent phenotype characteristic of this differentiation pathway. However, adherent TPA-treated HL-60 cells that secondarily detached from the flask demonstrated internucleosomal DNA fragmentation associated with morphologic changes characteristic of apoptosis. Similarly, HL-60 cells that never became adherent after TPA treatment underwent rapid apoptosis. Granulocytic differentiation by retinoic acid (RA) treatment also induced apoptosis although more slowly. Interestingly, in both TPA- and RA-treated cells, apoptotic bodies appeared to be phagocytosed by differentiated cells from the same lineage. Internucleosomal DNA fragmentation was also identified in HL-60 cells induced to differentiate by sodium butyrate and dimethylsulfoxide treatment, suggesting that apoptosis could be the common mode of death of terminally differentiated HL-60 cells. JF - Leukemia AU - Solary, E AU - Bertrand, R AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 792 EP - 797 VL - 8 IS - 5 SN - 0887-6924, 0887-6924 KW - DNA, Neoplasm KW - 0 KW - Nucleosomes KW - Tretinoin KW - 5688UTC01R KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tretinoin -- pharmacology KW - Tumor Cells, Cultured -- ultrastructure KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Nucleosomes -- metabolism KW - Granulocytes -- pathology KW - DNA Damage -- drug effects KW - DNA, Neoplasm -- drug effects KW - Macrophages -- pathology KW - Monocytes -- pathology KW - Tumor Cells, Cultured -- pathology KW - Microscopy, Electron KW - Cell Differentiation -- drug effects KW - Phagocytosis KW - DNA, Neoplasm -- metabolism KW - Cell Adhesion KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Leukemia, Promyelocytic, Acute -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76485983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Apoptosis+of+human+leukemic+HL-60+cells+induced+to+differentiate+by+phorbol+ester+treatment.&rft.au=Solary%2C+E%3BBertrand%2C+R%3BPommier%2C+Y&rft.aulast=Solary&rft.aufirst=E&rft.date=1994-05-01&rft.volume=8&rft.issue=5&rft.spage=792&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-10 N1 - Date created - 1994-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Production, purification and immunogenicity of a malaria transmission-blocking vaccine candidate: TBV25H expressed in yeast and purified using nickel-NTA agarose. AN - 76482415; 7764708 AB - We have constructed a second generation malaria transmission-blocking vaccine candidate based on Pfs25, the predominate surface protein of Plasmodium falciparum zygotes, to overcome potential production problems with the original construct. Four modifications were made: (1) addition of the last cysteine residue of the fourth epidermal growth factor like-domain of Pfs25; (2) mutagenesis of asparagine-linked glycosylation sites with glutamine rather than alanine; (3) addition of a six histidine tag at the carboxy-terminus for highly efficient purification of recombinant protein on nickel-NTA agarose; and (4) fermentation that combines continuous glucose fed-batch methodology with pH-controlled glucose addition and a terminal ethanol feed. The resulting product, TBV25H (Transmission-Blocking Vaccine based on Pfs25 with a Histidine tag), appears to be a more potent antigen and immunogen than the original construct, and the fermentation and post-fermentation processing methodology easily lend themselves to technology transfer to the ultimate users, newly industrialized countries. JF - Bio/technology (Nature Publishing Company) AU - Kaslow, D C AU - Shiloach, J AD - Molecular Vaccine Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 494 EP - 499 VL - 12 IS - 5 SN - 0733-222X, 0733-222X KW - Antibodies, Protozoan KW - 0 KW - Malaria Vaccines KW - Pfs25 protein, Plasmodium falciparum KW - Protozoan Proteins KW - Recombinant Proteins KW - Vaccines, Synthetic KW - transmission-Blocking Vaccine based on Pfs25 KW - Biotechnology KW - Animals KW - Genetic Vectors KW - Antibodies, Protozoan -- blood KW - Molecular Sequence Data KW - Gene Expression KW - Mice KW - Amino Acid Sequence KW - Plasmids KW - Malaria, Falciparum -- prevention & control KW - Malaria Vaccines -- isolation & purification KW - Protozoan Proteins -- genetics KW - Malaria Vaccines -- biosynthesis KW - Vaccines, Synthetic -- isolation & purification KW - Protozoan Proteins -- chemistry KW - Saccharomyces cerevisiae -- genetics KW - Vaccines, Synthetic -- immunology KW - Malaria Vaccines -- immunology KW - Malaria, Falciparum -- transmission KW - Plasmodium falciparum -- immunology KW - Vaccines, Synthetic -- biosynthesis KW - Protozoan Proteins -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76482415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bio%2Ftechnology+%28Nature+Publishing+Company%29&rft.atitle=Production%2C+purification+and+immunogenicity+of+a+malaria+transmission-blocking+vaccine+candidate%3A+TBV25H+expressed+in+yeast+and+purified+using+nickel-NTA+agarose.&rft.au=Kaslow%2C+D+C%3BShiloach%2C+J&rft.aulast=Kaslow&rft.aufirst=D&rft.date=1994-05-01&rft.volume=12&rft.issue=5&rft.spage=494&rft.isbn=&rft.btitle=&rft.title=Bio%2Ftechnology+%28Nature+Publishing+Company%29&rft.issn=0733222X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. AN - 76479170; 8182131 AB - Glycogen storage disease (GSD) type 1a is an autosomal recessive inborn error of metabolism caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Southern blot hybridization analysis using a panel of human-hamster hybrids showed that human G6Pase is a single-copy gene located on chromosome 17. To correlate specific defects with clinical manifestations of this disorder, we identified mutations in the G6Pase gene of GSD type 1a patients. In the G6Pase gene of a compound heterozygous patient (LLP), two mutations in exon 2 of one allele and exon 5 of the other allele were identified. The exon 2 mutation converts an arginine at codon 83 to a cysteine (R83C). This mutation, previously identified by us in another GSD type 1a patient, was shown to have no detectable phosphohydrolase activity. The exon 5 mutation in the G6Pase gene of LLP converts a glutamine codon at 347 to a stop (Q347SP). This Q347SP mutation was also detected in all exon 5 subclones (five for each patient) of two homozygous patients, KB and CB, siblings of the same parents. The predicted Q347SP mutant G6Pase is a truncated protein of 346 amino acids, 11 amino acids shorter than the wild type G6Pase of 357 residues. Site-directed mutagenesis and transient expression assays demonstrated that G6Pase-Q347SP was devoid of G6Pase activity. G6Pase is an endoplasmic reticulum (ER) membrane-associated protein containing an ER retention signal, two lysines (KK), located at residues 354 and 355. We showed that the G6Pase-K355SP mutant containing a lysine-355 to stop codon mutation is enzymatically active. Our data demonstrate that the ER protein retention signal in human G6Pase is not essential for activity. However, residues 347-354 may be required for optimal G6Pase catalysis. JF - The Journal of clinical investigation AU - Lei, K J AU - Pan, C J AU - Shelly, L L AU - Liu, J L AU - Chou, J Y AD - Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 1994 EP - 1999 VL - 93 IS - 5 SN - 0021-9738, 0021-9738 KW - Glucose-6-Phosphatase KW - EC 3.1.3.9 KW - Abridged Index Medicus KW - Index Medicus KW - Pedigree KW - Exons -- genetics KW - Endoplasmic Reticulum -- metabolism KW - Chromosomes, Human, Pair 17 KW - Base Sequence KW - Humans KW - Heterozygote KW - Molecular Sequence Data KW - Hybrid Cells KW - Male KW - Female KW - Sequence Deletion KW - Glycogen Storage Disease Type I -- genetics KW - Glycogen Storage Disease Type I -- enzymology KW - Mutation KW - Glucose-6-Phosphatase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76479170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Identification+of+mutations+in+the+gene+for+glucose-6-phosphatase%2C+the+enzyme+deficient+in+glycogen+storage+disease+type+1a.&rft.au=Lei%2C+K+J%3BPan%2C+C+J%3BShelly%2C+L+L%3BLiu%2C+J+L%3BChou%2C+J+Y&rft.aulast=Lei&rft.aufirst=K&rft.date=1994-05-01&rft.volume=93&rft.issue=5&rft.spage=1994&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1984 Jan 19;310(3):171-5 [6581385] J Biol Chem. 1980 Nov 10;255(21):10396-406 [6253473] Hum Genet. 1988 Feb;78(2):151-5 [3338800] Clin Chim Acta. 1988 Apr 15;173(2):183-91 [2837351] Adv Enzymol Relat Areas Mol Biol. 1989;62:93-117 [2543189] Cell. 1989 Aug 25;58(4):707-18 [2527615] EMBO J. 1990 Oct;9(10):3153-62 [2120038] Mutat Res. 1993 Jan;285(1):61-7 [7678134] Somat Cell Mol Genet. 1993 May;19(3):275-83 [8332935] Science. 1993 Oct 22;262(5133):580-3 [8211187] J Biol Chem. 1952 Dec;199(2):661-7 [13022673] Biochemistry. 1977 Oct 18;16(21):4743-51 [911786] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Cell. 1987 Mar 13;48(5):899-907 [3545499] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cholera toxin and pertussis toxin on prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinase production by human monocytes. AN - 76478376; 8179336 AB - Activation of human monocytes induces the production of matrix metalloproteinases (MMPs) through a prostaglandin E2 (PGE2)-cAMP-dependent pathway. Since G-proteins have been documented to modulate adenylyl cyclase, we examined the effect of G-protein ADP-ribosylating agents, cholera toxin (CT) and pertussis toxin (PT), on the signal transduction pathway that culminates in the production of monocyte MMPs. Although CT elevated cAMP levels in both unstimulated and concanavalin A (Con A)-stimulated monocytes, it enhanced the production of prostaglandin H synthase-2 (PGH synthase-2, PGHS-2) protein, prostaglandins, interstitial collagenase, and 92-kDa type IV collagenase/gelatinase only in Con A-stimulated monocytes. Additionally, the indomethacin-mediated suppression of Con A-induced monocyte interstitial collagenase and 92-kDa type IV collagenase/gelatinase production could be reversed by CT. In contrast to the actions of CT, PT treatment suppressed the levels of cAMP, PGHS-2, PGE2, interstitial and 92-kDa type IV collagenase/gelatinase in Con A-stimulated monocytes. The regulation of MMP production by these toxins appears to be mediated primarily through their effect on adenylyl cyclase since the release of arachidonic acid was relatively unaffected by these agents. These findings provide evidence that G-proteins may be involved in either the enhancement or suppression of the eicosanoid-cAMP-dependent signal transduction pathway that results in the production of monocyte MMPs. JF - Archives of biochemistry and biophysics AU - Corcoran, M L AU - Stetler-Stevenson, W G AU - DeWitt, D L AU - Wahl, L M AD - Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05/01/ PY - 1994 DA - 1994 May 01 SP - 481 EP - 488 VL - 310 IS - 2 SN - 0003-9861, 0003-9861 KW - Adenylate Cyclase Toxin KW - 0 KW - Isoenzymes KW - Virulence Factors, Bordetella KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Collagenases KW - EC 3.4.24.- KW - Gelatinases KW - Metalloendopeptidases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Isoenzymes -- blood KW - Cyclic AMP -- blood KW - Kinetics KW - Isoenzymes -- biosynthesis KW - Humans KW - Gelatinases -- blood KW - Gelatinases -- isolation & purification KW - Cell Separation KW - Gelatinases -- biosynthesis KW - Monocytes -- enzymology KW - Cholera Toxin -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- blood KW - Metalloendopeptidases -- isolation & purification KW - Virulence Factors, Bordetella -- pharmacology KW - Collagenases -- isolation & purification KW - Dinoprostone -- blood KW - Metalloendopeptidases -- blood KW - Monocytes -- metabolism KW - Collagenases -- biosynthesis KW - Monocytes -- drug effects KW - Metalloendopeptidases -- biosynthesis KW - Collagenases -- blood KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76478376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+cholera+toxin+and+pertussis+toxin+on+prostaglandin+H+synthase-2%2C+prostaglandin+E2%2C+and+matrix+metalloproteinase+production+by+human+monocytes.&rft.au=Corcoran%2C+M+L%3BStetler-Stevenson%2C+W+G%3BDeWitt%2C+D+L%3BWahl%2C+L+M&rft.aulast=Corcoran&rft.aufirst=M&rft.date=1994-05-01&rft.volume=310&rft.issue=2&rft.spage=481&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 - 1994-06-08 N1 - Date created - 1994-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in the localization of F-actin, fibronectin, and thrombospondin occur prior to neoplastic transformation in rat tracheal epithelial cells. AN - 76477125; 8174636 AB - Structural glycoproteins and cytoskeletal proteins play a major role in the regulation of cellular organization and function. Changes in the structure and function of these proteins are involved in the cascade of events which lead to neoplastic transformation. We evaluated RNA levels, protein localization, and organization of selected proteins in an in vitro model system of respiratory carcinogenesis to examine alterations in cell architecture. Localization of fibronectin (Fn), thrombospondin (Tsp), and F-actin was examined in (1) primary rat tracheal epithelial (RTE) cells; (2) spontaneously immortalized nonneoplastic cells (SPOC-1); and (3) neoplastic cells (EGV5T) derived from tumors arising following transplantation of an N-methyl-N'-nitro-N-nitrosoguanidine-transformed RTE cell line into nude mice. Proteins were stained with fluorescein-labeled antibodies or phalloidin compound and analysis was performed with a confocal laser scanning microscope. Primary RTE cells display organized F-actin stress fibers, perinuclear Fn and Tsp, and pericellular Fn in fibrillar arrays. In larger colonies, Tsp occurs between cells and occasionally in fibrillar arrays. SPOC-1 cells, unlike primary RTE cells and neoplastic EGV5T cells, seldom form junctions and exhibit few cell surface extensions. F-actin stress fibers are reduced in these immortalized cells. F-actin in SPOC-1 cells occurs in the perinuclear region, scattered diffusely throughout the cell and in punctate adhesions. Fn and Tsp are localized to the perinuclear region with Fn staining more intensely. EGV5T neoplastic cells also display a dramatic loss of stress fibers and F-actin is concentrated mainly near the cell periphery. Perinuclear staining of Fn and Tsp occurs in some cells within the colony. Levels of Tsp RNA and Fn RNA and protein are significantly reduced in both cell lines compared to primary RTE cells. We conclude that structural protein disruptions are early events in the transformation of these respiratory epithelial cells. JF - Experimental cell research AU - Carter, C A AU - Doherty, M M AU - Rusnak, D W AU - Nettesheim, P AU - Ferriola, P C AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 141 EP - 150 VL - 212 IS - 1 SN - 0014-4827, 0014-4827 KW - Actins KW - 0 KW - Fibronectins KW - Membrane Glycoproteins KW - RNA, Messenger KW - Thrombospondins KW - Index Medicus KW - Rats KW - Animals KW - Epithelial Cells KW - Cells, Cultured KW - Cell Compartmentation KW - RNA, Messenger -- analysis KW - Fluorescent Antibody Technique KW - Cell Division KW - Actins -- isolation & purification KW - Fibronectins -- isolation & purification KW - Fibronectins -- genetics KW - Trachea -- cytology KW - Cell Transformation, Neoplastic KW - Membrane Glycoproteins -- isolation & purification KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76477125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Alterations+in+the+localization+of+F-actin%2C+fibronectin%2C+and+thrombospondin+occur+prior+to+neoplastic+transformation+in+rat+tracheal+epithelial+cells.&rft.au=Carter%2C+C+A%3BDoherty%2C+M+M%3BRusnak%2C+D+W%3BNettesheim%2C+P%3BFerriola%2C+P+C&rft.aulast=Carter&rft.aufirst=C&rft.date=1994-05-01&rft.volume=212&rft.issue=1&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Exp Cell Res 1994 Sep;214(1):437-8 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of lead acetate on nitrite production by murine brain endothelial cell cultures. AN - 76476690; 7514316 AB - One of the mechanisms by which lead may cause a perturbation in the nervous system is the alteration of endothelial cell function. This study investigated the effect of lead acetate on constitutive and cytokine-induced production of nitrite, a marker of nitric oxide, in brain microvascular endothelial cells. Nitric oxide synthase may be a target for lead and changes in its function can result in a cascade of physiological effects seen in vivo. Concentrations of 10, 100, and 1000 nM lead acetate, in the presence or absence of 100 ng lipopolysaccharide/ml, 400 U interferon-gamma/ml and 100 U tumor necrosis factor-alpha/ml, were added to confluent cultures of brain microvascular endothelial cells. Concentrations of lead acetate as low as 10 nM decreased constitutive levels of nitrite by 50% without inhibiting the inducible levels. Addition of 1 microM lead acetate had no effect on [3H]L-leucine incorporation, lactate dehydrogenase release, or cellular morphology, indicating that the effect was selective. Increasing the concentration of extracellular calcium to 2 mM abolished the inhibitory effect of lead acetate on the constitutive production of nitrite. These studies suggest that low concentrations of lead are capable of inhibiting nitrite produced by the calcium-dependent constitutive form of nitric oxide synthase while the calcium-independent, inducible form of nitric oxide synthase is not affected. These data provide another testable hypothesis for the as yet undetermined mechanisms of lead neurotoxicity. JF - Toxicology and applied pharmacology AU - Blazka, M E AU - Harry, G J AU - Luster, M I AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 191 EP - 194 VL - 126 IS - 1 SN - 0041-008X, 0041-008X KW - Lipopolysaccharides KW - 0 KW - Nitrites KW - Organometallic Compounds KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - Calcium Chloride KW - M4I0D6VV5M KW - lead acetate KW - RX077P88RY KW - Index Medicus KW - Calcium Chloride -- metabolism KW - Protein Biosynthesis KW - Animals KW - Amino Acid Oxidoreductases -- drug effects KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Lipopolysaccharides -- pharmacology KW - L-Lactate Dehydrogenase -- drug effects KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- drug effects KW - Endothelium, Vascular -- cytology KW - Nitrites -- metabolism KW - Brain -- blood supply KW - Organometallic Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76476690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Effect+of+lead+acetate+on+nitrite+production+by+murine+brain+endothelial+cell+cultures.&rft.au=Blazka%2C+M+E%3BHarry%2C+G+J%3BLuster%2C+M+I&rft.aulast=Blazka&rft.aufirst=M&rft.date=1994-05-01&rft.volume=126&rft.issue=1&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-10 N1 - Date created - 1994-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Somatostatin analogues suppress the inflammatory reaction in vivo. AN - 76474896; 7514191 AB - Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of endocrine and neural cells. Recent studies have suggested that Sms has significant immunomodulatory properties. In this study, we examine the effects of two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014 (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject to carrageenin-induced aseptic inflammation, at doses of 2-10 micrograms/rat, given either systemically or locally. Animals were killed 7 h after the induction of the inflammation, and the inflammatory exudates were aspirated and quantitated in terms of volume and leukocyte concentration. Sms analogues, administered via either route, significantly reduced the volume and the leukocyte concentration of the exudate in a time- and dose-dependent fashion. In corroboration of these, immunohistochemical evaluation of the levels of local inflammatory mediators, such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin-releasing hormone, was inhibited significantly by Sms analogue treatment. These findings suggest that Sms analogues have significant antiinflammatory effects in vivo, associated with suppression of proinflammatory cytokines and neuropeptides. Furthermore, these data suggest that Sms agonists may be useful in the control of inflammatory reaction. JF - The Journal of clinical investigation AU - Karalis, K AU - Mastorakos, G AU - Chrousos, G P AU - Tolis, G AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 2000 EP - 2006 VL - 93 IS - 5 SN - 0021-9738, 0021-9738 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Peptides, Cyclic KW - Tumor Necrosis Factor-alpha KW - lanreotide KW - 0G3DE8943Y KW - Substance P KW - 33507-63-0 KW - Somatostatin KW - 51110-01-1 KW - Carrageenan KW - 9000-07-1 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Octreotide KW - RWM8CCW8GP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Substance P -- analysis KW - Carrageenan -- pharmacology KW - Animals KW - Somatostatin -- analysis KW - Tumor Necrosis Factor-alpha -- analysis KW - Immunohistochemistry KW - Male KW - Corticotropin-Releasing Hormone -- analysis KW - Granuloma -- chemically induced KW - Octreotide -- pharmacology KW - Inflammation -- chemically induced KW - Inflammation -- metabolism KW - Granuloma -- metabolism KW - Peptides, Cyclic -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76474896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Somatostatin+analogues+suppress+the+inflammatory+reaction+in+vivo.&rft.au=Karalis%2C+K%3BMastorakos%2C+G%3BChrousos%2C+G+P%3BTolis%2C+G&rft.aulast=Karalis&rft.aufirst=K&rft.date=1994-05-01&rft.volume=93&rft.issue=5&rft.spage=2000&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anasth Intensivther Notfallmed. 1985 Aug;20(4):165-70 [2866726] J Immunol. 1985 Dec;135(6):3972-7 [2999236] Neurol Clin. 1986 Nov;4(4):833-52 [2432390] Ric Clin Lab. 1987 Apr-Jun;17(2):155-62 [2888182] Science. 1987 Oct 23;238(4826):522-4 [2821621] J Steroid Biochem. 1988 Jun;29(6):591-8 [2838686] Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459-63 [2845968] J Biol Chem. 1989 Jan 15;264(2):949-52 [2562957] Annu Rev Med. 1989;40:341-52 [2471450] Lymphokine Res. 1990 Summer;9(2):137-45 [1971032] Endocrinology. 1990 Jun;126(6):2876-81 [2161738] Cancer Res. 1990 Jul 15;50(14):4360-5 [1973071] J Clin Endocrinol Metab. 1990 Aug;71(2):391-7 [2199479] Neurosci Res. 1990 Jul;8(3):179-88 [1977111] Science. 1991 Oct 18;254(5030):421-3 [1925600] Arthritis Rheum. 1992 Apr;35(4):369-75 [1373619] Horm Res. 1991;36(1-2):86-7 [1814807] Ann Intern Med. 1993 Dec 15;119(12):1198-208 [8239251] J Clin Endocrinol Metab. 1993 Dec;77(6):1690-4 [8263159] Nat New Biol. 1972 Jul 26;238(82):104-6 [4505422] Recent Prog Horm Res. 1975;31:365-97 [1105719] Experientia. 1978 Jul 15;34(7):860-2 [307497] Metabolism. 1978 Sep;27(9 Suppl 1):1381-6 [683006] Nature. 1980 Apr 10;284(5756):515-21 [6154244] Diabetes. 1981 Feb;30(2):127-31 [6110596] Am J Clin Pathol. 1981 May;75(5):734-8 [6165237] J Histochem Cytochem. 1981 Apr;29(4):577-80 [6166661] Proc Natl Acad Sci U S A. 1981 Jul;78(7):4644-7 [6170069] Acta Physiol Scand. 1981 Oct;113(2):155-9 [6172003] Annu Rev Pharmacol Toxicol. 1982;22:491-515 [6123297] Life Sci. 1982 Sep 13;31(11):1133-40 [6128648] N Engl J Med. 1983 Dec 15;309(24):1495-501 [6139753] J Clin Endocrinol Metab. 1984 Dec;59(6):1103-8 [6092407] J Immunol. 1985 Aug;135(2 Suppl):783s-786s [2409166] J Immunol. 1985 Aug;135(2 Suppl):802s-805s [2409168] Clin Immunol Immunopathol. 1986 Nov;41(2):290-4 [2876793] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Investigation of methacrylonitrile metabolism and the metabolic basis for the differences in its toxicity in rats and mice. AN - 76474142; 8182524 AB - Methacrylonitrile (MAN) is an industrial chemical used to manufacture plastics and elastomers. The reported p.o. LD50 of MAN is 200 to 230 mg/kg in rats and 17 mg/kg in mice. Present investigations were undertaken to further characterize MAN metabolism and to study the metabolic basis for the species differences in its toxicity. Male F344 rats and B6C3F1 mice received a single gavage dose of 11.5 or 1.15 mg of [14C]MAN/kg and were placed in glass metabolism cages. Elimination of MAN in rats occurred primarily in expired air as unchanged MAN, acetone and CO2. Three major urinary metabolites of MAN were identified as N-acetyl-S-(2-cyanopropyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine and a deoxyuridine isomer. Quantitatively, rats and mice excreted ca. 7 and 49% of the high MAN dose in urine as N-acetyl-S-(2-hydroxypropyl)-L-cysteine, respectively. In addition, rats eliminated significantly more MAN-derived CO2 and deoxyuridine than mice. MAN elimination was almost complete within 24 hr after dosing and the tissue concentrations of MAN-derived radioactivity were, with the exception of the urinary bladder, consistently higher in rats than in mice. In conclusion, a quantitative difference between rats and mice in forming the epoxide intermediate, higher efficiency of mice to conjugate this intermediate with glutathione and greater capacity of rats to degrade it to acetone and CO2 are thought to contribute to the higher sensitivity of mice to MAN acute toxicity. JF - The Journal of pharmacology and experimental therapeutics AU - Ghanayem, B I AU - Sanchez, I M AU - Burka, L T AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 581 EP - 588 VL - 269 IS - 2 SN - 0022-3565, 0022-3565 KW - Methacrylates KW - 0 KW - Nitriles KW - methacrylonitrile KW - 04S4K38612 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mice KW - Spectrometry, Mass, Fast Atom Bombardment KW - Male KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Nitriles -- urine KW - Methacrylates -- toxicity KW - Nitriles -- metabolism KW - Methacrylates -- metabolism KW - Nitriles -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76474142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Investigation+of+methacrylonitrile+metabolism+and+the+metabolic+basis+for+the+differences+in+its+toxicity+in+rats+and+mice.&rft.au=Ghanayem%2C+B+I%3BSanchez%2C+I+M%3BBurka%2C+L+T&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1994-05-01&rft.volume=269&rft.issue=2&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-16 N1 - Date created - 1994-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Orally administered clarithromycin for the treatment of systemic Mycobacterium avium complex infection in children with acquired immunodeficiency syndrome. AN - 76470889; 8176574 AB - To determine the safety, tolerance, pharmacokinetics, and antimycobacterial activity of orally administered clarithromycin in children with acquired immunodeficiency syndrome and disseminated Mycobacterium avium complex (MAC) infection. Phase I study with a 10-day pharmacokinetic phase followed by a 12-week continuation therapy phase. Twenty-five patients with a median age of 8.3 years were enrolled. Ten were receiving zidovudine and 13 were receiving didanosine at the time of enrollment. Clarithromycin suspension was administered to each patient at one of three dose levels: 3.75, 7.5, and 15 mg/kg per dose every 12 hours. Clarithromycin and antiretroviral pharmacokinetics were measured during single-drug and concurrent-drug administration. Clinical and laboratory monitoring was performed biweekly. Clarithromycin was well tolerated at all dose levels. Plasma clarithromycin concentrations increased proportionately with increasing doses, and significant pharmacokinetic interactions were not observed during concurrent administration with zidovudine or didanosine. Decreases in mycobacterial load in blood were observed only at the highest clarithromycin dose level. Decreased susceptibility to clarithromycin developed rapidly (within 12 to 16 weeks) in the majority of MAC strains isolated from study patients. JF - The Journal of pediatrics AU - Husson, R N AU - Ross, L A AU - Sandelli, S AU - Inderlied, C B AU - Venzon, D AU - Lewis, L L AU - Woods, L AU - Conville, P S AU - Witebsky, F G AU - Pizzo, P A AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 807 EP - 814 VL - 124 IS - 5 Pt 1 SN - 0022-3476, 0022-3476 KW - Clarithromycin KW - H1250JIK0A KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Administration, Oral KW - Humans KW - Child KW - Adolescent KW - Microbial Sensitivity Tests KW - Recurrence KW - Male KW - Female KW - Child, Preschool KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Mycobacterium avium Complex -- isolation & purification KW - Mycobacterium avium Complex -- drug effects KW - Mycobacterium avium-intracellulare Infection -- drug therapy KW - Clarithromycin -- pharmacokinetics KW - AIDS-Related Opportunistic Infections -- microbiology KW - Mycobacterium avium-intracellulare Infection -- microbiology KW - Clarithromycin -- therapeutic use KW - Clarithromycin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76470889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics&rft.atitle=Orally+administered+clarithromycin+for+the+treatment+of+systemic+Mycobacterium+avium+complex+infection+in+children+with+acquired+immunodeficiency+syndrome.&rft.au=Husson%2C+R+N%3BRoss%2C+L+A%3BSandelli%2C+S%3BInderlied%2C+C+B%3BVenzon%2C+D%3BLewis%2C+L+L%3BWoods%2C+L%3BConville%2C+P+S%3BWitebsky%2C+F+G%3BPizzo%2C+P+A&rft.aulast=Husson&rft.aufirst=R&rft.date=1994-05-01&rft.volume=124&rft.issue=5+Pt+1&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-03 N1 - Date created - 1994-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The basis of molecular strategies for treating coronary restenosis after angioplasty. AN - 76466489; 8176084 AB - Excessive smooth muscle cell proliferation significantly contributes to restenosis, which occurs in 25% to 50% of patients within 6 months of coronary angioplasty. Because successful treatment will probably depend on our acquiring a comprehensive knowledge of the molecular and cellular mechanisms involved, this report reviews 1) information relevant to the molecular and cellular mechanisms responsible for the smooth muscle cell(s) response to vascular injury, and 2) several molecular-based therapeutic strategies currently being explored as possible approaches to the control of restenosis, including recombinant DNA technology to target delivery of cytotoxic molecules to proliferating smooth muscle cell(s), antisense strategies to inhibit expression of gene products necessary for cell proliferation and gene therapy. JF - Journal of the American College of Cardiology AU - Epstein, S E AU - Speir, E AU - Unger, E F AU - Guzman, R J AU - Finkel, T AD - Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 1278 EP - 1288 VL - 23 IS - 6 SN - 0735-1097, 0735-1097 KW - Antisense Elements (Genetics) KW - 0 KW - Immunotoxins KW - Abridged Index Medicus KW - Index Medicus KW - Signal Transduction -- physiology KW - Muscle, Smooth, Vascular -- physiopathology KW - Humans KW - Cell Cycle -- physiology KW - Immunotoxins -- therapeutic use KW - Genetic Therapy KW - Recurrence KW - Coronary Disease -- etiology KW - Coronary Disease -- prevention & control KW - Coronary Disease -- physiopathology KW - Coronary Disease -- genetics KW - Coronary Disease -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76466489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.atitle=The+basis+of+molecular+strategies+for+treating+coronary+restenosis+after+angioplasty.&rft.au=Epstein%2C+S+E%3BSpeir%2C+E%3BUnger%2C+E+F%3BGuzman%2C+R+J%3BFinkel%2C+T&rft.aulast=Epstein&rft.aufirst=S&rft.date=1994-05-01&rft.volume=23&rft.issue=6&rft.spage=1278&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-06 N1 - Date created - 1994-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of interferon-alpha 2b in combination with interleukin-2 in patients with human immunodeficiency virus infection. AN - 76457722; 7909550 AB - Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4+ T cells/mm3. A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4+ T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 x 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity. JF - The Journal of infectious diseases AU - Schnittman, S M AU - Vogel, S AU - Baseler, M AU - Lane, H C AU - Davey, R T AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 981 EP - 989 VL - 169 IS - 5 SN - 0022-1899, 0022-1899 KW - Interferon-alpha KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - CD4-Positive T-Lymphocytes KW - Leukocyte Count KW - Drug Therapy, Combination KW - Recombinant Proteins -- toxicity KW - Adult KW - Middle Aged KW - Adolescent KW - Sarcoma, Kaposi -- therapy KW - Female KW - Male KW - Recombinant Proteins -- therapeutic use KW - Sarcoma, Kaposi -- pathology KW - Interleukin-2 -- adverse effects KW - Interferon-alpha -- therapeutic use KW - Interferon-alpha -- adverse effects KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- therapy KW - HIV Infections -- immunology KW - HIV Infections -- pathology KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76457722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+phase+I+study+of+interferon-alpha+2b+in+combination+with+interleukin-2+in+patients+with+human+immunodeficiency+virus+infection.&rft.au=Schnittman%2C+S+M%3BVogel%2C+S%3BBaseler%2C+M%3BLane%2C+H+C%3BDavey%2C+R+T&rft.aulast=Schnittman&rft.aufirst=S&rft.date=1994-05-01&rft.volume=169&rft.issue=5&rft.spage=981&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidation of proteins in neonatal lungs. AN - 76457522; 8165075 AB - To develop a method capable of quantifying the oxidative modification of proteins in pulmonary fluid obtained during routine suctioning of neonates receiving ventilation, thus providing an integrated assessment of antioxidant defenses. Consecutive sample of neonates receiving ventilation. Neonatal intensive care unit. Twenty-six neonates receiving ventilation with a gestational age of 24 to 42 weeks, from whom 246 samples were collected and analyzed. The carbonyl content in the lavage samples was measured by reaction with 2,4-dinitrophenylhydrazine followed by high-pressure liquid chromatography. Oxidation of proteins caused introduction of carbonyl groups into the side chains of the protein, providing a convenient and relatively specific marker of oxidative damage. On the first day of life, the initial protein-bound carbonyl for each neonate was usually low and consequently was not significantly related to birth weight, gestational age, or initial ventilatory requirements. Examination of the changes in pulmonary protein carbonyl in the first days of life revealed correlations of interest. In the first day of life, four neonates whose average inspired oxygen were 40% showed an average increase in carbonyl of 51% (P 3 days was correlated with elevated carbonyl in those first 3 days. The carbonyl content averaged over the first 3 days was 0.13 +/- 0.02 mol carbonyl/mol protein for the eight neonates receiving ventilation < 72 hours, whereas the nine needing longer ventilation had a carbonyl content of 0.28 +/- 0.03 mol carbonyl/mol protein (P < .05). Seven neonates were treated with dexamethasone because of ventilator dependence at 14 days of age. In these neonates, treatment was associated with a 50% reduction in carbonyl content within 48 hours (P < .02). Oxidative damage to pulmonary proteins can be quantitated in samples obtained during routine suctioning of neonates receiving ventilation. The amount of oxidatively modified protein may provide a quantitative assessment of oxygen toxicity and of pulmonary antioxidant defenses. JF - Pediatrics AU - Gladstone, I M AU - Levine, R L AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 764 EP - 768 VL - 93 IS - 5 SN - 0031-4005, 0031-4005 KW - Ketones KW - 0 KW - Phenylhydrazines KW - Proteins KW - 2,4-dinitrophenylhydrazine KW - 1N39KD7QPJ KW - Dexamethasone KW - 7S5I7G3JQL KW - Oxygen KW - S88TT14065 KW - Abridged Index Medicus KW - Index Medicus KW - Lung Diseases -- drug therapy KW - Dexamethasone -- therapeutic use KW - Dexamethasone -- pharmacology KW - Humans KW - Infant, Newborn KW - Lung Diseases -- metabolism KW - Respiration, Artificial KW - Oxygen -- adverse effects KW - Chromatography, High Pressure Liquid KW - Oxidation-Reduction KW - Respiratory Distress Syndrome, Newborn -- metabolism KW - Ketones -- analysis KW - Chronic Disease KW - Female KW - Male KW - Infant, Newborn, Diseases -- metabolism KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Proteins -- isolation & purification KW - Lung -- chemistry KW - Lung -- metabolism KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76457522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Oxidation+of+proteins+in+neonatal+lungs.&rft.au=Gladstone%2C+I+M%3BLevine%2C+R+L&rft.aulast=Gladstone&rft.aufirst=I&rft.date=1994-05-01&rft.volume=93&rft.issue=5&rft.spage=764&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-26 N1 - Date created - 1994-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid enhances adhesiveness, laminin and integrin beta 1 synthesis, and retinoic acid receptor expression in F9 teratocarcinoma cells. AN - 76456858; 7512975 AB - The teratocarcinoma-derived F9 cells respond to retinoic acid (RA) and RA plus dibutyrylcyclic adenosine monophosphate (dcAMP) by differentiating into endoderm cells, which elaborate a laminin and type IV collagen-rich matrix. We found that the induction of differentiation is accompanied by a small but consistent increase in cell adhesiveness to a variety of substrates, including laminin. Therefore we investigated biochemical mechanisms involved in this phenomenon. Endoglycosidase treatment showed that laminin contains complex and hybrid oligosaccharide structures. RA enhanced general biosynthesis of laminin without a specific increase in galactose incorporation: this sugar was mainly in polylactosamine structures in the A chain of laminin and as terminal galactose alpha 1,3 galactose in the B chain. Laminin receptor analysis showed that RA decreased laminin binding protein-37 (LBP-37) but increased the amount of beta 1 integrin, suggesting the involvement of beta 1 integrin in the attachment process. Northern blot analysis showed increased expression of retinoid receptors within hours of RA exposure. These studies demonstrate that RA increases cell to substrate interactions by increasing the biosynthesis of laminin and beta 1 integrin. These effects are most likely subsequent to the RA-induced biosynthesis of the retinoid receptors. JF - Journal of cellular physiology AU - Ross, S A AU - Ahrens, R A AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 263 EP - 273 VL - 159 IS - 2 SN - 0021-9541, 0021-9541 KW - Integrins KW - 0 KW - Laminin KW - Lectins KW - Oligosaccharides KW - Receptors, Laminin KW - Receptors, Retinoic Acid KW - Tretinoin KW - 5688UTC01R KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Tumor Cells, Cultured KW - Galactose -- metabolism KW - Receptors, Laminin -- metabolism KW - Cell Differentiation KW - Cell Adhesion -- drug effects KW - Staining and Labeling KW - Oligosaccharides -- chemistry KW - Receptors, Retinoic Acid -- metabolism KW - Tretinoin -- pharmacology KW - Laminin -- chemistry KW - Laminin -- biosynthesis KW - Teratocarcinoma -- metabolism KW - Teratocarcinoma -- pathology KW - Integrins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76456858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Retinoic+acid+enhances+adhesiveness%2C+laminin+and+integrin+beta+1+synthesis%2C+and+retinoic+acid+receptor+expression+in+F9+teratocarcinoma+cells.&rft.au=Ross%2C+S+A%3BAhrens%2C+R+A%3BDe+Luca%2C+L+M&rft.aulast=Ross&rft.aufirst=S&rft.date=1994-05-01&rft.volume=159&rft.issue=2&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-23 N1 - Date created - 1994-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation. AN - 76453120; 8164676 AB - Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) impairs translation initiation by inhibiting the guanine nucleotide exchange factor for eIF-2, known as eIF-2B. In Saccharomyces cerevisiae, phosphorylation of eIF-2 alpha by the protein kinase GCN2 specifically stimulates translation of GCN4 mRNA in addition to reducing general protein synthesis. We isolated mutations in several unlinked genes that suppress the growth-inhibitory effect of eIF-2 alpha phosphorylation catalyzed by mutationally activated forms of GCN2. These suppressor mutations, affecting eIF-2 alpha and the essential subunits of eIF-2B encoded by GCD7 and GCD2, do not reduce the level of eIF-2 alpha phosphorylation in cells expressing the activated GCN2c kinase. Four GCD7 suppressors were shown to reduce the derepression of GCN4 translation in cells containing wild-type GCN2 under starvation conditions or in GCN2c strains. A fifth GCD7 allele, constructed in vitro by combining two of the GCD7 suppressors mutations, completely impaired the derepression of GCN4 translation, a phenotype characteristic of deletions in GCN1, GCN2, or GCN3. This double GCD7 mutation also completely suppressed the lethal effect of expressing the mammalian eIF-2 alpha kinase dsRNA-PK in yeast cells, showing that the translational machinery had been rendered completely insensitive to phosphorylated eIF-2. None of the GCD7 mutations had any detrimental effect on cell growth under nonstarvation conditions, suggesting that recycling of eIF-2 occurs efficiently in the suppressor strains. We propose that GCD7 and GCD2 play important roles in the regulatory interaction between eIF-2 and eIF-2B and that the suppressor mutations we isolated in these genes decrease the susceptibility of eIF-2B to the inhibitory effects of phosphorylated eIF-2 without impairing the essential catalytic function of eIF-2B in translation initiation. JF - Molecular and cellular biology AU - Vazquez de Aldana, C R AU - Hinnebusch, A G AD - Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 3208 EP - 3222 VL - 14 IS - 5 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - Eukaryotic Initiation Factor-2 KW - Eukaryotic Initiation Factor-2B KW - Fungal Proteins KW - GCD7 protein, S cerevisiae KW - Guanine Nucleotide Exchange Factors KW - Macromolecular Substances KW - Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Mammals KW - Amino Acid Sequence KW - Plasmids KW - Gene Deletion KW - Mutagenesis KW - Genotype KW - Polymerase Chain Reaction KW - Alleles KW - Base Sequence KW - Phosphorylation KW - Molecular Sequence Data KW - Suppression, Genetic KW - Sequence Homology, Amino Acid KW - Gene Expression Regulation, Fungal KW - Genes, Fungal KW - Peptide Chain Initiation, Translational KW - Repressor Proteins -- metabolism KW - Fungal Proteins -- genetics KW - Proteins -- genetics KW - Proteins -- metabolism KW - Repressor Proteins -- genetics KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Genes, Suppressor UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76453120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutations+in+the+GCD7+subunit+of+yeast+guanine+nucleotide+exchange+factor+eIF-2B+overcome+the+inhibitory+effects+of+phosphorylated+eIF-2+on+translation+initiation.&rft.au=Vazquez+de+Aldana%2C+C+R%3BHinnebusch%2C+A+G&rft.aulast=Vazquez+de+Aldana&rft.aufirst=C&rft.date=1994-05-01&rft.volume=14&rft.issue=5&rft.spage=3208&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 - 1994-05-25 N1 - Date created - 1994-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1974 Mar;117(3):1131-40 [4360539] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4616-20 [8099443] Gene. 1979 Dec;8(1):121-33 [395029] Proc Natl Acad Sci U S A. 1982 Apr;79(8):2537-40 [6953412] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] J Biol Chem. 1983 Mar 10;258(5):3402-8 [6826566] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5350-4 [8506384] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Mol Cell Biol. 1993 Aug;13(8):5099-111 [8336737] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7215-9 [8102207] Proc Natl Acad Sci U S A. 1983 May;80(9):2559-63 [6573671] Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374-8 [6351059] Proc Natl Acad Sci U S A. 1984 Jan;81(2):352-6 [6320181] Mol Cell Biol. 1984 Jul;4(7):1326-33 [6095062] Biochem J. 1986 May 1;235(3):625-37 [3530248] Mol Cell Biol. 1986 Nov;6(11):3990-8 [3540603] J Biol Chem. 1987 Jan 25;262(3):1206-12 [2948954] Genetics. 1987 Nov;117(3):409-19 [3319768] J Biol Chem. 1988 Apr 25;263(12):5526-33 [3356695] Eur J Biochem. 1988 Jul 15;175(1):93-9 [3402451] Cell. 1988 Aug 26;54(5):621-32 [3136928] Microbiol Rev. 1988 Jun;52(2):248-73 [3045517] Nucleic Acids Res. 1988 Oct 11;16(19):9253-65 [3050897] Mol Cell Biol. 1988 Nov;8(11):4808-20 [3062370] Yeast. 1985 Dec;1(2):83-138 [3916863] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2784-8 [2649894] Genetics. 1989 May;122(1):19-27 [2659436] Genetics. 1989 Jul;122(3):543-50 [2668116] Mol Cell Biol. 1990 Jun;10(6):2820-31 [2188100] Cell. 1990 Jul 27;62(2):379-90 [1695551] Genetics. 1990 Nov;126(3):549-62 [2249755] Mol Cell Biol. 1991 Jan;11(1):486-96 [1986242] Methods Enzymol. 1991;194:195-230 [2005788] Mol Cell Biol. 1991 Jun;11(6):3217-28 [2038327] Annu Rev Biochem. 1991;60:717-55 [1883206] Cell. 1992 Feb 7;68(3):585-96 [1739968] EMBO J. 1992 Apr;11(4):1553-62 [1348691] Microbiol Rev. 1992 Jun;56(2):291-315 [1620067] Cell. 1992 Aug 21;70(4):647-57 [1505029] Mol Cell Biol. 1992 Dec;12(12):5801-15 [1448107] Mol Cell Biol. 1993 Jan;13(1):506-20 [8417348] Mol Cell Biol. 1993 Mar;13(3):1920-32 [8441423] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study. AN - 76452904; 7909412 AB - Magnetic resonance imaging was used to measure the volumes of the caudate, putamen, and globus pallidus of 25 schizophrenic patients (17 men and eight women) and 26 age- and sex-matched comparison subjects (18 men and eight women). Schizophrenic patients had significantly larger right and left globus pallidus and right putamen volumes than comparison subjects. There were no significant differences between schizophrenic patients with and without persistent tardive dyskinesia in the volume of any of the three structures. JF - The American journal of psychiatry AU - Elkashef, A M AU - Buchanan, R W AU - Gellad, F AU - Munson, R C AU - Breier, A AD - NIMH Neuroscience Center, St. Elizabeths Hospital, Washington, D.C. 20032. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 752 EP - 755 VL - 151 IS - 5 SN - 0002-953X, 0002-953X KW - Antipsychotic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Globus Pallidus -- pathology KW - Caudate Nucleus -- anatomy & histology KW - Hypertrophy -- pathology KW - Humans KW - Globus Pallidus -- anatomy & histology KW - Caudate Nucleus -- pathology KW - Adult KW - Antipsychotic Agents -- adverse effects KW - Male KW - Functional Laterality KW - Female KW - Magnetic Resonance Imaging KW - Dyskinesia, Drug-Induced -- pathology KW - Schizophrenia -- diagnosis KW - Dyskinesia, Drug-Induced -- diagnosis KW - Schizophrenia -- drug therapy KW - Dyskinesia, Drug-Induced -- etiology KW - Schizophrenia -- pathology KW - Basal Ganglia -- anatomy & histology KW - Basal Ganglia -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76452904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Basal+ganglia+pathology+in+schizophrenia+and+tardive+dyskinesia%3A+an+MRI+quantitative+study.&rft.au=Elkashef%2C+A+M%3BBuchanan%2C+R+W%3BGellad%2C+F%3BMunson%2C+R+C%3BBreier%2C+A&rft.aulast=Elkashef&rft.aufirst=A&rft.date=1994-05-01&rft.volume=151&rft.issue=5&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-25 N1 - Date created - 1994-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of G0-G1 arrest in quiescent and senescent cells treated with phosphatase inhibitors. AN - 76446736; 8162573 AB - The majority of signal transduction studies have focused on events induced by mitogen stimulation. However, little is known about the negative control signals that cause or maintain growth arrest and must be overcome for mitogenesis to occur. We investigated the possible role of protein phosphatases in this negative regulatory process. Treatment of quiescent hamster and human fibroblasts with low doses of the phosphatase inhibitors sodium o-vanadate or okadaic acid allowed 30-40% of cells to progress from G0-G1 arrest to S phase. This was accompanied by phosphorylation of the retinoblastoma and MAP-kinase proteins, as well as induction of the cdc2 protein. Furthermore, we observed that protein phosphatase inhibitor treatment could override the block to DNA synthesis in senescent cells, which are normally nonresponsive to mitogens. These data suggest that protein phosphatases may play a role in the negative regulation of cell growth and maintenance of growth arrest. JF - Cancer research AU - Afshari, C A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1994/05/01/ PY - 1994 DA - 1994 May 01 SP - 2317 EP - 2321 VL - 54 IS - 9 SN - 0008-5472, 0008-5472 KW - Ethers, Cyclic KW - 0 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Vanadates KW - 3WHH0066W5 KW - DNA KW - 9007-49-2 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Humans KW - Enzyme Induction KW - DNA -- biosynthesis KW - Signal Transduction KW - Cell Line KW - Cricetinae KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Vanadates -- pharmacology KW - S Phase KW - G1 Phase -- drug effects KW - Ethers, Cyclic -- pharmacology KW - Resting Phase, Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76446736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disruption+of+G0-G1+arrest+in+quiescent+and+senescent+cells+treated+with+phosphatase+inhibitors.&rft.au=Afshari%2C+C+A%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1994-05-01&rft.volume=54&rft.issue=9&rft.spage=2317&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 - 1994-05-24 N1 - Date created - 1994-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo evidence that nonneuronal beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum. AN - 76443977; 8158123 AB - We applied in vivo microdialysis to assess the effects of dopaminergic and beta-adrenergic receptor stimulation on cyclic AMP efflux in rat striatum under chloral hydrate anesthesia. Dopamine (up to 1 mM) infused for 20 min through the probe did not increase cyclic AMP, whereas both the selective dopamine D1 agonist SKF 38393 and D2 antagonist sulpiride produced modest increases. It is interesting that the beta-adrenoceptor agonist isoproterenol produced a marked increase (204.7% of basal level at 1 mM) which was antagonized by the beta-adrenoceptor antagonist propranolol. Pretreatment with a glial selective metabolic inhibitor, fluorocitrate (1 mM), by a 5-h infusion through the probe attenuated basal cyclic AMP efflux by 30.3% and significantly blocked the response to isoproterenol. By contrast, striatal injection of a neurotoxin, kainic acid (2.5 micrograms), 2 days before the dialysis experiment did not affect basal cyclic AMP or the response to isoproterenol, but blocked the response to SKF 38393. These data demonstrate the beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum in vivo. They also suggest that basal and beta-adrenoceptor-stimulated cyclic AMP efflux are substantially dependent on intact glial cells. JF - Journal of neurochemistry AU - Suyama, K AU - Dykstra, K H AU - Masana, M I AU - Manji, H K AU - Potter, W Z AD - Section on Clinical Pharmacology, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 1734 EP - 1740 VL - 62 IS - 5 SN - 0022-3042, 0022-3042 KW - Citrates KW - 0 KW - Receptors, Adrenergic, beta KW - Receptors, Dopamine KW - fluorocitrate KW - 357-89-1 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Propranolol KW - 9Y8NXQ24VQ KW - Cyclic AMP KW - E0399OZS9N KW - Isoproterenol KW - L628TT009W KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Kainic Acid -- pharmacology KW - Analysis of Variance KW - Kinetics KW - Citrates -- administration & dosage KW - Citrates -- pharmacology KW - Infusions, Parenteral KW - Male KW - Receptors, Dopamine -- drug effects KW - Receptors, Dopamine -- physiology KW - Propranolol -- pharmacology KW - Corpus Striatum -- metabolism KW - Cyclic AMP -- metabolism KW - Corpus Striatum -- drug effects KW - Receptors, Adrenergic, beta -- physiology KW - Receptors, Adrenergic, beta -- drug effects KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- administration & dosage KW - Isoproterenol -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=In+vivo+evidence+that+nonneuronal+beta-adrenoceptors+as+well+as+dopamine+receptors+contribute+to+cyclic+AMP+efflux+in+rat+striatum.&rft.au=Suyama%2C+K%3BDykstra%2C+K+H%3BMasana%2C+M+I%3BManji%2C+H+K%3BPotter%2C+W+Z&rft.aulast=Suyama&rft.aufirst=K&rft.date=1994-05-01&rft.volume=62&rft.issue=5&rft.spage=1734&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-18 N1 - Date created - 1994-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. AN - 76443127; 7909277 AB - p53 is known to play a central role in the control of cell proliferation and carcinogenesis. In non-small cell lung cancer, however, the clinicopathological studies of p53 have yielded conflicting results. In the current study, we examined 123 non-small cell lung cancers with detailed clinical information, 71 primary and 52 metastatic tumors, using formalin-fixed and paraffin-embedded surgical specimens to show the clinicopathological correlation of the immunohistochemical (DO-7) overexpression of p53. Nuclear specific p53 overexpression appeared in 48 (39%; any number of tumor cells positive) of 123 tumors (35% of primary and 44% of metastatic tumors). The distribution and intensity of staining were variable. Ninety-eight % of all tumors also expressed nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA; PC 10) to a varying degree. In a univariate analysis, both p53 (> 10% of tumor cells positive; n = 11) and PCNA (> 50% of tumor cells positive; n = 32) were associated with shorter survival in the curative intent group (stages I, II, and IIIA) of 63 patients. In a multivariate analysis including all clinicopathological variables, the overexpression of p53 (but not PCNA) was found to be an independent prognostic factor (P2 = 0.0011) in the curative intent group. No correlation was detected between the immunoreactivities and patient characteristics, such as age, gender, or smoking. Double immunohistochemistry of both p53 and PCNA revealed a distinct pattern, whereas its clinicopathological correlation remained elusive. We conclude that p53 overexpression in non-small cell lung cancer (but not PCNA) is independently associated with a shortened survival and may be of prognostic significance in selected patients with earlier stage cancer. JF - Cancer research AU - Ebina, M AU - Steinberg, S M AU - Mulshine, J L AU - Linnoila, R I AD - Biomarkers and Prevention Research Branch, National Cancer Institute, NIH, Rockville, Maryland 20850. Y1 - 1994/05/01/ PY - 1994 DA - 1994 May 01 SP - 2496 EP - 2503 VL - 54 IS - 9 SN - 0008-5472, 0008-5472 KW - p53 KW - Nuclear Proteins KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Lymphatic Metastasis KW - Humans KW - Prognosis KW - Infant, Newborn KW - Aged KW - Child KW - Child, Preschool KW - Infant KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Survival Analysis KW - Cell Division KW - Nuclear Proteins -- analysis KW - Tumor Suppressor Protein p53 -- analysis KW - Lung Neoplasms -- chemistry KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Lung Neoplasms -- mortality KW - Carcinoma, Non-Small-Cell Lung -- chemistry KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Relationship+of+p53+overexpression+and+up-regulation+of+proliferating+cell+nuclear+antigen+with+the+clinical+course+of+non-small+cell+lung+cancer.&rft.au=Ebina%2C+M%3BSteinberg%2C+S+M%3BMulshine%2C+J+L%3BLinnoila%2C+R+I&rft.aulast=Ebina&rft.aufirst=M&rft.date=1994-05-01&rft.volume=54&rft.issue=9&rft.spage=2496&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 - 1994-05-24 N1 - Date created - 1994-05-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular feminization of mouse seminal vesicle by prenatal exposure to diethylstilbestrol: altered expression of messenger RNA. AN - 76439620; 8158792 AB - Exposure to estrogens during critical stages of development has been reported to cause irreversible changes in estrogen target tissues such as the reproductive tract. In fact, recent studies using mice describe prenatal estrogen exposure resulting in the expression of the major estrogen-inducible uterine secretory protein, lactoferrin (LF), by the seminal vesicles of the male offspring. Thus, we have studied the role of estrogens in abnormal and normal gene expression in the developing male reproductive tract using LF and seminal vesicle secretory protein IV (SVS IV), an androgen-regulated murine seminal vesicle secretory protein, as markers. Lactoferrin and SVS IV protein and mRNA expression were studied in histological samples by using the techniques of in situ hybridization (ISH) and immunohistochemistry (IHC). Seminal vesicle secretory protein IV was expressed in all (100%) epithelial cells of the control seminal vesicle, but this protein was decreased by castration. However, LF expression was undetectable by ISH or IHC in control seminal vesicle epithelium. Lactoferrin was inducible in 2% of the seminal vesicle epithelial cells from adult castrated mice treated with estradiol 17 beta (E2; 20 micrograms/kg/day for 3 days), indicating that a small percentage of the seminal vesicle cells could be induced to secrete LF after modification of the endocrine environment. Prenatal DES treatment (100 micrograms./kg. maternal body weight on days 9 through 16 of gestation) resulted in the male offspring exhibiting constitutive expression of LF in 5% of the seminal vesicle epithelial cells, while expression of the androgen-regulated protein SVS IV was slightly decreased. The maximal contrast between LF and SVS IV expression was observed in prenatally DES-treated mice that were subsequently castrated as adults and further treated with E2; LF was detected in 40% of the epithelial cells in these mice. Double immunostaining techniques revealed that epithelial cells which were making LF had ceased production of SVS IV. Since a large percentage of the epithelial cells in the intact prenatal DES exposed male was capable of expressing the normal gene product, SVS IV, it was concluded that DES treatment during prenatal development appears to imprint or induce estrogenic sensitivity in the adult seminal vesicle, causing increased production of LF. The results suggest that this altered protein response may be an example of atypical gene expression in male reproductive tract tissues following hormonal manipulation early in development. JF - The Journal of urology AU - Beckman, W C AU - Newbold, R R AU - Teng, C T AU - McLachlan, J A AD - Developmental Endocrinology and Pharmacology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 1370 EP - 1378 VL - 151 IS - 5 SN - 0022-5347, 0022-5347 KW - Prostatic Secretory Proteins KW - 0 KW - Proteins KW - RNA, Messenger KW - Seminal Plasma Proteins KW - beta-microseminoprotein KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Lactoferrin KW - EC 3.4.21.- KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Protein Biosynthesis KW - Estradiol -- pharmacology KW - Gene Expression KW - Mice KW - Proteins -- genetics KW - Orchiectomy KW - Pregnancy KW - Mice, Inbred Strains KW - In Situ Hybridization KW - Immunohistochemistry KW - Female KW - Male KW - Seminal Vesicles -- metabolism KW - Lactoferrin -- genetics KW - Lactoferrin -- analysis KW - Lactoferrin -- biosynthesis KW - Diethylstilbestrol -- toxicity KW - RNA, Messenger -- analysis KW - Seminal Vesicles -- drug effects KW - Seminal Vesicles -- pathology KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76439620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urology&rft.atitle=Molecular+feminization+of+mouse+seminal+vesicle+by+prenatal+exposure+to+diethylstilbestrol%3A+altered+expression+of+messenger+RNA.&rft.au=Beckman%2C+W+C%3BNewbold%2C+R+R%3BTeng%2C+C+T%3BMcLachlan%2C+J+A&rft.aulast=Beckman&rft.aufirst=W&rft.date=1994-05-01&rft.volume=151&rft.issue=5&rft.spage=1370&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors TFIID and TFIIA. AN - 76425931; 8151790 AB - Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV replication when present in the context of an LTR containing a Sp1 mutation (deletion or site specific); no effect was observed on the infectivity of wild-type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription systems, the altered TATA box motifs led to elevated basal levels of RNA synthesis from NF-kappa B- and Sp1-mutagenized and wild-type templates, respectively, but did not increase responsiveness to Tat transactivation. The revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and stabilized their association with the promoter. The revertants did not assemble a more-processive elongation complex. These results suggest that in the context of an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV revertants emerge which contain LTR alterations that significantly augment basal RNA synthesis. The TATA motif revertants are capable of rescuing the enhancer/promoter defect and sustain virus infectivity. JF - Journal of virology AU - Kashanchi, F AU - Shibata, R AU - Ross, E K AU - Brady, J N AU - Martin, M A AD - Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 3298 EP - 3307 VL - 68 IS - 5 SN - 0022-538X, 0022-538X KW - Gene Products, tat KW - 0 KW - Macromolecular Substances KW - NF-kappa B KW - RNA, Viral KW - Recombinant Fusion Proteins KW - Sp1 Transcription Factor KW - Transcription Factor TFIIA KW - Transcription Factor TFIID KW - Transcription Factors KW - tat Gene Products, Human Immunodeficiency Virus KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Recombinant Fusion Proteins -- biosynthesis KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Transcription Factors -- metabolism KW - Humans KW - Transcription, Genetic KW - Protein Binding KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Sp1 Transcription Factor -- metabolism KW - Gene Products, tat -- metabolism KW - NF-kappa B -- metabolism KW - HIV-1 -- genetics KW - TATA Box -- genetics KW - RNA, Viral -- biosynthesis KW - HIV Long Terminal Repeat -- genetics KW - HIV-1 -- growth & development KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76425931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Second-site+long+terminal+repeat+%28LTR%29+revertants+of+replication-defective+human+immunodeficiency+virus%3A+effects+of+revertant+TATA+box+motifs+on+virus+infectivity%2C+LTR-directed+expression%2C+in+vitro+RNA+synthesis%2C+and+binding+of+basal+transcription+factors+TFIID+and+TFIIA.&rft.au=Kashanchi%2C+F%3BShibata%2C+R%3BRoss%2C+E+K%3BBrady%2C+J+N%3BMartin%2C+M+A&rft.aulast=Kashanchi&rft.aufirst=F&rft.date=1994-05-01&rft.volume=68&rft.issue=5&rft.spage=3298&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 - 1994-05-12 N1 - Date created - 1994-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1980 Jul;77(7):3855-9 [6933441] J Virol. 1993 Apr;67(4):1752-60 [8445708] Science. 1984 May 4;224(4648):497-500 [6200935] J Immunol. 1984 Jul;133(1):123-8 [6327821] Cell. 1985 Jul;41(3):813-23 [2988790] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] Science. 1985 Aug 9;229(4713):563-6 [2992081] Science. 1986 May 9;232(4751):755-9 [3008338] J Virol. 1986 Aug;59(2):284-91 [3016298] Science. 1986 Nov 21;234(4779):988-92 [3490693] Nucleic Acids Res. 1986 Dec 22;14(24):10009-26 [3808945] Nature. 1987 Apr 16-22;326(6114):711-3 [3031512] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845-9 [3498942] J Virol. 1993 Jun;67(6):3639-43 [8497072] EMBO J. 1993 Jul;12(7):2749-62 [7687540] J Virol. 1993 Oct;67(10):6253-8 [8371358] EMBO J. 1993 Sep;12(9):3551-8 [8253080] Nature. 1994 Jan 20;367(6460):295-9 [8121496] J Virol. 1992 Jul;66(7):4445-51 [1602552] J Virol. 1992 Sep;66(9):5594-7 [1501293] Genes Dev. 1992 Oct;6(10):1964-74 [1398073] Gene Expr. 1992;2(4):391-407 [1282057] J Virol. 1988 Jan;62(1):139-47 [3257102] Mol Cell Biol. 1987 Oct;7(10):3759-66 [3500398] Nature. 1987 Nov 26-Dec 2;330(6146):391-5 [2825023] Science. 1987 Dec 11;238(4833):1575-8 [2825351] EMBO J. 1987 Dec 1;6(12):3761-70 [3428273] Science. 1988 Mar 4;239(4844):1150-3 [2964084] EMBO J. 1987 Dec 20;6(13):4067-71 [3443102] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700-4 [3133660] Science. 1988 Jul 8;241(4862):202-5 [3260404] EMBO J. 1988 Jul;7(7):2117-30 [3138113] EMBO J. 1989 Mar;8(3):765-78 [2721501] J Virol. 1989 Jun;63(6):2585-91 [2657100] J Virol. 1989 Sep;63(9):3595-600 [2547987] J Virol. 1989 Sep;63(9):4115-9 [2760991] J Virol. 1989 Nov;63(11):4919-24 [2795721] J Virol. 1990 Aug;64(8):3779-91 [2370681] Cell. 1990 Nov 16;63(4):791-802 [2225077] J Virol. 1991 Mar;65(3):1414-9 [1995951] J Virol. 1991 Jun;65(6):2853-60 [2033658] J Virol. 1991 Aug;65(8):4350-8 [2072454] Cell. 1991 Aug 9;66(3):563-76 [1907890] J Virol. 1991 Sep;65(9):4555-64 [1714513] Cell. 1991 Sep 6;66(5):981-93 [1889091] Genes Dev. 1991 Dec;5(12A):2212-24 [1748279] J Virol. 1992 Jan;66(1):139-49 [1727476] J Virol. 1993 Mar;67(3):1658-62 [8437235] EMBO J. 1993 Feb;12(2):489-99 [8440239] Nucleic Acids Res. 1993 Jan 11;21(1):5-12 [8441620] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simian virus 40 small-t antigen stimulates viral DNA replication in permissive monkey cells. AN - 76424944; 8151779 AB - The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication and for late viral gene expression, but the role of the SV40 small-t antigen in these processes is still unclear. We have previously demonstrated that small t inhibits SV40 DNA replication in vitro. In this study, we investigated the effect of small t on SV40 replication in cultured cells. CV1 monkey cell infection experiments indicated that mutant viruses that lack small t replicate less efficiently than the wild-type virus. We next microinjected CV1 cells with SV40 DNA with and without purified small-t protein and analyzed viral DNA replication efficiency by Southern blotting. Replication of either wild-type SV40 or small-t deletion mutant DNA was increased three- to fivefold in cells coinjected with purified small t. Thus, in contrast to our in vitro observation, small t stimulated viral DNA replication in vivo. This result suggests that small t has cellular effects that are not detectable in a reconstituted in vitro replication system. We also found that small t stimulated progression of permissive monkey cells--but not of nonpermissive rodent cells--from G0-G1 to the S phase of the cell cycle, possibly leading to an optimal intracellular environment for viral replication. JF - Journal of virology AU - Cicala, C AU - Avantaggiati, M L AU - Graessmann, A AU - Rundell, K AU - Levine, A S AU - Carbone, M AD - Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1994/05// PY - 1994 DA - May 1994 SP - 3138 EP - 3144 VL - 68 IS - 5 SN - 0022-538X, 0022-538X KW - Antigens, Viral, Tumor KW - 0 KW - DNA, Viral KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Protein Kinases -- metabolism KW - Animals KW - Phosphorylation KW - Cells, Cultured KW - Cercopithecus aethiops KW - Mice KW - Microinjections KW - Mutation KW - Cell Cycle -- drug effects KW - Virus Replication KW - DNA, Viral -- biosynthesis KW - Antigens, Viral, Tumor -- metabolism KW - Simian virus 40 -- growth & development KW - Antigens, Viral, Tumor -- genetics KW - Antigens, Viral, Tumor -- pharmacology KW - Simian virus 40 -- immunology KW - DNA Replication -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76424944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Simian+virus+40+small-t+antigen+stimulates+viral+DNA+replication+in+permissive+monkey+cells.&rft.au=Cicala%2C+C%3BAvantaggiati%2C+M+L%3BGraessmann%2C+A%3BRundell%2C+K%3BLevine%2C+A+S%3BCarbone%2C+M&rft.aulast=Cicala&rft.aufirst=C&rft.date=1994-05-01&rft.volume=68&rft.issue=5&rft.spage=3138&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 - 1994-05-12 N1 - Date created - 1994-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2521-5 [2157202] J Virol. 1976 May;18(2):664-71 [178902] Proc Natl Acad Sci U S A. 1978 Mar;75(3):1279-83 [206892] J Cell Biol. 1978 Apr;77(1):1-13 [659508] Cell. 1978 May;14(1):79-88 [208777] Proc Natl Acad Sci U S A. 1978 May;75(5):2473-7 [209467] Cell. 1978 Oct;15(2):579-85 [214244] Cell. 1979 Jul;17(3):635-43 [225037] J Virol. 1979 Apr;30(1):394-6 [225524] J Virol. 1980 Mar;33(3):1208-10 [6245271] Exp Cell Res. 1981 Mar;132(1):215-23 [6258954] J Virol. 1981 Feb;37(2):802-12 [6261020] Adv Cancer Res. 1981;35:111-49 [6280457] J Virol. 1982 Oct;44(1):116-33 [6292479] Methods Enzymol. 1983;101:482-92 [6310338] J Virol. 1984 Apr;50(1):1-12 [6321781] J Virol. 1984 May;50(2):623-8 [6323762] J Mol Biol. 1984 Nov 25;180(1):111-29 [6096557] J Virol. 1990 May;64(5):2380-3 [2157892] Cell. 1990 Jun 1;61(5):735-8 [2160857] Science. 1990 Nov 9;250(4982):786-91 [2173140] Exp Cell Res. 1991 Mar;193(1):236-9 [1847332] J Virol. 1991 Mar;65(3):1479-90 [1847465] Mol Cell Biol. 1991 Apr;11(4):1988-95 [1706474] Mol Cell Biol. 1991 Apr;11(4):1996-2003 [1848668] J Virol. 1991 Aug;65(8):4414-23 [1649337] J Virol. 1991 Dec;65(12):6535-43 [1658359] Methods Enzymol. 1991;201:110-49 [1943760] Cell Regul. 1991 Aug;2(8):589-98 [1663787] J Virol. 1992 Mar;66(3):1289-93 [1310750] J Virol. 1992 Mar;66(3):1746-51 [1310775] J Virol. 1992 Mar;66(3):1804-8 [1310784] Oncogene. 1992 May;7(5):837-47 [1570154] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4549-53 [1316611] Virology. 1992 Sep;190(1):475-9 [1529547] J Virol. 1993 Jun;67(6):3671-3 [8388518] Cell. 1993 Dec 3;75(5):887-97 [8252625] Virology. 1985 Oct 30;146(2):246-61 [2996219] Cell. 1987 Jan 30;48(2):321-30 [3026642] EMBO J. 1987 Jan;6(1):153-60 [3034573] J Virol. 1987 Nov;61(11):3373-80 [2822947] J Virol. 1989 Jun;63(6):2820-8 [2542592] EMBO J. 1989 Dec 1;8(12):3891-8 [2555176] Annu Rev Cell Biol. 1989;5:197-245 [2557059] Cell. 1990 Jan 12;60(1):167-76 [2153055] Cell. 1990 Jan 26;60(2):181-4 [2153460] Proc Natl Acad Sci U S A. 1976 Feb;73(2):366-70 [174105] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C. Modeling of the binding site and prediction of binding constants. AN - 76472043; 8176711 AB - A detailed examination of the mode of binding of phorbol esters to protein kinase C led to a model of the phorbol binding site in the enzyme. The efficacy with which various synthetic diacylglycerol analogs and ribonolactones are able to bind to this site was determined by means of semiempirical quantum mechanical calculations using PM3, and an estimate of the binding energy was made in each case. Sixteen synthetic analogs of 1,2-diacylglycerol and two natural products were studied, and their calculated energies of binding to this model were correlated with the measured Ki values. The binding energies calculated for this receptor model, together with solubility and entropy considerations, allow prediction through regressive fit of free energies of binding which correlate very well with the measured binding constants. JF - Journal of medicinal chemistry AU - Wang, S AU - Milne, G W AU - Nicklaus, M C AU - Marquez, V E AU - Lee, J AU - Blumberg, P M AD - Laboratory of Medicinal Chemistry, DCT, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/04/29/ PY - 1994 DA - 1994 Apr 29 SP - 1326 EP - 1338 VL - 37 IS - 9 SN - 0022-2623, 0022-2623 KW - 1,2-diacylglycerol KW - 0 KW - Diglycerides KW - Lactones KW - Lyngbya Toxins KW - Phorbol Esters KW - dipalmitin KW - 26657-95-4 KW - debromoaplysiatoxin KW - 52423-28-6 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Molecular Structure KW - Phorbol Esters -- chemistry KW - Diglycerides -- chemistry KW - Phorbol Esters -- metabolism KW - Lyngbya Toxins -- metabolism KW - Computer Simulation KW - Thermodynamics KW - Lactones -- chemistry KW - Enzyme Activation KW - Lyngbya Toxins -- chemistry KW - Lactones -- metabolism KW - Diglycerides -- metabolism KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Models, Molecular KW - Protein Kinase C -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76472043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protein+kinase+C.+Modeling+of+the+binding+site+and+prediction+of+binding+constants.&rft.au=Wang%2C+S%3BMilne%2C+G+W%3BNicklaus%2C+M+C%3BMarquez%2C+V+E%3BLee%2C+J%3BBlumberg%2C+P+M&rft.aulast=Wang&rft.aufirst=S&rft.date=1994-04-29&rft.volume=37&rft.issue=9&rft.spage=1326&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 - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Med Chem 1994 Dec 9;37(25):4422 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The inherent cytotoxicity of melanin precursors: a revision. AN - 76462759; 8167148 AB - The potential cytotoxicity of the melanogenic intermediates DOPA, (L-3,4-dihydroxyphenylalanine) and DHI (5,6-dihydroxyindole) has long been recognized and exploited as a targeting concept in experimental melanoma therapy. In recent years, however, a novel branchpoint in the melanin biosynthetic pathway has been shown to divert the metabolism of DOPAchrome to a carboxylated derivative termed DHICA (DHI-2-carboxylic acid) rather than to DHI. In order to evaluate the biological implications of this regulatory control, we have reexamined the inherent cytotoxicity of DHICA versus DHI on different cell lines. We found that under the usual conditions of the biological assay, the apparent cytotoxicity of the two indoles reflect their instability in the culture medium, the less stable DHI being generally more toxic than DHICA to melanoma cells and nonmelanocytic cells. Moreover, the observed cytotoxic effects increased with the time of incubation and were markedly reduced by the addition of catalase to the medium, suggesting that they were probably due to the generation of reactive oxygen species (particularly H2O2) during the autoxidation of the melanin precursors outside the cells. To circumvent this problem, we then tested the diacetylated derivatives of DHI and DHICA (DAI and DAICA) which are sufficiently stable until taken up into the cells whereupon they may be converted by endogenous esterases back to the parent indoles. Although DAI proved to be cytotoxic for nonmelanocytic cells, it had no detectable activity on melanoma cells, whereas DAICA showed no effect on any of the cells examined. These results, when combined with other studies, point to a reconsideration of the inherent cytotoxicity of the 5,6-dihydroxyindoles, as well as DOPA, to melanin producing cells. JF - Biochimica et biophysica acta AU - Urabe, K AU - Aroca, P AU - Tsukamoto, K AU - Mascagna, D AU - Palumbo, A AU - Prota, G AU - Hearing, V J AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/28/ PY - 1994 DA - 1994 Apr 28 SP - 272 EP - 278 VL - 1221 IS - 3 SN - 0006-3002, 0006-3002 KW - Indoles KW - 0 KW - Melanins KW - Protein Precursors KW - 5,6-dihydroxy-2-indolylcarboxylic acid KW - 4790-08-3 KW - Dihydroxyphenylalanine KW - 63-84-3 KW - Hydrogen Peroxide KW - BBX060AN9V KW - 5,6-dihydroxyindole KW - Z3OC8499KG KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - 3T3 Cells KW - Microscopy, Phase-Contrast KW - Tumor Cells, Cultured KW - Indoles -- toxicity KW - Cell Survival -- drug effects KW - Hydrogen Peroxide -- metabolism KW - Cell Division -- drug effects KW - Mice KW - Dihydroxyphenylalanine -- toxicity KW - Melanins -- biosynthesis KW - Protein Precursors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76462759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=The+inherent+cytotoxicity+of+melanin+precursors%3A+a+revision.&rft.au=Urabe%2C+K%3BAroca%2C+P%3BTsukamoto%2C+K%3BMascagna%2C+D%3BPalumbo%2C+A%3BProta%2C+G%3BHearing%2C+V+J&rft.aulast=Urabe&rft.aufirst=K&rft.date=1994-04-28&rft.volume=1221&rft.issue=3&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-01 N1 - Date created - 1994-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes. AN - 76466680; 8170984 AB - To identify the potential involvement of tumor-suppressor gene inactivation during neoplastic development in B6C3F1 mice, genetic losses were determined from allelotypes of butadiene-induced lung and mammary adenocarcinomas. By using length polymorphisms in restriction fragments and simple sequence repeats, or "microsatellites," markers on each autosome were analyzed for allele losses in tumor DNAs. Losses of heterozygosity on chromosome 11 were observed at several loci surrounding the p53 tumor-suppressor gene (Trp53) in 12 of 17 mammary tumors and 2 of 8 lung tumors. Although most of these alterations appeared to result from nondisjunction, at least two examples of somatic recombination or deletion were also observed. Southern analysis revealed a homozygous deletion of the remaining Trp53 allele of one of these mammary tumors. Losses of heterozygosity were also detected at the Rb-1 tumor-suppressor gene in 7 of 17 mammary tumors and 1 lung tumor. Finally, frequent allele losses were observed on chromosome 4 in lung tumors. Analysis of nine chromosome 4 loci defined an interstitial deletion containing the Ifa gene cluster in one of the lung tumors. A tumor-suppressor gene was previously mapped to this region of chromosome 4 in studies with somatic cell hybrids. In addition, homozygous deletions have been reported in a homologous region of human chromosome 9p for acute lymphocytic leukemias, glioblastomas, melanomas, and lung carcinomas. These findings suggest that the inactivation of tumor-suppressor genes including Trp53, Rb-1, and an unidentified gene on chromosome 4 plays a significant role during carcinogenesis in mice. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wiseman, R W AU - Cochran, C AU - Dietrich, W AU - Lander, E S AU - Söderkvist, P AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/04/26/ PY - 1994 DA - 1994 Apr 26 SP - 3759 EP - 3763 VL - 91 IS - 9 SN - 0027-8424, 0027-8424 KW - Acrb KW - Mtv-1 KW - Mtv-11 KW - Mtv-17 KW - Mtv-8 KW - Mtv-9 KW - Pnd KW - Trf KW - Trp53 KW - Butadienes KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Animals KW - Polymorphism, Genetic KW - Humans KW - Mice KW - Chromosome Mapping KW - Alleles KW - Base Sequence KW - Genes, Retinoblastoma KW - Heterozygote KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - DNA, Neoplasm -- genetics KW - Female KW - Male KW - Sequence Deletion KW - DNA Primers -- chemistry KW - Genes, Tumor Suppressor KW - Mammary Neoplasms, Experimental -- genetics KW - Lung Neoplasms -- genetics KW - Adenocarcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76466680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Allelotyping+of+butadiene-induced+lung+and+mammary+adenocarcinomas+of+B6C3F1+mice%3A+frequent+losses+of+heterozygosity+in+regions+homologous+to+human+tumor-suppressor+genes.&rft.au=Wiseman%2C+R+W%3BCochran%2C+C%3BDietrich%2C+W%3BLander%2C+E+S%3BS%C3%B6derkvist%2C+P&rft.aulast=Wiseman&rft.aufirst=R&rft.date=1994-04-26&rft.volume=91&rft.issue=9&rft.spage=3759&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 - 1994-06-01 N1 - Date created - 1994-06-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Acrb; Mtv-1; Mtv-11; Mtv-17; Mtv-8; Mtv-9; Pnd; Trf; Trp53 N1 - SuppNotes - Cited By: Science. 1993 Oct 1;262(5130):57-66 [8211130] Carcinogenesis. 1993 May;14(5):803-10 [8504472] J Virol. 1982 May;42(2):379-88 [6283161] Gene. 1983 Dec;26(2-3):181-8 [6689487] J Virol. 1986 Sep;59(3):574-83 [3016321] Hypertension. 1987 May;9(5):518-21 [2883119] Cancer Res. 1988 Jun 15;48(12):3302-6 [3370633] Adv Cancer Res. 1988;51:147-82 [3066145] Annu Rev Genet. 1988;22:479-519 [3071256] Science. 1989 Apr 14;244(4901):207-11 [2565047] J Biol Chem. 1989 May 5;264(13):7611-6 [2708381] Genomics. 1989 Jul;5(1):118-23 [2570024] Genomics. 1989 Jul;5(1):70-5 [2570031] Nature. 1989 Dec 7;342(6250):705-8 [2531845] Mol Cell Biol. 1989 Nov;9(11):5154-62 [2601714] Adv Cancer Res. 1990;54:25-62 [2404380] Genomics. 1989 Oct;5(3):454-62 [2482246] Cell. 1990 May 4;61(3):407-17 [2185890] Cell. 1990 Jun 1;61(5):759-67 [2188735] Cancer Res. 1990 Aug 1;50(15):4818-23 [2196119] Nucleic Acids Res. 1990 Jul 25;18(14):4123-30 [2377456] J Virol. 1990 Sep;64(9):4568-72 [2166832] Cancer Res. 1990 Oct 15;50(20):6592-9 [2208121] Cancer Res. 1990 Nov 15;50(22):7184-9 [1977515] Nature. 1991 Jun 13;351(6327):542-7 [1675432] Lancet. 1991 Jul 13;338(8759):82-3 [1676470] Science. 1991 Jul 5;253(5015):49-53 [1905840] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7590-4 [1909026] Cancer Res. 1991 Oct 1;51(19):5118-22 [1655245] Cancer Res. 1991 Nov 1;51(21):5794-9 [1682035] Science. 1991 Nov 22;254(5035):1138-46 [1659741] Cancer Res. 1991 Dec 15;51(24):6615-21 [1742735] Oncogene. 1991 Dec;6(12):2363-9 [1766680] Mamm Genome. 1991;1(4):273-82 [1794058] Mol Carcinog. 1992;5(1):9-15 [1543544] Nature. 1992 Mar 19;356(6366):215-21 [1552940] Cancer Res. 1992 May 1;52(9):2478-81 [1314694] Cancer Res. 1992 May 1;52(9):2624-7 [1568230] Am J Hum Genet. 1992 Jun;50(6):1235-42 [1598904] FASEB J. 1992 Jul;6(10):2826-35 [1634045] Genetics. 1992 Jun;131(2):423-47 [1353738] Mamm Genome. 1992;3 Spec No:S136-52 [1498428] Mamm Genome. 1992;3 Spec No:S162-81 [1498430] Mamm Genome. 1992;3 Spec No:S206-19 [1498434] Mamm Genome. 1992;3 Spec No:S55-64 [1498443] Genomics. 1992 Oct;14(2):437-43 [1385305] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10557-61 [1438246] Science. 1992 Nov 13;258(5085):1148-52 [1439824] Cancer Res. 1993 May 15;53(10 Suppl):2410-5 [7683574] Am J Hum Genet. 1980 May;32(3):314-31 [6247908] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding. AN - 76463804; 8170939 AB - Transcription initiation factor TFIID plays a central role in transcriptional regulation. Drosophila TFIID is a multimeric protein consisting of the TATA box-binding polypeptide (TBP) and a number of tightly associated polypeptides. Previously, the largest subunit of TFIID (p230) was cloned and demonstrated to inhibit the TATA-box binding of TBP in the absence of other subunits. Here we demonstrate that p230 contains at least two sites of interaction with TBP and that the N-terminal site mediates both strong physical interactions with TBP and inhibition of the TBP function. A detailed mutagenesis study shows that the inhibitory domain is indistinguishable from the strong TBP-binding domain, thus indicating that interaction of the p230 N-terminal region with TBP may directly control TATA-box binding. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kokubo, T AU - Yamashita, S AU - Horikoshi, M AU - Roeder, R G AU - Nakatani, Y AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/26/ PY - 1994 DA - 1994 Apr 26 SP - 3520 EP - 3524 VL - 91 IS - 9 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Macromolecular Substances KW - TATA-Box Binding Protein KW - Transcription Factor TFIID KW - Transcription Factors KW - Index Medicus KW - Animals KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Sequence Deletion KW - Transcription Factors -- metabolism KW - TATA Box KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76463804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+between+the+N-terminal+domain+of+the+230-kDa+subunit+and+the+TATA+box-binding+subunit+of+TFIID+negatively+regulates+TATA-box+binding.&rft.au=Kokubo%2C+T%3BYamashita%2C+S%3BHorikoshi%2C+M%3BRoeder%2C+R+G%3BNakatani%2C+Y&rft.aulast=Kokubo&rft.aufirst=T&rft.date=1994-04-26&rft.volume=91&rft.issue=9&rft.spage=3520&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 - 1994-06-01 N1 - Date created - 1994-06-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1991 Jun;11(6):3317-25 [2038334] Nature. 1993 Apr 8;362(6420):511-7 [8464492] Genes Dev. 1993 Jun;7(6):1033-46 [8504928] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5896-900 [8327460] EMBO J. 1993 Jul;12(7):2749-62 [7687540] J Biol Chem. 1993 Aug 15;268(23):17554-8 [8349634] Nature. 1993 Oct 7;365(6446):512-20 [8413604] Nature. 1993 Oct 7;365(6446):520-7 [8413605] Mol Cell Biol. 1993 Dec;13(12):7859-63 [8247000] Nature. 1994 Feb 3;367(6462):484-7 [7545910] J Biol Chem. 1985 Mar 25;260(6):3269-74 [3838311] Methods Enzymol. 1987;154:367-82 [3323813] EMBO J. 1988 Jun;7(6):1683-7 [3169001] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9158-62 [2251257] Cell. 1991 Aug 9;66(3):563-76 [1907890] Cell. 1991 Nov 1;67(3):557-67 [1934060] Genes Dev. 1991 Dec;5(12A):2212-24 [1748279] Cell. 1992 Aug 7;70(3):477-89 [1339312] Genes Dev. 1992 Oct;6(10):1964-74 [1398073] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11809-13 [1465404] Cell. 1993 Jan 29;72(2):247-60 [7678780] EMBO J. 1993 Feb;12(2):489-99 [8440239] Nature. 1993 Mar 11;362(6416):175-9 [7680771] Nature. 1993 Mar 11;362(6416):179-81 [8450888] Nature. 1993 May 13;363(6425):176-9 [8483503] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Choleragen catalyzes ADP-ribosylation of the stimulatory G protein heterotrimer but not its free alpha-subunit. AN - 76442206; 8161545 AB - The heterotrimeric (alpha beta gamma) stimulatory G protein (Gs) mediates activation of adenylylcyclase. Gs is inactive when GDP is bound to the guanine nucleotide binding site of the alpha-subunit (Gs alpha). Gs can be activated by fluoroaluminate or by binding GTP or GTP analogues, (e.g., GTP gamma S) in place of GDP. Magnesium ion is also required for the activation of Gs, and Gs alpha is a substrate for ADP-ribosylation catalyzed by choleragen (CT). Gs activation can also be accompanied by dissociation of Gs alpha from the G beta gamma-subunit complex. When dissociated Gs subunits were separated by chromatography, isolated Gs alpha could not be ADP-ribosylated by CT unless G beta was added back. RM/1 antiserum against Gs alpha was used to immunoprecipitate Gs, and the subunit composition of the immunoprecipitate was determined. When Gs was incubated with 2 mM MgCl2, the Gs heterotrimer was immunoprecipitated, and Gs alpha could be ADP-ribosylated by CT. Activation of Gs with GTP gamma S or fluoroaluminate in the presence of 2 mM MgCl2 did not cause Gs subunit dissociation nor did it affect the ability of Gs alpha to be ADP-ribosylated by CT. MgCl2 caused a dose-dependent decrease in the amount of G beta that coprecipitated with Gs alpha in the absence as well as the presence of GTP gamma S or fluoroaluminate. Gs subunit dissociation was accompanied by a corresponding decrease in CT-catalyzed ADP-ribosylation of Gs alpha regardless of whether or not GTP gamma S or fluoroaluminate was bound to Gs alpha.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Toyoshige, M AU - Okuya, S AU - Rebois, R V AD - Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04/26/ PY - 1994 DA - 1994 Apr 26 SP - 4865 EP - 4871 VL - 33 IS - 16 SN - 0006-2960, 0006-2960 KW - Magnesium Chloride KW - 02F3473H9O KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - fluoroaluminum KW - 21330-18-7 KW - Fluorine KW - 284SYP0193 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Cholera Toxin KW - 9012-63-9 KW - Aluminum KW - CPD4NFA903 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Immunoblotting KW - Tumor Cells, Cultured KW - Adenylyl Cyclases -- metabolism KW - Precipitin Tests KW - Protein Binding KW - Catalysis KW - Binding Sites KW - GTP-Binding Proteins -- metabolism KW - Adenosine Diphosphate Ribose -- metabolism KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76442206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Choleragen+catalyzes+ADP-ribosylation+of+the+stimulatory+G+protein+heterotrimer+but+not+its+free+alpha-subunit.&rft.au=Toyoshige%2C+M%3BOkuya%2C+S%3BRebois%2C+R+V&rft.aulast=Toyoshige&rft.aufirst=M&rft.date=1994-04-26&rft.volume=33&rft.issue=16&rft.spage=4865&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-25 N1 - Date created - 1994-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. AN - 76451148; 8163464 AB - Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors. In this study we have identified the peroxisome proliferator-activated receptor (PPAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein, heterodimerizing with THR in solution. Although these heterodimers do not recognize a classical thyroid hormone response element (TRE) characterized by direct repeat separated by four nucleotides (DR+4), PPAR behaves as a dominant negative regulator of thyroid hormone (TH) action. However, a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE (DR+2). The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain. Hence, PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype. JF - The Journal of biological chemistry AU - Bogazzi, F AU - Hudson, L D AU - Nikodem, V M AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04/22/ PY - 1994 DA - 1994 Apr 22 SP - 11683 EP - 11686 VL - 269 IS - 16 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Macromolecular Substances KW - Oligodeoxyribonucleotides KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Thyroid Hormone KW - Recombinant Fusion Proteins KW - Thyroid Hormones KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Protein Biosynthesis KW - 3T3 Cells KW - Animals KW - Thyroid Hormones -- pharmacology KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - DNA -- metabolism KW - Humans KW - Rabbits KW - Mice KW - Amino Acid Sequence KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Transfection KW - DNA -- genetics KW - Reticulocytes -- metabolism KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Receptors, Thyroid Hormone -- biosynthesis KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- chemistry KW - Transcription Factors -- chemistry KW - Receptors, Thyroid Hormone -- metabolism KW - Receptors, Thyroid Hormone -- chemistry KW - Receptors, Cytoplasmic and Nuclear -- biosynthesis KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76451148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+novel+heterodimerization+partner+for+thyroid+hormone+receptor.+Peroxisome+proliferator-activated+receptor.&rft.au=Bogazzi%2C+F%3BHudson%2C+L+D%3BNikodem%2C+V+M&rft.aulast=Bogazzi&rft.aufirst=F&rft.date=1994-04-22&rft.volume=269&rft.issue=16&rft.spage=11683&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 - 1994-05-26 N1 - Date created - 1994-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation of a potentially functional Y-box protein (MSY-1) processed pseudogene from mouse: evolutionary relationships within the EF1A/dbpB/YB-1 gene family. AN - 76451212; 8163198 AB - A processed pseudogene from Mus musculus, designated psi MSY-2, was obtained with a MSY-1 cDNA (encoding mouse Y-box factor 1) probe. Mouse psi MSY-2 is intronless and has an ORF with an in-frame translational stop. The pseudogene has repeat sequences at the 5' and 3' boundaries, suggestive of an origin as a retroposon, and exhibits mutagenesis of CpG residues at a frequency at least tenfold higher than predicted from random mutagenesis. This indicates that 'repeat-induced point mutagenesis' or ripping has occurred. We find that the mouse genome contains many DNA sequences with homology to a cDNA encoding the DNA-binding domain of the Y-box proteins. We estimate that there are at least 15 copies per haploid genome. JF - Gene AU - Familari, M AU - Almouzni, G AU - Wolffe, A P AD - Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/20/ PY - 1994 DA - 1994 Apr 20 SP - 255 EP - 259 VL - 141 IS - 2 SN - 0378-1119, 0378-1119 KW - msy-2 KW - DNA, Complementary KW - 0 KW - DNA-Binding Proteins KW - Nsep1 protein, mouse KW - enhancer factor 1(A), rat KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Biological Evolution KW - Multigene Family KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Pseudogenes KW - Mice -- genetics KW - DNA-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76451212?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Isolation+of+a+potentially+functional+Y-box+protein+%28MSY-1%29+processed+pseudogene+from+mouse%3A+evolutionary+relationships+within+the+EF1A%2FdbpB%2FYB-1+gene+family.&rft.au=Familari%2C+M%3BAlmouzni%2C+G%3BWolffe%2C+A+P&rft.aulast=Familari&rft.aufirst=M&rft.date=1994-04-20&rft.volume=141&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-24 N1 - Date created - 1994-05-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - msy-2 N1 - Genetic sequence - L14608; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA replication fidelity with 8-oxodeoxyguanosine triphosphate. AN - 76444530; 8161527 AB - Oxidative metabolism is known to generate mutagenic compounds within cells, among which is 8-oxodeoxyguanosine. Here the mutagenic potential of the triphosphate form of this base analog (8-O-dGTP) is investigated during replication in vitro of the lacZ alpha-complementation sequence in M13mp2 DNA. Adding 8-O-dGTP at equimolar concentration with the normal dNTPs to polymerization reactions decreases the fidelity of DNA synthesis by exonuclease-deficient Klenow, T4, and Thermus thermophilus DNA polymerases. Sequence analysis of mutants suggests that 8-O-dGMP is misincorporated opposite template adenines, yielding A-->C transversions. The degree of polymerase selectivity against this error is enzyme-dependent, with rates varying by > 25-fold. To determine if the A.8-O-dGMP mispair is proofread, a direct comparison of the fidelity of proofreading-proficient and proofreading-deficient Klenow and T4 DNA polymerases was made. Although the exonuclease activity of Klenow polymerase did not substantially reduce overall misincorporation of 8-O-dGMP, misincorporation was lower for the proofreading-proficient T4 enzyme as compared to its proofreading-deficient derivative. These data suggest that the A.8-O-dGMP mispair can be proofread. The mutagenic potential of 8-O-dGTP with eukaryotic systems was also examined. Misincorporation of 8-O-dGTP opposite adenine was observed during SV40 origin-dependent replication of double-stranded DNA in HeLa cell extracts. When present during replication at a concentration equal to the four normal dNTPs, 8-O-dGTP was at least 13-fold more mutagenic for A.T-->C.G transversions than was a 100-fold excess of normal dGTP.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Pavlov, Y I AU - Minnick, D T AU - Izuta, S AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/04/19/ PY - 1994 DA - 1994 Apr 19 SP - 4695 EP - 4701 VL - 33 IS - 15 SN - 0006-2960, 0006-2960 KW - MutM KW - MutY KW - Deoxyguanine Nucleotides KW - 0 KW - 8-oxodeoxyguanosine triphosphate KW - 139307-94-1 KW - DNA KW - 9007-49-2 KW - DNA Polymerase I KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Thermus thermophilus -- enzymology KW - Bacteriophage T4 -- enzymology KW - Base Composition KW - Transfection KW - Escherichia coli -- genetics KW - Glycosylation KW - Mutagenesis KW - DNA-Directed DNA Polymerase -- metabolism KW - Deoxyguanine Nucleotides -- metabolism KW - DNA -- biosynthesis KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76444530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DNA+replication+fidelity+with+8-oxodeoxyguanosine+triphosphate.&rft.au=Pavlov%2C+Y+I%3BMinnick%2C+D+T%3BIzuta%2C+S%3BKunkel%2C+T+A&rft.aulast=Pavlov&rft.aufirst=Y&rft.date=1994-04-19&rft.volume=33&rft.issue=15&rft.spage=4695&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-26 N1 - Date created - 1994-05-26 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MutM; MutY N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gonadectomy does not prevent novelty or drug-induced motor hyperresponsiveness in rats with neonatal hippocampal damage. AN - 76582841; 8026079 AB - To explore the possibility that gonadal hormones are required for triggering the postpubertal emergence of enhanced dopamine-related behaviors in rats with neonatal excitotoxic lesions of the ventral hippocampus (VH), we assessed behavioral changes in castrated VH lesioned rats. The VH of rat pups was lesioned with ibotenic acid on day 7 after birth (PD7). Rats were castrated on PD21. Novelty- and amphetamine-induced locomotor activity were tested on PD56, and apomorphine-induced stereotypic behaviors and locomotion were evaluated on PD98. As demonstrated previously, the VH lesioned rats expressed enhanced novelty-, amphetamine- and apomorphine-induced hyperlocomotion (PD56) as well as potentiated apomorphine-induced stereotypic behaviors (PD98) in young adulthood as compared with sham-lesioned counterparts. Castration had no significant effect on novelty-induced locomotion or apomorphine-induced stereotypies but potentiated amphetamine- and apomorphine-induced hyperactivity in lesioned rats. These results indicate that the absence of gonadal hormones not only does not prevent the appearance in adulthood of behavioral disturbances linked to increased DA transmission in rats with neonatal lesions of the VH but even exaggerates those linked primarily to the mesolimbic DA system. JF - Brain research. Developmental brain research AU - Lipska, B K AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neuroscience Center at St. Elizabeths, Washington, DC 20032. Y1 - 1994/04/15/ PY - 1994 DA - 1994 Apr 15 SP - 253 EP - 258 VL - 78 IS - 2 SN - 0165-3806, 0165-3806 KW - Ibotenic Acid KW - 2552-55-8 KW - Amphetamine KW - CK833KGX7E KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Animals KW - Reference Values KW - Random Allocation KW - Apomorphine -- pharmacology KW - Stereotyped Behavior -- drug effects KW - Pregnancy KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Ibotenic Acid -- toxicity KW - Time Factors KW - Amphetamine -- pharmacology KW - Female KW - Male KW - Hippocampus -- physiology KW - Motor Activity -- drug effects KW - Hippocampus -- pathology KW - Orchiectomy KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76582841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=Gonadectomy+does+not+prevent+novelty+or+drug-induced+motor+hyperresponsiveness+in+rats+with+neonatal+hippocampal+damage.&rft.au=Lipska%2C+B+K%3BWeinberger%2C+D+R&rft.aulast=Lipska&rft.aufirst=B&rft.date=1994-04-15&rft.volume=78&rft.issue=2&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-05 N1 - Date created - 1994-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence that the pathway of transferrin receptor mRNA degradation involves an endonucleolytic cleavage within the 3' UTR and does not involve poly(A) tail shortening. AN - 76456481; 7909515 AB - The stability of transferrin receptor (TfR) mRNA is regulated by iron availability. When a human plasma-cytoma cell line (ARH-77) is treated with an iron source (hemin), the TfR mRNA is destabilized and a shorter TfR RNA appears. A similar phenomenon is also observed in mouse fibroblasts expressing a previously characterized iron-regulated human TfR mRNA (TRS-1). In contrast, mouse cells expressing a constitutively unstable human TfR mRNA (TRS-4) display the shorter RNA irrespective of iron treatment. These shorter RNAs found in both the hemin-treated ARH-77 cells and in the mouse fibroblasts are shown to be the result of a truncation within the 3' untranslated regions of the mRNAs. The truncated RNA is generated by an endonuclease, as most clearly evidenced by the detection of the matching 3' endonuclease product. The cleavage site of the human TfR mRNA in the mouse fibroblasts has been mapped to single nucleotide resolution to a single-stranded region near one of the iron-responsive elements contained in the 3' UTR. Site-directed mutagenesis demonstrates that the sequence surrounding the mapped endonuclease cleavage site is required for both iron-regulated mRNA turnover and generation of the truncated degradation intermediate. The TfR mRNA does not undergo poly(A) tail shortening prior to rapid degradation since the length of the poly(A) tail does not decrease during iron-induced destabilization. Moreover, the 3' endonuclease cleavage product is apparently polyadenylated to the same extent as the full-length mRNA. JF - The EMBO journal AU - Binder, R AU - Horowitz, J A AU - Basilion, J P AU - Koeller, D M AU - Klausner, R D AU - Harford, J B AD - Cell Biology and Metabolism Branch, NICHD, NIH, Bethesda, MD 20892. Y1 - 1994/04/15/ PY - 1994 DA - 1994 Apr 15 SP - 1969 EP - 1980 VL - 13 IS - 8 SN - 0261-4189, 0261-4189 KW - RNA, Messenger KW - 0 KW - RNA-Binding Proteins KW - Receptors, Transferrin KW - Poly A KW - 24937-83-5 KW - Hemin KW - 743LRP9S7N KW - Endoribonucleases KW - EC 3.1.- KW - Single-Strand Specific DNA and RNA Endonucleases KW - EC 3.1.30.1 KW - Index Medicus KW - Animals KW - RNA-Binding Proteins -- metabolism KW - DNA Mutational Analysis KW - Humans KW - Mice KW - Nucleic Acid Conformation KW - Poly A -- metabolism KW - Hemin -- pharmacology KW - Regulatory Sequences, Nucleic Acid -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Plasmacytoma KW - Molecular Sequence Data KW - Single-Strand Specific DNA and RNA Endonucleases -- metabolism KW - RNA, Messenger -- metabolism KW - Receptors, Transferrin -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Endoribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76456481?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+that+the+pathway+of+transferrin+receptor+mRNA+degradation+involves+an+endonucleolytic+cleavage+within+the+3%27+UTR+and+does+not+involve+poly%28A%29+tail+shortening.&rft.au=Binder%2C+R%3BHorowitz%2C+J+A%3BBasilion%2C+J+P%3BKoeller%2C+D+M%3BKlausner%2C+R+D%3BHarford%2C+J+B&rft.aulast=Binder&rft.aufirst=R&rft.date=1994-04-15&rft.volume=13&rft.issue=8&rft.spage=1969&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 - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1980;65(1):499-560 [6246368] Nucleic Acids Res. 1993 Sep 25;21(19):4627-31 [8233801] J Mol Biol. 1983 May 25;166(3):309-27 [6854649] Cell. 1986 Aug 29;46(5):659-67 [3488815] Curr Top Microbiol Immunol. 1986;132:148-52 [3792031] Mol Cell Biol. 1986 Dec;6(12):4362-71 [3467177] Proc Natl Acad Sci U S A. 1988 Mar;85(6):1787-91 [3162307] Science. 1988 May 13;240(4854):924-8 [2452485] Cell. 1988 Jun 3;53(5):815-25 [3370673] Mol Cell Biol. 1988 Apr;8(4):1697-708 [3380094] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Cell. 1988 Dec 23;55(6):1115-22 [3060261] Mol Cell Biol. 1989 Feb;9(2):769-75 [2523515] Proc Natl Acad Sci U S A. 1989 May;86(10):3574-8 [2498873] J Mol Biol. 1989 Jun 20;207(4):771-81 [2760930] Cell. 1989 Sep 8;58(5):857-67 [2673535] J Biol Chem. 1989 Oct 5;264(28):16910-8 [2550465] J Biol Chem. 1989 Nov 5;264(31):18742-50 [2478550] Science. 1989 Nov 3;246(4930):664-6 [2814487] EMBO J. 1989 Dec 1;8(12):3693-9 [2583116] Trends Biochem Sci. 1989 Sep;14(9):373-7 [2688202] Mol Cell Biol. 1989 Nov;9(11):4738-45 [2557539] Mol Cell Biol. 1989 Nov;9(11):5055-61 [2601708] Methods Enzymol. 1989;180:212-27 [2515419] Mol Cell Biol. 1990 Dec;10(12):6132-40 [1701014] Genes Dev. 1990 Nov;4(11):1925-35 [1980477] Mol Endocrinol. 1990 Apr;4(4):531-42 [2126342] Mol Cell Biol. 1991 May;11(5):2460-6 [1901943] J Biol Chem. 1991 May 25;266(15):9605-9 [1709638] Mol Cell Biol. 1991 Jun;11(6):3288-95 [2038332] Mol Cell Biol. 1991 Jun;11(6):3355-64 [1903842] Nucleic Acids Res. 1991 May 11;19(9):2289-94 [1904152] Curr Opin Cell Biol. 1990 Dec;2(6):1092-8 [2099802] Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7778-82 [1909029] Biochem Biophys Res Commun. 1991 Sep 30;179(3):1509-16 [1656956] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1296-300 [1311093] Mol Cell Biol. 1992 Mar;12(3):1149-61 [1545796] Nucleic Acids Res. 1992 Mar 11;20(5):1123-7 [1549476] Genes Dev. 1992 Apr;6(4):642-54 [1559612] Mol Cell Biol. 1992 Jul;12(7):2931-40 [1620106] Mol Cell Biol. 1992 Jul;12(7):2986-96 [1320194] New Biol. 1992 Apr;4(4):330-8 [1320397] Annu Rev Nutr. 1992;12:345-68 [1323982] Cell. 1992 Sep 18;70(6):961-73 [1339314] Genes Dev. 1992 Nov;6(11):2088-99 [1358757] Cell. 1993 Jan 15;72(1):19-28 [8380757] Int J Biochem. 1993 Mar;25(3):287-95 [8462718] Genes Dev. 1993 Aug;7(8):1620-31 [8339937] Cell. 1993 Aug 13;74(3):413-21 [7688664] Prog Nucleic Acid Res Mol Biol. 1982;27:53-83 [7048421] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional role of a cytoplasmic aromatic amino acid in muscarinic receptor-mediated activation of phospholipase C. AN - 76441537; 8157684 AB - The N-terminal portion of the third intracellular loop (i3) of muscarinic acetylcholine and other G protein-coupled receptors has been shown to largely determine the G protein coupling profile of a given receptor subtype. Using the rat m3 muscarinic receptor as a model system, we have recently demonstrated that a tyrosine residue (Tyr-254), located at the beginning of the i3 domain, is critically involved in muscarinic receptor-mediated stimulation of phosphatidylinositol (PI) hydrolysis (Blüml, K., Mutschler, E., and Wess, J. (1994) J. Biol. Chem. 269, 402-405). This study was designed to investigate the functional role of this amino acid in further molecular detail. Replacement of Tyr-254 (rat m3 receptor) with alanine or exchange of its position with Ile-253 virtually abolished receptor-mediated stimulation of PI hydrolysis studied in transfected COS-7 cells. In contrast, substitution of Tyr-254 by other aromatic residues such as phenylalanine or tryptophan resulted in mutant receptors that behaved functionally similar to the wild type m3 receptor. Introduction of Tyr-254 into the corresponding position (Ser-210) of the m2 muscarinic receptor (which is only poorly coupled to PI turnover) did not result in an enhanced PI response. However, "reinsertion" of Tyr-254 into a functionally inactive chimeric m3/m2 muscarinic receptor (containing m2 receptor sequence at the N terminus of the i3 loop) yielded a mutant receptor that was able to stimulate PI hydrolysis to a similar maximum extent as the wild type m3 receptor. Taken together, our data provide strong evidence that muscarinic receptor-mediated stimulation of PI metabolism is critically dependent on the presence and proper positioning of an aromatic residue at the beginning of the i3 loop. JF - The Journal of biological chemistry AU - Blüml, K AU - Mutschler, E AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDKD, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04/15/ PY - 1994 DA - 1994 Apr 15 SP - 11537 EP - 11541 VL - 269 IS - 15 SN - 0021-9258, 0021-9258 KW - Phosphatidylinositols KW - 0 KW - Receptors, Muscarinic KW - Scopolamine Derivatives KW - Tyrosine KW - 42HK56048U KW - Carbachol KW - 8Y164V895Y KW - Type C Phospholipases KW - EC 3.1.4.- KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - N-Methylscopolamine KW - VDR09VTQ8U KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Scopolamine Derivatives -- metabolism KW - Enzyme Activation KW - Models, Molecular KW - Amino Acid Sequence KW - Carbachol -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Transfection KW - Cytoplasm -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Cell Line KW - Protein Conformation KW - Receptors, Muscarinic -- genetics KW - Protein Structure, Secondary KW - Receptors, Muscarinic -- chemistry KW - Type C Phospholipases -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76441537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Functional+role+of+a+cytoplasmic+aromatic+amino+acid+in+muscarinic+receptor-mediated+activation+of+phospholipase+C.&rft.au=Bl%C3%BCml%2C+K%3BMutschler%2C+E%3BWess%2C+J&rft.aulast=Bl%C3%BCml&rft.aufirst=K&rft.date=1994-04-15&rft.volume=269&rft.issue=15&rft.spage=11537&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 - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zinc finger domains and phorbol ester pharmacophore. Analysis of binding to mutated form of protein kinase C zeta and the vav and c-raf proto-oncogene products. AN - 76438047; 8157692 AB - The phorbol ester binding domain consists of a cysteine-rich region with a postulated consensus sequence for binding that includes 15 amino acids (Ahmed, S., Kozma, R., Lee, J., Monfries, C., Harden, N., and Lim, L. (1991) Biochem. J. 280, 233-241). In PKC zeta, the only PKC isoform lacking phorbol ester binding, this region differs in a single residue from the consensus (proline in position 11 of the motif). Restoration of this proline by site-directed mutagenesis of PKC zeta does not restore binding of either [3H]phorbol 12,13-dibutyrate or of the ultrapotent ligand [3H]bryostatin 1, suggesting that even a low affinity ligand interaction is absent. In addition, the vav and c-raf proto-oncogene products, proteins that possess cysteine-rich regions with high homology to PKC isozymes and other phorbol ester receptors, are unable to bind any of these ligands. Instead, all of these cysteine-rich regions bind zinc. Our results suggest that other amino acids besides those postulated for the consensus must be necessary for ligand binding and argue against direct modulation of PKC zeta, Vav, and c-Raf by phorbol esters. JF - The Journal of biological chemistry AU - Kazanietz, M G AU - Bustelo, X R AU - Barbacid, M AU - Kolch, W AU - Mischak, H AU - Wong, G AU - Pettit, G R AU - Bruns, J D AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/04/15/ PY - 1994 DA - 1994 Apr 15 SP - 11590 EP - 11594 VL - 269 IS - 15 SN - 0021-9258, 0021-9258 KW - c-raf KW - vav KW - Bryostatins KW - 0 KW - Cell Cycle Proteins KW - DNA Primers KW - Isoenzymes KW - Lactones KW - Macrolides KW - Oligodeoxyribonucleotides KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-vav KW - Recombinant Proteins KW - VAV1 protein, human KW - Vav1 protein, mouse KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - bryostatin 1 KW - 37O2X55Y9E KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Lactones -- metabolism KW - Isoenzymes -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Isoenzymes -- biosynthesis KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Amino Acid Sequence KW - Mice KW - Moths KW - Protein Binding KW - Cloning, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - Transfection KW - Restriction Mapping KW - Cell Line KW - Protein Kinase C -- metabolism KW - Proto-Oncogene Proteins -- biosynthesis KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Zinc -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Zinc Fingers KW - Protein Kinase C -- biosynthesis KW - Proto-Oncogenes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76438047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Zinc+finger+domains+and+phorbol+ester+pharmacophore.+Analysis+of+binding+to+mutated+form+of+protein+kinase+C+zeta+and+the+vav+and+c-raf+proto-oncogene+products.&rft.au=Kazanietz%2C+M+G%3BBustelo%2C+X+R%3BBarbacid%2C+M%3BKolch%2C+W%3BMischak%2C+H%3BWong%2C+G%3BPettit%2C+G+R%3BBruns%2C+J+D%3BBlumberg%2C+P+M&rft.aulast=Kazanietz&rft.aufirst=M&rft.date=1994-04-15&rft.volume=269&rft.issue=15&rft.spage=11590&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 - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-raf; vav N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to different flavonoids. AN - 76438933; 8155716 AB - The inhibitory and stimulatory effects of six flavonoids with distinct hydroxylation patterns on the recombinant and hepatic mouse and human CYP1A P-450s were studied. cDNA-expressed mouse CYP1A1 and CYP1A2 differed in their sensitivity to both hydroxylated and nonhydroxylated flavonoids, respectively. A comparison between the mouse and human CYP1A2 revealed that alpha-naphthoflavone and flavone did not change the benzo[a]pyrene 3-hydroxylation activity of human CYP1A2 but inhibited its 7-ethoxyresorufin and 7-methoxyresorufin O-dealkylation activities. In contrast, hydroxylated flavonoids increased the 7-methoxyresorufin O-demethylation and acetanilide 4-hydroxylation activities of cDNA-expressed human CYP1A2 and in human liver microsomes. These compounds inhibited the benzo[a]pyrene 3-hydroxylase activity of cDNA-expressed CYP1A1 and CYP1A2s as well as in mouse and human liver microsomes. Hydroxylated flavonoids did not inhibit NADPH-cytochrome P-450 oxidoreductase activity but inhibited NADPH-2,6-dichlorophenolindophenol oxidoreductase activity in liver microsomes and in microsomes from recombinant Hep G2 cells. Structure-activity relationships indicated the importance of hydroxyl groups in the 5- and 7-positions on the A ring of the flavane nucleus. These hydroxyl groups accounted for the inhibitory potency of chrysin on each of the activities of the expressed P-450s, while presence of a hydroxyl group at the 4'-position on the B ring decreased the inhibitory potency of naringenin compared to that of chrysin. The ortho-orientation of a hydroxyl group on the B ring was of importance, inasmuch as quercetin was more potent than morin as an inhibitor of cDNA-expressed and hepatic microsomal monooxygenases. JF - Biochimica et biophysica acta AU - Tsyrlov, I B AU - Mikhailenko, V M AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/13/ PY - 1994 DA - 1994 Apr 13 SP - 325 EP - 335 VL - 1205 IS - 2 SN - 0006-3002, 0006-3002 KW - Cytochrome P-450 Enzyme Inhibitors KW - 0 KW - Flavonoids KW - Isoenzymes KW - Recombinant Proteins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Index Medicus KW - Recombinant Proteins -- drug effects KW - NADH, NADPH Oxidoreductases -- drug effects KW - Animals KW - Humans KW - Microsomes, Liver -- enzymology KW - Mice KW - Species Specificity KW - Structure-Activity Relationship KW - Oxidoreductases, N-Demethylating -- drug effects KW - Isoenzymes -- drug effects KW - Flavonoids -- pharmacology KW - Cytochrome P-450 Enzyme System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76438933?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Isozyme-+and+species-specific+susceptibility+of+cDNA-expressed+CYP1A+P-450s+to+different+flavonoids.&rft.au=Tsyrlov%2C+I+B%3BMikhailenko%2C+V+M%3BGelboin%2C+H+V&rft.aulast=Tsyrlov&rft.aufirst=I&rft.date=1994-04-13&rft.volume=1205&rft.issue=2&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-19 N1 - Date created - 1994-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cooperative interactions between the interleukin 2 receptor alpha and beta chains alter the interleukin 2-binding affinity of the receptor subunits. AN - 76437939; 8159750 AB - The interleukin 2 (IL-2) receptor (IL-2R) is a multisubunit receptor that includes three major IL-2 binding subunits, the IL-2R alpha, beta, and gamma chains. We have detected and analyzed cooperative interactions between the IL-2R alpha and beta chains (IL-2R alpha and IL-2R beta, respectively) in COS cells transfected with cDNAs encoding the IL-2R alpha, the IL-2R beta, or both cDNAs. We demonstrated that IL-2 F42A, an analog that fails to bind to the isolated IL-2R alpha subunit and would be predicted by the hierarchical affinity-conversion model to have impaired binding to cells expressing both chains, instead readily binds to the IL-2R alpha/beta heterodimer in COS cells. Furthermore, this binding is abolished by the antibody HIEI that separates the two IL-2R subunits. The monoclonal antibodies anti-Tac and Mik-beta 1 directed at the IL-2-binding sites on IL-2R alpha and IL-2R beta, respectively, block ligand binding to the heterodimer. This binding pattern is inconsistent with the strict hierarchical affinity-conversion model that mandates an initial binding of IL-2 to IL-2R alpha followed by binding of the IL-2/IL-2R alpha complex to IL-2R beta. Instead, our results support an alternative model of preformed complexes of IL-2R beta with other IL-2R subunits. In this alternative model, IL-2R alpha and -beta exist in part as preformed complexes in which the affinity of IL-2R beta for IL-2 is altered by the proximity of IL-2R alpha, through mechanisms that do not require the prior binding of IL-2 to IL-2R alpha. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Roessler, E AU - Grant, A AU - Ju, G AU - Tsudo, M AU - Sugamura, K AU - Waldmann, T A AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/12/ PY - 1994 DA - 1994 Apr 12 SP - 3344 EP - 3347 VL - 91 IS - 8 SN - 0027-8424, 0027-8424 KW - Interleukin-2 KW - 0 KW - Macromolecular Substances KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Transfection KW - Protein Binding KW - Cell Line KW - Structure-Activity Relationship KW - Receptors, Interleukin-2 -- metabolism KW - Interleukin-2 -- metabolism KW - Receptors, Interleukin-2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76437939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cooperative+interactions+between+the+interleukin+2+receptor+alpha+and+beta+chains+alter+the+interleukin+2-binding+affinity+of+the+receptor+subunits.&rft.au=Roessler%2C+E%3BGrant%2C+A%3BJu%2C+G%3BTsudo%2C+M%3BSugamura%2C+K%3BWaldmann%2C+T+A&rft.aulast=Roessler&rft.aufirst=E&rft.date=1994-04-12&rft.volume=91&rft.issue=8&rft.spage=3344&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 - 1994-05-16 N1 - Date created - 1994-05-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int Immunol. 1989;1(2):160-8 [2487683] J Biol Chem. 1991 Feb 15;266(5):2681-4 [1993646] Int Immunol. 1990;2(12):1167-77 [2090200] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4636-40 [2052547] Lymphokine Cytokine Res. 1991 Jun;10(3):219-24 [1883916] J Immunol. 1991 Nov 15;147(10):3396-401 [1940342] Int Immunol. 1992 Jan;4(1):23-32 [1540547] J Immunol. 1992 Apr 1;148(7):2154-8 [1545122] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2022-6 [1549560] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2165-9 [1549576] Science. 1992 Jul 17;257(5068):379-82 [1631559] J Exp Med. 1992 Aug 1;176(2):531-41 [1500859] J Exp Med. 1992 Nov 1;176(5):1265-72 [1402672] Baillieres Clin Haematol. 1992 Jul;5(3):551-73 [1457964] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2428-32 [7681595] Cell. 1993 Apr 9;73(1):5-8 [8462103] J Immunol. 1993 Apr 15;150(8 Pt 1):3357-65 [8468475] J Immunol. 1981 Apr;126(4):1393-7 [6970774] J Exp Med. 1981 Nov 1;154(5):1455-74 [6975347] Nature. 1982 Nov 18;300(5889):267-9 [6815536] J Exp Med. 1984 Oct 1;160(4):1126-46 [6090574] Nature. 1984 Oct 18-24;311(5987):626-31 [6090948] Hybridoma. 1985 Summer;4(2):91-102 [2408992] J Exp Med. 1985 Jul 1;162(1):363-8 [2989411] Science. 1985 Nov 8;230(4726):633-9 [2996141] Microbiol Immunol. 1985;29(10):959-72 [2417094] Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694-8 [3099289] J Biol Chem. 1987 Apr 25;262(12):5723-31 [3106342] J Immunol. 1988 Jul 15;141(2):476-82 [3133409] Mol Biol Med. 1988 Apr;5(2):123-38 [3135461] Proc Natl Acad Sci U S A. 1989 Mar;86(6):1982-6 [2467293] Science. 1989 May 5;244(4904):551-6 [2785715] Annu Rev Biochem. 1989;58:875-911 [2673025] Cell. 1989 Dec 1;59(5):837-45 [2590941] J Immunol. 1989 Dec 15;143(12):4039-43 [2592767] J Immunol. 1990 Jul 15;145(2):599-606 [2365996] J Immunol. 1990 Oct 1;145(7):2177-82 [2398275] Int Immunol. 1990;2(6):521-30 [2085490] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromate-mediated free radical generation from cysteine, penicillamine, hydrogen peroxide, and lipid hydroperoxides. AN - 76434054; 8155741 AB - The Cr(VI)-mediated free radical generation from cysteine, penicillamine, hydrogen peroxide, and model lipid hydroperoxides was investigated utilizing the electron spin resonance (ESR) spin trapping technique. Incubation of Cr(VI) with cysteine (Cys) generated cysteinyl radical. Radical yield depended on the relative concentrations of Cr(VI) and Cys. The radical generation became detectable at a cysteine:Cr(VI) ratio of about 5, reached its highest level at a ratio of 30, and declined thereafter. Cr(VI) or Cys alone did not generate a detectable amount of free radicals. Similar results were obtained with penicillamine. Incubation of Cr(VI), Cys or penicillamine and H2O2 led to hydroxyl (.OH) radical generation, which was verified by quantitative competition experiments utilizing ethanol. The mechanism for .OH radical generation is considered to be a Cr(VI)-mediated Fenton-like reaction. When model lipid hydroperoxides such as t-butyl hydroperoxide and cumene hydroperoxide were used in place of H2O2, hydroperoxide-derived free radicals were produced. Since thiols, such as Cys, exist in cellular systems at relatively high concentrations, Cr(VI)-mediated free radical generation in the presence of thiols may participate in the mechanisms of Cr(VI)-induced toxicity and carcinogenesis. JF - Biochimica et biophysica acta AU - Shi, X AU - Dong, Z AU - Dalal, N S AU - Gannett, P M AD - Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/04/12/ PY - 1994 DA - 1994 Apr 12 SP - 65 EP - 72 VL - 1226 IS - 1 SN - 0006-3002, 0006-3002 KW - Chromates KW - 0 KW - Free Radicals KW - Lipid Peroxides KW - Hydroxyl Radical KW - 3352-57-6 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Penicillamine KW - GNN1DV99GX KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Hydroxyl Radical -- chemistry KW - Electron Spin Resonance Spectroscopy KW - Cysteine -- chemistry KW - Lipid Peroxides -- chemistry KW - Penicillamine -- chemistry KW - Chromates -- chemistry KW - Free Radicals -- chemistry KW - Hydrogen Peroxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76434054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Chromate-mediated+free+radical+generation+from+cysteine%2C+penicillamine%2C+hydrogen+peroxide%2C+and+lipid+hydroperoxides.&rft.au=Shi%2C+X%3BDong%2C+Z%3BDalal%2C+N+S%3BGannett%2C+P+M&rft.aulast=Shi&rft.aufirst=X&rft.date=1994-04-12&rft.volume=1226&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-13 N1 - Date created - 1994-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a lens-specific regulatory region (LSR) of the murine alpha B-crystallin gene. AN - 19629155; 8738460 AB - Previous studies have shown that the -661/+44 sequence of the murine alpha B-crystallin gene contains a muscle-preferred enhancer (-426/-257) and can drive the bacterial chloramphenicol acetyltransferase (CAT) gene in the lens, skeletal muscle and heart of transgenic mice. Here we show that transgenic mice carrying a truncated -164/+44 fragment of the alpha B-crystallin gene fused to the CAT gene expressed exclusively in the lens; by contrast mice carrying a -426/+44 fragment of the alpha B gene fused to CAT expressed highly in the lens, skeletal muscle and heart, and slightly in the lung, brain, kidney, spleen and liver. DNase I protection experiments indicated that the -147/-118 sequence is protected by nuclear proteins from alpha TN4-1 lens cell line, but not by nuclear proteins from myotubes of the C2C12 cell line. Site directed mutagenesis of this sequence decreased promoter activity in transiently-transfected lens cells, consistent with this sequence being a lens-specific regulatory region (LSR). We conclude that the -426/-257 enhancer is required for expression in skeletal muscle, heart and possibly other tissues, and that the -164/+44 sequence of the alpha B-crystallin gene is sufficient for expression in the lens of transgenic mice. Images JF - Nucleic Acids Research AU - Gopal-Srivastava, R AU - Piatigorsky, J AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04/11/ PY - 1994 DA - 1994 Apr 11 SP - 1281 EP - 1286 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 22 IS - 7 SN - 0305-1048, 0305-1048 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Regulatory sequences KW - Brain KW - Cardiac muscle KW - Spleen KW - Transgenic mice KW - alpha -Crystallin KW - Mutagenesis KW - Promoters KW - Enhancers KW - Chloramphenicol O-acetyltransferase KW - Lung KW - Myotubes KW - CAT gene KW - Liver KW - Kidney KW - Skeletal muscle KW - Deoxyribonuclease KW - J 02310:Genetics & Taxonomy KW - N 14835:Protein-Nucleic Acids Association KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19629155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Identification+of+a+lens-specific+regulatory+region+%28LSR%29+of+the+murine+alpha+B-crystallin+gene.&rft.au=Gopal-Srivastava%2C+R%3BPiatigorsky%2C+J&rft.aulast=Gopal-Srivastava&rft.aufirst=R&rft.date=1994-04-11&rft.volume=22&rft.issue=7&rft.spage=1281&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 - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Regulatory sequences; Brain; Spleen; Cardiac muscle; Transgenic mice; alpha -Crystallin; Mutagenesis; Enhancers; Promoters; Chloramphenicol O-acetyltransferase; Lung; CAT gene; Myotubes; Kidney; Liver; Deoxyribonuclease; Skeletal muscle ER - TY - JOUR T1 - Reversible transcriptional activation of mdr1 by sodium butyrate treatment of human colon cancer cells. AN - 76419405; 7908296 AB - We investigated the mechanism of sodium butyrate (NaB)-mediated induction of mdr1 mRNA in parental (wild type) and multidrug-resistant (Ad1000) SW620 colon cancer cell lines. NaB treatment resulted in reversible, time-dependent increases in nuclear run-on transcription of endogenous mdr1 in these cell lines that paralleled the reversible increases of mdr1 mRNA in both timing and magnitude. In contrast, NaB treatment had no effect on mdr1 mRNA stability. Thus, the effects of NaB on mdr1 mRNA levels are fully attributable to altered mdr1 transcription. Furthermore, NaB induces the expression of transiently transfected chloramphenicol acetyltransferase reporter plasmids that are under the transcriptional control of the mdr1 promoter (mdrCAT vectors). Transfections using mdrCAT vectors modified by deletion and site-directed mutagenesis of the mdr1 promoter indicate that NaB-mediated induction of these vectors is at least partially dependent upon sequences present in the basal mdr1 promoter between -89 and +11 relative to the start site of transcription. The Y-box motif located between -82 and -73 contributes to NaB inducibility of mdrCAT vector expression in Ad1000 SW620 cells. JF - The Journal of biological chemistry AU - Morrow, C S AU - Nakagawa, M AU - Goldsmith, M E AU - Madden, M J AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04/08/ PY - 1994 DA - 1994 Apr 08 SP - 10739 EP - 10746 VL - 269 IS - 14 SN - 0021-9258, 0021-9258 KW - mdr1 KW - Butyrates KW - 0 KW - Carrier Proteins KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA, Messenger KW - Butyric Acid KW - 107-92-6 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Index Medicus KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Promoter Regions, Genetic KW - Tumor Cells, Cultured KW - Humans KW - Drug Resistance KW - RNA, Messenger -- biosynthesis KW - Colonic Neoplasms -- genetics KW - Carrier Proteins -- genetics KW - Butyrates -- pharmacology KW - Transcription, Genetic KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76419405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reversible+transcriptional+activation+of+mdr1+by+sodium+butyrate+treatment+of+human+colon+cancer+cells.&rft.au=Morrow%2C+C+S%3BNakagawa%2C+M%3BGoldsmith%2C+M+E%3BMadden%2C+M+J%3BCowan%2C+K+H&rft.aulast=Morrow&rft.aufirst=C&rft.date=1994-04-08&rft.volume=269&rft.issue=14&rft.spage=10739&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - Gene symbol - mdr1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diagnosis of chronic hepatitis C: comparison of immunoassays and the polymerase chain reaction. AN - 85227158; pmid-8147348 AB - We evaluated a series of first- and second-generation enzyme-linked immunoassays for anti-HCV and compared the findings to those with two confirmatory assays, the recombinant immunoblot assay and serum HCV RNA, in patients with chronic hepatitis C, primary biliary cirrhosis, and chronic hepatitis B. All second-generation immunoassays had good sensitivities (98-100%). Interestingly, detection of HCV RNA had a sensitivity of only 93%, although it was 100% specific. The recombinant immunoblot assay and a peptide-based immunoassay also had good specificity (97% and 100%, respectively), whereas the second-generation immunoassay based on recombinant proteins had a high rate of false positivity, particularly among patients with primary biliary cirrhosis and hyperglobulinemia (specificity 68%). Thus, the diagnosis of HCV infection appears to require the use of more than one test. Whereas a second-generation enzyme-linked immunoassay can be used as an initial test, a confirmatory test (such as recombinant immunoblot assay or determination of hepatitis C viral RNA) may be required if the diagnosis remains uncertain. JF - The American Journal of Gastroenterology AU - Silva, A E AU - Hosein, B AU - Boyle, R W AU - Fang, C T AU - Shindo, M AU - Waggoner, J G AU - Hoofnagle, J H AU - Di Bisceglie A M AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland. PY - 1994 SP - 493 EP - 496 VL - 89 IS - 4 SN - 0002-9270, 0002-9270 KW - Sensitivity and Specificity KW - Immunoblotting KW - Hepacivirus KW - Hepatitis, Chronic KW - Human KW - RNA, Viral KW - False Positive Reactions KW - Polymerase Chain Reaction KW - Comparative Study KW - Cohort Studies KW - Hepatitis B KW - Hepatitis C KW - Liver Cirrhosis, Biliary KW - Immunoenzyme Techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85227158?accountid=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+Gastroenterology&rft.atitle=Diagnosis+of+chronic+hepatitis+C%3A+comparison+of+immunoassays+and+the+polymerase+chain+reaction.&rft.au=Silva%2C+A+E%3BHosein%2C+B%3BBoyle%2C+R+W%3BFang%2C+C+T%3BShindo%2C+M%3BWaggoner%2C+J+G%3BHoofnagle%2C+J+H%3BDi+Bisceglie+A+M&rft.aulast=Silva&rft.aufirst=A&rft.date=1994-04-01&rft.volume=89&rft.issue=4&rft.spage=493&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Gastroenterology&rft.issn=00029270&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Ondansetron: prevention of nausea & vomiting in cisplatin based chemotherapy. AN - 77714337; 7844494 AB - Ondansetron in the prophylaxis of Cisplatin-induced emesis and nausea. The 5-HT3 antagonist ondansetron clearly offers a new approach to the control of Cisplatin-induced emesis and has been evaluated in Thailand. To evaluate anti-emetic efficacy of ondansetron in the prevention of nausea and vomiting induced by Cisplatin containing cancer chemotherapy regimen, we carried out an open multicentre study from January 1991 to December 1992. In this study, patients receiving Cisplatin based chemotherapy received ondansetron 32 mg as a single intravenous dose over 15 minutes prior to the administration of Cisplatin. This was followed by oral ondansetron 8 mg three times a day, preferably one hour before each meal for 5 days. All patients were chemotherapy naive in-patients and were at least 18 years or older with Karnofsky performance status of at least 60 per cent. The number of emetic episodes, nausea and food intake were recorded during the 24 hours following Cisplatin administration. A total of 103 patients were recruited with 84 (81.6%) evaluable patients (48 men and 36 women) scheduled to receive cisplatin chemotherapy at dose 60 mg/m2 or more (60-100 mg/m2), either as single agent or combination therapy. Complete response (complete control of emesis) was achieved in 60 per cent; major response (1-2 emetic episodes) was 13 per cent; minor response (3-5 emetic episodes) was 13 per cent; and failure (5+ emetic episodes) was 10 per cent. Side effects were very mild and not significant. We conclude that ondansetron is efficacious in protecting patients from Cisplatin induced emesis and nausea. JF - Journal of the Medical Association of Thailand = Chotmaihet thangphaet AU - Cheirsilpa, A AU - Ratanatharathorn, V AU - Sinlarat, P AU - Chindavijak, K AU - Lousoontornsiri, W AU - Chakrapee-Sirisuk, S AU - Srimuninimit, V AD - National Cancer Institute, Bangkok, Thailand. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 201 EP - 206 VL - 77 IS - 4 SN - 0125-2208, 0125-2208 KW - Ondansetron KW - 4AF302ESOS KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Drug Administration Schedule KW - Aged, 80 and over KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Male KW - Female KW - Nausea -- chemically induced KW - Vomiting -- prevention & control KW - Ondansetron -- therapeutic use KW - Ondansetron -- administration & dosage KW - Nausea -- prevention & control KW - Vomiting -- chemically induced KW - Cisplatin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77714337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medical+Association+of+Thailand+%3D+Chotmaihet+thangphaet&rft.atitle=Ondansetron%3A+prevention+of+nausea+%26amp%3B+vomiting+in+cisplatin+based+chemotherapy.&rft.au=Cheirsilpa%2C+A%3BRatanatharathorn%2C+V%3BSinlarat%2C+P%3BChindavijak%2C+K%3BLousoontornsiri%2C+W%3BChakrapee-Sirisuk%2C+S%3BSrimuninimit%2C+V&rft.aulast=Cheirsilpa&rft.aufirst=A&rft.date=1994-04-01&rft.volume=77&rft.issue=4&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Medical+Association+of+Thailand+%3D+Chotmaihet+thangphaet&rft.issn=01252208&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-08 N1 - Date created - 1995-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fusion between enveloped viruses and erythrocyte membranes is induced by the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane). AN - 77097776; 7796384 AB - Pristane (2,6,10,14-tetramethylpentadecane) is an isoprenoid alkane that induces plasma cell tumors in mice. Infection with certain retroviruses accelerates tumorigenesis but the nature of the cooperation between pristane and viruses is unknown. The purpose of this study was to investigate the potential influence of pristane on the fusion between enveloped viruses and mammalian plasma membranes. Using a fluorescence dequenching assay, we found that micromolar amounts of pristane induced fusion between erythrocyte membranes and both vesicular stomatitis virus and influenza virus. Induction of fusion occurred with as little as 5 microM pristane and reached saturation at roughly 50 microM alkane. Control experiments revealed that induction of fluorescence dequenching was not due to extraneous phenomena such as lipid transfer or non-specific interactions with the carrier for pristane (beta-cyclodextrin). Fusion was also induced by standard protocols which involve lowering the pH of the incubation medium. In the presence of pristane, low pH-triggered fusion was enhanced. The extent to which pristane induced fusion was dependent upon the orientation of the lipids in the target membrane. That is, fusion was most effective with erythrocyte ghosts which had a symmetric lipid distribution and was less effective with ghosts in which the native lipid asymmetry was maintained. Intact erythrocytes, which have an asymmetric lipid distribution, were the least effective targets. This result exactly parallels the pattern observed with acid-induced fusion. Similar patterns were also observed in the temperature dependence of fusion induced by these two protocols. The novel fusogenic activity of pristane is discussed with regard to current models of virus/membrane fusion. JF - Cancer biochemistry biophysics AU - Janz, S AU - Shacter, E AU - Herrmann, A AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 1 EP - 14 VL - 14 IS - 1 SN - 0305-7232, 0305-7232 KW - Carcinogens KW - 0 KW - Membrane Lipids KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Index Medicus KW - Membrane Lipids -- chemistry KW - Spectrometry, Fluorescence KW - Plasmacytoma -- chemically induced KW - Humans KW - Hydrogen-Ion Concentration KW - Temperature KW - Erythrocyte Membrane -- chemistry KW - Influenza A virus -- drug effects KW - Biophysical Phenomena KW - Biophysics KW - Kinetics KW - In Vitro Techniques KW - Vesicular stomatitis Indiana virus -- drug effects KW - Erythrocyte Membrane -- drug effects KW - Terpenes -- toxicity KW - Membrane Fusion -- drug effects KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77097776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+biochemistry+biophysics&rft.atitle=Fusion+between+enveloped+viruses+and+erythrocyte+membranes+is+induced+by+the+isoprenoid+alkane+pristane+%282%2C6%2C10%2C14-tetramethylpentadecane%29.&rft.au=Janz%2C+S%3BShacter%2C+E%3BHerrmann%2C+A&rft.aulast=Janz&rft.aufirst=S&rft.date=1994-04-01&rft.volume=14&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+biochemistry+biophysics&rft.issn=03057232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-03 N1 - Date created - 1995-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective up-regulation of neuropeptide synthesis by blocking the neuronal activity: galanin expression in septohippocampal neurons. AN - 76746890; 7523176 AB - Neuronal activity regulates expression of phenotype-specific genes, including galanin, which coexists with choline acetyltransferase in septal and basal forebrain neurons. Transections of the fornix and the diagonal band alter galanin expression in septohippocampal neurons attributed to a deficit in target-derived trophic factors. The present study demonstrates that tetrodotoxin-induced blockade of neuronal activity fully mimicked the effect of axotomy (transection of the septohippocampal fibers) in the neurons of the nucleus of the diagonal band, and caused a dramatic, although temporary, up-regulation of galanin immunoreactivity and galanin mRNA without significant alteration in choline acetyltransferase expression. This finding suggests that in the septohippocampal cholinergic system perturbance of electrical activity alone can lead to temporary up-regulation of galanin expression, previously attributed exclusively to a "lesion effect." JF - Experimental neurology AU - Agoston, D V AU - Komoly, S AU - Palkovits, M AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 247 EP - 255 VL - 126 IS - 2 SN - 0014-4886, 0014-4886 KW - Neuropeptides KW - 0 KW - RNA, Messenger KW - Tetrodotoxin KW - 4368-28-9 KW - Galanin KW - 88813-36-9 KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Index Medicus KW - Animals KW - Choline O-Acetyltransferase -- biosynthesis KW - Choline O-Acetyltransferase -- analysis KW - Gene Expression KW - RNA, Messenger -- analysis KW - Mice KW - Homeostasis KW - Microinjections KW - In Situ Hybridization KW - RNA, Messenger -- metabolism KW - Mice, Inbred C57BL KW - Time Factors KW - Immunohistochemistry KW - Nerve Fibers -- physiology KW - Peptide Biosynthesis KW - Neurons -- metabolism KW - Hippocampus -- physiology KW - Neurons -- drug effects KW - Hippocampus -- metabolism KW - Neurons -- physiology KW - Tetrodotoxin -- administration & dosage KW - Neuropeptides -- biosynthesis KW - Tetrodotoxin -- pharmacology KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76746890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Selective+up-regulation+of+neuropeptide+synthesis+by+blocking+the+neuronal+activity%3A+galanin+expression+in+septohippocampal+neurons.&rft.au=Agoston%2C+D+V%3BKomoly%2C+S%3BPalkovits%2C+M&rft.aulast=Agoston&rft.aufirst=D&rft.date=1994-04-01&rft.volume=126&rft.issue=2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-17 N1 - Date created - 1994-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Environmental risk factors for osteoporosis. AN - 76736591; 7925179 JF - Environmental health perspectives AU - Goyer, R A AU - Epstein, S AU - Bhattacharyya, M AU - Korach, K S AU - Pounds, J Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 390 EP - 394 VL - 102 IS - 4 KW - Environmental Pollutants KW - 0 KW - Estrogens KW - Cadmium KW - 00BH33GNGH KW - Lead KW - 2P299V784P KW - Aluminum KW - CPD4NFA903 KW - Fluorides KW - Q80VPU408O KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Aluminum -- adverse effects KW - Lead -- adverse effects KW - Cadmium -- adverse effects KW - Calcium -- adverse effects KW - Risk Factors KW - Humans KW - Forecasting KW - Research KW - Estrogens -- adverse effects KW - Fluorides -- adverse effects KW - Osteoporosis -- epidemiology KW - Osteoporosis -- metabolism KW - Osteoporosis -- chemically induced KW - Environmental Pollutants -- adverse effects KW - Population Surveillance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76736591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Environmental+risk+factors+for+osteoporosis.&rft.au=Goyer%2C+R+A%3BEpstein%2C+S%3BBhattacharyya%2C+M%3BKorach%2C+K+S%3BPounds%2C+J&rft.aulast=Goyer&rft.aufirst=R&rft.date=1994-04-01&rft.volume=102&rft.issue=4&rft.spage=390&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-26 N1 - Date created - 1994-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic toxicity studies of the potential cancer preventive 2-(difluoromethyl)-dl-ornithine. AN - 76644571; 8050630 AB - The synthetic compound 2-(difluoromethyl)-dl-ornithine irreversibly inhibits ornithine decarboxylase and reduces the intracellular levels of the polyamine cell cycle factors putrescine and spermidine. The drug has shown chemopreventive efficacy in numerous laboratory epithelial cancer models and is a prototype for antiproliferative agents. Chronic toxicity studies in rats and dogs were performed to characterize the toxicities of the compound at high dosages and to support its further development in clinical trials as a potential chemopreventive agent. Chronic administration (52 weeks) by gavage to Charles River CD rats at dosages of 400, 800, and 1600 mg/kg produced weight loss, increased platelets, alopecia and skin abrasions, dermatitis, liver necrosis, and gastric inflammation. The no-effect dose in this study was considered 400 mg/kg. Chronic administration by capsule to dogs at dosages of 50, 100, and 200 mg/kg produced conjunctivitis, hyperkeratosis and alopecia, and cystic intestinal crypts. A no-effect dose was not determined in this study. The toxicities demonstrated in these studies may be minimized at lower dosages and support the further development of this compound in chemopreventive clinical investigations. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Crowell, J A AU - Goldenthal, E I AU - Kelloff, G J AU - Malone, W F AU - Boone, C W AD - Chemoprevention Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 341 EP - 354 VL - 22 IS - 3 SN - 0272-0590, 0272-0590 KW - Anticarcinogenic Agents KW - 0 KW - Hemoglobins KW - Eflornithine KW - ZQN1G5V6SR KW - Index Medicus KW - Eating -- drug effects KW - Animals KW - Dermatitis -- pathology KW - Blood Chemical Analysis KW - Chemical and Drug Induced Liver Injury -- pathology KW - Sex Characteristics KW - Skin -- pathology KW - Cell Division -- drug effects KW - Conjunctivitis -- pathology KW - Rats KW - Hemoglobins -- metabolism KW - Conjunctivitis -- chemically induced KW - Body Weight -- drug effects KW - Dogs KW - Intestinal Mucosa -- pathology KW - Species Specificity KW - Male KW - Blood Cell Count -- drug effects KW - Female KW - Organ Size -- drug effects KW - Eflornithine -- toxicity KW - Anticarcinogenic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76644571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Chronic+toxicity+studies+of+the+potential+cancer+preventive+2-%28difluoromethyl%29-dl-ornithine.&rft.au=Crowell%2C+J+A%3BGoldenthal%2C+E+I%3BKelloff%2C+G+J%3BMalone%2C+W+F%3BBoone%2C+C+W&rft.aulast=Crowell&rft.aufirst=J&rft.date=1994-04-01&rft.volume=22&rft.issue=3&rft.spage=341&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative toxicities of o-, m-, and p-nitrotoluene in 13-week feed studies in F344 rats and B6C3F1 mice. AN - 76643679; 7519572 AB - Nitrotoluenes are high-production-volume chemicals used in the synthesis of agricultural chemicals and in various dyes. Because of differences in the metabolism of the three isomers and their capabilities to bind to DNA, comparative toxicity studies of o-, m-, and p-nitrotoluene were conducted in F344 rats and B6C3F1 mice. o-, m-, or p-Nitrotoluene was administered in the feed to male and female rats and mice at doses ranging from 625 to 10,000 ppm for 13 weeks. These doses delivered approximately 40 to 700 mg/kg body wt/day for rats and 100 to 1700 mg/kg/day for mice. There were no treatment-related effects on survival in any of the studies. Decreased body weights relative to controls occurred in dosed rats and mice in all studies at the higher dose levels and were most pronounced in rats receiving o-nitrotoluene. Mesotheliomas of the tunica vaginalis were observed in 3 of 10 male rats receiving o-nitrotoluene at 5000 ppm, and mesothelial cell hyperplasia was observed in 2 of 10 male rats receiving o-nitrotoluene at 10,000 ppm. Kidney toxicity was observed in male rats receiving o-, m-, or p-nitrotoluene and included hyaline droplet nephropathy and an associated increase in the renal concentration of alpha 2U-globulin. Evidence of liver toxicity in the male rats receiving o-nitrotoluene included hepatocyte vacuolization, oval cell hyperplasia, and increased serum bile acids, sorbitol dehydrogenase, and alanine aminotransferase. Although there was no histopathologic evidence of hepatic toxicity in male or female rats given the m- or p-isomers or in female rats given the o-isomer, treatment-related hepatic effects were detected in these groups, as measured by an increase in the relative liver weights and by elevations in serum bile acids and liver-specific enzymes. The spleens of treated male and female rats had a mild increase in hematopoiesis, hemosiderin deposition, and/or congestion. These splenic changes were slightly more prominent in rats administered the o- and p-isomers. Administration of o-, m-, or p-nitrotoluene impaired testicular function in the rat, as shown by testicular degeneration and reduction in the density, motility, and number of sperm cells. Administration of each isomer to rats caused increases in the length of the estrus cycle. The only histopathologic evidence for treatment-related toxicity in mice in the 13-week studies occurred in animals receiving the o-nitrotoluene isomer where the chemical caused degeneration and metaplasia of the olfactory epithelium.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Dunnick, J K AU - Elwell, M R AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 411 EP - 421 VL - 22 IS - 3 SN - 0272-0590, 0272-0590 KW - Alpha-Globulins KW - 0 KW - alpha(2)-microglobulin KW - 3-nitrotoluene KW - 29A9W826KQ KW - Toluene KW - 3FPU23BG52 KW - 2-nitrotoluene KW - 6Q9N88YIAY KW - 4-nitrotoluene KW - E88IMG14EX KW - Index Medicus KW - Eating -- drug effects KW - Weight Gain -- drug effects KW - Animals KW - Kidney Diseases -- pathology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Genitalia -- pathology KW - Mice KW - Splenic Diseases -- chemically induced KW - Alpha-Globulins -- metabolism KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Animal Feed -- analysis KW - Splenic Diseases -- pathology KW - Female KW - Male KW - Kidney Diseases -- chemically induced KW - Toluene -- analogs & derivatives KW - Toluene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76643679?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Comparative+toxicities+of+o-%2C+m-%2C+and+p-nitrotoluene+in+13-week+feed+studies+in+F344+rats+and+B6C3F1+mice.&rft.au=Dunnick%2C+J+K%3BElwell%2C+M+R%3BBucher%2C+J+R&rft.aulast=Dunnick&rft.aufirst=J&rft.date=1994-04-01&rft.volume=22&rft.issue=3&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The relationship between use of the maximum tolerated dose and study sensitivity for detecting rodent carcinogenicity. AN - 76642672; 8050633 AB - The relationship between maximum tolerated dose (MTD) and study sensitivity for detecting rodent carcinogenicity was evaluated for 216 chemicals found to be carcinogens in laboratory animal studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). Approximately two-thirds of these rodent carcinogens would have been detected even without the top dose (estimated MTD), but in many of these studies, some site-specific carcinogenic effects would have been missed. Among the remaining one-third of the rodent carcinogens that required the top dose for statistical significance, approximately 80% had numerically elevated rates of the same site-specific tumors at lower doses as well. Only 13 of the NCI/NTP rodent carcinogens had increased tumor rates limited to the top dose for all sites of carcinogenicity. Alternatively, of the 838 site-specific carcinogenic effects observed in the NCI/NTP studies, 447 (53%) would have been detected even without the top dose. Of the remaining effects, 75% (294/391) showed numerically elevated site-specific tumor rates at lower doses. Our evaluation indicates that most carcinogenic effects observed at the top dose in rodent studies are also present (with reduced incidence that might or might not be statistically significant) at the lower doses typically employed (1/2MTD, 1/4MTD). JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Haseman, J K AU - Lockhart, A AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 382 EP - 391 VL - 22 IS - 3 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Rats KW - Animals KW - Databases, Factual KW - Organ Specificity KW - Mice KW - Male KW - Female KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76642672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=The+relationship+between+use+of+the+maximum+tolerated+dose+and+study+sensitivity+for+detecting+rodent+carcinogenicity.&rft.au=Haseman%2C+J+K%3BLockhart%2C+A&rft.aulast=Haseman&rft.aufirst=J&rft.date=1994-04-01&rft.volume=22&rft.issue=3&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-06 N1 - Date created - 1994-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies with transfected and permeabilized RBL-2H3 cells reveal unique inhibitory properties of protein kinase C gamma. AN - 76631754; 8054687 AB - To characterize protein kinase C (PKC) gamma, an isozyme found exclusively in brain and spinal cord, its cDNA was introduced into basophilic RBL-2H3 cells that lack this isozyme. The expression of PKC gamma significantly attenuated antigen-induced responses including hydrolysis of inositol phospholipids, increase in cytosolic calcium, and secretion of granules but enhanced antigen-induced release of arachidonic acid. Instead of a sustained increase in cytosolic calcium, antigen now induced calcium oscillations; possibly as a consequence of suppression of the phospholipase C activity and incomplete emptying of internal calcium stores. In addition, PKC gamma appeared to inhibit activation of other PKC isozymes because phorbol 12-myristate 13-acetate failed to act synergistically with the Ca(2+)-ionophore on secretion. This was confirmed in other studies where PKC gamma was shown to suppress the transduction of stimulatory signals by other isozymes of PKC on provision of these isozymes to PKC-depleted permeabilized cells. The studies in total indicated that only PKC gamma was capable of inhibiting both early and distal signals for secretion including those signals transduced by endogenous isozymes of PKC. JF - Molecular biology of the cell AU - Baumgartner, R A AU - Ozawa, K AU - Cunha-Melo, J R AU - Yamada, K AU - Gusovsky, F AU - Beaven, M A AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 475 EP - 484 VL - 5 IS - 4 SN - 1059-1524, 1059-1524 KW - DNA, Complementary KW - 0 KW - Dinitrophenols KW - Isoenzymes KW - Phosphatidylinositols KW - Serum Albumin, Bovine KW - dinitrophenyl-bovine serum albumin KW - Arachidonic Acid KW - 27YG812J1I KW - Prkcd protein, rat KW - EC 2.7.1.- KW - protein kinase C gamma KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C beta KW - Protein Kinase C-delta KW - beta-N-Acetylhexosaminidases KW - EC 3.2.1.52 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Phosphatidylinositols -- metabolism KW - Arachidonic Acid -- metabolism KW - Rats KW - Calcium -- metabolism KW - Transfection KW - beta-N-Acetylhexosaminidases -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Serum Albumin, Bovine -- pharmacology KW - Dinitrophenols -- pharmacology KW - Cell Membrane Permeability KW - Moloney murine leukemia virus -- genetics KW - Cell Membrane -- metabolism KW - Hydrolysis -- drug effects KW - Cell Line KW - Protein Kinase C -- metabolism KW - Exocytosis -- physiology KW - Exocytosis -- drug effects KW - Protein Kinase C -- genetics KW - Mast Cells -- physiology KW - Protein Kinase C -- pharmacology KW - Isoenzymes -- genetics KW - Mast Cells -- drug effects KW - Isoenzymes -- pharmacology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76631754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=Studies+with+transfected+and+permeabilized+RBL-2H3+cells+reveal+unique+inhibitory+properties+of+protein+kinase+C+gamma.&rft.au=Baumgartner%2C+R+A%3BOzawa%2C+K%3BCunha-Melo%2C+J+R%3BYamada%2C+K%3BGusovsky%2C+F%3BBeaven%2C+M+A&rft.aulast=Baumgartner&rft.aufirst=R&rft.date=1994-04-01&rft.volume=5&rft.issue=4&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-14 N1 - Date created - 1994-09-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Immunol. 1981 Apr;11(4):317-23 [6166481] Cell. 1993 Dec 31;75(7):1253-62 [8269509] J Biol Chem. 1984 Jun 10;259(11):7129-36 [6202691] Biochem Biophys Res Commun. 1984 Jun 15;121(2):573-8 [6203533] Cell. 1984 Jul;37(3):1053-62 [6331674] Nature. 1985 Jan 3-9;313(5997):59-60 [2578217] Immunol Lett. 1984;8(5):237-41 [6240439] Proc Natl Acad Sci U S A. 1985 Jun;82(11):3871-5 [3923482] J Biol Chem. 1986 Feb 25;261(6):2583-92 [2419319] Mol Immunol. 1986 Mar;23(3):279-84 [3086712] Cell. 1986 Aug 15;46(4):491-502 [3755379] J Cell Biol. 1987 Sep;105(3):1129-36 [2443506] J Biol Chem. 1988 Apr 5;263(10):4523-6 [3280565] J Neurosci. 1988 May;8(5):1678-83 [3367216] J Biol Chem. 1988 Jul 15;263(20):9868-73 [3133370] Nature. 1988 Aug 25;334(6184):661-5 [3045562] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460-4 [3413107] Prog Allergy. 1988;42:123-84 [2845425] J Neurosci. 1988 Nov;8(11):4262-8 [3183723] J Neurosci. 1988 Dec;8(12):4734-44 [2462028] J Biol Chem. 1989 Jul 25;264(21):12492-501 [2473073] JAMA. 1989 Oct 6;262(13):1826-33 [2674488] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5149-53 [1905018] J Biol Chem. 1991 Jul 25;266(21):13646-53 [1906881] FEBS Lett. 1991 Sep 2;289(1):47-50 [1832647] J Biol Chem. 1991 Dec 25;266(36):24237-40 [1662204] Nature. 1992 Jan 2;355(6355):78-80 [1370575] Immunol Rev. 1992 Feb;125:37-48 [1532373] J Biol Chem. 1992 Apr 15;267(11):7310-4 [1373133] J Biol Chem. 1992 Jun 25;267(18):12606-13 [1535623] Immunol Today. 1992 Jun;13(6):195-7 [1320890] J Immunol. 1992 Aug 1;149(3):1031-7 [1378861] Science. 1992 Oct 23;258(5082):607-14 [1411571] J Biol Chem. 1993 Jan 25;268(3):1749-56 [8420951] J Biol Chem. 1993 Feb 5;268(4):2280-3 [8381401] Immunol Today. 1993 May;14(5):222-6 [8517921] J Biol Chem. 1993 Oct 15;268(29):21486-8 [8407996] Methods Enzymol. 1983;99:288-98 [6316094] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor incidence in a chemical carcinogenesis study of nonhuman primates. AN - 76627632; 8041912 AB - This report covers a 32-year period of an ongoing chemical carcinogenesis study in nonhuman primates, which was initiated by the National Cancer Institute in 1961. Autopsy records of 373 breeders and normal controls showed very low incidence of spontaneous malignant tumors in cynomolgus (1.5%) and rhesus (2.8%) monkeys, but considerably higher incidence in African green monkeys (8%). A large number of substances including a variety of food additives, food components, environmental contaminants, N-nitroso compounds, "classical" rodent carcinogens, antineoplastic agents, and immunosuppressive agents have been evaluated for long-term carcinogenic activity. Food components tested which are probably most relevant to human exposure are the artificial sweeteners, cyclamate and saccharin. After 22 years of continuous dosing, neither cyclamate nor saccharin have shown any evidence of carcinogenic effects. Similarly, the tumorigenic potential of arsenic and DDT was negligible after dosing for 15-22 years. In contrast, the fungal food contaminants, aflatoxin B1 (AFB1) and sterigmatocystin (SMT), were found to be potent hepatocarcinogens. AFB1 also induced adenocarcinomas of the pancreas, osteosarcomas, and other tumors. Also, the aglycone of cycasin, MAM acetate, induced a variety of tumors, but primarily hepatocellular and renal cell carcinomas. The compounds most recently introduced into the colony include three heterocyclic amines present in cooked meat. One of these compounds, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has proven to be one of the most potent hepatocarcinogens in the history of the monkey project, inducing malignant liver tumors in 65% of animals over a 7-year period of exposure. Of the classical rodent carcinogens studied, urethane was the only one which produced malignant tumors in the monkeys. Conversely, all except two of the N-nitroso compounds were carcinogenic. Diethylnitrosamine (DENA) was the most potent and predictable hepatocarcinogen in cynomolgus, rhesus, and African green monkeys. However, when administered intraperitoneally to galagos (a prosimian), DENA induced primarily mucoepidermoid carcinoma of the nasal cavity. N-Methyl-N-nitrosourea (MNU) was the only carcinogen persistently producing tumors in the digestive tract, mostly squamous cell carcinomas of the esophagus. Among the antineoplastic and immunosuppressive agents, procarbazine (MIH) was the only unequivocal carcinogen, with a 33% tumor incidence, causing acute nonlymphocytic leukemia in most of the cases. JF - Regulatory toxicology and pharmacology : RTP AU - Thorgeirsson, U P AU - Dalgard, D W AU - Reeves, J AU - Adamson, R H AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 130 EP - 151 VL - 19 IS - 2 SN - 0273-2300, 0273-2300 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - Environmental Pollutants KW - Food Additives KW - Immunosuppressive Agents KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Environmental Pollutants -- toxicity KW - Immunosuppressive Agents -- toxicity KW - Cercopithecus aethiops KW - Antineoplastic Agents -- toxicity KW - Macaca mulatta KW - Food Additives -- toxicity KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76627632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.atitle=Tumor+incidence+in+a+chemical+carcinogenesis+study+of+nonhuman+primates.&rft.au=Thorgeirsson%2C+U+P%3BDalgard%2C+D+W%3BReeves%2C+J%3BAdamson%2C+R+H&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1994-04-01&rft.volume=19&rft.issue=2&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Regulatory+toxicology+and+pharmacology+%3A+RTP&rft.issn=02732300&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-24 N1 - Date created - 1994-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between age and drinking patterns and drinking problems among Japanese, Japanese-Americans, and Caucasians. AN - 76621861; 8048731 AB - Comparing alcohol consumption patterns by age and gender among Japanese in Japan and Japanese-Americans and Caucasians in the United States, this study examined the associations between age and both heavy drinking and social problems using logistic regression for each ethnic group of male current drinkers. As reported in previous studies of Caucasians, men drink more alcohol than women, older respondents are more likely than younger ones to be abstainers, and the percentages of heavier drinkers and problem drinkers are higher among the young than among older people. Although Japanese-Americans reported consuming less alcohol than Caucasians, their drinking patterns by age were similar: among both United States populations, younger respondents are at higher risk for drinking problems than older respondents, even when alcohol consumption and sociodemographic variables are controlled by logistic regression. However, this association of age and drinking patterns and drinking problems is not universal. Japanese men consumed more alcohol and had a higher proportion of heavier drinkers in the middle age groups; the association between age and drinking problems also varied in this group. In addition to aging, sociocultural factors such as drinking norms probably account for the differences in drinking behavior among different age groups. This study may stimulate further cross-cultural comparison of drinking patterns and problems. JF - Alcoholism, clinical and experimental research AU - Higuchi, S AU - Parrish, K M AU - Dufour, M C AU - Towle, L H AU - Harford, T C AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 305 EP - 310 VL - 18 IS - 2 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Aged KW - Japan -- epidemiology KW - Cross-Sectional Studies KW - Acculturation KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Social Environment KW - Alcohol Drinking -- ethnology KW - Cross-Cultural Comparison KW - Alcoholism -- ethnology KW - Alcohol Drinking -- adverse effects KW - Asian Americans -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76621861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Relationship+between+age+and+drinking+patterns+and+drinking+problems+among+Japanese%2C+Japanese-Americans%2C+and+Caucasians.&rft.au=Higuchi%2C+S%3BParrish%2C+K+M%3BDufour%2C+M+C%3BTowle%2C+L+H%3BHarford%2C+T+C&rft.aulast=Higuchi&rft.aufirst=S&rft.date=1994-04-01&rft.volume=18&rft.issue=2&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-01 N1 - Date created - 1994-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisocial behavior, family history, and alcohol dependence symptoms. AN - 76621809; 8048725 AB - Drawing on data from the National Longitudinal Survey of young adults, this study examines the effects of antisocial behavior on alcohol dependence among young men and women in the United States. An analysis of the data from the study indicates that there are effects of antisocial behavior and that these effects cannot be attributed to a lower social class family of origin or to a positive family history of alcoholism. The analysis also indicates that the strongest effects are found among young adults with both antisocial behavior and a positive family history. JF - Alcoholism, clinical and experimental research AU - Harford, T C AU - Parker, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 265 EP - 268 VL - 18 IS - 2 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - United States KW - Socioeconomic Factors KW - Risk Factors KW - Humans KW - Adult KW - Personality Development KW - Longitudinal Studies KW - Adolescent KW - Male KW - Female KW - Social Environment KW - Child of Impaired Parents -- psychology KW - Antisocial Personality Disorder -- genetics KW - Antisocial Personality Disorder -- psychology KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76621809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Antisocial+behavior%2C+family+history%2C+and+alcohol+dependence+symptoms.&rft.au=Harford%2C+T+C%3BParker%2C+D+A&rft.aulast=Harford&rft.aufirst=T&rft.date=1994-04-01&rft.volume=18&rft.issue=2&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-01 N1 - Date created - 1994-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mice provide genetic evidence that transforming growth factor alpha promotes skin tumorigenesis via H-ras-dependent and H-ras-independent pathways. AN - 76619195; 8043512 AB - The epidermal growth factor receptor (EGFR), which mediates the mitogenic activity of transforming growth factor alpha (TGF-alpha), has been shown to activate Ras in cultured cells through well-defined intermediary proteins. To examine the in vivo relationship between EGFR and Ras, chemical carcinogenesis of TGF-alpha transgenic mouse skin was chosen as an experimental model. Transgenic mice overexpressing TGF-alpha in a wide variety of epithelial tissues by virtue of a metallothionein promoter demonstrate a multitude of premalignant and neoplastic lesions but not spontaneous skin tumors. Transgenic skin was initiated with a single dose of 7,12-dimethylbenz[a]anthracene (DMBA), shown previously to induce, in concert with a tumor promoter, murine papillomas that consistently contain specific H-ras mutations. Virtually all DMBA-treated TGF-alpha transgenic mice, but not treated control animals, developed hyperplasias, papillomas, sebaceous adenomas, and more infrequently, sebaceous and squamous cell carcinomas. Therefore, TGF-alpha functions as an autonomous tumor promoter in DMBA-initiated transgenic skin. Skin tumors could be separated into two mutually exclusive genetic classes. In tumors harboring mutant H-ras, TGF-alpha transgene expression was relatively low and essentially unchanged relative to untreated skin; however, only 42% of skin tumors contained mutations in H-ras. Conversely, in most tumors with wild-type H-ras, transgenic TGF-alpha transcripts were enhanced 10- to 20-fold. These results suggest that strong constitutive EGFR stimulation, through TGF-alpha transgene overexpression, can substitute functionally for mutational activation of H-ras in skin tumorigenesis. Moreover, because H-ras mutational activation could not induce skin tumors without TGF-alpha transgene activity, simultaneous stimulation of an EGFR-mediated H-Ras-independent pathway appears to be required for tumor development as well. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Jhappan, C AU - Takayama, H AU - Dickson, R B AU - Merlino, G AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 385 EP - 394 VL - 5 IS - 4 SN - 1044-9523, 1044-9523 KW - H-ras KW - Transforming Growth Factor alpha KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Base Sequence KW - Skin -- metabolism KW - Models, Genetic KW - Molecular Sequence Data KW - Mice KW - Mice, Transgenic KW - Mutation KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Transforming Growth Factor alpha -- toxicity KW - Receptor, Epidermal Growth Factor -- genetics KW - Skin Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76619195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Transgenic+mice+provide+genetic+evidence+that+transforming+growth+factor+alpha+promotes+skin+tumorigenesis+via+H-ras-dependent+and+H-ras-independent+pathways.&rft.au=Jhappan%2C+C%3BTakayama%2C+H%3BDickson%2C+R+B%3BMerlino%2C+G&rft.aulast=Jhappan&rft.aufirst=C&rft.date=1994-04-01&rft.volume=5&rft.issue=4&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-31 N1 - Date created - 1994-08-31 N1 - Date revised - 2017-01-13 N1 - Gene symbol - H-ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Temporal association between implementation of universal precautions and a sustained, progressive decrease in percutaneous exposures to blood. AN - 76618788; 8038311 AB - To evaluate whether implementation of universal precautions was temporally associated with a decrease in reported parenteral exposures to blood, we analyzed data on self-reported parenteral injuries that were prospectively collected at the Clinical Center, National Institutes of Health (Bethesda, MD), from 1985 through 1991. We also assessed whether implementation of universal precautions, in concert with initiation of a program of postexposure chemoprophylaxis with zidovudine, was associated with decreased time to reporting of occupational exposures. Our data, possibly confounded by the occurrence of an occupational infection due to human immunodeficiency virus infection in 1988, nonetheless demonstrate a temporal association between a progressive, significant decrease in percutaneous injuries and the implementation of universal precautions that has been sustained through subsequent years. The analysis remains significant, regardless of the surrogate denominator chosen for analysis. No trend toward more rapid reporting of exposures was identified. Implementation of universal precautions appears to have contributed to decreased parenteral injuries in our hospital but did not affect reporting efficiency. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Beekmann, S E AU - Vlahov, D AU - Koziol, D E AU - McShalley, E D AU - Schmitt, J M AU - Henderson, D K AD - Hospital Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 562 EP - 569 VL - 18 IS - 4 SN - 1058-4838, 1058-4838 KW - Index Medicus KW - AIDS/HIV KW - Occupational Exposure -- statistics & numerical data KW - Occupational Exposure -- prevention & control KW - HIV Infections -- transmission KW - Humans KW - National Institutes of Health (U.S.) KW - Infectious Disease Transmission, Patient-to-Professional -- statistics & numerical data KW - Blood-Borne Pathogens KW - Databases, Factual KW - Infectious Disease Transmission, Patient-to-Professional -- prevention & control KW - United States -- epidemiology KW - Time Factors KW - Hepatitis B -- transmission KW - Needlestick Injuries -- prevention & control KW - Universal Precautions -- statistics & numerical data KW - Needlestick Injuries -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76618788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Temporal+association+between+implementation+of+universal+precautions+and+a+sustained%2C+progressive+decrease+in+percutaneous+exposures+to+blood.&rft.au=Beekmann%2C+S+E%3BVlahov%2C+D%3BKoziol%2C+D+E%3BMcShalley%2C+E+D%3BSchmitt%2C+J+M%3BHenderson%2C+D+K&rft.aulast=Beekmann&rft.aufirst=S&rft.date=1994-04-01&rft.volume=18&rft.issue=4&rft.spage=562&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-24 N1 - Date created - 1994-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice. AN - 76614772; 8048747 AB - Ethanol-dependent mice were treated with the 5-HT3 antagonist MDL 72222 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10, and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose-dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after withdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display any seizures. Treatment with another 5-HT3 antagonist, ICS 205-930 (23 and 46 mg/kg), or the 5-HT2 receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure. JF - Alcoholism, clinical and experimental research AU - Grant, K A AU - Hellevuo, K AU - Tabakoff, B AD - Division of Clinical and Biologic Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 410 EP - 414 VL - 18 IS - 2 SN - 0145-6008, 0145-6008 KW - Receptors, Serotonin KW - 0 KW - Serotonin Antagonists KW - Tropanes KW - Ketanserin KW - 97F9DE4CT4 KW - bemesetron KW - O98T3677PA KW - Index Medicus KW - Stimulation, Chemical KW - Evoked Potentials -- drug effects KW - Animals KW - Postural Balance -- physiology KW - Dose-Response Relationship, Drug KW - Mice, Inbred C57BL KW - Evoked Potentials -- physiology KW - Mice KW - Ketanserin -- pharmacology KW - Male KW - Postural Balance -- drug effects KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Tropanes -- pharmacology KW - Serotonin Antagonists -- pharmacology KW - Seizures -- physiopathology KW - Alcohol Withdrawal Delirium -- physiopathology KW - Electroencephalography -- drug effects KW - Receptors, Serotonin -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76614772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=The+5-HT3+antagonist+MDL-72222+exacerbates+ethanol+withdrawal+seizures+in+mice.&rft.au=Grant%2C+K+A%3BHellevuo%2C+K%3BTabakoff%2C+B&rft.aulast=Grant&rft.aufirst=K&rft.date=1994-04-01&rft.volume=18&rft.issue=2&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-01 N1 - Date created - 1994-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits. AN - 76598699; 8031034 AB - A unilamellar liposomal formulation of amphotericin B (LAmB) known as AmBisome was safely administered intravenously to 20 rabbits at 0.5, 1.0, 2.5, 5, or 10 mg/kg of body weight, whereas of 12 rabbits given desoxycholate amphotericin B (DAmB) intravenously at 0.5, 1.0, or 1.5 mg/kg, 2 died of acute cardiac toxicity when DAmB was administered at the highest dose. Single-dose LAmB (1 mg/kg) achieved a maximum concentration in serum (Cmax) of 26 +/- 2.4 micrograms/ml and an area under the curve to infinity (AUC0-infinity) of 60 +/- 16 micrograms.h/ml, while single-dose DAmB (1.0 mg/kg), by comparison, achieved a lower Cmax (4.7 +/- 0.2 micrograms/ml; P = 0.001) and a lower AUC0-infinity (30.6 +/- 2.2 micrograms.h/ml; P = 0.07). Following administration of a single dose of LAmB (10 mg/kg), a disproportionately higher Cmax (287 +/- 14 micrograms/ml) and AUC0-infinity (2,223 +/- 246 micrograms.h/ml) occurred, indicating saturable elimination. After chronic dosing (n = 4) with LAmB at 5.0 mg/kg/day for 28 days or DAmB at 1.0 mg/kg/day for 28 days, LAmB achieved daily peak levels of 122.8 +/- 5.8 micrograms/ml and trough levels of 34.9 +/- 1.8 micrograms/ml, while DAmB reached a peak of only 1.76 +/- 0.11 microgram/ml and a trough of 0.46 +/- 0.04 microgram/ml (P < or = 0.001). Significant accumulations of amphotericin B into reticuloendothelial organs were observed, with 239 +/- 39 micrograms/g found in the liver after chronic LAmB dosing (5 mg/kg/day), which was seven times higher than the 33 +/- 6 micrograms/g after DAmB dosing (1 mg/kg/day) (P = 0.002). Accumulation in kidneys, however, remained 14-fold lower (P =0.04) following LAmB dosing (0.87 +/- 0.61 microgram/g) than after DAmB dosing (12.7 +/- 4.6 microgram/g). Nephrotoxicity occurred in only one of four LAmB treated animals, while it occurred in all four chronically DAmB-treated animals: mild hepatozicity with transaminase elevations was seen in one LAmB-treated rabbit. We conclude that LAmB safely achieved higher Cmax(s) and AUC0-infinity(s) and demonstrated saturable, nonlinear elimination from plasma via reticuloendothelial organ uptake. Take reduced nephrotoxicity of LAmB correlated with diminished levels of amphotericin B in the kidneys. JF - Antimicrobial agents and chemotherapy AU - Lee, J W AU - Amantea, M A AU - Francis, P A AU - Navarro, E E AU - Bacher, J AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 713 EP - 718 VL - 38 IS - 4 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Drug Combinations KW - Liposomes KW - liposomal amphotericin B KW - Deoxycholic Acid KW - 005990WHZZ KW - Amphotericin B KW - 7XU7A7DROE KW - amphotericin B, deoxycholate drug combination KW - 87687-70-5 KW - Index Medicus KW - Deoxycholic Acid -- pharmacokinetics KW - Animals KW - Antifungal Agents -- toxicity KW - Antifungal Agents -- pharmacokinetics KW - Spectrophotometry, Ultraviolet KW - Rabbits KW - Tissue Distribution KW - Chromatography, High Pressure Liquid KW - Deoxycholic Acid -- administration & dosage KW - Antifungal Agents -- administration & dosage KW - Deoxycholic Acid -- toxicity KW - Female KW - Kidney Diseases -- chemically induced KW - Amphotericin B -- pharmacokinetics KW - Amphotericin B -- administration & dosage KW - Amphotericin B -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76598699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Pharmacokinetics+and+safety+of+a+unilamellar+liposomal+formulation+of+amphotericin+B+%28AmBisome%29+in+rabbits.&rft.au=Lee%2C+J+W%3BAmantea%2C+M+A%3BFrancis%2C+P+A%3BNavarro%2C+E+E%3BBacher%2C+J%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Lee&rft.aufirst=J&rft.date=1994-04-01&rft.volume=38&rft.issue=4&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1981 Dec 23;666(3):493-503 [7034780] Science. 1983 Apr 29;220(4596):502-5 [6836294] Cancer Res. 1984 Jan;44(1):375-8 [6317172] Can Med Assoc J. 1984 Nov 15;131(10):1245-7 [6594184] J Chromatogr. 1987 Aug 7;419:401-7 [3667799] J Antimicrob Chemother. 1991 Oct;28 Suppl B:93-104 [1778896] J Antimicrob Chemother. 1991 Oct;28 Suppl B:105-9 [1778887] J Antimicrob Chemother. 1991 Oct;28 Suppl B:39-48 [1778891] J Antimicrob Chemother. 1991 Oct;28 Suppl B:49-61 [1778892] J Antimicrob Chemother. 1991 Oct;28 Suppl B:73-82 [1778894] J Antimicrob Chemother. 1991 Oct;28 Suppl B:83-91 [1778895] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of ADCI against convulsant and locomotor stimulant effects of cocaine: comparison with the structural analogs dizocilpine and carbamazepine. AN - 76594633; 8029253 AB - Both the antiepileptic, carbamazepine, and the N-methyl-D-aspartate receptor antagonist, dizocilpine, have shown preclinical efficacy against behavioral and toxic effects of cocaine. Nonetheless, side effects or toxicity of these compounds either alone or in conjunction with cocaine are problematic. 5-Aminocarbonyl-10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,1 0-imine (ADCI), a molecular hybrid of these compounds, has been shown to have a broad anticonvulsant profile with a good protective index (behavioral TD50/anticonvulsant ED50). In male Swiss Webster mice, ADCI and dizocilpine produced dose-dependent protection against the convulsant effects of cocaine that were insensitive to carbamazepine. However, in contrast to dizocilpine, ADCI did not produce behavioral impairment on the inverted screen test demonstrating a protective index of greater than 15; the protective index for dizocilpine was 1.2. All three compounds attenuated the locomotor stimulant effects of cocaine without significantly decreasing locomotor activity on their own, although the cocaine antagonism was not always dose dependent. Only dizocilpine increased spontaneous locomotor activity when given alone and augmented the locomotor stimulant effects of cocaine. The results confirm the novel anticonvulsant activity of ADCI and its lack of phencyclidine-like behavioral side effects. The data also suggest a modest blocking action of these compounds against the locomotor stimulatory effects of cocaine. JF - Pharmacology, biochemistry, and behavior AU - Seidleck, B K AU - Thurkauf, A AU - Witkin, J M AD - Psychobiology Section, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 839 EP - 844 VL - 47 IS - 4 SN - 0091-3057, 0091-3057 KW - Anticonvulsants KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - 5-aminocarbonyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine KW - 124070-15-1 KW - Carbamazepine KW - 33CM23913M KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Dose-Response Relationship, Drug KW - Substance-Related Disorders -- drug therapy KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Carbamazepine -- pharmacology KW - Seizures -- drug therapy KW - Motor Activity -- drug effects KW - Mice KW - Drug Evaluation, Preclinical KW - Male KW - Anticonvulsants -- pharmacology KW - Dizocilpine Maleate -- toxicity KW - Anticonvulsants -- toxicity KW - Cocaine -- toxicity KW - Anticonvulsants -- administration & dosage KW - Dizocilpine Maleate -- administration & dosage KW - Dizocilpine Maleate -- pharmacology KW - Dizocilpine Maleate -- analogs & derivatives KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76594633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Evaluation+of+ADCI+against+convulsant+and+locomotor+stimulant+effects+of+cocaine%3A+comparison+with+the+structural+analogs+dizocilpine+and+carbamazepine.&rft.au=Seidleck%2C+B+K%3BThurkauf%2C+A%3BWitkin%2C+J+M&rft.aulast=Seidleck&rft.aufirst=B&rft.date=1994-04-01&rft.volume=47&rft.issue=4&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of vitamin/mineral supplementation on the proliferation of esophageal squamous epithelium in Linxian, China. AN - 76585605; 8019379 AB - Abnormalities of epithelial proliferation have been proposed as an early step in gastrointestinal carcinogenesis. To determine whether micronutrient supplementation may reduce squamous epithelial proliferation in the esophagus, we evaluated proliferation in subjects participating in a randomized nutrition intervention trial in Linxian, China, where esophageal cancer rates are among the highest in the world. After 30 months of intervention involving daily supplementation with multiple vitamins and minerals, an endoscopic survey was performed and squamous biopsies from 512 subjects were labeled with tritiated thymidine and autoradiographed. Analysis showed no treatment effect on the overall amount of squamous epithelial proliferation measured by the total labeling index. However, a measure of the vertical distribution of labeled cells showed lower values with supplementation: a 14% reduction in all subjects (P = 0.29), and a 29% reduction in nonsmokers (P = 0.03). These results suggest a potential modest benefit for short-term intervention with multiple vitamins and minerals on squamous epithelial cell proliferation of the esophagus in this high-risk population. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Rao, M AU - Liu, F S AU - Dawsey, S M AU - Yang, K AU - Lipkin, M AU - Li, J Y AU - Taylor, P R AU - Li, B AU - Blot, W J AU - Wang, G Q AD - National Cancer Institute, Bethesda, Maryland 20892. PY - 1994 SP - 277 EP - 279 VL - 3 IS - 3 SN - 1055-9965, 1055-9965 KW - Trace Elements KW - 0 KW - Vitamins KW - Tritium KW - 10028-17-8 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Hyperplasia -- pathology KW - Double-Blind Method KW - Humans KW - Linear Models KW - Smoking -- adverse effects KW - Aged KW - Biopsy KW - Autoradiography KW - Esophagoscopy KW - Prospective Studies KW - Primary Prevention KW - Risk Factors KW - China -- epidemiology KW - Adult KW - Mitotic Index KW - Middle Aged KW - Epithelium -- pathology KW - Male KW - Female KW - Esophagus -- pathology KW - Vitamins -- therapeutic use KW - Trace Elements -- therapeutic use KW - Precancerous Conditions -- drug therapy KW - Esophageal Neoplasms -- diagnosis KW - Precancerous Conditions -- diagnosis KW - Precancerous Conditions -- epidemiology KW - Esophageal Neoplasms -- epidemiology KW - Esophageal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76585605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+vitamin%2Fmineral+supplementation+on+the+proliferation+of+esophageal+squamous+epithelium+in+Linxian%2C+China.&rft.au=Rao%2C+M%3BLiu%2C+F+S%3BDawsey%2C+S+M%3BYang%2C+K%3BLipkin%2C+M%3BLi%2C+J+Y%3BTaylor%2C+P+R%3BLi%2C+B%3BBlot%2C+W+J%3BWang%2C+G+Q&rft.aulast=Rao&rft.aufirst=M&rft.date=1994-04-01&rft.volume=3&rft.issue=3&rft.spage=277&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 - 1994-08-02 N1 - Date created - 1994-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An update on approaches to the development of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccines. AN - 76584206; 8030364 AB - RSV and PIV3 are responsible for about 30% of severe viral respiratory tract disease leading to hospitalization of infants and children. For this reason, there is a need to develop vaccines effective against these viruses. Since these viruses cause severe disease in early infancy, vaccines must be effective in the presence of maternal antibody. Currently, several strategies for immunization against these viruses are being explored including peptide vaccines, subunit vaccines, vectored vaccines (e.g., vaccinia-RSV or adenovirus-RSV recombinants), and live attenuated virus vaccines. The current status of these approaches is reviewed. In addition, the immunologic basis for the disease potentiation seen in vaccinees immunized with formalin-inactivated RSV during subsequent RSV infection is reviewed. The efficacy of immunization in the presence of maternal antibody is discussed. Much progress for a RSV and PIV3 vaccine has been made and successful immunization against each of these pathogens should be achieved within this decade. JF - Virus research AU - Murphy, B R AU - Hall, S L AU - Kulkarni, A B AU - Crowe, J E AU - Collins, P L AU - Connors, M AU - Karron, R A AU - Chanock, R M AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 13 EP - 36 VL - 32 IS - 1 SN - 0168-1702, 0168-1702 KW - Antibodies, Anti-Idiotypic KW - 0 KW - Antibodies, Viral KW - ISCOMs KW - Influenza Vaccines KW - Peptide Fragments KW - Vaccines, Attenuated KW - Vaccines, Synthetic KW - Viral Vaccines KW - Index Medicus KW - Animals KW - Humans KW - Immunity, Maternally-Acquired KW - Clinical Trials as Topic KW - Infant, Newborn KW - Mice KW - Sigmodontinae KW - Vaccination KW - Peptide Fragments -- immunology KW - Antibodies, Viral -- immunology KW - Peptide Fragments -- chemical synthesis KW - Pan troglodytes KW - Antibodies, Viral -- biosynthesis KW - Infant KW - Influenza, Human -- prevention & control KW - Adult KW - Antibodies, Anti-Idiotypic -- immunology KW - Respiratory Syncytial Virus Infections -- prevention & control KW - Respiratory Syncytial Viruses -- immunology KW - Influenza Vaccines -- toxicity KW - Influenza Vaccines -- immunology KW - Viral Vaccines -- immunology KW - Viral Vaccines -- toxicity KW - Parainfluenza Virus 3, Human -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76584206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virus+research&rft.atitle=An+update+on+approaches+to+the+development+of+respiratory+syncytial+virus+%28RSV%29+and+parainfluenza+virus+type+3+%28PIV3%29+vaccines.&rft.au=Murphy%2C+B+R%3BHall%2C+S+L%3BKulkarni%2C+A+B%3BCrowe%2C+J+E%3BCollins%2C+P+L%3BConnors%2C+M%3BKarron%2C+R+A%3BChanock%2C+R+M&rft.aulast=Murphy&rft.aufirst=B&rft.date=1994-04-01&rft.volume=32&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Virus+research&rft.issn=01681702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans. AN - 76583618; 7517677 AB - (+/-)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular recreational drug, is known to damage brain serotonin 5-hydroxytryptamine (5-HT) neurons in experimental animals. Whether MDMA is neurotoxic in humans has not been established. Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function. Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid (CSF), prolactin responses to L-tryptophan, nociceptive responses to ischemic pain, and personality characteristics in which 5-HT has been implicated (i.e., impulsivity and aggression). Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid (the major metabolite of 5-HT) than controls (p = .001). Although they resembled controls in their prolactin response to L-tryptophan and their response to ischemic pain, MDMA users had lower scores on personality measures of impulsivity (p = .004) and indirect hostility (p = .009). The CSF findings suggest that 5-HT neurotoxicity may be a potential complication of MDMA use. Further, differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits. Additional studies of MDMA-exposed individuals are needed to confirm and extend the present findings. Such studies could help elucidate the role of 5-HT in normal brain function as well as in neuropsychiatric disease states. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - McCann, U D AU - Ridenour, A AU - Shaham, Y AU - Ricaurte, G A AD - Unit on Anxiety and Affective Disorders, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 129 EP - 138 VL - 10 IS - 2 SN - 0893-133X, 0893-133X KW - Street Drugs KW - 0 KW - Serotonin KW - 333DO1RDJY KW - 3,4-Methylenedioxyamphetamine KW - 4764-17-4 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Prolactin KW - 9002-62-4 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Prolactin -- blood KW - Analysis of Variance KW - Pain -- physiopathology KW - Personality Tests KW - Humans KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Pain Measurement KW - Homovanillic Acid -- cerebrospinal fluid KW - Adult KW - Middle Aged KW - Female KW - Male KW - 3,4-Methylenedioxyamphetamine -- analogs & derivatives KW - Street Drugs -- toxicity KW - Serotonin -- metabolism KW - 3,4-Methylenedioxyamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76583618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serotonin+neurotoxicity+after+%28%2B%2F-%293%2C4-methylenedioxymethamphetamine+%28MDMA%3B+%22Ecstasy%22%29%3A+a+controlled+study+in+humans.&rft.au=McCann%2C+U+D%3BRidenour%2C+A%3BShaham%2C+Y%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1994-04-01&rft.volume=10&rft.issue=2&rft.spage=129&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 - 1994-08-10 N1 - Date created - 1994-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium treatment restores clonidine's effect in an animal model of depression. AN - 76582586; 8029274 AB - IP administration of various doses of clonidine produces significant increases in growth hormone levels in the Wistar rats but not in the Fawn-Hooded (FH) rats, a rat strain suggested to be a genetic model of depression. However, short-term lithium treatment restores clonidine's effect on growth hormone levels in the Fawn-Hooded rats. Potentiation of clonidine's effect on growth hormone levels following short-term lithium treatment appears most likely due to increased serotonergic function as a consequence of enhanced 5-HT concentrations at postsynaptic 5-HT1C receptor sites. Thus, the reversal of a deficit state in Fawn-Hooded rats by lithium treatment supports earlier studies suggesting this rat strain to represent a genetic model of depression. JF - Pharmacology, biochemistry, and behavior AU - Aulakh, C S AU - Hill, J L AU - Murphy, D L AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 985 EP - 987 VL - 47 IS - 4 SN - 0091-3057, 0091-3057 KW - Receptors, Serotonin KW - 0 KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Growth Hormone KW - 9002-72-6 KW - Clonidine KW - MN3L5RMN02 KW - Index Medicus KW - Receptors, Serotonin -- drug effects KW - Rats KW - Animals KW - Growth Hormone -- blood KW - Disease Models, Animal KW - Receptors, Serotonin -- metabolism KW - Drug Synergism KW - Time Factors KW - Male KW - Growth Hormone -- secretion KW - Lithium Carbonate -- therapeutic use KW - Depression -- physiopathology KW - Clonidine -- administration & dosage KW - Depression -- drug therapy KW - Clonidine -- therapeutic use KW - Lithium Carbonate -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76582586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Lithium+treatment+restores+clonidine%27s+effect+in+an+animal+model+of+depression.&rft.au=Aulakh%2C+C+S%3BHill%2C+J+L%3BMurphy%2C+D+L&rft.aulast=Aulakh&rft.aufirst=C&rft.date=1994-04-01&rft.volume=47&rft.issue=4&rft.spage=985&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypertrehalosemic hormone effects on transcriptional activity in the fat body of the cockroach, Blaberus discoidalis. AN - 76578908; 8025557 AB - Gene expression was examined in the fat body of adult male Blaberus discoidalis cockroaches in response to the hypertrehalosemic hormone (HTH). HTH regulates a natural peak of heme synthesis in the fat body at day 4 of adult life. Inhibition of transcriptional activity by alpha-amanitin suppressed both the natural increase in heme biosynthesis at day 4, and the increase that was induced in decapitated animals by HTH administration. In contrast, the regimen of alpha-amanitin treatments that suppressed HTH-responsive heme biosynthesis had no effect on the ability of HTH to increase hemolymph carbohydrate. HTH administration to decapitated animals produced a 25% increase in total fat body RNA and a 3-fold increase in [3H]uridine incorporation. In vitro translation of fat body RNA showed that HTH increased the synthesis of polypeptides at 24, 60 and 77 kDa. The results suggest that HTH affects fat body heme synthesis through gene expression, and evidence was obtained for three polypeptides that increase in the fat body in response to HTH. JF - Insect biochemistry and molecular biology AU - Lee, Y H AU - Keeley, L L AD - National Cancer Institute, National Institute of Health, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 357 EP - 362 VL - 24 IS - 4 SN - 0965-1748, 0965-1748 KW - Amanitins KW - 0 KW - Carbohydrates KW - Insect Hormones KW - Neuropeptides KW - Peptides KW - RNA, Messenger KW - hypertrehalosemic hormone KW - Heme KW - 42VZT0U6YR KW - Index Medicus KW - Heme -- biosynthesis KW - Protein Biosynthesis -- drug effects KW - Animals KW - Amanitins -- pharmacology KW - RNA, Messenger -- analysis KW - Peptides -- analysis KW - Peptides -- chemistry KW - Carbohydrates -- blood KW - Hemolymph -- chemistry KW - RNA, Messenger -- biosynthesis KW - Molecular Weight KW - Male KW - Neuropeptides -- pharmacology KW - Transcription, Genetic -- drug effects KW - Fat Body -- metabolism KW - Cockroaches -- genetics KW - Fat Body -- drug effects KW - Insect Hormones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76578908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Insect+biochemistry+and+molecular+biology&rft.atitle=Hypertrehalosemic+hormone+effects+on+transcriptional+activity+in+the+fat+body+of+the+cockroach%2C+Blaberus+discoidalis.&rft.au=Lee%2C+Y+H%3BKeeley%2C+L+L&rft.aulast=Lee&rft.aufirst=Y&rft.date=1994-04-01&rft.volume=24&rft.issue=4&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Insect+biochemistry+and+molecular+biology&rft.issn=09651748&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-08 N1 - Date created - 1994-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro radiosensitivity of fibroblasts from thyroid and skin cancer patients treated with X-rays for tinea capitis. AN - 76565845; 8019372 AB - To investigate the hypothesis that persons who developed thyroid or skin cancer subsequent to scalp irradiation for tinea capitis are particularly sensitive to radiation, possibly because of a high frequency of ataxia-telangiectasia, we used an in vitro cell survival assay to evaluate radiosensitivity of their fibroblast cell strains. Study subjects were selected from a cohort of 10,834 Israelis irradiated during childhood for tinea capitis. Skin fibroblasts were obtained from thyroid and skin cancer patients (cases) as well as a sample of subjects who did not have cancer (controls). Fibroblasts were cultured and then loss of colony-forming ability as a result of acute X-irradiation was evaluated. Comparison of survival curve parameters (mean inverse of the slope and the dose needed to reduce colony survival to 10%) between 12 thyroid cancer and 12 control strains showed no differences (P > 0.5). A slightly increased radiation sensitivity of the skin cancer cases compared with their controls was observed. Although based on few subjects (14 cases and 11 controls), the findings were similar whether the mean inverse of the slope (P = 0.06) or the dose needed to reduce colony survival to 10% (P = 0.05) was evaluated. However, because of the small size of the study and potential errors inherent in survival assays, our finding that cell strains derived from patients who developed skin cancer exhibit enhanced radiosensitivity should be viewed as preliminary and interpreted cautiously. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Ron, E AU - Tarone, R E AU - Modan, B AU - Chaki, R AU - Alfandary, E AU - Parry, D M AU - Makar, M AU - Setlow, N AU - Mulvihill, J J AU - Miller, R W AD - Epidemiology and Biostatistics Program, National Cancer Institute, NIH, Bethesda, MD 20892. PY - 1994 SP - 229 EP - 232 VL - 3 IS - 3 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Radiation Dosage KW - Israel -- epidemiology KW - Humans KW - Biopsy KW - Jews -- genetics KW - Cell Survival KW - Ataxia Telangiectasia -- genetics KW - Ataxia Telangiectasia -- epidemiology KW - Cells, Cultured KW - Risk Factors KW - Radiotherapy Dosage KW - Heterozygote KW - Cohort Studies KW - Case-Control Studies KW - Middle Aged KW - Bias (Epidemiology) KW - Colony-Forming Units Assay KW - Male KW - Female KW - Tinea Capitis -- radiotherapy KW - Thyroid Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Skin Neoplasms -- etiology KW - Radiation Tolerance KW - Skin Neoplasms -- pathology KW - Thyroid Neoplasms -- etiology KW - Fibroblasts -- cytology KW - Neoplasms, Radiation-Induced -- genetics KW - Skin Neoplasms -- genetics KW - Thyroid Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- pathology KW - Skin Neoplasms -- epidemiology KW - Thyroid Neoplasms -- pathology KW - Fibroblasts -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76565845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+radiosensitivity+of+fibroblasts+from+thyroid+and+skin+cancer+patients+treated+with+X-rays+for+tinea+capitis.&rft.au=Ron%2C+E%3BTarone%2C+R+E%3BModan%2C+B%3BChaki%2C+R%3BAlfandary%2C+E%3BParry%2C+D+M%3BMakar%2C+M%3BSetlow%2C+N%3BMulvihill%2C+J+J%3BMiller%2C+R+W&rft.aulast=Ron&rft.aufirst=E&rft.date=1994-04-01&rft.volume=3&rft.issue=3&rft.spage=229&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 - 1994-08-02 N1 - Date created - 1994-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of phosphocholine-specific antibodies in X-linked immune deficient mice: in vivo protection against a Streptococcus pneumoniae challenge. AN - 76563873; 8018596 AB - X-linked immune deficient (XID) mice are susceptible to infection with Streptococcus pneumoniae because they fail to mount an immune response to the immunodominant phosphocholine (PC) epitope on the bacterial cell wall. It is difficult to induce PC-specific antibodies in XID mice because PC-specific B cells expressing the T15-, M167- and M603 idiotype (Id), which provide protection against S. pneumoniae, are deleted in these mice via an antigen-specific, receptor-mediated process. In addition, the standard PC hapten, p-diazophenylphosphocholine (DPPC), induces high affinity phenylphosphocholine (PPC)-specific antibodies in XID mice, which are not protective against S. pneumoniae. We have used a novel PC hapten, p-nitrophenyl-6-(O-phosphocholine)hydroxyhexanoate (EPC), to induce PC-specific antibodies in XID mice. The immune response to EPC-keyhole limpet hemacyanin (KLH) is dominated by IgG1, VH1+, T15-Id-, PC-inhibitable antibodies. A small IgM anti-PC response having a consistent T15-Id+ component is also induced in XID mice, whereas normal mice produce a large IgM response dominated by T15-Id+ antibodies. The immune response to EPC-KLH remains predominantly PC-inhibitable even after multiple immunizations, while the response to DPPC-KLH becomes dominated by PPC-specific antibodies. C.CBA/N mice immunized twice with EPC-KLH are protected against 10(4) S. pneumoniae while as few as 10 bacteria are 100% lethal for the unimmunized controls. The ability of EPC-protein to induce a long-lived, PC-specific response should make this hapten a potential TD vaccine candidate for S. pneumoniae. JF - International immunology AU - Kenny, J J AU - Guelde, G AU - Fischer, R T AU - Longo, D L AD - Biological Carcinogenesis Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 561 EP - 568 VL - 6 IS - 4 SN - 0953-8178, 0953-8178 KW - Azo Compounds KW - 0 KW - Bacterial Vaccines KW - Caproates KW - Haptens KW - Phosphorylcholine KW - 107-73-3 KW - 4-diazophenylphosphocholine KW - 69731-89-1 KW - 4-nitrophenyl-6-(O-phosphocholine)hydroxyhexanoate KW - 73785-43-0 KW - Hemocyanin KW - 9013-72-3 KW - keyhole-limpet hemocyanin KW - FV4Y0JO2CX KW - Index Medicus KW - Hemolytic Plaque Technique KW - Animals KW - Caproates -- immunology KW - Azo Compounds -- immunology KW - Immunologic Deficiency Syndromes -- genetics KW - Mice KW - Mice, Inbred BALB C KW - Mice, Inbred DBA KW - Immunologic Deficiency Syndromes -- immunology KW - Mice, Inbred CBA KW - Hemocyanin -- immunology KW - Immunotherapy, Adoptive KW - Haptens -- immunology KW - Female KW - Male KW - Phosphorylcholine -- immunology KW - Streptococcus pneumoniae -- immunology KW - Phosphorylcholine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76563873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunology&rft.atitle=Induction+of+phosphocholine-specific+antibodies+in+X-linked+immune+deficient+mice%3A+in+vivo+protection+against+a+Streptococcus+pneumoniae+challenge.&rft.au=Kenny%2C+J+J%3BGuelde%2C+G%3BFischer%2C+R+T%3BLongo%2C+D+L&rft.aulast=Kenny&rft.aufirst=J&rft.date=1994-04-01&rft.volume=6&rft.issue=4&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extended mortality follow-up among men and women in a U.S. furniture workers union. AN - 76551775; 8010296 AB - The addition of 5 years of follow-up and over 411,000 person-years of observation to a cohort of 34,081 men and women employed in U.S. furniture and other related industries allowed the investigation of mortality patterns among women and minority races in addition to white men. A significant excess of pleural mesotheliomas occurred among white men (standardized mortality ratio [SMR] = 3.7, 95% confidence interval [CI] = 1.2-8.7) but could not be linked to a particular type of furniture manufacturing. SMRs for myeloid leukemia and chronic nephritis were elevated among white men employed in the wood furniture industry but were not statistically significant. Males in the black/other race categories in wood furniture plants showed nonsignificant mortality excesses for infectious diseases and cancers of the prostate and colon and rectum. Among white women employed in wood furniture plants, mortality was elevated for cancers of the pancreas and lung during the most recent follow-up period. In metal furniture plants, mortality was raised among men in both race groups for kidney cancer (black/other SMR = 8.0, 95% CI = 1.6-23.2; white SMR = 2.1, 95% CI = 0.4-6.2) and diabetes mellitus (black/other SMR = 2.2, 95% CI = 0.6-5.6; white SMR = 1.8, 95% CI = 0.7-3.9). Stomach cancer mortality was significantly elevated (SMR = 3.3, 95% CI = 1.3-6.8) among white men in metal furniture plants and was of the same magnitude over both the previous and the most recent follow-up periods. Among those working with textiles, SMRs were significantly elevated for leukemia (SMR = 6.1, 95% CI = 1.2-7.8) and cancers of the colon and rectum (SMR = 3.2, 95% CI = 1.3-4.5) for white women. Lung cancer mortality was increased for white men and women in textile operations, but SMRs were not statistically significant. SMRs for a number of other causes of death that were elevated at the end of the earlier follow-up period were not increased during the new follow-up period. JF - American journal of industrial medicine AU - Miller, B A AU - Blair, A AU - Reed, E J AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 537 EP - 549 VL - 25 IS - 4 SN - 0271-3586, 0271-3586 KW - Air Pollutants, Occupational KW - 0 KW - Dust KW - Index Medicus KW - Sex Factors KW - Neoplasms -- mortality KW - Pleural Neoplasms -- mortality KW - Humans KW - Mesothelioma -- etiology KW - Labor Unions KW - Risk Factors KW - Cohort Studies KW - Mesothelioma -- mortality KW - Follow-Up Studies KW - African Continental Ancestry Group KW - Female KW - Male KW - Neoplasms -- etiology KW - Pleural Neoplasms -- etiology KW - Interior Design and Furnishings KW - Air Pollutants, Occupational -- adverse effects KW - Occupational Diseases -- etiology KW - Wood KW - Occupational Exposure -- adverse effects KW - Dust -- adverse effects KW - Cause of Death KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76551775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extended+mortality+follow-up+among+men+and+women+in+a+U.S.+furniture+workers+union.&rft.au=Miller%2C+B+A%3BBlair%2C+A%3BReed%2C+E+J&rft.aulast=Miller&rft.aufirst=B&rft.date=1994-04-01&rft.volume=25&rft.issue=4&rft.spage=537&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 - 1994-07-15 N1 - Date created - 1994-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate modulates [Ca2+]i and gonadotropin-releasing hormone secretion in immortalized hypothalamic GT1-7 neurons. AN - 76534581; 7911229 AB - Glutamate and its receptors are present in the hypothalamus and have been proposed to participate in neuroendocrine regulation, including the control of GnRH secretion. To address the mechanism of glutamate action, we measured [Ca2+]i, inositol phosphate, and secretory responses to glutamate receptor subtype agonists and antagonists in the immortalized GT1-7 cell line of GnRH-secreting hypothalamic neurons. Glutamate, N-methyl-D-aspartate (NMDA), kainate, and trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid increased GnRH secretion. In monolayer cultures of GT1-7 cells, L- but not D-glutamate induced a moderate, concentration-dependent rise in [Ca2+]i. The action of glutamate on [Ca2+]i was mimicked by NMDA, alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA), and kainate. Responses to NMDA were potentiated by the coagonist, glycine, and were inhibited by an antagonist of the glycine site on the NMDA receptor, 5,7-dichlorokynurenic acid (DCKA). NMDA-induced [Ca2+]i responses were also inhibited by Mg2+ and by the NMDA receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,1 0-imine hydrogen maleate (MK-801), but not by the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In contrast, responses to AMPA and kainate were inhibited by CNQX but not by Mg2+, DCKA, or MK-801. Responses to glutamate were more inhibited by MK-801 plus CNQX than by either antagonist alone. All [Ca2+]i responses were nearly abolished in Ca(2+)-free solution. None of the agonists stimulated inositol phosphate formation.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neuroendocrinology AU - Spergel, D J AU - Krsmanovic, L Z AU - Stojilkovic, S S AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 309 EP - 317 VL - 59 IS - 4 SN - 0028-3835, 0028-3835 KW - Excitatory Amino Acid Antagonists KW - 0 KW - Glutamates KW - Inositol Phosphates KW - Neurotoxins KW - Receptors, AMPA KW - Receptors, Glutamate KW - Receptors, N-Methyl-D-Aspartate KW - Cycloleucine KW - 0TQU7668EI KW - 1-amino-1,3-dicarboxycyclopentane KW - 111900-32-4 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Glutamic Acid KW - 3KX376GY7L KW - Calcium KW - SY7Q814VUP KW - Fura-2 KW - TSN3DL106G KW - Index Medicus KW - Animals KW - Receptors, AMPA -- drug effects KW - Inositol Phosphates -- biosynthesis KW - Neurotoxins -- metabolism KW - Spectrometry, Fluorescence KW - Receptors, Glutamate -- drug effects KW - Receptors, Glutamate -- metabolism KW - Cycloleucine -- analogs & derivatives KW - Mice KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, AMPA -- metabolism KW - Mice, Transgenic KW - Receptors, AMPA -- antagonists & inhibitors KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Cells, Cultured KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Cycloleucine -- metabolism KW - Calcium -- metabolism KW - Gonadotropin-Releasing Hormone -- metabolism KW - Neurons -- metabolism KW - Glutamates -- physiology KW - Glutamates -- pharmacology KW - Hypothalamus -- metabolism KW - Hypothalamus -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76534581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroendocrinology&rft.atitle=Glutamate+modulates+%5BCa2%2B%5Di+and+gonadotropin-releasing+hormone+secretion+in+immortalized+hypothalamic+GT1-7+neurons.&rft.au=Spergel%2C+D+J%3BKrsmanovic%2C+L+Z%3BStojilkovic%2C+S+S%3BCatt%2C+K+J&rft.aulast=Spergel&rft.aufirst=D&rft.date=1994-04-01&rft.volume=59&rft.issue=4&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Neuroendocrinology&rft.issn=00283835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Neuroendocrinology 1994 Jul;60(1):95 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extension of one-sided test to multiple treatment trials. AN - 76525373; 8205803 AB - In a two-treatment clinical trial, a one-sided test is sometimes used in reaching a decision. Usually we are interested in doing a one-sided test because of the existence of an unequal preference between the two treatments. When a standard control is just as good or better than the new experimental treatment (which has more toxicity or cost), we will stay with the standard control. In this paper, we extend the concept of a one-sided test to the multiple treatment trial where three or more treatments are involved. We assume that there is an order of strictly decreasing preference among the treatments. We propose two multiple-step decision procedures that are similar to the bubble sorting algorithm and will guarantee a high probability of finally selecting the correct treatment. We also provide methods to calculate the sample size required to detect a specific difference. The derivation is based on normal data, and the extension to binomial or exponential data with random censoring is through large sample approximation. JF - Controlled clinical trials AU - Chen, T T AU - Simon, R M AD - Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 124 EP - 134 VL - 15 IS - 2 SN - 0197-2456, 0197-2456 KW - Index Medicus KW - Teaching -- methods KW - Head and Neck Neoplasms -- therapy KW - Survival Rate KW - Humans KW - Carcinoma, Squamous Cell -- mortality KW - Sampling Studies KW - Mathematical Computing KW - Algorithms KW - Head and Neck Neoplasms -- mortality KW - Decision Making KW - Carcinoma, Squamous Cell -- therapy KW - Models, Statistical KW - Randomized Controlled Trials as Topic -- methods KW - Randomized Controlled Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76525373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Controlled+clinical+trials&rft.atitle=Extension+of+one-sided+test+to+multiple+treatment+trials.&rft.au=Chen%2C+T+T%3BSimon%2C+R+M&rft.aulast=Chen&rft.aufirst=T&rft.date=1994-04-01&rft.volume=15&rft.issue=2&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=Controlled+clinical+trials&rft.issn=01972456&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-11 N1 - Date created - 1994-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine abuse in Japan. AN - 76509729; 8192614 AB - During the past several years, Japan has seen an emergence of cocaine abuse. Although there were only 43 cocaine-related arrests in 1988, the number in 1989 jumped to 96-more than double the previous year. In 1991, the number increased to 122. National Police Agency data shows that about 50% of methamphetamine (MAP) violators had been arrested for drug use. In comparison, only about 5% of cocaine arrests were for drug use, whereas about 50% were for possession, a pattern more similar to that of marijuana violators than MAP violators. More violators were in their 20's for cocaine and marijuana violations than for MAP violations. The percentage of foreigners involved was about 27% for cocaine and about 10% for marijuana, figures greater than the percentage for MAP (about 4%). The first cocaine patients to emerge were the two reported in a 1989 nationwide psychiatric hospital survey. This came two years after the first reporting of marijuana patients. In a similar 1991 survey, two more cocaine patients were reported. Three of the four cocaine patients had abused marijuana prior to abusing cocaine. Marijuana patients and MAP patients have the following demographic differences: about 57% of marijuana patients but only about 4% of MAP patients had enrolled in junior colleges, colleges or universities; and about 71% of marijuana patients but only about 5% of MAP patients were from high income families. Only about 14% of marijuana patients but about 74% of MAP patients had previously been apprehended. These patterns suggest that, demographically, cocaine abusers in Japan are more similar to marijuana abusers than MAP abusers. JF - Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence AU - Wada, K AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba-ken, Japan. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 83 EP - 91 VL - 29 IS - 2 SN - 0389-4118, 0389-4118 KW - Methamphetamine KW - 44RAL3456C KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Japan -- epidemiology KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Female KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76509729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arukoru+kenkyu+to+yakubutsu+izon+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=Cocaine+abuse+in+Japan.&rft.au=Wada%2C+K&rft.aulast=Wada&rft.aufirst=K&rft.date=1994-04-01&rft.volume=29&rft.issue=2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Arukoru+kenkyu+to+yakubutsu+izon+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=03894118&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-22 N1 - Date created - 1994-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factor-assisted DNA binding as a possible general mechanism for steroid receptors. Functional heterogeneity among activated receptor-steroid complexes. AN - 76488213; 8180104 AB - We previously reported that activated glucocorticoid receptor-steroid complexes from rat HTC cell cytosol exist as at least two sub-populations, one of which requires a low molecular weight (700-3000 Da) factor(s) for binding to DNA. This factor is removed by Sephadex G-50 chromatography and is found predominantly in extracts of crude HTC cell nuclei. We have now determined that factor is not limited to HTC cells since an apparently identical factor(s) was found in nuclear extracts of rat kidney and liver as well as human HeLa and MCF-7 cells. Furthermore, the DNA binding of a sub-population of human glucocorticoid receptors depends on factor. While these results were obtained with agonist (dexamethasone) bound receptors, a sub-population of HTC cell receptors covalently labeled by the antiglucocorticoid dexamethasone 21-mesylate also displayed factor-dependent DNA binding. This receptor heterogeneity was not an artifact of cell-free activation since the cell-free nuclear binding of dexamethasone mesylate labeled complexes was, as in intact cells, less than that for dexamethasone bound complexes. Earlier results suggested that the increased DNA binding with factor involved a direct interaction of receptor with factor(s). We now find that the factor-induced DNA binding is retained by amino terminal truncated (42 kDa) glucocorticoid receptors from HTC cells. Thus the ability of receptor to interact with factor(s) is encoded by the DNA and/or steroid binding domains. Two dimensional gel electrophoresis analysis of dexamethasone-mesylate labeled 98 kDa receptors revealed multiple charged isoforms for both sub-populations but no differences in the amount of the various isoforms in each sub-population. Finally, activated progesterone and estrogen receptor complexes were also found to be heterogeneous, with a similar, if not identical, small molecular weight factor(s) being required for the DNA binding of one sub-population. The observations that functional heterogeneity of receptors is not unique to glucocorticoid receptors, whether bound by an agonist or antagonist, and that the factor(s) is neither species nor tissue specific suggests that factor-assisted DNA binding may be a general mechanism for all steroid receptors. JF - The Journal of steroid biochemistry and molecular biology AU - Cavanaugh, A H AU - Simons, S S AD - Steroid Hormones Section, Laboratory of Molecular and Cellular Biology, NIDDK/NIH, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 433 EP - 446 VL - 48 IS - 5-6 SN - 0960-0760, 0960-0760 KW - Arsenites KW - 0 KW - Biological Factors KW - DNA-Binding Proteins KW - Receptors, Estrogen KW - Receptors, Glucocorticoid KW - Receptors, Progesterone KW - Sodium Compounds KW - methyl methanethiosulfonate KW - 2949-92-0 KW - sodium arsenite KW - 48OVY2OC72 KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Animals KW - Arsenites -- pharmacology KW - Receptors, Estrogen -- drug effects KW - Receptors, Progesterone -- drug effects KW - Cell Nucleus -- metabolism KW - HeLa Cells KW - Humans KW - Receptors, Estrogen -- metabolism KW - Protein Binding KW - Methyl Methanesulfonate -- analogs & derivatives KW - Methyl Methanesulfonate -- pharmacology KW - Rats KW - Sodium Compounds -- pharmacology KW - Rats, Sprague-Dawley KW - Receptors, Progesterone -- metabolism KW - Tumor Cells, Cultured KW - Electrophoresis, Gel, Two-Dimensional KW - Cell Line KW - Male KW - Receptors, Glucocorticoid -- drug effects KW - DNA -- metabolism KW - Biological Factors -- metabolism KW - Receptors, Glucocorticoid -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76488213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.atitle=Factor-assisted+DNA+binding+as+a+possible+general+mechanism+for+steroid+receptors.+Functional+heterogeneity+among+activated+receptor-steroid+complexes.&rft.au=Cavanaugh%2C+A+H%3BSimons%2C+S+S&rft.aulast=Cavanaugh&rft.aufirst=A&rft.date=1994-04-01&rft.volume=48&rft.issue=5-6&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.issn=09600760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-10 N1 - Date created - 1994-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. AN - 76476495; 7513770 AB - Stem cell factor (SCF) and its receptor, c-kit, are known to play important roles in hematopoiesis, melanogenesis, and gametogenesis. The biologic effects of the SCF/c-kit system are believed to involve survival, proliferation, and migration of early stem cell progeny. Although SCF and c-kit receptor are widely expressed during normal embryonic development, their expression in the adult is limited. The expression of SCF and c-kit genes was examined during liver regeneration via the oval cell compartment utilizing partial hepatectomy (PH) combined with the administration of a noncarcinogenic dose of 2-acetylaminofluorene (AAF) for 8 days (AAF/PH model). Both the ligand and the receptor genes were expressed during the early stages of oval cell proliferation after partial hepatectomy in the AAF/PH model, while neither simple partial hepatectomy nor AAF administration alone induced a noticeable expression of the SCF/c-kit system. The level of SCF mRNA increased within 12 hours after partial hepatectomy and reached a peak around day 4. Thus, the expression of SCF preceded the major expansion of the oval cell compartment. The level of c-kit transcripts gradually increased from the 12-hour time point and stayed elevated until day 11, when a large proportion of the oval cells differentiated into small basophilic hepatocytes. Separation of liver cells at day 3 in the AAF/PH model into parenchymal and nonparenchymal fractions demonstrated that the expression of both SCF and c-kit receptor genes was restricted to the nonparenchymal cells. Furthermore, in situ hybridization revealed that the c-kit transcripts were restricted to oval cells, whereas the SCF transcripts were expressed in both oval cells and Ito cells. The transcripts for the c-kit receptor are expressed in the early progeny of the hepatic stem cells. The SCF/c-kit system may, possibly in combination with other growth factor/receptor systems, be involved in the early activation of the hepatic stem cells as well as in the expansion and differentiation of oval cells. JF - Laboratory investigation; a journal of technical methods and pathology AU - Fujio, K AU - Evarts, R P AU - Hu, Z AU - Marsden, E R AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 511 EP - 516 VL - 70 IS - 4 SN - 0023-6837, 0023-6837 KW - SCF KW - c-kit KW - Hematopoietic Cell Growth Factors KW - 0 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Receptors, Colony-Stimulating Factor KW - Stem Cell Factor KW - alpha-Fetoproteins KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cells, Cultured KW - Gene Expression KW - Stem Cells -- metabolism KW - alpha-Fetoproteins -- genetics KW - RNA, Messenger -- genetics KW - Male KW - Female KW - Receptors, Colony-Stimulating Factor -- genetics KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Hematopoietic Cell Growth Factors -- metabolism KW - Receptors, Colony-Stimulating Factor -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Liver -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Liver Regeneration KW - Hematopoietic Cell Growth Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76476495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Expression+of+stem+cell+factor+and+its+receptor%2C+c-kit%2C+during+liver+regeneration+from+putative+stem+cells+in+adult+rat.&rft.au=Fujio%2C+K%3BEvarts%2C+R+P%3BHu%2C+Z%3BMarsden%2C+E+R%3BThorgeirsson%2C+S+S&rft.aulast=Fujio&rft.aufirst=K&rft.date=1994-04-01&rft.volume=70&rft.issue=4&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-03 N1 - Date created - 1994-06-03 N1 - Date revised - 2017-01-13 N1 - Gene symbol - SCF; c-kit N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of excess dietary retinoic acid on skin papilloma and carcinoma formation induced by a complete carcinogenesis protocol in female Sencar mice. AN - 76473885; 8180970 AB - Previously, we have shown that dietary retinoic acid (RA) at pharmacological doses (30 micrograms/g of diet) inhibited the malignant conversion of skin papillomas to carcinomas induced by a two-stage carcinogenesis protocol with 7,12-dimethylbenz[a]anthracene as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter (De Luca et al., Carcinogenesis, 14 (1993) 539-542). The purpose of this study was to determine the effect of dietary RA on skin papilloma and carcinoma formation induced by a complete carcinogenesis protocol with repeated DMBA treatment in female Sencar mice. Mice at 3 weeks of age were weaned onto a diet containing either 3 (control) or 30 (excess) micrograms of RA/g of diet and treated topically with DMBA (25.5 micrograms) once per week for 20 weeks. Mice fed excess dietary RA did not significantly differ from control mice in the following parameters: body weight, survival rate, papilloma incidence, cumulative carcinoma incidence (19.4% versus 23.7%), carcinoma yield (0.19 versus 0.26 per mouse), carcinoma conversion efficiency (5.2% versus 3.9%), and average age of carcinoma development (22.7 +/- 4.7 versus 23.3 +/- 2.8 weeks). However, papilloma yield was decreased by about 50% (i.e. 3.7 versus 7.0 at week 20, P < 0.01) between weeks 17 and 22 of age by excess dietary RA treatment. Contrary to other routes of administration (i.e. topical and systemic) of RA (Verma et al., Cancer Res., 42 (1982) 3519-3525), excess dietary RA did not enhance skin tumor formation. In addition, excess dietary RA failed to inhibit malignant conversion of papillomas to carcinomas in the complete carcinogenesis protocol. Thus, the modulation of RA on skin papilloma and carcinoma formation is dependent on carcinogenesis protocol and route of RA administration. JF - Cancer letters AU - Chen, L C AU - Kirchhoff, S AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 63 EP - 67 VL - 78 IS - 1-3 SN - 0304-3835, 0304-3835 KW - Tretinoin KW - 5688UTC01R KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Mice KW - Diet KW - Female KW - Skin Neoplasms -- chemically induced KW - Tretinoin -- administration & dosage KW - Papilloma -- chemically induced KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76473885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Effect+of+excess+dietary+retinoic+acid+on+skin+papilloma+and+carcinoma+formation+induced+by+a+complete+carcinogenesis+protocol+in+female+Sencar+mice.&rft.au=Chen%2C+L+C%3BKirchhoff%2C+S%3BDe+Luca%2C+L+M&rft.aulast=Chen&rft.aufirst=L&rft.date=1994-04-01&rft.volume=78&rft.issue=1-3&rft.spage=63&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated stimulation of pepsinogen secretion. AN - 76468803; 8179000 AB - The roles of Ca2+ in agonist-induced pepsinogen secretion from guinea pig chief cells remain unclear. We used cholecystokinin octapeptide (CCK-8) or secretin alone or with thapsigargin (TG) to clarify these roles. TG releases Ca2+ from intracellular stores by inhibiting microsomal Ca(2+)-adenosinetriphosphatase (ATPase), thereby depleting intracellular Ca2+ (Cai2+) stores. In most cells TG also causes Ca2+ influx. In the present study, with an extracellular Ca2+ concentration ([Ca2+]o) of 1.5 mM, CCK-8 (0.1 microM) caused a rapid increase in pepsinogen secretion; however, the rate decreased with time. With [Ca2+]o = 0, the initial increase was similar but later secretion was abolished, suggesting that Ca2+ influx was important for sustained secretion. With [Ca2+]o = 1.5 mM, TG (0.1 microM) caused a 2.7-fold sustained increase in in Cai2+ concentration ([Ca2+]i) and a ninefold sustained increase in pepsinogen secretion. With [Ca2+]o = 0, TG caused a transient 66% increase in [Ca2+]i and a 50% increase in pepsinogen secretion. The time course of TG-induced pepsinogen secretion correlated with the time course of TG-induced increases in [Ca2+]i. These data demonstrated that Ca2+ influx itself was a potent stimulant of pepsinogen secretion. We further focused on the roles of increasing [Ca2+]i from Cai2+ stores. With or without extracellular Ca2+ (Cao2+) present, addition of CCK-8 (0.1 microM) 10 min after TG caused no further increase in [Ca2+]i, demonstrating depletion of the inositol 1,4,5-trisphosphate-sensitive pool. The Ca(2+)-mobilizing agent CCK-8 caused no pepsinogen secretion 10 min after TG preincubation, demonstrating that mobilization of Ca2+ from intracellular stores was important in the rapid initial phase stimulation of pepsinogen secretion caused by CCK-8. In contrast, preincubation with TG had no effect on pepsinogen secretion by secretin, an agent that increases adenosine 3',5'-cyclic monophosphate. A 6-min preincubation with TG potentiated the subsequent stimulation of pepsinogen secretion caused by secretin in the presence of Cao2+ where [Ca2+]i remained elevated. However, TG-induced potentiations of secretin-stimulated pepsinogen secretion was abolished once [Ca2+]i had returned to the basal level in the absence of Cao2+.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The American journal of physiology AU - Kitsukawa, Y AU - Felley, C AU - Metz, D C AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - G613 EP - G623 VL - 266 IS - 4 Pt 1 SN - 0002-9513, 0002-9513 KW - Pepsinogens KW - 0 KW - Plant Extracts KW - Terpenes KW - Secretin KW - 1393-25-5 KW - Thapsigargin KW - 67526-95-8 KW - Sincalide KW - M03GIQ7Z6P KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Plant Extracts -- pharmacology KW - Animals KW - Guinea Pigs KW - Dose-Response Relationship, Drug KW - Kinetics KW - Secretin -- pharmacology KW - Drug Synergism KW - Sincalide -- pharmacology KW - Male KW - Pepsinogens -- secretion KW - Calcium -- physiology KW - Terpenes -- pharmacology KW - Gastric Mucosa -- cytology KW - Gastric Mucosa -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76468803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Thapsigargin+defines+roles+of+Ca2%2B+in+initial%2C+sustained%2C+and+potentiated+stimulation+of+pepsinogen+secretion.&rft.au=Kitsukawa%2C+Y%3BFelley%2C+C%3BMetz%2C+D+C%3BJensen%2C+R+T&rft.aulast=Kitsukawa&rft.aufirst=Y&rft.date=1994-04-01&rft.volume=266&rft.issue=4+Pt+1&rft.spage=G613&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salivary gland dysfunction: causes, symptoms, treatment. AN - 76467104; 8176076 AB - The three most common known causes of salivary gland dysfunction are medication usage, radiation therapy and Sjogren's syndrome. Current therapeutic options to treat salivary dysfunction are limited. Clinical considerations as well as the outlook for individuals experiencing salivary dysfunction are discussed. JF - Journal of the American Dental Association (1939) AU - Atkinson, J C AU - Wu, A J AD - Patient Care Branch, National Institute of Dental Research, National Institutes of Health. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 409 EP - 416 VL - 125 IS - 4 SN - 0002-8177, 0002-8177 KW - Antifungal Agents KW - 0 KW - Fluorides, Topical KW - Parasympatholytics KW - Dentistry KW - Index Medicus KW - Salivary Glands -- drug effects KW - Candidiasis, Oral -- drug therapy KW - Humans KW - Aged KW - Parasympatholytics -- adverse effects KW - Sjogren's Syndrome -- epidemiology KW - Antifungal Agents -- therapeutic use KW - Xerostomia -- etiology KW - Xerostomia -- complications KW - Stimulation, Chemical KW - Dental Caries -- etiology KW - Salivary Glands -- radiation effects KW - Candidiasis, Oral -- etiology KW - Cranial Irradiation -- adverse effects KW - United States -- epidemiology KW - Sjogren's Syndrome -- complications KW - Fluorides, Topical -- therapeutic use KW - Prevalence KW - Salivary Gland Diseases -- drug therapy KW - Salivary Gland Diseases -- physiopathology KW - Salivary Gland Diseases -- epidemiology KW - Salivary Gland Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76467104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Dental+Association+%281939%29&rft.atitle=Salivary+gland+dysfunction%3A+causes%2C+symptoms%2C+treatment.&rft.au=Atkinson%2C+J+C%3BWu%2C+A+J&rft.aulast=Atkinson&rft.aufirst=J&rft.date=1994-04-01&rft.volume=125&rft.issue=4&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Dental+Association+%281939%29&rft.issn=00028177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-06 N1 - Date created - 1994-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments. AN - 76465457; 8169857 AB - Chronic (14 day) but not acute (1 day) treatment of mice with clinically active antidepressants produces a significant (approximately 1.8-4.3 fold) reduction in the potency of glycine to inhibit [3H]-5,7-dichlorkynurenic acid (5,7-DCKA) binding to strychnine-insensitive glycine receptors in neocortical membranes. Moreover, these effects were not observed following chronic treatment with a variety of nonantidepressant drugs such as D-deprenyl, chlorpromazine, salbutamol, scopolamine and chlordiazepoxide. The time course and dose-response relationships for this effect were examined after treatment with two representative antidepressant drugs (imipramine and citalopram) and electriconvulsive shock (ECS). Increases in the IC50 of glycine to inhibit [3H]-5,7-DCKA binding were observed after treatment for 7 days with ECS, 10 days with citalopram and 14 days with imipramine, respectively, and were no longer apparent by the 10th day after cessation of treatment. These findings indicate that the antidepressant-induced reduction in the IC50 of glycine to inhibit [3H]-5,7-DCKA binding is: 1) a slowly developing, adaptive phenomenon; 2) remarkably persistent after cessation of treatment; and 3) a significantly better predictor of antidepressant activity (22 of 23 drugs) than either beta adrenoceptor down-regulation (15 of 23 drugs) or efficacy in the forced swim test (13 of 23 drugs) [P < .01 vs. each measure, Fisher's Exact Test]. The ability of antidepressants drawn from every principal therapeutic class to effect adaptive changes in the N-methyl-D-aspartate receptor complex is consistent with the hypothesis that this ligand-gated ion channel serves as a final common pathway of antidepressant action and indicates that glutamatergic pathways may be involved in the pathophysiology of depression. JF - The Journal of pharmacology and experimental therapeutics AU - Paul, I A AU - Nowak, G AU - Layer, R T AU - Popik, P AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute on Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 95 EP - 102 VL - 269 IS - 1 SN - 0022-3565, 0022-3565 KW - Antidepressive Agents KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Citalopram KW - 0DHU5B8D6V KW - Tritium KW - 10028-17-8 KW - Kynurenic Acid KW - H030S2S85J KW - Strychnine KW - H9Y79VD43J KW - Imipramine KW - OGG85SX4E4 KW - 5,7-dichlorokynurenic acid KW - T61ORK73PY KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Dose-Response Relationship, Drug KW - Kynurenic Acid -- metabolism KW - Citalopram -- pharmacology KW - Mice KW - Kynurenic Acid -- antagonists & inhibitors KW - Glycine -- pharmacology KW - Imipramine -- pharmacology KW - Strychnine -- pharmacology KW - Adaptation, Physiological KW - Kynurenic Acid -- analogs & derivatives KW - Electroshock KW - Time Factors KW - Male KW - Antidepressive Agents -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Receptors, N-Methyl-D-Aspartate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76465457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Adaptation+of+the+N-methyl-D-aspartate+receptor+complex+following+chronic+antidepressant+treatments.&rft.au=Paul%2C+I+A%3BNowak%2C+G%3BLayer%2C+R+T%3BPopik%2C+P%3BSkolnick%2C+P&rft.aulast=Paul&rft.aufirst=I&rft.date=1994-04-01&rft.volume=269&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The reduced unsubstituted pteroate moiety is required for folate toxicity of cultured cerebellar granule neurons. AN - 76465307; 8169846 AB - The proconvulsive and putative excitotoxic properties of folates led us to study folate toxicity in cultured rat cerebellar granule neurons. Exposure of these neurons to tetrahydrofolate (THF) (EC50 = 263 +/- 12 microM) and dihydrofolate (EC50 = 709 +/- 29 microM), but not to folate, formyl-THF, methyl-THF or methotrexate, resulted in a concentration-dependent neurotoxicity. THF and dihydrofolate toxicity were characterized by prominent neuronal swelling and early loss of neurite networking and could not be blocked by glutamate receptor antagonists, L-channel calcium blockers or anticonvulsants. Cleavage of THF into glutamate and tetrahydropteroate by glutamate carboxypeptidase in the presence of 1 microM MK-801 and 5 microM 6-cyano-7-nitroquinoxaline-2,3,dione shifted the concentration-toxicity curve to the left (EC50 = 47 +/- 4 microM). These results suggest (1) that the glutamate moiety is not necessary for folate toxicity, (2) that the unsubstituted reduced pteroate moiety is required for folate toxicity and (3) that unsubstituted reduced pteroates are previously unrecognized neurotoxins. Because there is no endogenous glutamate carboxypeptidase activity in cerebellar granule neuron cultures and no increase of glutamate levels in the medium of cultures exposed to THF or dihydrofolate, pteroate metabolites are unlikely to mediate the THF or dihydrofolate toxicity of cultured cerebellar granule neurons. JF - The Journal of pharmacology and experimental therapeutics AU - Weller, M AU - Marini, A M AU - Martin, B AU - Paul, S M AD - Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 393 EP - 401 VL - 269 IS - 1 SN - 0022-3565, 0022-3565 KW - Culture Media KW - 0 KW - Tetrahydrofolates KW - dihydrofolate KW - 4033-27-6 KW - 5,6,7,8-tetrahydrofolic acid KW - 43ZWB253H4 KW - Folic Acid KW - 935E97BOY8 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Carboxypeptidases KW - EC 3.4.- KW - glutamate carboxypeptidase KW - EC 3.4.17.11 KW - Index Medicus KW - Rats KW - Oxidation-Reduction KW - Animals KW - Cells, Cultured KW - Astrocytes -- drug effects KW - Carboxypeptidases -- metabolism KW - Tetrahydrofolates -- toxicity KW - Tetrahydrofolate Dehydrogenase -- metabolism KW - Structure-Activity Relationship KW - Cerebellar Diseases -- chemically induced KW - Cerebellum -- cytology KW - Neurons -- drug effects KW - Folic Acid -- analogs & derivatives KW - Cerebellum -- drug effects KW - Neurons -- enzymology KW - Folic Acid -- toxicity KW - Cerebellum -- enzymology KW - Cytoplasmic Granules -- drug effects KW - Neurons -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76465307?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=The+reduced+unsubstituted+pteroate+moiety+is+required+for+folate+toxicity+of+cultured+cerebellar+granule+neurons.&rft.au=Weller%2C+M%3BMarini%2C+A+M%3BMartin%2C+B%3BPaul%2C+S+M&rft.aulast=Weller&rft.aufirst=M&rft.date=1994-04-01&rft.volume=269&rft.issue=1&rft.spage=393&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass. AN - 76460119; 8166557 AB - Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Annals of thoracic surgery AU - Mendeloff, E N AU - Liang, I Y AU - Swain, J A AU - Clark, R E AD - Surgery Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 999 EP - 1006 VL - 57 IS - 4 SN - 0003-4975, 0003-4975 KW - Protamines KW - 0 KW - Receptors, Thromboxane KW - SQ 30741 KW - 107332-47-8 KW - Thromboxane A2 KW - 57576-52-0 KW - Heparin KW - 9005-49-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Interactions KW - Injections, Intravenous KW - Infusions, Intravenous KW - Sheep KW - Drug Evaluation, Preclinical KW - Male KW - Female KW - Complement Activation KW - Hemodynamics -- drug effects KW - Myocardial Reperfusion Injury -- immunology KW - Cardiopulmonary Bypass -- adverse effects KW - Myocardial Reperfusion Injury -- drug therapy KW - Heparin -- pharmacology KW - Receptors, Thromboxane -- antagonists & inhibitors KW - Thromboxane A2 -- antagonists & inhibitors KW - Thromboxane A2 -- pharmacology KW - Hypothermia, Induced -- adverse effects KW - Thromboxane A2 -- analogs & derivatives KW - Protamines -- adverse effects KW - Myocardial Reperfusion Injury -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76460119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Annals+of+thoracic+surgery&rft.atitle=Thromboxane+A2+receptor-specific+antagonism+in+hypothermic+cardiopulmonary+bypass.&rft.au=Mendeloff%2C+E+N%3BLiang%2C+I+Y%3BSwain%2C+J+A%3BClark%2C+R+E&rft.aulast=Mendeloff&rft.aufirst=E&rft.date=1994-04-01&rft.volume=57&rft.issue=4&rft.spage=999&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+thoracic+surgery&rft.issn=00034975&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-24 N1 - Date created - 1994-05-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Thorac Surg. 1995 Feb;59(2):550-1 [7847996] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene mutations. AN - 76455041; 7513291 AB - Cystic fibrosis is a common, fatal disorder caused by abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a chloride channel that regulates secretion in many exocrine tissues. The presentation of cystic fibrosis is highly variable as measured by the age of onset of disease, the presence of pancreatic insufficiency, or the progression of lung disease. Over 400 mutations in the CFTR gene have been described in cystic fibrosis patients and considerable effort has focused on the correlation between specific mutations and genotypes and clinical characteristics. Individual tissues display variation in their sensitivity to CFTR mutations. The vas deferens is functionally disrupted in nearly all males, whereas mild and severe pancreatic involvement is determined by the patient's genotype. The severity of pulmonary disease is poorly correlated with genotype, suggesting that there are other important genetic and/or environmental factors that contribute to lung infections and the subsequent disruption of lung function. JF - Human genetics AU - Dean, M AU - Santis, G AD - Laboratory of Viral Carcinogenesis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 364 EP - 368 VL - 93 IS - 4 SN - 0340-6717, 0340-6717 KW - CFTR KW - CFTR protein, human KW - 0 KW - Membrane Proteins KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Index Medicus KW - Severity of Illness Index KW - Diabetes Mellitus, Type 1 -- physiopathology KW - Infertility, Male -- physiopathology KW - Humans KW - Vas Deferens -- physiopathology KW - Exocrine Glands -- physiopathology KW - Lung Diseases -- physiopathology KW - Pancreas -- physiopathology KW - Male KW - Cystic Fibrosis -- genetics KW - Cystic Fibrosis -- physiopathology KW - Membrane Proteins -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76455041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Heterogeneity+in+the+severity+of+cystic+fibrosis+and+the+role+of+CFTR+gene+mutations.&rft.au=Dean%2C+M%3BSantis%2C+G&rft.aulast=Dean&rft.aufirst=M&rft.date=1994-04-01&rft.volume=93&rft.issue=4&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=Human+genetics&rft.issn=03406717&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-01 N1 - Date created - 1994-06-01 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CFTR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of nitric oxide in uveitis. AN - 76437670; 8155054 AB - To evaluate the possible role played by nitric oxide in the pathogenesis of uveitis. Uveitis was induced in rats with subcutaneous lipopolysaccharide. Lipopolysaccharide stimulates nitric oxide production from L-arginine. The animals were treated with NG-nitro-L-arginine methyl ester, an L-arginine analogue acting as a specific inhibitor of nitric oxide synthesis. Ocular inflammation was evaluated by measuring protein concentration and leukocyte number in the aqueous humor of one eye, and by histopathologic examination of the contralateral eye. Aqueous humor protein levels were reduced 73% to 82% and cellular infiltration was almost abrogated in NG-nitro-L-arginine methyl ester-treated rats compared with controls. The histopathologic examination also showed a similar inhibition of uveal tissue inflammation in treated rats. By inhibiting nitric oxide synthesis, NG-nitro-L-arginine methyl ester inhibits the induction of endotoxin-induced uveitis in the rat. This observation demonstrates that nitric oxide is an important mediator of anterior uveitis in this model system and suggests that nitric oxide may also be implicated in human uveitis. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Parks, D J AU - Cheung, M K AU - Chan, C C AU - Roberge, F G AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Betheda, MD. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 544 EP - 546 VL - 112 IS - 4 SN - 0003-9950, 0003-9950 KW - Bacterial Toxins KW - 0 KW - Endotoxins KW - Eye Proteins KW - Lipopolysaccharides KW - salmonella toxin KW - Nitric Oxide KW - 31C4KY9ESH KW - Arginine KW - 94ZLA3W45F KW - NG-Nitroarginine Methyl Ester KW - V55S2QJN2X KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Aqueous Humor -- metabolism KW - Rats, Inbred Lew KW - Eye Proteins -- metabolism KW - Aqueous Humor -- cytology KW - Disease Models, Animal KW - Leukocyte Count KW - Arginine -- pharmacology KW - Rats KW - Arginine -- analogs & derivatives KW - Male KW - Uveitis, Anterior -- physiopathology KW - Uveitis, Anterior -- chemically induced KW - Nitric Oxide -- antagonists & inhibitors KW - Uveitis, Anterior -- pathology KW - Nitric Oxide -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76437670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=The+role+of+nitric+oxide+in+uveitis.&rft.au=Parks%2C+D+J%3BCheung%2C+M+K%3BChan%2C+C+C%3BRoberge%2C+F+G&rft.aulast=Parks&rft.aufirst=D&rft.date=1994-04-01&rft.volume=112&rft.issue=4&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-12 N1 - Date created - 1994-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C regulates keratinocyte transglutaminase (TGK) gene expression in cultured primary mouse epidermal keratinocytes induced to terminally differentiate by calcium. AN - 76436105; 7908680 AB - During the final stage of epidermal differentiation, activation of keratinocyte transglutaminase results in covalent crosslinking of a variety of proteins to form highly protective cornified cell envelopes. We have studied the regulation of keratinocyte transglutaminase (TGK) gene expression in murine epidermal keratinocytes induced to terminally differentiate in vitro by increasing the level of extracellular Ca++ or treatment with the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA). Raising extracellular Ca++ induces squamous differentiation of cultured keratinocytes and elicits a concentration-dependent increase in expression of TGK mRNA; keratinocytes grown for 24 h in 0.12 mM Ca++ medium express approximately 12 times as much TGK mRNA as basal cells (grown in 0.05 mM Ca++ medium), whereas cultures exposed to 1.4 mM Ca++ express approximately 17 times as much. TPA induces squamous differentiation and TGK mRNA even in basal keratinocyte cultures grown in 0.05 mM Ca++ medium, suggesting that expression of this differentiation marker is regulated by the PKC signaling pathway. Induction of TGK mRNA in response to TPA treatment is transient, reaching a peak at 6-8 h and returning to baseline by 24 h. In contrast, elevation of TGK mRNA levels in response to Ca++ persists for at least 24 h. The increased abundance of TGK mRNA reflects increased transcription of the TGK gene, based on nuclear run-on analysis of Ca(++)- and TPA-treated keratinocytes. Induction of TGK mRNA by either TPA or Ca++ is blocked in the presence of cycloheximide, suggesting that a PKC-dependent protein factor is required for TGK gene expression in response to both stimuli. Furthermore, the accumulation of TGK mRNA in keratinocytes treated with TPA or Ca++ is blocked in cells treated with the PKC inhibitor GF 109203X or bryostatin. These results suggest that the induction of TGK gene expression by Ca++ is dependent on PKC, providing further support for the hypothesis that PKC plays a central role in regulating the late stages of epidermal differentiation. JF - The Journal of investigative dermatology AU - Długosz, A A AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 409 EP - 414 VL - 102 IS - 4 SN - 0022-202X, 0022-202X KW - TGK KW - Proteins KW - 0 KW - RNA, Messenger KW - Transglutaminases KW - EC 2.3.2.13 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - Proteins -- antagonists & inhibitors KW - Enzyme Activation KW - Cells, Cultured KW - Epidermis -- cytology KW - RNA, Messenger -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription, Genetic KW - Mice KW - Mice, Inbred BALB C KW - Gene Expression Regulation, Enzymologic KW - Transglutaminases -- genetics KW - Keratinocytes -- enzymology KW - Calcium -- pharmacology KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76436105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+investigative+dermatology&rft.atitle=Protein+kinase+C+regulates+keratinocyte+transglutaminase+%28TGK%29+gene+expression+in+cultured+primary+mouse+epidermal+keratinocytes+induced+to+terminally+differentiate+by+calcium.&rft.au=D%C5%82ugosz%2C+A+A%3BYuspa%2C+S+H&rft.aulast=D%C5%82ugosz&rft.aufirst=A&rft.date=1994-04-01&rft.volume=102&rft.issue=4&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TGK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the sites of reaction of three polycyclic aromatic hydrocarbons in the supF gene. AN - 76433496; 7512208 AB - The distribution of hydrocarbon-DNA adducts through the supF gene in plasmid pS189 was examined using the polymerase arrest assay. For three hydrocarbon dihydrodiol epoxides, derived from 5-methylchrysene, 7-methylbenz[a]anthracene, and benzo[a]pyrene, that exhibit a preference for reaction with guanine residues in DNA, polymerase arrest spectra were similar but not identical. For each agent, guanines in different sequence contexts exhibited varying reactivities and each specific guanine did not necessarily respond to each agent in the same fashion. Thus, sequence context together with the individual dihydrodiol epoxide's chemical and physical properties all play a role in determining sites and extents of reaction within a specific gene. The polymerase arrest data were not predictive of the known sites of mutation hotspots for these dihydrodiol epoxides in the supF gene indicating that further action upon the adducted DNA by repair systems is probably necessary to determine which specific chemical adducts will ultimately give rise to mutation. JF - Mutation research AU - Ross, H L AU - Lee, H AU - Harvey, R G AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 91 EP - 101 VL - 306 IS - 1 SN - 0027-5107, 0027-5107 KW - supF KW - Benz(a)Anthracenes KW - 0 KW - Carcinogens KW - Chrysenes KW - DNA Adducts KW - Epoxy Compounds KW - benzo(a)pyrene-DNA adduct KW - Benzo(a)pyrene KW - 3417WMA06D KW - DNA KW - 9007-49-2 KW - 7-methylbenzanthracene KW - F0662CQU1Q KW - 5-methylchrysene KW - O66195MC8L KW - Index Medicus KW - Base Sequence KW - Epoxy Compounds -- metabolism KW - Molecular Sequence Data KW - Epoxy Compounds -- toxicity KW - Structure-Activity Relationship KW - Chrysenes -- toxicity KW - Carcinogens -- metabolism KW - DNA -- toxicity KW - DNA -- metabolism KW - Benzo(a)pyrene -- toxicity KW - Chrysenes -- metabolism KW - Benz(a)Anthracenes -- toxicity KW - Mutation KW - Benz(a)Anthracenes -- metabolism KW - Benzo(a)pyrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76433496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Comparison+of+the+sites+of+reaction+of+three+polycyclic+aromatic+hydrocarbons+in+the+supF+gene.&rft.au=Ross%2C+H+L%3BLee%2C+H%3BHarvey%2C+R+G%3BDipple%2C+A&rft.aulast=Ross&rft.aufirst=H&rft.date=1994-04-01&rft.volume=306&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. AN - 76429074; 8154877 AB - The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with "ragged-red"-like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta-oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within "cracks" or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine supplementation. JF - Annals of neurology AU - Dalakas, M C AU - Leon-Monzon, M E AU - Bernardini, I AU - Gahl, W A AU - Jay, C A AD - Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 482 EP - 487 VL - 35 IS - 4 SN - 0364-5134, 0364-5134 KW - Zidovudine KW - 4B9XT59T7S KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Middle Aged KW - Male KW - Carnitine -- deficiency KW - Zidovudine -- adverse effects KW - Muscles -- metabolism KW - Mitochondrial Myopathies -- chemically induced KW - Muscles -- pathology KW - Mitochondrial Myopathies -- metabolism KW - Mitochondrial Myopathies -- pathology KW - Lipid Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76429074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Zidovudine-induced+mitochondrial+myopathy+is+associated+with+muscle+carnitine+deficiency+and+lipid+storage.&rft.au=Dalakas%2C+M+C%3BLeon-Monzon%2C+M+E%3BBernardini%2C+I%3BGahl%2C+W+A%3BJay%2C+C+A&rft.aulast=Dalakas&rft.aufirst=M&rft.date=1994-04-01&rft.volume=35&rft.issue=4&rft.spage=482&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-10 N1 - Date created - 1994-05-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Neurol. 1994 Oct;36(4):680-1 [7944307] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Determination of the allelic frequencies of an L-myc and a p53 polymorphism in human lung cancer. AN - 76425199; 7908608 AB - The L-myc and p53 genes have been implicated in lung cancer. Both of these genes have restriction fragment length polymorphisms (RFLPs) that could account for differential expression or activity of variant forms. An EcoRI restriction site in the L-myc gene was previously reported to be a predictor of poor prognosis in Japanese lung cancer patients. There are several RFLPs in the p53 gene. In exon 4 there is a polymorphism that codes for either an arginine or proline residue at codon 72. We previously reported the frequency of DNA-RFLPs at these gene loci revealed by EcoRI and AccII respectively. Here we report results from a study comparing lung cancer cases (n = 31) with chronic obstructive pulmonary disease controls (n = 49). No association was found between these RFLPs and disease status. Previous observations that the frequencies of these RFLPs varied by race were confirmed. The p53 arginine allele was found to be more common in Caucasians (0.71) than African-Americans (0.50). The EcoRI restriction site present allele in L-myc was more frequent in African-Americans (0.71) than Caucasians (0.49). Thus, the allelic frequency for L-myc was similar in African-Americans to that reported for Japanese, and the allelic frequency for p53 was similar in Caucasians to that reported for Japanese. JF - Carcinogenesis AU - Weston, A AU - Ling-Cawley, H M AU - Caporaso, N E AU - Bowman, E D AU - Hoover, R N AU - Trump, B F AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 583 EP - 587 VL - 15 IS - 4 SN - 0143-3334, 0143-3334 KW - L-myc KW - p53 KW - DNA Primers KW - 0 KW - Index Medicus KW - Base Sequence KW - Gene Frequency KW - African Continental Ancestry Group -- genetics KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Molecular Sequence Data KW - Middle Aged KW - European Continental Ancestry Group -- genetics KW - Male KW - Lung Diseases, Obstructive -- genetics KW - Female KW - DNA Primers -- chemistry KW - Genes, p53 KW - Genes, myc KW - Lung Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76425199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Determination+of+the+allelic+frequencies+of+an+L-myc+and+a+p53+polymorphism+in+human+lung+cancer.&rft.au=Weston%2C+A%3BLing-Cawley%2C+H+M%3BCaporaso%2C+N+E%3BBowman%2C+E+D%3BHoover%2C+R+N%3BTrump%2C+B+F%3BHarris%2C+C+C&rft.aulast=Weston&rft.aufirst=A&rft.date=1994-04-01&rft.volume=15&rft.issue=4&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-12 N1 - Date created - 1994-05-12 N1 - Date revised - 2017-01-13 N1 - Gene symbol - L-myc; p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infrequent transforming mutations in the transmembrane domain of the neu oncogene in spontaneous rat schwannomas. AN - 76424127; 7908527 AB - Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the cranial, spinal, and peripheral nerves, with a high frequency of mutations in the neu proto-oncogene. To establish the requirement for such mutations in tumorigenesis of the Schwann cell, spontaneous schwannomas from BD-VI rats were evaluated for transforming mutations in the transmembrane domain of the protein encoded by the neu proto-oncogene. While all five schwannomas induced transplacentally with ENU were shown to contain T-->A transversions in base 2012 of neu by selective oligonucleotide hybridization and dideoxy sequencing of polymerase chain reaction-amplified products from paraffin sections, only one of nine spontaneous schwannomas from untreated rats had the same mutation. Examination of tumors for mutations in codon 12 of Ki-ras revealed normal alleles. Therefore, the high frequency of mutations in neu in ENU-induced tumors may be directly attributable to the carcinogen or to the period of development at which exposure occurred, and transforming mutations of the transmembrane domain of neu are not required for tumorigenesis of the Schwann cell. JF - Molecular carcinogenesis AU - Perantoni, A O AU - Turusov, V S AU - Buzard, G S AU - Rice, J M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21701. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 230 EP - 235 VL - 9 IS - 4 SN - 0899-1987, 0899-1987 KW - Ki-ras KW - neu KW - DNA Primers KW - 0 KW - Proto-Oncogene Proteins KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Index Medicus KW - Rats KW - Genes, ras KW - Animals KW - Base Sequence KW - Oncogenes KW - Molecular Sequence Data KW - Sarcoma, Experimental -- genetics KW - Mutation KW - Male KW - Female KW - DNA Primers -- chemistry KW - Receptor, Epidermal Growth Factor -- genetics KW - Neurilemmoma -- genetics KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76424127?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Infrequent+transforming+mutations+in+the+transmembrane+domain+of+the+neu+oncogene+in+spontaneous+rat+schwannomas.&rft.au=Perantoni%2C+A+O%3BTurusov%2C+V+S%3BBuzard%2C+G+S%3BRice%2C+J+M&rft.aulast=Perantoni&rft.aufirst=A&rft.date=1994-04-01&rft.volume=9&rft.issue=4&rft.spage=230&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 - 1994-05-10 N1 - Date created - 1994-05-10 N1 - Date revised - 2017-01-13 N1 - Gene symbol - Ki-ras; neu N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ADP-ribosylation factor amino-terminal deletions on its GTP-dependent stimulation of cholera toxin activity. AN - 76424001; 8144566 AB - It has been proposed that the amino-terminal domain of ADP-ribosylation factor (ARF) is critical for its stimulation of cholera toxin ADP-ribosyltransferase activity. In this study, recombinant ARF1 (rARF1), r delta 13ARF1 (recombinant ARF1 lacking the first 13 amino acids) and rPKA14ARF1 (recombinant ARF1 in which the first 14 amino acids were replaced by the first 7 amino acids of the cAMP-dependent protein kinase catalytic subunit) were used to assess the effect of the amino terminus on the ability of ARF to enhance ADP-ribosylation of agmatine by the cholera toxin A subunit. The GTP-dependent ARF activities of r delta 13ARF1 and rPKA14ARF1 were similar to that of rARF1, whereas the GTP requirement for half-maximal activation of cholera toxin A, was somewhat higher for rARF1 than it was for r delta 13ARF1 and rPKA14ARF1. These results are consistent with the view that the amino terminus of ARF1 is not critical for its action as a GTP-dependent activator of cholera toxin. JF - The Journal of biological chemistry AU - Hong, J X AU - Haun, R S AU - Tsai, S C AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 9743 EP - 9745 VL - 269 IS - 13 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - DNA Primers KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Recombinant Proteins -- pharmacology KW - Carrier Proteins -- metabolism KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Adenosine Diphosphate Ribose -- metabolism KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Kinetics KW - Molecular Sequence Data KW - Sequence Deletion KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Cholera Toxin -- pharmacology KW - GTP-Binding Proteins -- genetics KW - Guanosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76424001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Effect+of+ADP-ribosylation+factor+amino-terminal+deletions+on+its+GTP-dependent+stimulation+of+cholera+toxin+activity.&rft.au=Hong%2C+J+X%3BHaun%2C+R+S%3BTsai%2C+S+C%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Hong&rft.aufirst=J&rft.date=1994-04-01&rft.volume=269&rft.issue=13&rft.spage=9743&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U25269; GENBANK; U25273 N1 - SuppNotes - Erratum In: J Biol Chem 1994 Jun 10;269(23):16519 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Excision of a P4-like cryptic prophage leads to Alp protease expression in Escherichia coli. AN - 76423241; 7511583 AB - The Escherichia coli K-12 alpA gene product, when overproduced from a multicopy plasmid, leads to suppression of the capsule overproduction and UV sensitivity phenotypes of cells mutant for the Lon ATP-dependent protease. This suppression has previously been shown to correlate with increased in vivo activity of a previously unknown energy-dependent proteolytic activity capable of degrading Lon substrates, the Alp protease. We show in an accompanying paper that alpA, which has homology to a short open reading frame in bacteriophage P4, acts as a positive transcriptional regulator of slpA, a gene linked to alpA and necessary for suppression of lon mutants (J. E. Trempy, J. E. Kirby, and S. Gottesman, J. Bacteriol. 176:2061-2067). The sequence of slpA suggests that it encodes an integrase gene closely related to P4 int and that both alpA and slpA are part of a cryptic P4-like prophage. AlpA expression increases SlpA synthesis. Increased SlpA leads, in turn, to the excision and loss of the cryptic prophage. Excision is dependent on integration host factor as well as on SlpA. Prophage excision is necessary but not sufficient for full expression of the Alp protease. A second function (named AHA) allows full protease expression; this function can be provided by the kanamycin resistance element from Tn903 when the element is present on a multicopy plasmid. Excision and loss of the cryptic prophage apparently allow expression of the Alp protease by inactivating a small stable RNA (10Sa RNA) encoded by the ssrA gene. The precursor of this RNA has its 3' end within the cryptic prophage; the mature 3' end lies within the prophage attL site. Inactivation of ssrA by insertional mutagenesis is sufficient to allow expression of the suppressing Alp protease, even in the presence of the cryptic prophage. Therefore, 10Sa RNA acts as a negative regulator of protease synthesis or activity, and prophage excision must inactivate this inhibitory function of the RNA. JF - Journal of bacteriology AU - Kirby, J E AU - Trempy, J E AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2068 EP - 2081 VL - 176 IS - 7 SN - 0021-9193, 0021-9193 KW - AlpA protein, E coli KW - 0 KW - Bacterial Outer Membrane Proteins KW - Bacterial Proteins KW - Escherichia coli Proteins KW - Integration Host Factors KW - RNA, Bacterial KW - Transcription Factors KW - surface layer protein A, Bacteria KW - Endopeptidases KW - EC 3.4.- KW - Alp protease KW - EC 3.4.99.- KW - Index Medicus KW - Bacterial Proteins -- genetics KW - Sequence Homology, Nucleic Acid KW - Genes, Bacterial -- genetics KW - Amino Acid Sequence KW - RNA, Bacterial -- genetics KW - Sequence Analysis, DNA KW - Transcription Factors -- genetics KW - Cloning, Molecular KW - Base Sequence KW - RNA, Bacterial -- biosynthesis KW - Bacterial Outer Membrane Proteins -- genetics KW - Molecular Sequence Data KW - Helper Viruses -- genetics KW - Sequence Homology, Amino Acid KW - Sequence Deletion KW - Gene Expression Regulation, Bacterial KW - Endopeptidases -- biosynthesis KW - Proviruses -- genetics KW - Escherichia coli -- genetics KW - Coliphages -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76423241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Excision+of+a+P4-like+cryptic+prophage+leads+to+Alp+protease+expression+in+Escherichia+coli.&rft.au=Kirby%2C+J+E%3BTrempy%2C+J+E%3BGottesman%2C+S&rft.aulast=Kirby&rft.aufirst=J&rft.date=1994-04-01&rft.volume=176&rft.issue=7&rft.spage=2068&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 - 1994-05-02 N1 - Date created - 1994-05-02 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - U03737; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Nucleic Acids Res. 1990 May 11;18(9):2820 [1692615] Gene. 1982 Oct;19(3):259-68 [6295879] J Mol Biol. 1983 May 5;166(1):1-19 [6304321] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] J Bacteriol. 1984 May;158(2):551-61 [6327610] Proc Natl Acad Sci U S A. 1984 Jul;81(14):4490-4 [6087326] Cell. 1984 Dec;39(3 Pt 2):707-16 [6096022] J Biol Chem. 1985 Apr 10;260(7):4468-77 [2984205] EMBO J. 1986 Feb;5(2):433-40 [3011407] J Bacteriol. 1986 Jul;167(1):191-200 [2941412] J Bacteriol. 1987 Mar;169(3):981-9 [3029041] Cell. 1987 Jul 31;50(3):495-508 [3038334] Nature. 1987 Sep 3-9;329(6134):21 [3041224] J Bacteriol. 1990 Jul;172(7):3541-8 [2193910] J Bacteriol. 1990 Aug;172(8):4708-9 [1695897] J Mol Evol. 1990 Jun;30(6):489-92 [2165531] Nucleic Acids Res. 1990 Sep 11;18(17):5305 [1698282] J Mol Biol. 1990 Oct 5;215(3):403-10 [2231712] Nucleic Acids Res. 1991 Feb 11;19(3):637-47 [2011534] Annu Rev Genet. 1990;24:465-90 [2088176] Infect Immun. 1991 May;59(5):1860-3 [1840573] Science. 1991 May 17;252(5008):969-71 [1709758] J Bacteriol. 1991 Jul;173(13):4171-81 [1712012] Mol Gen Genet. 1991 Sep;229(1):52-6 [1716727] Mol Microbiol. 1991 Jul;5(7):1599-606 [1943696] Gene. 1991 Oct 30;107(1):43-52 [1720755] Microbiol Rev. 1987 Sep;51(3):301-19 [3118156] J Mol Biol. 1987 Aug 5;196(3):445-55 [2824781] Nucleic Acids Res. 1992 Jan 11;20(1):138 [1371186] J Biol Chem. 1992 Apr 5;267(10):6859-64 [1551893] J Bacteriol. 1992 Jun;174(11):3834-5 [1534329] Biotechniques. 1992 Feb;12(2):223-5 [1319720] Protein Eng. 1992 Jan;5(1):87-91 [1631049] J Bacteriol. 1992 Dec;174(23):7495-9 [1447124] Microbiol Rev. 1992 Dec;56(4):592-621 [1480111] J Bacteriol. 1994 Apr;176(7):2061-7 [7511582] J Bacteriol. 1994 Apr;176(7):2082-9 [8144474] J Mol Biol. 1987 Aug 5;196(3):487-96 [3119856] J Virol. 1988 May;62(5):1697-704 [2833620] J Bacteriol. 1988 Jun;170(6):2599-611 [2836365] Cell. 1988 Nov 18;55(4):545-54 [2972385] Nucleic Acids Res. 1989 Mar 11;17(5):1907-14 [2467253] J Bacteriol. 1989 Jun;171(6):3348-53 [2656652] Proc Natl Acad Sci U S A. 1989 Jun;86(11):3973-7 [2657731] Mol Microbiol. 1989 Nov;3(11):1481-5 [2482406] Annu Rev Genet. 1989;23:163-98 [2694929] Virology. 1981 Aug;113(1):20-38 [7023020] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adduction of the heterocyclic amine food mutagens IQ and PhIP to mitochondrial and nuclear DNA in the liver of Fischer-344 rats. AN - 76423058; 8149474 AB - The heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogens that form DNA adducts. In the present study, we used the 32P-postlabeling method to measure the levels of IQ and PhIP adducts in hepatic nuclear and mitochondrial DNA of Fischer-344 rats given a single dose (100 mg/kg, p.o.) or 10 doses of either carcinogen. After a single dose of IQ, adduct levels were > 2-fold higher in hepatic nuclear than in mitochondrial DNA; however, after repeated IQ exposure, the levels of adducts in nuclear and mitochondrial DNA were not significantly different. In contrast, after a single dose of PhIP, there were no significant differences in adduct levels in nuclear and mitochondrial DNA; however, after multiple doses of PhIP, adduct levels were significantly higher in mitochondrial DNA than in nuclear DNA. The percentages of individual IQ or PhIP adducts were different between nuclear DNA and mitochondrial DNA, particularly after 10 doses. With IQ, the C8-guanine adduct accounted for 72% of the total IQ adduct levels in nuclear DNA but only 40% of total adduct levels in mitochondrial DNA. After 10 doses of PhIP, the C8-guanine adduct accounted for 48% and 15% of total adduct levels in nuclear DNA and mitochondrial DNA respectively. In addition, the percentage of an uncharacterized PhIP adduct was 14% in nuclear DNA but < 1% in mitochondrial DNA. The percentages of individual adducts were approximately the same 3, 24, 120 and 240 h after a single dose of either compound, though total IQ and PhIP adduct levels appeared to decline over time in both organelles. The significance of IQ and PhIP mitochondrial DNA adduction and the influence of distinct heterocyclic amine adducts on carcinogenesis merit further investigation. JF - Carcinogenesis AU - Davis, C D AU - Schut, H A AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 641 EP - 645 VL - 15 IS - 4 SN - 0143-3334, 0143-3334 KW - DNA, Mitochondrial KW - 0 KW - Imidazoles KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - DNA KW - 9007-49-2 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Mitochondria, Liver -- metabolism KW - Male KW - Quinolines -- metabolism KW - DNA Damage KW - Cell Nucleus -- metabolism KW - Imidazoles -- metabolism KW - DNA -- metabolism KW - DNA, Mitochondrial -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76423058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adduction+of+the+heterocyclic+amine+food+mutagens+IQ+and+PhIP+to+mitochondrial+and+nuclear+DNA+in+the+liver+of+Fischer-344+rats.&rft.au=Davis%2C+C+D%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1994-04-01&rft.volume=15&rft.issue=4&rft.spage=641&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-12 N1 - Date created - 1994-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alp suppression of Lon: dependence on the slpA gene. AN - 76419142; 7511582 AB - We have previously found that plasmids carrying the Escherichia coli alp gene (now to be called alpA) suppress two phenotypes of a delta lon protease mutant, overproduction of capsular polysaccharide and sensitivity to UV light. Suppression of these lon phenotypes is most likely explained by the increased degradation of the Lon substrates responsible for these phenotypes. We have called this suppressing protease activity Alp protease. The Alp protease activity is detected in cells after introduction of plasmids carrying the alpA gene, which encodes an open reading frame of 70 amino acids. Insertions which abolish Alp activity interrupt this open reading frame. We have used Tn10 and lambda placMu mutagenesis to identify a chromosomal locus, slpA, that is required for alpA+ suppression of delta lon. This locus maps at 57 min, close to the chromosomal location of alpA. The expression of beta-galactosidase from a lac transcriptional fusion to slpA is increased six- to eightfold when the alpA+ gene is present on a multicopy plasmid. Therefore, AlpA acts as a transcriptional regulator of the slpA gene(s); activation of slpA transcription is necessary to suppress the phenotypes of a delta lon mutation. In an accompanying paper (J. E. Kirby, J. E. Trempy, and S. Gottesman, J. Bacteriol. 176:2068-2081, 1994), we show that neither AlpA nor SlpA is a component of the protease itself but that they are part of a regulatory cascade which leads to expression of the Alp protease. JF - Journal of bacteriology AU - Trempy, J E AU - Kirby, J E AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2061 EP - 2067 VL - 176 IS - 7 SN - 0021-9193, 0021-9193 KW - alpA KW - lon KW - slpA KW - AlpA protein, E coli KW - 0 KW - Bacterial Outer Membrane Proteins KW - Bacterial Proteins KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - RNA, Bacterial KW - Transcription Factors KW - surface layer protein A, Bacteria KW - Endopeptidases KW - EC 3.4.- KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - Alp protease KW - EC 3.4.99.- KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - DNA Mutational Analysis KW - Genes, Bacterial -- genetics KW - Amino Acid Sequence KW - Coliphages -- genetics KW - RNA, Bacterial -- genetics KW - Sequence Analysis, DNA KW - Base Sequence KW - Blotting, Southern KW - Restriction Mapping KW - Molecular Sequence Data KW - Proviruses -- genetics KW - Sequence Homology, Amino Acid KW - Endopeptidases -- genetics KW - Serine Endopeptidases -- genetics KW - Bacterial Outer Membrane Proteins -- genetics KW - Suppression, Genetic KW - Escherichia coli -- genetics KW - Transcription Factors -- genetics KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76419142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alp+suppression+of+Lon%3A+dependence+on+the+slpA+gene.&rft.au=Trempy%2C+J+E%3BKirby%2C+J+E%3BGottesman%2C+S&rft.aulast=Trempy&rft.aufirst=J&rft.date=1994-04-01&rft.volume=176&rft.issue=7&rft.spage=2061&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 - 1994-05-02 N1 - Date created - 1994-05-02 N1 - Date revised - 2017-01-13 N1 - Gene symbol - alpA; lon; slpA N1 - Genetic sequence - U03737; GENBANK N1 - SuppNotes - Cited By: Nature. 1981 Apr 30;290(5809):797-9 [7012641] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4530-3 [159458] Proc Natl Acad Sci U S A. 1983 Jan;80(2):358-62 [6300834] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Proc Natl Acad Sci U S A. 1984 Jul;81(14):4490-4 [6087326] Gene. 1984 Dec;32(3):369-79 [6099322] Proc Natl Acad Sci U S A. 1985 May;82(9):2880-4 [3157994] J Bacteriol. 1985 Jun;162(3):1092-9 [2987183] J Bacteriol. 1985 Jun;162(3):1111-9 [3888955] J Bacteriol. 1987 Mar;169(3):981-9 [3029041] Cell. 1987 Jul 31;50(3):495-508 [3038334] J Bacteriol. 1988 Jun;170(6):2599-611 [2836365] J Bacteriol. 1989 Jun;171(6):3348-53 [2656652] J Mol Biol. 1989 Jun 20;207(4):675-93 [2760929] Annu Rev Genet. 1989;23:163-98 [2694929] J Bacteriol. 1990 Jul;172(7):3541-8 [2193910] J Bacteriol. 1990 Aug;172(8):4708-9 [1695897] J Bacteriol. 1991 Mar;173(5):1738-47 [1999391] Annu Rev Genet. 1990;24:465-90 [2088176] J Bacteriol. 1991 Jul;173(13):4171-81 [1712012] Mol Microbiol. 1991 Jul;5(7):1599-606 [1943696] Methods Enzymol. 1991;204:139-80 [1658561] Methods Enzymol. 1991;204:18-43 [1943777] J Bacteriol. 1994 Apr;176(7):2068-81 [7511583] Anal Biochem. 1975 Feb;63(2):350-60 [1092200] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Bacteriol. 1978 Feb;133(2):844-51 [146704] Cell. 1981 Apr;24(1):225-33 [6453650] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. AN - 76418141; 7908520 AB - To identify the role of methotrexate (MTX) in the treatment of persistent or recurrent Takayasu arteritis that is refractory to treatment with glucocorticoids (GC) alone. An open-label pilot study of weekly low-dose MTX+GC treatment was performed. Outcome was evaluated according to clinical characteristics, laboratory abnormalities, findings on routinely performed angiographic studies, and ability to withdraw GC and MTX therapy. Eighteen patients entered the study; 2 dropped out, and 16 were followed up for a mean period of 2.8 years (range 1.3-4.8 years). Weekly administration of MTX (mean stable dose of 17.1 mg) and GC resulted in remissions in 13 of 16 patients (81%). However, 7 patients (44%) had relapses as GC was tapered to or near discontinuation. Retreatment again led to remission, and 3 of 7 patients in this group have successfully stopped GC therapy. Of those patients who achieved remission, 8 (50%) have sustained remissions of 4-34 months (mean 18 months), and 4 of this group have not required GC or MTX therapy for 7-18 months (mean 11.3 months). Three patients experienced disease progression in spite of treatment. About half of all Takayasu arteritis patients have chronic active disease for which GC therapy alone does not provide sustained remissions that allow withdrawal of treatment. Weekly low-dose MTX is an effective means of inducing remission and minimizing GC therapy and toxicity in most of these patients. Further long-term studies will be required to assess the durability of remission and the need for maintenance MTX therapy in this subset of Takayasu arteritis patients. JF - Arthritis and rheumatism AU - Hoffman, G S AU - Leavitt, R Y AU - Kerr, G S AU - Rottem, M AU - Sneller, M C AU - Fauci, A S AD - National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 578 EP - 582 VL - 37 IS - 4 SN - 0004-3591, 0004-3591 KW - Glucocorticoids KW - 0 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Drug Administration Schedule KW - Humans KW - Adult KW - Drug Resistance KW - Pilot Projects KW - Middle Aged KW - Adolescent KW - Recurrence KW - Male KW - Female KW - Remission Induction KW - Methotrexate -- adverse effects KW - Takayasu Arteritis -- drug therapy KW - Glucocorticoids -- administration & dosage KW - Takayasu Arteritis -- complications KW - Methotrexate -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76418141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Treatment+of+glucocorticoid-resistant+or+relapsing+Takayasu+arteritis+with+methotrexate.&rft.au=Hoffman%2C+G+S%3BLeavitt%2C+R+Y%3BKerr%2C+G+S%3BRottem%2C+M%3BSneller%2C+M+C%3BFauci%2C+A+S&rft.aulast=Hoffman&rft.aufirst=G&rft.date=1994-04-01&rft.volume=37&rft.issue=4&rft.spage=578&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potential use of nitroxides in radiation oncology. AN - 76409275; 8137329 AB - The identification of radioprotectors is an important goal for those involved in radiation oncology and for those interested in the investigation of the mechanisms of radiation cytotoxicity. Recently, a new class of in vitro and in vivo radioprotectors, the nitroxides, has been discovered. The nitroxides are low-molecular-weight stable free radicals which are freely membrane permeable and which have been shown to act as superoxide dismutase mimics. Further investigation of these compounds has shown that a water-soluble nitroxide, Tempol, protects cultured Chinese hamster V79 cells from the cytotoxicity caused by superoxide, hydrogen peroxide, and t-butyl hydroperoxide. Tempol and five other water-soluble nitroxides have also been shown to protect V79 cells against radiation-induced cytotoxicity. Potential mechanisms of protection by the nitroxides include oxidation of reduced transition metals, superoxide dismutase-like activity, and scavenging of oxy- and carbon-based free radicals. In vivo studies reveal that Tempol protects C3H mice from the lethal effects of radiation with a dose causing 50% lethality within 30 days of 9.97 Gy and 7.84 Gy in Tempol-treated and saline-treated mice, respectively, and a dose modification factor of 1.3. The nitroxides represent a new class of non-thiol radioprotectors which may also have application as general antioxidants. Additional work is necessary to screen other nitroxides for in vivo radioprotection and toxicity as well as to fully evaluate the extent to which these compounds protect tumors. JF - Cancer research AU - Hahn, S M AU - Krishna, C M AU - Samuni, A AU - DeGraff, W AU - Cuscela, D O AU - Johnstone, P AU - Mitchell, J B AD - Radiation Biology Section, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 2006s EP - 2010s VL - 54 IS - 7 Suppl SN - 0008-5472, 0008-5472 KW - Cyclic N-Oxides KW - 0 KW - Cytotoxins KW - Peroxides KW - Radiation-Protective Agents KW - Spin Labels KW - Superoxides KW - 11062-77-4 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Hydrogen Peroxide KW - BBX060AN9V KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Hydrogen Peroxide -- toxicity KW - Animals KW - Cricetulus KW - Mice, Inbred C3H KW - Peroxides -- toxicity KW - Mice KW - Dose-Response Relationship, Radiation KW - Superoxides -- toxicity KW - Cell Line KW - Cricetinae KW - Cyclic N-Oxides -- therapeutic use KW - Radiation-Protective Agents -- therapeutic use KW - Cytotoxins -- toxicity KW - Cell Survival -- drug effects KW - Cyclic N-Oxides -- pharmacology KW - Radiation-Protective Agents -- pharmacology KW - Cell Survival -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76409275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Potential+use+of+nitroxides+in+radiation+oncology.&rft.au=Hahn%2C+S+M%3BKrishna%2C+C+M%3BSamuni%2C+A%3BDeGraff%2C+W%3BCuscela%2C+D+O%3BJohnstone%2C+P%3BMitchell%2C+J+B&rft.aulast=Hahn&rft.aufirst=S&rft.date=1994-04-01&rft.volume=54&rft.issue=7+Suppl&rft.spage=2006s&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The human immunodeficiency virus type 1 Tat protein transactivates tumor necrosis factor beta gene expression through a TAR-like structure. AN - 76408254; 8139045 AB - We have previously shown that the Tat protein of human immunodeficiency virus type 1 (HIV-1) transactivates tumor necrosis factor alpha and beta (TNF alpha and TNF beta) gene expression in HIV-1-infected and in tat-transfected T-lymphocytic and monocytic cell lines. The product encoded by the first exon of the tat gene (amino acids 1 to 72) is sufficient for this transactivation. Here we show that (i) the NF-kappa B and Sp1 binding sites of the TNF beta promoter are required for Tat-mediated transactivation and (ii) a predicted stem-loop structure in the TNF beta mRNA leader region, which resembles the Tat-responsive element of the HIV-1 long terminal repeat (TAR) and which is therefore termed TAR-like, is essential for TNF beta transactivation by Tat. These data suggest that similar promoter regulatory elements are necessary for Tat-mediated transactivation of both TNF beta and HIV-1 gene expression. This represents the first demonstration of a cellular gene with a regulatory element downstream of the transcriptional initiation site that, like TAR, may function as an RNA element. JF - Journal of virology AU - Buonaguro, L AU - Buonaguro, F M AU - Giraldo, G AU - Ensoli, B AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2677 EP - 2682 VL - 68 IS - 4 SN - 0022-538X, 0022-538X KW - Gene Products, tat KW - 0 KW - Gene Products, tax KW - Lymphotoxin-alpha KW - tat Gene Products, Human Immunodeficiency Virus KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation KW - Sequence Analysis, DNA KW - Gene Products, tax -- pharmacology KW - Lymphotoxin-alpha -- biosynthesis KW - HIV-1 -- genetics KW - Lymphotoxin-alpha -- genetics KW - Transcriptional Activation -- drug effects KW - Promoter Regions, Genetic -- genetics KW - Gene Products, tat -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76408254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+human+immunodeficiency+virus+type+1+Tat+protein+transactivates+tumor+necrosis+factor+beta+gene+expression+through+a+TAR-like+structure.&rft.au=Buonaguro%2C+L%3BBuonaguro%2C+F+M%3BGiraldo%2C+G%3BEnsoli%2C+B&rft.aulast=Buonaguro&rft.aufirst=L&rft.date=1994-04-01&rft.volume=68&rft.issue=4&rft.spage=2677&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1986 Mar 28;44(6):941-7 [2420471] Virology. 1986 Jan 15;148(1):226-31 [3002031] Science. 1986 May 9;232(4751):755-9 [3008338] Cell. 1986 Sep 12;46(6):807-17 [3638988] Cell. 1987 Feb 27;48(4):691-701 [3643816] Cell. 1987 Apr 10;49(1):47-56 [3030566] Nature. 1987 Apr 16-22;326(6114):711-3 [3031512] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845-9 [3498942] Nature. 1987 Dec 3-9;330(6147):489-93 [2825027] Science. 1987 Dec 11;238(4833):1575-8 [2825351] J Virol. 1988 Mar;62(3):673-9 [2828663] Nature. 1988 Apr 7;332(6164):551-3 [2833703] Nature. 1988 Jun 23;333(6175):776-8 [2838755] Nature. 1988 Jul 14;334(6178):165-7 [3386755] Mol Cell Biol. 1988 Jun;8(6):2555-61 [2841583] Science. 1988 Sep 23;241(4873):1652-5 [2843985] Gene. 1988 Jul 30;67(2):271-7 [3169576] Nucleic Acids Res. 1989 Jan 25;17(2):723-33 [2915928] EMBO J. 1989 Mar;8(3):765-78 [2721501] Proc Natl Acad Sci U S A. 1989 Jul;86(13):4858-62 [2544877] Cell. 1989 Oct 20;59(2):273-82 [2478293] Cell. 1989 Oct 20;59(2):283-92 [2553266] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7828-32 [2510154] EMBO J. 1989 Oct;8(10):3019-27 [2573513] J Virol. 1990 Mar;64(3):1402-6 [2406460] Cell. 1990 Aug 24;62(4):757-67 [2201451] J Virol. 1990 Nov;64(11):5412-9 [1976820] Genes Dev. 1990 Aug;4(8):1365-73 [2227414] J Biol Chem. 1990 Nov 25;265(33):20091-3 [2243081] Immunol Rev. 1992 Jun;127:147-55 [1506004] J Immunol. 1992 Dec 1;149(11):3727-34 [1431144] J Virol. 1992 Dec;66(12):7159-67 [1279199] J Virol. 1992 Dec;66(12):7355-61 [1331525] Blood. 1993 Jan 1;81(1):95-100 [8417807] Gene Expr. 1992;2(4):391-407 [1282057] Anal Biochem. 1976 May 7;72:248-54 [942051] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Cell. 1985 Jul;41(3):813-23 [2988790] Science. 1985 Jul 5;229(4708):69-73 [2990040] Science. 1985 Jul 5;229(4708):74-7 [2990041] Nucleic Acids Res. 1985 Sep 11;13(17):6361-73 [2995927] Nature. 1986 Mar 27-Apr 2;320(6060):367-71 [3007995] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp120. AN - 76407279; 8139032 AB - The domains of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein that are required for envelope function have been partially characterized. Little is known, however, about the nature of the interactions between these domains. To identify regions of the HIV-1 envelope glycoprotein that are involved in interactions necessary for proper envelope function, we constructed a series of 14 envelope recombinants between the env genes of two HIV-1 isolates. The envelope chimeras were examined for their ability to induce syncytia, to be proteolytically processed, and to function during a spreading viral infection. Our results demonstrate that the exchange between the two isolates of the first and second hypervariable regions (V1/V2) of gp120 results in defects in envelope glycoprotein processing, syncytium formation, and infectivity. Long-term passage of cultures infected with virus bearing a V1/V2 chimeric envelope glycoprotein leads to the emergence of a revertant virus with replication characteristics comparable to those of the wild type. Analysis of the revertant indicated that an Ile-->Met change in the C4 region of gp120 (between hypervariable regions V4 and V5) is responsible for the revertant phenotype. This single amino acid change restores infectivity without significantly affecting gp160 processing, CD4 binding, or the levels of virion-associated gp120. While the Ile-->Met change in C4 greatly enhances the fusogenic potential of the V1/V2 chimeric envelope glycoprotein, it has a detrimental effect on syncytium formation when analyzed in the context of the wild-type envelope. These results suggest that an interaction required for proper envelope glycoprotein function occurs between the V1/V2 and C4 regions of gp120. JF - Journal of virology AU - Freed, E O AU - Martin, M A AD - laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2503 EP - 2512 VL - 68 IS - 4 SN - 0022-538X, 0022-538X KW - Antigens, CD4 KW - 0 KW - HIV Envelope Protein gp120 KW - HIV Envelope Protein gp41 KW - Recombinant Fusion Proteins KW - Index Medicus KW - AIDS/HIV KW - Virulence KW - Base Sequence KW - Cell Fusion KW - Humans KW - Protein Processing, Post-Translational KW - HIV Envelope Protein gp41 -- genetics KW - Molecular Sequence Data KW - Protein Binding KW - Recombinant Fusion Proteins -- physiology KW - Mutagenesis KW - Cloning, Molecular KW - HIV Envelope Protein gp120 -- physiology KW - HIV-1 -- pathogenicity KW - HIV-1 -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76407279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+a+functional+interaction+between+the+V1%2FV2+and+C4+domains+of+human+immunodeficiency+virus+type+1+envelope+glycoprotein+gp120.&rft.au=Freed%2C+E+O%3BMartin%2C+M+A&rft.aulast=Freed&rft.aufirst=E&rft.date=1994-04-01&rft.volume=68&rft.issue=4&rft.spage=2503&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1990 Jun 25;265(18):10373-82 [2355006] J Virol. 1994 Feb;68(2):1029-39 [7904656] J Virol. 1990 Dec;64(12):5701-7 [2243375] J Virol. 1990 Dec;64(12):6314-8 [2243396] J Virol. 1991 Jan;65(1):190-4 [1985197] Nature. 1991 Jan 10;349(6305):167-9 [1986308] AIDS Res Hum Retroviruses. 1991 Oct;7(10):807-11 [1720627] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 [1729720] J Virol. 1992 Apr;66(4):2577-82 [1548783] J Virol. 1992 Aug;66(8):4748-56 [1629954] AIDS Res Hum Retroviruses. 1992 Sep;8(9):1669-77 [1457211] J Virol. 1993 May;67(5):2747-55 [8474172] J Virol. 1993 Jun;67(6):3232-9 [7684463] J Virol. 1993 Jun;67(6):3674-9 [8497077] Virology. 1993 Jul;195(1):167-74 [8317093] J Virol. 1993 Aug;67(8):4932-44 [7687306] J Virol. 1993 Sep;67(9):5635-9 [8350416] J Virol. 1993 Oct;67(10):6136-51 [7690418] J Virol. 1993 Oct;67(10):6253-8 [8371358] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7 [6096719] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] Proc Natl Acad Sci U S A. 1985 Jul;82(14):4813-7 [2991896] Science. 1985 Aug 23;229(4715):759-62 [2992084] Science. 1986 Jan 24;231(4736):382-5 [3001934] Cell. 1986 Jun 6;45(5):637-48 [2423250] Science. 1986 Jun 20;232(4757):1548-53 [3012778] Cell. 1986 Jul 4;46(1):1-4 [3013415] Cell. 1986 Jul 4;46(1):63-74 [2424612] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5038-42 [3014529] J Virol. 1986 Aug;59(2):284-91 [3016298] Nature. 1986 Jul 31-Aug 6;322(6078):470-4 [3016552] Cell. 1986 Nov 7;47(3):333-48 [3094962] Nature. 1986 Oct 23-29;323(6090):725-8 [3095663] Science. 1986 Nov 28;234(4780):1120-3 [2430333] Cell. 1987 Jun 5;49(5):659-68 [3107838] J Virol. 1987 Sep;61(9):2852-6 [3039173] Cell. 1987 Sep 11;50(6):975-85 [2441877] Science. 1987 Sep 11;237(4820):1351-5 [3629244] J Virol. 1988 Jan;62(1):139-47 [3257102] Cell. 1988 Apr 8;53(1):55-67 [2450679] Nature. 1988 Aug 4;334(6181):440-4 [3405290] Nature. 1988 Aug 4;334(6181):444-7 [2841608] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] Virology. 1989 Jun;170(2):566-70 [2543131] J Virol. 1989 Sep;63(9):3595-600 [2547987] Nature. 1989 Aug 17;340(6234):571-4 [2475780] J Virol. 1989 Nov;63(11):4670-5 [2677400] J Virol. 1990 May;64(5):2416-20 [2325207] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4650-4 [2191297] Nature. 1990 Nov 1;348(6296):69-73 [2172833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine-mediated induction of human immunodeficiency virus (HIV) expression and cell death in chronically infected U1 cells: do tumor necrosis factor alpha and gamma interferon selectively kill HIV-infected cells? AN - 76407259; 7511175 AB - Infection with several DNA or RNA viruses induces a state of increased sensitivity to cell lysis mediated by tumor necrosis factor (TNF), particularly in the presence of gamma interferon (IFN-gamma). Infection of human cells with the human immunodeficiency virus (HIV) may induce a similar phenomenon. However, TNF and IFN-gamma are known upregulators of HIV replication, raising the question of the potential role of these cytokines in the selective elimination of cells infected with this virus. The present study demonstrates that chronically infected U1 cells were killed with much greater efficiency by costimulation with TNF-alpha and IFN-gamma than their uninfected parental cell line U937. However, synergistic induction of viral expression also occurred in U1 cells as a consequence of treatment with the two cytokines. Cell death in U1 cells was not caused by the massive production of virions, in that costimulation with glucocorticoid hormones and TNF-alpha or IFN-gamma resulted in high levels of virion production without cytopathicity. To investigate the nature of the selective cytotoxic effect observed in U1 cells costimulated with TNF-alpha plus IFN-gamma, a panel of uninfected cell clones was generated by limiting dilution of U937 cells and tested for response to TNF-alpha and/or IFN-gamma. In contrast to the uncloned bulk parental U937 cell line, most uninfected cell clones showed a very high susceptibility to being killed by TNF-alpha and IFN-gamma. Similar findings were obtained when both infected U1 cells and several uninfected U937 cell clones were costimulated with an anti-Fas monoclonal antibody in the presence of IFN-gamma, although, unlike cells stimulated with TNF-alpha, cells treated with anti-Fas antibody did not express virus. Therefore, the increased susceptibility to cytokine-mediated lysis observed in cell lines infected with HIV is likely due to the selection of preexisting cell clones rather than viral infection. JF - Journal of virology AU - Biswas, P AU - Poli, G AU - Orenstein, J M AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2598 EP - 2604 VL - 68 IS - 4 SN - 0022-538X, 0022-538X KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD95 KW - Antigens, Surface KW - Receptors, Interferon KW - Receptors, Tumor Necrosis Factor KW - Tumor Necrosis Factor-alpha KW - interferon gamma receptor KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - AIDS/HIV KW - Receptors, Interferon -- analysis KW - Virus Replication -- drug effects KW - Humans KW - Receptors, Tumor Necrosis Factor -- analysis KW - Cell Membrane -- chemistry KW - Antibodies, Monoclonal -- pharmacology KW - Drug Synergism KW - Antigens, Surface -- immunology KW - HIV -- growth & development KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interferon-gamma -- pharmacology KW - Cell Death -- drug effects KW - Clone Cells -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76407259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cytokine-mediated+induction+of+human+immunodeficiency+virus+%28HIV%29+expression+and+cell+death+in+chronically+infected+U1+cells%3A+do+tumor+necrosis+factor+alpha+and+gamma+interferon+selectively+kill+HIV-infected+cells%3F&rft.au=Biswas%2C+P%3BPoli%2C+G%3BOrenstein%2C+J+M%3BFauci%2C+A+S&rft.aulast=Biswas&rft.aufirst=P&rft.date=1994-04-01&rft.volume=68&rft.issue=4&rft.spage=2598&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1976 May 7;72:248-54 [942051] Semin Immunol. 1993 Jun;5(3):165-73 [7688596] Science. 1986 Feb 21;231(4740):850-3 [2418502] J Virol. 1986 Aug;59(2):284-91 [3016298] Nature. 1986 Oct 30-Nov 5;323(6091):819-22 [2430188] Nature. 1987 Dec 10-16;330(6148):581-3 [2960901] J Immunol. 1988 Jan 1;140(1):120-4 [3121735] J Immunol. 1988 Feb 15;140(4):1117-22 [2449497] Cell. 1988 May 6;53(3):341-6 [3365766] Science. 1988 Sep 23;241(4873):1673-5 [3047875] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336-40 [2494664] J Exp Med. 1989 May 1;169(5):1747-56 [2469768] Nature. 1989 May 4;339(6219):70-3 [2654643] J Virol. 1989 Jun;63(6):2504-9 [2470917] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974-8 [2762307] J Immunol. 1989 Dec 15;143(12):4193-200 [2531778] J Exp Med. 1990 Jul 1;172(1):151-8 [2193094] Cell. 1990 Jun 29;61(7):1271-6 [2364429] Science. 1990 Sep 21;249(4975):1431-3 [1698311] FASEB J. 1990 Nov;4(14):3215-23 [2172061] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9620-4 [1702216] J Virol. 1991 Jul;65(7):3968-71 [1710293] Immunol Rev. 1991 Jun;121:29-65 [1937533] J Exp Med. 1992 Sep 1;176(3):739-50 [1512539] AIDS Res Hum Retroviruses. 1992 May;8(5):581-7 [1515211] Immunol Today. 1992 Nov;13(11):427-8 [1282318] AIDS Res Hum Retroviruses. 1993 Jun;9(6):547-51 [8347399] Science. 1986 Feb 7;231(4738):600-2 [3003906] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and purification of the mouse mammary tumor virus gag-pro transframe protein p30 and characterization of its dUTPase activity. AN - 76407126; 8139016 AB - The mouse mammary tumor virus gag-pro transframe protein (p30) contains the nucleocapsid protein domain derived from the 3' end of gag, fused to 154 residues encoded by the 5' region of the pro open reading frame. The DNA coding for p30 was cloned into the plasmid pALTER-1, and an additional nucleotide was inserted by site-directed mutagenesis to allow the read-through from the gag into the pro open reading frame. The obtained insert was then cloned into pGEX-2T, a plasmid containing the glutathione S-transferase gene of Schistosoma japonicum and a nucleotide sequence encoding for a thrombin cleavage site. The chimeric protein (GST-p30) was isolated by affinity chromatography on a glutathione-Sepharose 4B column, and after thrombin treatment, the excised p30 was further purified on a single-stranded DNA-agarose column. This protein showed dUTPase activity, with only negligible cleavage of dATP, dGTP, dCTP, dTTP, or UTP. Its apparent Km for dUTP was 28 microM. The enzyme was inhibited by EDTA, but its effect could be reversed by Mg2+ and other divalent cations. dUTPase activity was also detected in purified mouse mammary tumor virus, and p30 was the only protein recognized by antibodies directed towards the carboxyl-terminal sequence of the dUTPase coding region. JF - Journal of virology AU - Köppe, B AU - Menéndez-Arias, L AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2313 EP - 2319 VL - 68 IS - 4 SN - 0022-538X, 0022-538X KW - gag KW - pol KW - Cations, Divalent KW - 0 KW - Chelating Agents KW - Gene Products, gag KW - Gene Products, pol KW - Recombinant Proteins KW - Viral Core Proteins KW - Pyrophosphatases KW - EC 3.6.1.- KW - dUTP pyrophosphatase KW - EC 3.6.1.23 KW - Index Medicus KW - AIDS/HIV KW - Gene Products, gag -- genetics KW - Gene Expression KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Gene Products, pol -- genetics KW - Gene Products, gag -- metabolism KW - Cloning, Molecular KW - Gene Products, pol -- isolation & purification KW - Recombinant Proteins -- isolation & purification KW - Chelating Agents -- pharmacology KW - Base Sequence KW - Gene Products, gag -- isolation & purification KW - Recombinant Proteins -- metabolism KW - Reading Frames KW - Sequence Analysis KW - Gene Products, pol -- metabolism KW - Molecular Sequence Data KW - Substrate Specificity KW - Cations, Divalent -- pharmacology KW - Pyrophosphatases -- genetics KW - Pyrophosphatases -- drug effects KW - Viral Core Proteins -- genetics KW - Pyrophosphatases -- isolation & purification KW - Viral Core Proteins -- isolation & purification KW - Pyrophosphatases -- metabolism KW - Viral Core Proteins -- metabolism KW - Mammary Tumor Virus, Mouse -- enzymology KW - Viral Core Proteins -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76407126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression+and+purification+of+the+mouse+mammary+tumor+virus+gag-pro+transframe+protein+p30+and+characterization+of+its+dUTPase+activity.&rft.au=K%C3%B6ppe%2C+B%3BMen%C3%A9ndez-Arias%2C+L%3BOroszlan%2C+S&rft.aulast=K%C3%B6ppe&rft.aufirst=B&rft.date=1994-04-01&rft.volume=68&rft.issue=4&rft.spage=2313&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - gag; pol N1 - SuppNotes - Cited By: J Biol Chem. 1992 Jun 5;267(16):11392-8 [1375941] J Biol Chem. 1987 Jan 5;262(1):130-4 [3025197] J Virol. 1992 Nov;66(11):6706-13 [1328686] J Biol Chem. 1992 Nov 25;267(33):24134-9 [1331110] J Virol. 1993 May;67(5):2592-600 [8386267] Virology. 1993 Aug;195(2):863-5 [8393252] Virology. 1987 Feb;156(2):282-92 [3027979] Eur J Biochem. 1987 Apr 1;164(1):45-51 [3030754] Arch Biochem Biophys. 1987 Mar;253(2):350-6 [3032103] Proc Natl Acad Sci U S A. 1987 May;84(9):2693-7 [3106974] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4298-302 [3035577] Proc Natl Acad Sci U S A. 1987 Oct;84(20):7041-5 [2823251] Virology. 1987 Dec;161(2):321-31 [2825406] Gene. 1988 Jul 15;67(1):31-40 [3047011] Science. 1988 Nov 25;242(4882):1168-71 [2460924] Science. 1988 Nov 25;242(4882):1171-3 [2460925] Biochem Biophys Res Commun. 1989 Apr 28;160(2):486-94 [2541703] J Virol. 1989 Jun;63(6):2543-9 [2542570] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4152-5 [2657744] Infect Immun. 1989 Sep;57(9):2878-85 [2668192] EMBO J. 1990 May;9(5):1583-93 [1691709] Nucleic Acids Res. 1990 Jul 25;18(14):4105-10 [2165588] Virology. 1991 Nov;185(1):387-94 [1718086] J Virol. 1992 Mar;66(3):1791-4 [1310783] Nature. 1992 Feb 20;355(6362):740-3 [1311056] Adv Virus Res. 1992;41:193-239 [1575083] Virology. 1993 Oct;196(2):451-7 [8396797] Virology. 1993 Oct;196(2):557-63 [8372434] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1978 Jan;75(1):233-7 [203931] J Biol Chem. 1979 Apr 25;254(8):2897-901 [285077] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Proc Natl Acad Sci U S A. 1980 Apr;77(4):1956-60 [6929529] J Biol Chem. 1980 Nov 25;255(22):10630-7 [7430142] Nature. 1981 Jan 22;289(5795):253-8 [6256658] Anal Biochem. 1980 Jul 1;105(2):311-8 [7457837] Proc Natl Acad Sci U S A. 1981 Jun;78(6):3403-7 [6167985] J Biol Chem. 1984 Aug 25;259(16):10080-4 [6147344] J Virol. 1985 Sep;55(3):778-87 [3927012] Science. 1986 Mar 28;231(4745):1567-72 [3006247] Cell. 1986 May 9;45(3):375-85 [2421920] Plant Cell. 1992 Feb;4(2):149-59 [1321683] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Varicella-zoster virus open reading frame 4 encodes a transcriptional activator that is functionally distinct from that of herpes simplex virus homology ICP27. AN - 76406837; 8139031 AB - Varicella-zoster virus is the etiological agent of chickenpox and zoster in humans and belongs to the Alphaherpesvirinae subfamily within the family Herpesviridae. Much of the current understanding of gene regulation in alphaherpesviruses has been derived from studies of the prototype herpes simplex virus (HSV). In HSV, two virus-encoded, trans-regulatory proteins, ICP4 and ICP27, are essential for the replicative cycle of the virus. ICP4 is important in modulating HSV genes of all three kinetic classes, whereas the trans-regulatory effects of ICP27 are primarily associated with the expression of late genes. Recent evidence indicates that the trans-regulatory effects of ICP27 involve posttranscriptional processing of target gene transcripts (R. M. Sandri-Golding and G. E. Mendoza, Genes Dev. 6:848-863, 1992). The ICP27 homolog in varicella-zoster virus is a 452-amino-acid polypeptide encoded by the open reading frame 4 (ORF4) gene. Contrary to what is found with ICP27, we show that the ORF4 polypeptide is a transcriptional activator of diverse target promoters and has a critical requirement for the presence of upstream elements within these promoters to mediate its transcriptional effects. Evidence is also presented to implicate a critical role for the cysteine-rich, C-terminal region of the ORF4 polypeptide in its trans-regulatory functions. Specifically, by oligonucleotide-directed site-specific mutagenesis, we demonstrate that of 10 cysteine residues in the ORF4 polypeptide, only C-421 and C-426 are essential for transactivator function and suggest that these cysteine residues may participate in critical protein-protein interactions rather than protein-nucleic acid interactions to mediate ORF4 inducibility. JF - Journal of virology AU - Perera, L P AU - Kaushal, S AU - Kinchington, P R AU - Mosca, J D AU - Hayward, G S AU - Straus, S E AD - Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 2468 EP - 2477 VL - 68 IS - 4 SN - 0022-538X, 0022-538X KW - ICP27 protein, human herpesvirus 1 KW - 0 KW - Immediate-Early Proteins KW - Transcription Factors KW - Viral Proteins KW - Histidine KW - 4QD397987E KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Viral Proteins -- genetics KW - Base Sequence KW - Gene Expression Regulation, Viral KW - Histidine -- genetics KW - Cysteine -- genetics KW - Molecular Sequence Data KW - Open Reading Frames -- genetics KW - RNA Processing, Post-Transcriptional KW - Structure-Activity Relationship KW - Herpesvirus 3, Human -- genetics KW - Promoter Regions, Genetic -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76406837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Varicella-zoster+virus+open+reading+frame+4+encodes+a+transcriptional+activator+that+is+functionally+distinct+from+that+of+herpes+simplex+virus+homology+ICP27.&rft.au=Perera%2C+L+P%3BKaushal%2C+S%3BKinchington%2C+P+R%3BMosca%2C+J+D%3BHayward%2C+G+S%3BStraus%2C+S+E&rft.aulast=Perera&rft.aufirst=L&rft.date=1994-04-01&rft.volume=68&rft.issue=4&rft.spage=2468&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1974 Jul;14(1):8-19 [4365321] J Virol. 1991 Jul;65(7):3656-66 [1645788] J Virol. 1977 Mar;21(3):996-1001 [191658] J Virol. 1977 Jun;22(3):720-5 [195087] Cell. 1977 Sep;12(1):275-85 [198141] J Virol. 1979 Aug;31(2):447-62 [225564] J Virol. 1980 Jan;33(1):167-82 [6245226] Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453-7 [6292901] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707-11 [6300869] J Virol. 1983 May;46(2):371-7 [6302308] J Virol. 1993 Aug;67(8):4474-83 [8392592] Cell. 1983 Nov;35(1):79-87 [6313230] J Virol. 1984 Oct;52(1):108-18 [6090689] J Mol Biol. 1984 Nov 25;180(1):1-19 [6096556] Nature. 1985 Feb 7-13;313(6002):458-63 [2982105] Cell. 1985 Apr;40(4):767-74 [3886158] Nucleic Acids Res. 1985 Feb 11;13(3):825-39 [2987812] Cell. 1985 Jul;41(3):813-23 [2988790] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Virol. 1985 Sep;55(3):796-805 [2991596] EMBO J. 1985 Jun;4(6):1609-14 [4040853] J Virol. 1985 Nov;56(2):558-70 [2997476] Science. 1986 Feb 14;231(4739):699-704 [3080805] Cell. 1986 Aug 29;46(5):705-16 [3091258] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Mol Cell Biol. 1986 Jun;6(6):2279-83 [3785197] J Virol. 1987 Feb;61(2):276-84 [3027360] J Virol. 1992 Jan;66(1):359-66 [1309252] Trends Biochem Sci. 1991 Dec;16(12):478-81 [1664152] Genes Dev. 1992 May;6(5):848-63 [1315705] J Virol. 1992 Jun;66(6):3811-22 [1316484] J Virol. 1992 Jun;66(6):3899-903 [1316489] Virology. 1992 Jul;189(1):304-16 [1318606] J Virol. 1992 Sep;66(9):5298-304 [1323696] Virology. 1992 Nov;191(1):346-54 [1329324] J Virol. 1993 Feb;67(2):1105-9 [8380457] Sci Am. 1993 Feb;268(2):56-9, 62-5 [8430296] J Virol. 1993 May;67(5):2739-46 [8386275] J Virol. 1993 Jul;67(7):4290-5 [8389928] J Virol. 1993 Jul;67(7):4379-85 [8389935] Nucleic Acids Res. 1987 Jun 11;15(11):4491-511 [3035496] Science. 1987 Jun 5;236(4806):1252-8 [3296192] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408-12 [2823260] Cell. 1988 Apr 22;53(2):245-56 [2834065] Cell. 1988 Aug 26;54(5):659-64 [3044607] Nature. 1988 Oct 20;335(6192):683-9 [3050531] J Virol. 1988 Dec;62(12):4510-22 [2846867] J Virol. 1989 Jan;63(1):18-27 [2535723] Nature. 1989 Mar 2;338(6210):39-44 [2521923] Science. 1989 Jul 28;245(4916):371-8 [2667136] Nature. 1989 Oct 19;341(6243):624-30 [2571937] Nucleic Acids Res. 1989 Sep 25;17(18):7539 [2798115] Virology. 1989 Dec;173(2):700-9 [2556848] Mol Cell Biol. 1990 Apr;10(4):1329-37 [2157136] Proc Natl Acad Sci U S A. 1990 Oct;87(20):7799-803 [2172963] Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276-80 [165503] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation analysis of the THRA1 gene in breast cancer: deletion/fusion of the gene to a novel sequence on 17q in the BT474 cell line. AN - 76406608; 7511052 AB - We have previously described a common region of deletion and allele loss on chromosome 17q in sporadic breast cancers that is likely to contain a tumor suppressor gene. The region, mapped to 17q12-q21, was bordered by D17S250 and D17S579 on the centromeric and telomeric sides, respectively. This deletion region overlaps the BRCA1 locus, which predisposes to familial breast and ovarian cancer. The most frequent loss of heterozygosity was observed at the thyroid hormone receptor alpha (THRA1) locus. Southern analysis revealed a rearrangement of THRA1 in the BT474 breast cancer cell line. This rearrangement represented a deletion of exons 8-10 of one THRA1 allele that was also coamplified with ERBB2. Northern blots showed two mutant transcripts in BT474 cells. Analysis of the mutant transcripts revealed fusion of the THRA1 exon 7 by splicing to a novel sequence designated BTR for "BT474 transcribed rearrangement." BTR was found to be highly conserved and mapped to 17q. The deletion in BT474 cells spans the entire BRCA1 region. To search for additional mutations in the THRA1 gene, all nine protein-encoding exons of THRA1 were examined for point mutations via single strand conformation analysis in a series of primary breast tumors, breast cancer cell lines, and lymphoblastoid cell lines derived from the youngest affected members of several German breast cancer families. No point mutations were detected, including the unrearranged THRA1 allele in BT474. We have thus excluded THRA1 as a commonly mutated sporadic breast cancer tumor suppressor gene and as the BRCA1 gene. JF - Cancer research AU - Futreal, P A AU - Cochran, C AU - Marks, J R AU - Iglehart, J D AU - Zimmerman, W AU - Barrett, J C AU - Wiseman, R W AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 1791 EP - 1794 VL - 54 IS - 7 SN - 0008-5472, 0008-5472 KW - BRCA1 KW - BTR KW - THRA1 KW - DNA Primers KW - 0 KW - DNA, Neoplasm KW - Genetic Markers KW - RNA, Messenger KW - Receptors, Thyroid Hormone KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Blotting, Northern KW - Exons KW - Humans KW - Gene Rearrangement KW - Transcription, Genetic KW - RNA -- analysis KW - Amino Acid Sequence KW - DNA, Neoplasm -- isolation & purification KW - Chromosome Mapping KW - Polymerase Chain Reaction KW - Base Sequence KW - Poly A -- analysis KW - Tumor Cells, Cultured KW - Conserved Sequence KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Cell Line KW - Female KW - Breast Neoplasms -- genetics KW - Chromosomes, Human, Pair 17 KW - DNA Mutational Analysis KW - Receptors, Thyroid Hormone -- genetics KW - Point Mutation KW - Gene Deletion KW - Cloning, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76406608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+analysis+of+the+THRA1+gene+in+breast+cancer%3A+deletion%2Ffusion+of+the+gene+to+a+novel+sequence+on+17q+in+the+BT474+cell+line.&rft.au=Futreal%2C+P+A%3BCochran%2C+C%3BMarks%2C+J+R%3BIglehart%2C+J+D%3BZimmerman%2C+W%3BBarrett%2C+J+C%3BWiseman%2C+R+W&rft.aulast=Futreal&rft.aufirst=P&rft.date=1994-04-01&rft.volume=54&rft.issue=7&rft.spage=1791&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 - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Gene symbol - BRCA1; BTR; THRA1 N1 - Genetic sequence - S71020; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The pathway regulating GADD153 induction in response to DNA damage is independent of protein kinase C and tyrosine kinases. AN - 76405445; 8137309 AB - Treatment of cells with agents that damage DNA leads to the induction of numerous genes. Recent studies aimed at understanding the events preceding the transcriptional activation of some of these DNA damage-inducible genes in mammalian cells have demonstrated that various extranuclear protein kinases are involved in the signaling cascades. The mammalian GADD153 gene, a member of the CCAAT enhancer-binding protein family of transcription factors, is highly induced by a variety of DNA-damaging agents as well as by certain growth arrest conditions and oxidative stresses. We have examined the effects of numerous protein kinase and phosphatase inhibitors on the DNA damage-induced expression of GADD153, to identify the signal transduction components involved in its transcriptional regulation. In contrast to the transcriptional activation of c-jun and collagenase in response to DNA damage, GADD153 induction involves neither protein kinase C nor tyrosine kinases but does appear to require an unidentified serine-threonine-kinase. Elevation of intracellular glutathione levels by treatment with N-acetylcysteine did not affect the methyl methanesulfonate-induced expression of the GADD153 gene, although it did diminish cadmium chloride-induced expression. These findings suggest that oxidative stress and DNA damage regulate GADD153 transcription through different pathways. Based on our findings and those of others with respect to other DNA damage-inducible genes, we propose a model depicting the complex pathways which appear to be involved in the regulation of mammalian genes in response to genotoxic stress and in which the DNA damage-induced expression of GADD153 represents a unique pathway independent of either protein kinase C or tyrosine kinase. JF - Cancer research AU - Luethy, J D AU - Holbrook, N J AD - Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 1902s EP - 1906s VL - 54 IS - 7 Suppl SN - 0008-5472, 0008-5472 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DDIT3 protein, human KW - Isoflavones KW - Proto-Oncogene Proteins c-jun KW - Transcription Factors KW - Transcription Factor CHOP KW - 147336-12-7 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Genistein KW - DH2M523P0H KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Collagenases KW - EC 3.4.24.- KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Ultraviolet Rays KW - HeLa Cells KW - Isoflavones -- pharmacology KW - Humans KW - Transcription, Genetic KW - Acetylcysteine -- pharmacology KW - Proto-Oncogene Proteins c-jun -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Methyl Methanesulfonate -- toxicity KW - Collagenases -- biosynthesis KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - Genes, jun KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Protein Kinase C -- metabolism KW - DNA Repair -- genetics KW - Protein Biosynthesis KW - Protein Kinase C -- antagonists & inhibitors KW - DNA Damage KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76405445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathway+regulating+GADD153+induction+in+response+to+DNA+damage+is+independent+of+protein+kinase+C+and+tyrosine+kinases.&rft.au=Luethy%2C+J+D%3BHolbrook%2C+N+J&rft.aulast=Luethy&rft.aufirst=J&rft.date=1994-04-01&rft.volume=54&rft.issue=7+Suppl&rft.spage=1902s&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An in situ protocol for measuring the expression of chemically-induced mutations in mammalian cells. AN - 76402154; 7510835 AB - The generation of expression curves and the evaluation of mutagenic responses of mammalian cells using standard mutagenesis assays can be inaccurate because mutant and wild-type cells are usually mixed during the expression phase. If some mutant progenitors or mutants grow more slowly than the wild-type cells during the expression period, there will be a decrease in the mutant to wild-type ratio with time and the mutant fraction will not accurately represent the number of mutational events that occurred. The mutant fraction may also inaccurately assess the number of mutations if these mutations are expressed over a number of generations during the time before selection. We previously showed that recovery of L5178Y mouse cell mutants is not complete when mutations are allowed to express in suspension because slowly growing mutants and/or mutant progenitors are diluted out during this time (Rudd et al., 1990). In order to more accurately quantitate the mutagenic response of the cells, we developed an in situ procedure which segregates and immobilizes cells during expression. Because of this immobilization, slowly growing mutant progenitors and mutants expressed at different times will have an equal probability of being scored as mutants. Thus, one mutation leads to one mutant colony and the measurement of the mutagenic response of the cells to the chemical accurately reflects the mutational events that occurred. We plated L5178Y tk+/- mouse cells in semisolid medium immediately after treatment. As the cells grew and formed microcolonies, the selective agent TFT was added as an overlay at specified times, permitting only TFTr cells to survive. In this procedure, each mutation was captured as an individual colony; consequently, the measured mutation fraction accurately reflected the mutational events that occurred at the selected locus. In addition, the induced mutant colonies arising in the agar are the result of independent mutational events. We previously described the in situ protocol for L5178Y cells and showed that the spontaneous mutation rate measured was 50-fold greater than when the cells expressed the phenotype in suspension (Rudd et al., 1990). From this we concluded that the slow growth phenotype was expressed before TFT resistance. In the present paper, we evaluate the effect of chemical treatment on the mutation fraction as a function of the time to TFT addition. Using the in situ protocol, we generated expression curves for three nucleotide analogs, 5-azacytidine, TFT and AraC. The numbers of TFTr colonies produced at various times after treatment indicated that chemically-treated cultures had higher mutation fractions than the solvent controls.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Mutation research AU - Spencer, D L AU - Hines, K C AU - Caspary, W J AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1994/04// PY - 1994 DA - April 1994 SP - 85 EP - 97 VL - 312 IS - 2 SN - 0027-5107, 0027-5107 KW - tk KW - Mutagens KW - 0 KW - Cytarabine KW - 04079A1RDZ KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Azacitidine KW - M801H13NRU KW - Trifluridine KW - RMW9V5RW38 KW - Index Medicus KW - Animals KW - Drug Resistance -- genetics KW - Trifluridine -- toxicity KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Mice KW - Cell Separation KW - Leukemia L5178 KW - Phenotype KW - Tumor Cells, Cultured KW - Azacitidine -- toxicity KW - Cytarabine -- toxicity KW - Mutagenesis, Site-Directed KW - Mutagenicity Tests -- methods KW - Mutagens -- toxicity KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76402154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=An+in+situ+protocol+for+measuring+the+expression+of+chemically-induced+mutations+in+mammalian+cells.&rft.au=Spencer%2C+D+L%3BHines%2C+K+C%3BCaspary%2C+W+J&rft.aulast=Spencer&rft.aufirst=D&rft.date=1994-04-01&rft.volume=312&rft.issue=2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-19 N1 - Date created - 1994-04-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - tk N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer. AN - 76401910; 8137283 AB - Phenylacetate has recently been shown to suppress tumor growth and promote differentiation in experimental models. A phase I trial of phenylacetate was conducted in 17 patients with advanced solid tumors. Each patient received a single i.v. bolus dose followed by a 14-day continuous i.v. infusion of the drug. Twenty-one cycles of therapy were administered at four dose levels, achieved by increasing the rate of the continuous i.v. infusion. Phenylacetate displayed nonlinear pharmacokinetics [Km = 105.1 +/- 44.5 (SD) microgram/ml, Vmax = 24.1 +/- 5.2 mg/kg/h and Vd = 19.2 +/- 3.3 L]. There was also evidence for induction of drug clearance. Ninety-nine % of phenylacetate elimination was accounted for by conversion to phenylacetylglutamine, which was excreted in the urine. Continuous i.v. infusion rates resulting in serum phenylacetate concentrations exceeding Km often resulted in rapid drug accumulation and dose-limiting toxicity, which consisted of reversible central nervous system depression, preceded by emesis. Three of nine patients with metastatic, hormone-refractory prostate cancer maintained stable prostatic specific antigen levels for more than 2 months; another had less bone pain. One of six patients with glioblastoma multiforme, whose steroid dosage has remained unchanged for the duration of therapy, has sustained functional improvement for more than 9 months. The use of adaptive control with feedback for the dosing of each patient enabled us to safely maintain stable phenylacetate concentrations up to the range of 200-300 micrograms/ml, which resulted in clinical improvement in some patients with advanced disease. JF - Cancer research AU - Thibault, A AU - Cooper, M R AU - Figg, W D AU - Venzon, D J AU - Sartor, A O AU - Tompkins, A C AU - Weinberger, M S AU - Headlee, D J AU - McCall, N A AU - Samid, D AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 1690 EP - 1694 VL - 54 IS - 7 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Phenylacetates KW - Glutamine KW - 0RH81L854J KW - phenylacetic acid KW - ER5I1W795A KW - Index Medicus KW - Brain Neoplasms -- pathology KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Injections, Intravenous KW - Humans KW - Glutamine -- blood KW - Aged KW - Glioblastoma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Glioblastoma -- pathology KW - Adult KW - Middle Aged KW - Male KW - Female KW - Phenylacetates -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Phenylacetates -- blood KW - Antineoplastic Agents -- pharmacokinetics KW - Neoplasms -- blood KW - Phenylacetates -- toxicity KW - Antineoplastic Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76401910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+phase+I+and+pharmacokinetic+study+of+intravenous+phenylacetate+in+patients+with+cancer.&rft.au=Thibault%2C+A%3BCooper%2C+M+R%3BFigg%2C+W+D%3BVenzon%2C+D+J%3BSartor%2C+A+O%3BTompkins%2C+A+C%3BWeinberger%2C+M+S%3BHeadlee%2C+D+J%3BMcCall%2C+N+A%3BSamid%2C+D&rft.aulast=Thibault&rft.aufirst=A&rft.date=1994-04-01&rft.volume=54&rft.issue=7&rft.spage=1690&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 - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat. AN - 76401824; 8137276 AB - We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened tumor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24-5531 significantly enhanced the ability of tamoxifen to reduce total tumor burden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast cancer cell lines as well as primary cultures of cells from 2 patients with acute myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, "deltanoids," for the set of molecules composed of vitamin D and its synthetic analogues, in a manner similar to the naming of "retinoids" for the corresponding set of molecules related to vitamin A. JF - Cancer research AU - Anzano, M A AU - Smith, J M AU - Uskoković, M R AU - Peer, C W AU - Mullen, L T AU - Letterio, J J AU - Welsh, M C AU - Shrader, M W AU - Logsdon, D L AU - Driver, C L AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/04/01/ PY - 1994 DA - 1994 Apr 01 SP - 1653 EP - 1656 VL - 54 IS - 7 SN - 0008-5472, 0008-5472 KW - Anticarcinogenic Agents KW - 0 KW - Ro 24-5531 KW - Tamoxifen KW - 094ZI81Y45 KW - Methylnitrosourea KW - 684-93-5 KW - Calcitriol KW - FXC9231JVH KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Neoplasm Invasiveness KW - Animals KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Calcium -- blood KW - Humans KW - Cell Division -- drug effects KW - Breast Neoplasms KW - Diet KW - Female KW - Cell Line KW - Anticarcinogenic Agents -- toxicity KW - Anticarcinogenic Agents -- therapeutic use KW - Adenocarcinoma -- chemically induced KW - Calcitriol -- therapeutic use KW - Tamoxifen -- therapeutic use KW - Calcitriol -- analogs & derivatives KW - Tamoxifen -- administration & dosage KW - Anticarcinogenic Agents -- administration & dosage KW - Adenocarcinoma -- pathology KW - Mammary Neoplasms, Experimental -- pathology KW - Mammary Neoplasms, Experimental -- chemically induced KW - Calcitriol -- toxicity KW - Calcitriol -- administration & dosage KW - Adenocarcinoma -- prevention & control KW - Mammary Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76401824?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=1+alpha%2C25-Dihydroxy-16-ene-23-yne-26%2C27-hexafluorocholecalciferol+%28Ro24-5531%29%2C+a+new+deltanoid+%28vitamin+D+analogue%29+for+prevention+of+breast+cancer+in+the+rat.&rft.au=Anzano%2C+M+A%3BSmith%2C+J+M%3BUskokovi%C4%87%2C+M+R%3BPeer%2C+C+W%3BMullen%2C+L+T%3BLetterio%2C+J+J%3BWelsh%2C+M+C%3BShrader%2C+M+W%3BLogsdon%2C+D+L%3BDriver%2C+C+L&rft.aulast=Anzano&rft.aufirst=M&rft.date=1994-04-01&rft.volume=54&rft.issue=7&rft.spage=1653&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 - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genital human papillomavirus infection. AN - 76415621; 8146136 AB - Genital human papillomavirus (HPV) infection is a common sexually transmitted disease that at the present time is not effectively controlled or treated. Many infections are inapparent and transient. However, some HPV infections result in persistent lesions that in some cases undergo carcinogenic progression. A subset of genital HPVs, designated high-risk types, are preferentially associated with high-grade dysplasias and carcinomas. About 90% of cervical cancers contain high-risk HPV DNA, most often HPV16. Development of a subunit vaccine against high-risk genital HPVs is a desirable and, it appears, an increasingly feasible long-term goal. The viral E6 and E7 oncoproteins are selectively maintained and expressed in progressed HPV tumors and could potentially be targets for therapeutic vaccines. The L1 major virion structural proteins have recently been shown to self-assemble into virus-like particles when expressed in insect cells. These particles might serve as the basis for a prophylactic vaccine to prevent genital HPV infection. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lowy, D R AU - Kirnbauer, R AU - Schiller, J T AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/03/29/ PY - 1994 DA - 1994 Mar 29 SP - 2436 EP - 2440 VL - 91 IS - 7 SN - 0027-8424, 0027-8424 KW - Antibodies, Viral KW - 0 KW - DNA, Viral KW - Index Medicus KW - Antibodies, Viral -- blood KW - Humans KW - DNA, Viral -- blood KW - Female KW - Uterine Cervical Neoplasms -- prevention & control KW - Papillomaviridae -- pathogenicity KW - Papillomavirus Infections -- blood KW - Papillomavirus Infections -- prevention & control KW - Papillomaviridae -- immunology KW - Tumor Virus Infections -- prevention & control KW - Papillomaviridae -- ultrastructure KW - Uterine Cervical Neoplasms -- virology KW - Tumor Virus Infections -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76415621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genital+human+papillomavirus+infection.&rft.au=Lowy%2C+D+R%3BKirnbauer%2C+R%3BSchiller%2C+J+T&rft.aulast=Lowy&rft.aufirst=D&rft.date=1994-03-29&rft.volume=91&rft.issue=7&rft.spage=2436&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 - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1984 May;3(5):1151-7 [6329740] Cancer. 1993 Feb 15;71(4 Suppl):1413-21 [8381707] Int J Cancer. 1986 Jan 15;37(1):55-9 [3000954] Ciba Found Symp. 1986;120:136-56 [3013520] Proc Natl Acad Sci U S A. 1986 Jul;83(13):4680-4 [3014503] EMBO J. 1986 Sep;5(9):2285-92 [3023067] Obstet Gynecol. 1987 Apr;69(4):554-62 [3029642] N Engl J Med. 1987 Oct 8;317(15):916-23 [3041217] EMBO J. 1988 Oct;7(10):3181-7 [2460337] J Virol. 1989 Jan;63(1):159-64 [2462058] JAMA. 1989 Feb 3;261(5):737-43 [2642983] Proc Natl Acad Sci U S A. 1989 Jan;86(2):563-7 [2463631] J Am Acad Dermatol. 1989 Jan;20(1):114-23 [2536408] Science. 1989 Feb 17;243(4893):934-7 [2537532] JAMA. 1989 Aug 18;262(7):931-4 [2754794] J Virol. 1989 Oct;63(10):4417-21 [2476573] J Virol. 1989 Nov;63(11):4898-903 [2552162] EMBO J. 1989 Dec 1;8(12):3905-10 [2555178] EMBO J. 1990 Jan;9(1):153-60 [2153075] J Virol. 1990 Feb;64(2):519-26 [2153221] Science. 1990 Apr 6;248(4951):76-9 [2157286] Lancet. 1990 May 19;335(8699):1171-4 [1971033] Obstet Gynecol. 1990 Oct;76(4):660-3 [2216199] Cell. 1990 Dec 21;63(6):1129-36 [2175676] JAMA. 1991 Jan 23-30;265(4):472-7 [1845912] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):110-4 [1846033] Virology. 1991 Mar;181(1):62-9 [1847269] Am J Public Health. 1991 May;81(5):582-6 [1849706] Int J Cancer. 1991 May 30;48(3):404-8 [1645699] J Virol. 1991 Jul;65(7):3943-8 [1645802] Oncogene. 1991 May;6(5):873-5 [1646990] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5523-7 [1648218] Mol Carcinog. 1991;4(3):171-5 [1648361] Oncogene. 1991 Jul;6(7):1251-7 [1650445] Virology. 1991 Sep;184(1):33-42 [1651594] Lancet. 1991 Oct 12;338(8772):910-3 [1681267] Bull World Health Organ. 1984;62(2):163-82 [6610488] Epidemiology. 1991 Mar;2(2):98-106 [1657209] Cell. 1991 Nov 1;67(3):547-56 [1657399] Gynecol Oncol. 1992 Jan;44(1):33-9 [1309717] Obstet Gynecol. 1992 Mar;79(3):328-37 [1310805] Am J Epidemiol. 1992 Jan 15;135(2):180-9 [1311142] J Natl Cancer Inst. 1992 Mar 18;84(6):394-8 [1311392] Virology. 1992 Apr;187(2):612-9 [1312271] N Engl J Med. 1992 Oct 29;327(18):1272-8 [1328880] J Natl Cancer Inst. 1993 Jan 6;85(1):19-24 [8380060] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180-4 [1334560] J Virol. 1993 Apr;67(4):1936-44 [8383219] J Natl Cancer Inst. 1993 Jun 16;85(12):934-5 [8388477] J Natl Cancer Inst. 1993 Jun 16;85(12):958-64 [8388478] J Natl Cancer Inst. 1993 Jul 7;85(13):1018-9 [8515480] Vaccine. 1993;11(6):603-11 [8391738] J Virol. 1993 Dec;67(12):6929-36 [8230414] Br J Dermatol. 1975 Jun;92(6):625-30 [1101940] Acta Cytol. 1976 Nov-Dec;20(6):505-9 [1069445] Virology. 1980 Jun;103(2):369-75 [6247821] N Engl J Med. 1983 May 26;308(21):1261-4 [6302507] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3812-5 [6304740] Arch Dermatol. 1984 Apr;120(4):476-83 [6546657] N Engl J Med. 1985 Sep 26;313(13):784-8 [2993887] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inherent versatility of P-450 oxygenase. Conferring dehydroepiandrosterone hydroxylase activity to P-450 2a-4 by a single amino acid mutation at position 117. AN - 76400023; 8132645 AB - Mouse steroid 15 alpha-hydroxylase P-450 2a-4 is restricted in its substrate specificity to the delta 4, 3-ketone steroids such as androstenedione. As a result, the P-450 exhibits little hydroxylase activity toward delta 5, 3-hydroxysteroids including dehydroepiandrosterone (DHEA). A single amino acid mutation of Ala at position 117 to Val, however, is enough to confer a high DHEA hydroxylase activity to P-450 2a-4 with 7 alpha-OH DHEA as one of the two major hydroxylated metabolites. Mouse coumarin 7-hydroxylase P-450 2a-5 contains Val at position 117, but it exhibits very low DHEA hydroxylase activity. P-450 2a-5 acquires high DHEA hydroxylase activity, however, by a mutation of Phe-209 to Asn. Moreover, the mutant P-450 2a-5 loses its activity when Val is replaced by Ala at position 117. The residue at position 117, therefore, plays the principal role in the determination of the DHEA hydroxylase activity of the P-450s. Conversely, mutations at residue 117 have little effect on the androstenedione hydroxylase activities of the P-450s. Further modeling of the DHEA binding orientation in the substrate-heme pocket of bacterial P-450cam (Iwasaki, M., Darden, T., Pedersen, L., Davis, D. G., Juvonen, R. O., Sueyoshi, T., and Negishi, M. (1993) J. Biol. Chem. 268, 759-762) provides support for the hypothesis that the type of residue at position 117 determines the steroid-substrate specificity of the P-450 depending on the substituent at the C3 position of steroid molecule. JF - The Journal of biological chemistry AU - Iwasaki, M AU - Darden, T A AU - Parker, C E AU - Tomer, K B AU - Pedersen, L G AU - Negishi, M AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/03/25/ PY - 1994 DA - 1994 Mar 25 SP - 9079 EP - 9083 VL - 269 IS - 12 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - Androstenedione KW - 409J2J96VR KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxygenases KW - EC 1.13.- KW - Steroid Hydroxylases KW - EC 1.14.- KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Mice KW - Substrate Specificity KW - Androstenedione -- metabolism KW - Structure-Activity Relationship KW - Dehydroepiandrosterone -- metabolism KW - Binding Sites KW - Oxygenases -- metabolism KW - Steroid Hydroxylases -- ultrastructure KW - Cytochrome P-450 Enzyme System -- chemistry KW - Steroid Hydroxylases -- metabolism KW - Steroid Hydroxylases -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76400023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inherent+versatility+of+P-450+oxygenase.+Conferring+dehydroepiandrosterone+hydroxylase+activity+to+P-450+2a-4+by+a+single+amino+acid+mutation+at+position+117.&rft.au=Iwasaki%2C+M%3BDarden%2C+T+A%3BParker%2C+C+E%3BTomer%2C+K+B%3BPedersen%2C+L+G%3BNegishi%2C+M&rft.aulast=Iwasaki&rft.aufirst=M&rft.date=1994-03-25&rft.volume=269&rft.issue=12&rft.spage=9079&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 - 1994-04-21 N1 - Date created - 1994-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of nitric-oxide synthase mRNA expression by interferon-gamma and picolinic acid. AN - 76400441; 7510678 AB - Picolinic acid, a catabolite of L-tryptophan, is a potent co-stimulatory agent for the induction of tumoricidal activity and the production of L-arginine-dependent reactive nitrogen intermediates (RNI) in murine macrophages. We studied whether picolinic acid could affect nitric-oxide synthase (NOS) expression at the gene level in the macrophage cell line ANA-1. NOS mRNA was neither constitutively expressed nor induced by treatment with picolinic acid alone. However, low levels of NOS mRNA were induced by interferon (IFN)-gamma alone. In contrast, a major increase of NOS mRNA expression was observed after treatment with IFN-gamma plus picolinic acid. The synergism was already detectable after 5-6 h and increased up to 20 h of treatment. The ability of picolinic acid to augment IFN-gamma-dependent NOS mRNA expression was associated with a parallel increase in transcription, as demonstrated by nuclear run-on experiments. Protein synthesis was required for the induction of NOS mRNA because addition of cycloheximide dramatically reduced IFN-gamma plus picolonic acid-induced NOS mRNA expression. Finally, interleukin-4 significantly decreased IFN-gamma plus picolinic acid-induced NOS mRNA expression and NOS transcription. These data provide evidence of a molecular event connecting arginine and tryptophan metabolic pathways in the generation of RNI, and they indicate that picolinic acid can induce transcriptional activation of gene expression. JF - The Journal of biological chemistry AU - Melillo, G AU - Cox, G W AU - Biragyn, A AU - Sheffler, L A AU - Varesio, L AD - Macrophage Cell Biology Section, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Maryland 21702-1201. Y1 - 1994/03/18/ PY - 1994 DA - 1994 Mar 18 SP - 8128 EP - 8133 VL - 269 IS - 11 SN - 0021-9258, 0021-9258 KW - Picolinic Acids KW - 0 KW - RNA, Messenger KW - Recombinant Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Amino Acid Oxidoreductases KW - EC 1.4.- KW - picolinic acid KW - QZV2W997JQ KW - Index Medicus KW - Macrophages -- enzymology KW - Animals KW - Transcription, Genetic -- drug effects KW - Blotting, Northern KW - Cell Nucleus -- metabolism KW - Kinetics KW - Mice, Inbred C57BL KW - Mice KW - Drug Synergism KW - Cell Line KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Amino Acid Oxidoreductases -- biosynthesis KW - Interferon-gamma -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Picolinic Acids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76400441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+nitric-oxide+synthase+mRNA+expression+by+interferon-gamma+and+picolinic+acid.&rft.au=Melillo%2C+G%3BCox%2C+G+W%3BBiragyn%2C+A%3BSheffler%2C+L+A%3BVaresio%2C+L&rft.aulast=Melillo&rft.aufirst=G&rft.date=1994-03-18&rft.volume=269&rft.issue=11&rft.spage=8128&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 - 1994-04-18 N1 - Date created - 1994-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor. AN - 76407023; 8137255 AB - Successful expression of the cytosine deaminase (CD) suicide gene in vivo is demonstrated in three weakly immunogenic murine tumor models: the 102 and 205 fibrosarcomas and the 38 adenocarcinoma. Normal mammalian cells do not contain cytosine deaminase, but tumor cells transduced with retroviral vectors containing the CD gene metabolize the relatively nontoxic prodrug 5-fluorocytosine to the highly toxic 5-fluorouracil. In vitro cells expressing the CD gene are killed by 5-fluorocytosine while unmodified cells are not. When injected into syngeneic mice, CD+ tumors can also be eliminated in vivo by systemic treatment with 5-fluorocytosine without significant toxicity to the host. Animals whose CD+ tumors were eliminated with prodrug treatment resist subsequent rechallenge with unmodified wild type tumor. This posttreatment immunity appears to be tumor specific. Applications of the CD system in gene therapy models are discussed. JF - Cancer research AU - Mullen, C A AU - Coale, M M AU - Lowe, R AU - Blaese, R M AD - Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892. Y1 - 1994/03/15/ PY - 1994 DA - 1994 Mar 15 SP - 1503 EP - 1506 VL - 54 IS - 6 SN - 0008-5472, 0008-5472 KW - CD KW - Bacterial Proteins KW - 0 KW - Flucytosine KW - D83282DT06 KW - Nucleoside Deaminases KW - EC 3.5.4.- KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Drug Screening Assays, Antitumor KW - Transduction, Genetic -- genetics KW - Gene Transfer Techniques KW - Immunity, Innate -- immunology KW - Tumor Cells, Cultured -- drug effects KW - Mice KW - Gene Expression -- genetics KW - Mice, Inbred C57BL KW - Genetic Vectors -- genetics KW - Retroviridae -- genetics KW - Nucleoside Deaminases -- immunology KW - Nucleoside Deaminases -- genetics KW - Flucytosine -- pharmacology KW - Neoplasms, Experimental -- enzymology KW - Bacterial Proteins -- genetics KW - Neoplasms, Experimental -- immunology KW - Neoplasms, Experimental -- genetics KW - Bacterial Proteins -- immunology KW - Bacterial Proteins -- metabolism KW - Nucleoside Deaminases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76407023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumors+expressing+the+cytosine+deaminase+suicide+gene+can+be+eliminated+in+vivo+with+5-fluorocytosine+and+induce+protective+immunity+to+wild+type+tumor.&rft.au=Mullen%2C+C+A%3BCoale%2C+M+M%3BLowe%2C+R%3BBlaese%2C+R+M&rft.aulast=Mullen&rft.aufirst=C&rft.date=1994-03-15&rft.volume=54&rft.issue=6&rft.spage=1503&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 - 1994-04-25 N1 - Date created - 1994-04-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CD N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. AN - 76399807; 8134379 AB - Chronic active hepatitis caused by infection with hepatitis B virus, a DNA virus, is a major risk factor for human hepatocellular carcinoma. Since the oncogenicity of several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene products, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX complexes with the wild-type p53 protein and inhibits its sequence-specific DNA binding in vitro. HBX expression also inhibits p53-mediated transcriptional activation in vivo and the in vitro association of p53 and ERCC3, a general transcription factor involved in nucleotide excision repair. Therefore, HBX may affect a wide range of p53 functions and contribute to the molecular pathogenesis of human hepatocellular carcinoma. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wang, X W AU - Forrester, K AU - Yeh, H AU - Feitelson, M A AU - Gu, J R AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/03/15/ PY - 1994 DA - 1994 Mar 15 SP - 2230 EP - 2234 VL - 91 IS - 6 SN - 0027-8424, 0027-8424 KW - DNA-Binding Proteins KW - 0 KW - Drosophila Proteins KW - Trans-Activators KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - haywire protein, Drosophila KW - 148998-67-8 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Humans KW - DNA -- metabolism KW - Protein Binding KW - Mutation KW - Cell Line KW - Trans-Activators -- metabolism KW - Tumor Suppressor Protein p53 -- antagonists & inhibitors KW - Transcription Factors -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76399807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hepatitis+B+virus+X+protein+inhibits+p53+sequence-specific+DNA+binding%2C+transcriptional+activity%2C+and+association+with+transcription+factor+ERCC3.&rft.au=Wang%2C+X+W%3BForrester%2C+K%3BYeh%2C+H%3BFeitelson%2C+M+A%3BGu%2C+J+R%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1994-03-15&rft.volume=91&rft.issue=6&rft.spage=2230&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 - 1994-04-21 N1 - Date created - 1994-04-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1979 Mar 15;278(5701):261-3 [218111] Cell. 1984 Aug;38(1):119-26 [6088057] Lancet. 1981 Nov 21;2(8256):1129-33 [6118576] Proc Natl Acad Sci U S A. 1987 Apr;84(8):2513-7 [3494252] Gene. 1988 Jul 15;67(1):31-40 [3047011] Science. 1989 Feb 17;243(4893):934-7 [2537532] Cell. 1989 May 5;57(3):379-92 [2541911] Jpn J Cancer Res. 1989 Jul;80(7):617-21 [2507484] EMBO J. 1990 Apr;9(4):1137-45 [2323335] EMBO J. 1990 Jun;9(6):1889-95 [2347309] Cell. 1990 Aug 24;62(4):777-91 [2167179] Science. 1990 Oct 5;250(4977):113-6 [2218501] Cell. 1990 Nov 16;63(4):687-95 [2225072] Nature. 1991 Apr 4;350(6317):427-8 [1849234] Nature. 1991 Apr 4;350(6317):429-31 [1672732] Science. 1991 May 10;252(5007):842-4 [1827531] Nature. 1991 May 23;351(6324):317-20 [2034275] Science. 1991 Jun 21;252(5013):1708-11 [2047879] Science. 1991 Jul 5;253(5015):49-53 [1905840] EMBO J. 1991 Dec;10(13):4129-35 [1661671] J Virol. 1992 Feb;66(2):983-91 [1309924] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2759-63 [1557382] Science. 1992 May 8;256(5058):827-30 [1589764] Nature. 1992 Jul 2;358(6381):80-3 [1614537] Cell. 1992 Jun 26;69(7):1237-45 [1535557] J Hepatol. 1991;13 Suppl 4:S61-5 [1822516] Cell. 1992 Nov 13;71(4):587-97 [1423616] Eur J Cancer. 1992;29A(1):101-7 [1332735] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 [1465435] Mol Cell Biol. 1993 Feb;13(2):775-84 [8380895] Nature. 1993 Feb 25;361(6414):742-5 [8441471] Science. 1993 Apr 2;260(5104):37-8 [8465198] Science. 1993 Apr 2;260(5104):58-63 [8465201] Oncogene. 1993 May;8(5):1109-17 [8386823] Mol Cell Biol. 1993 Jun;13(6):3291-300 [8497252] Carcinogenesis. 1993 May;14(5):987-92 [8389256] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5123-7 [7685115] Oncogene. 1993 Jul;8(7):1815-24 [8510927] Nat Genet. 1993 May;4(1):42-6 [8099841] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5455-9 [8390666] Nature. 1993 Sep 2;365(6441):79-82 [8361542] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8078-82 [8367466] N Engl J Med. 1993 Oct 28;329(18):1318-27 [8413413] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Cell. 1982 Feb;28(2):387-94 [6277513] Cell. 1979 May;17(1):43-52 [222475] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of Phe381 and Phe382 in the extracellular domain of the insulin receptor: effects on receptor biosynthesis, processing, and ligand-dependent internalization. AN - 76401690; 8137907 AB - Mutations of the extracellular domain of the insulin receptor impair processing and transport of receptors to the plasma membrane. We have previously reported that a mutation substituting Val for Phe382 in the alpha-subunit of the insulin receptor impairs intracellular processing and insulin-induced autophosphorylation of the mutant receptor. In this investigation, we have generated two independent mutations of amino acids Phe381 and Phe382 of the insulin receptor: Val for Phe381 and Leu for Phe382. These substitutions cause a slight impairment of intracellular processing and transport of the mutant receptors. Furthermore, insulin-dependent internalization of the mutant receptors is unaffected by these mutations. Thus, of the three substitutions studied to date, Val for Phe382 is the only mutation of the Phe381-Phe382 sequence that causes a major defect in post-translational processing of the receptor. JF - FEBS letters AU - Accili, D AU - Mosthaf, L AU - Levy-Toledano, R AU - Ullrich, A AU - Taylor, S I AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/03/14/ PY - 1994 DA - 1994 Mar 14 SP - 104 EP - 108 VL - 341 IS - 1 SN - 0014-5793, 0014-5793 KW - Insulin KW - 0 KW - Ligands KW - Phenylalanine KW - 47E5O17Y3R KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Animals KW - 3T3 Cells KW - Transfection KW - Humans KW - Biological Transport KW - Mice KW - Receptor, Insulin -- genetics KW - Phenylalanine -- metabolism KW - Protein Processing, Post-Translational KW - Receptor, Insulin -- biosynthesis KW - Insulin -- metabolism KW - Receptor, Insulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76401690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutagenesis+of+Phe381+and+Phe382+in+the+extracellular+domain+of+the+insulin+receptor%3A+effects+on+receptor+biosynthesis%2C+processing%2C+and+ligand-dependent+internalization.&rft.au=Accili%2C+D%3BMosthaf%2C+L%3BLevy-Toledano%2C+R%3BUllrich%2C+A%3BTaylor%2C+S+I&rft.aulast=Accili&rft.aufirst=D&rft.date=1994-03-14&rft.volume=341&rft.issue=1&rft.spage=104&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 - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective reduction in dopamine turnover in the rat frontal cortex and hypothalamus during withdrawal from repeated cocaine exposure. AN - 76525666; 8206108 AB - The effects of 7 days repeated cocaine administration on the dynamics of dopamine release and metabolism in four rat brain regions (frontal cortex, hypothalamus, nucleus accumbens and striatum) were evaluated 1 week (long-term effects) after the final cocaine injection. 3-Methoxytyramine and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were respectively used to assess the dynamics of dopamine release and metabolism. Consistent with a previous report, cocaine withdrawal was associated with marked reductions in DOPAC rate of formation in the frontal cortex and hypothalamus but not in the nucleus accumbens or the striatum. Dopamine release as indicated by 3-methoxytyramine steady-state concentration and its rate of formation was normal in all four brain regions 1 week after repeated cocaine exposure. The ratios of 3-methoxytyramine rate of formation to that of DOPAC were calculated and found to be increased in the frontal cortex and hypothalamus suggesting dopamine reuptake inhibition, at least 1 week after cocaine withdrawal, continued to be depressed in these regions. It is concluded that repeated cocaine has no long-term effect on dopamine release but produces selective long-term reductions in dopamine turnover in frontal cortex and hypothalamus. Cocaine withdrawal is therefore better associated with changes in dopamine turnover than with its release. JF - European journal of pharmacology AU - Karoum, F AU - Egan, M F AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Research Center, Washington, DC 20032. Y1 - 1994/03/11/ PY - 1994 DA - 1994 Mar 11 SP - 127 EP - 132 VL - 254 IS - 1-2 SN - 0014-2999, 0014-2999 KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Cocaine KW - I5Y540LHVR KW - 3-methoxytyramine KW - JCH2767EDP KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Male KW - Dopamine -- analogs & derivatives KW - Substance Withdrawal Syndrome -- metabolism KW - Prefrontal Cortex -- metabolism KW - Hypothalamus -- drug effects KW - Hypothalamus -- metabolism KW - Dopamine -- metabolism KW - Prefrontal Cortex -- drug effects KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76525666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selective+reduction+in+dopamine+turnover+in+the+rat+frontal+cortex+and+hypothalamus+during+withdrawal+from+repeated+cocaine+exposure.&rft.au=Karoum%2C+F%3BEgan%2C+M+F%3BWyatt%2C+R+J&rft.aulast=Karoum&rft.aufirst=F&rft.date=1994-03-11&rft.volume=254&rft.issue=1-2&rft.spage=127&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 - 1994-07-13 N1 - Date created - 1994-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pseudomonas exotoxin A mutants. Replacement of surface exposed residues in domain II with cysteine residues that can be modified with polyethylene glycol in a site-specific manner. AN - 76384525; 8125985 AB - Pseudomonas exotoxin A (PE) is a three-domain protein in which domain Ia is involved in recognition of receptors on eukaryotic target cells, domain II promotes translocation of PE into the cytosol, and domain III enzymatically ADP-ribosylates elongation factor 2. Modification of proteins with polyethylene glycol (PEG) has been shown to prolong circulating plasma lifetime and may reduce or eliminate immunogenicity. However, in the case of toxins, PEG may interfere with or block toxin activity. To investigate the effect of polyethylene glycolation on specific residues located on the surface of PE domain II, we substituted cysteine, for each of the five most exposed surface amino acids (H276, E282, N306, R313, and E327) in domain II. These cysteines can serve as unique sites for PEG modification. The PE-Cys proteins retained most of their cytotoxicity even when the free sulfhydryl group was blocked by 5,5'-dithiobis(nitrobenzoic acid) or glutathione. When the PE-Cys proteins were conjugated with ovalbumin using a cleavable disulfide linkage, cytotoxicity was retained, but it was lost with a non-cleavable thioether linkage. In contrast, cytotoxicity was maintained when PE-Cys mutants were coupled to 5- or 20-kDa mPEG, using either a disulfide or a thioether linkage. Unexpectedly in some cases, the thioether conjugate was more active than the disulfide linkage. Pharmacokinetic studies on one of the polyethylene-glycolated molecules (R313C) showed that the mean residence time (t 1/2) was prolonged to 72 min, compared to 20 min for unpolyethylene glycolated PE-Cys(R313C). These studies show it is possible to derivatize PE at specific residues in domain II, maintain significant cytotoxic activity, and alter pharmacokinetics. These studies also suggest that large mPEG molecules can be translocated to the cytosol while still attached to domain II of PE. JF - The Journal of biological chemistry AU - Kuan, C T AU - Wang, Q C AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03/11/ PY - 1994 DA - 1994 Mar 11 SP - 7610 EP - 7616 VL - 269 IS - 10 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Virulence Factors KW - Polyethylene Glycols KW - 30IQX730WE KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Pseudomonas aeruginosa -- metabolism KW - Animals KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Humans KW - Protein Folding KW - Mice KW - Mice, Inbred BALB C KW - Exotoxins -- genetics KW - Cysteine -- metabolism KW - Cysteine -- genetics KW - Exotoxins -- chemistry KW - Polyethylene Glycols -- pharmacology KW - Cysteine -- drug effects KW - Exotoxins -- pharmacokinetics KW - Bacterial Toxins -- genetics KW - Bacterial Toxins -- pharmacokinetics KW - Bacterial Toxins -- chemistry KW - Exotoxins -- toxicity KW - Bacterial Toxins -- toxicity KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76384525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pseudomonas+exotoxin+A+mutants.+Replacement+of+surface+exposed+residues+in+domain+II+with+cysteine+residues+that+can+be+modified+with+polyethylene+glycol+in+a+site-specific+manner.&rft.au=Kuan%2C+C+T%3BWang%2C+Q+C%3BPastan%2C+I&rft.aulast=Kuan&rft.aufirst=C&rft.date=1994-03-11&rft.volume=269&rft.issue=10&rft.spage=7610&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 - 1994-04-12 N1 - Date created - 1994-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetics of CO binding to cytochromes P450 in the endoplasmic reticulum. AN - 76376398; 8117709 AB - The kinetics of CO binding to cytochromes P450 in rat liver microsomes were examined using the flash photolysis technique. Modulation of the kinetics by P450 form-specific effectors such as anti-P450 monoclonal antibodies and substrates was used to elucidate the kinetic behavior of individual P450s within the endoplasmic reticulum. The problem of attributing a kinetic parameter to a single P450 in the presence of multiple microsomal P450s was overcome with a difference method that employs the difference of the kinetic profiles obtained in the presence and absence of a P450 effector. Applying this approach to study the conformation/dynamics of P450 2B1 in microsomes from phenobarbital-treated rats revealed that the substrate benzphetamine enhances while testosterone inhibits the rate of CO binding to this P450. Similar experiments with P450 1A1 in microsomes from 3-methylcholanthrene-treated rats showed that the substrate benzo[a]pyrene accelerates CO binding. These results show that the access channel between solvent and heme in the P450 interior can be altered in a substrate- and P450-dependent manner to either hinder or facilitate CO diffusion to the heme iron. These results also demonstrate that analytical difference methods may be employed to characterize the conformation of individual P450s in their native membrane environment in the endoplasmic reticulum. JF - Biochemistry AU - Koley, A P AU - Robinson, R C AU - Markowitz, A AU - Friedman, F K AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03/08/ PY - 1994 DA - 1994 Mar 08 SP - 2484 EP - 2489 VL - 33 IS - 9 SN - 0006-2960, 0006-2960 KW - Antibodies, Monoclonal KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Testosterone KW - 3XMK78S47O KW - Carbon Monoxide KW - 7U1EE4V452 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Benzo(a)pyrene -- pharmacology KW - Microsomes, Liver KW - Animals KW - Rats, Sprague-Dawley KW - Endoplasmic Reticulum KW - Kinetics KW - Male KW - Testosterone -- chemistry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Carbon Monoxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76376398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Kinetics+of+CO+binding+to+cytochromes+P450+in+the+endoplasmic+reticulum.&rft.au=Koley%2C+A+P%3BRobinson%2C+R+C%3BMarkowitz%2C+A%3BFriedman%2C+F+K&rft.aulast=Koley&rft.aufirst=A&rft.date=1994-03-08&rft.volume=33&rft.issue=9&rft.spage=2484&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a TPA-responsive element mediating preferential transactivation of the galanin gene promoter in chromaffin cells. AN - 76384602; 7509811 AB - The gene encoding the neuropeptide galanin is upregulated by second messenger signal transduction pathways in bovine chromaffin cells. To identify its transcriptional regulatory elements, 5'-flanking sequences of the galanin gene were transiently transfected into primary cultures of bovine chromaffin cells within reporter gene constructs. Multiple regions of the galanin 5' flank seem to be necessary for basal activity. The most promoter-proximal of these regions contains a sequence (TGACG) -66 to -62 nucleotides upstream from the transcriptional start site which mediates stimulation by 12-O-tetradecanoylphorbol-13-acetate (TPA), as demonstrated by site-directed mutagenesis and cis-activation experiments. This cis-regulatory element mediates preferential TPA stimulation of transcription from the galanin promoter in chromaffin cells compared with bovine endothelial or HeLa cells. DNA-protein binding assays indicate that an oligonucleotide that includes the galanin TPA-responsive element (GTRE) binds specifically to proteins from nuclear extracts of chromaffin cells. TPA treatment persistently increases this binding activity in chromaffin but not in endothelial cells. Mutation of the galanin promoter within the -66 to -62 region renders it unresponsive to transcriptional stimulation by TPA, and a correspondingly mutated oligonucleotide fails to bind chromaffin cell nuclear proteins in a gel-shift assay. Chromaffin cell nuclear extracts also contain proteins that bind consensus TPA-responsive (TRE) and cyclic AMP-responsive (CRE) elements. GTRE, TRE, and CRE oligonucleotides all compete more efficiently for protein binding to their labeled congeners than for protein binding to either of the other labeled oligonucleotides, suggesting that the GTRE, TRE, and CRE oligonucleotides, suggesting that the GTRE, TRE, and CRE oligonucleotides each bind unique as well as common proteins, likely to be members of the Jun/Fos and cAMP-responsive element-binding protein/activating transcription factors (CREB/ATF) families of transcription factors, in chromaffin cells. JF - The Journal of biological chemistry AU - Anouar, Y AU - MacArthur, L AU - Cohen, J AU - Iacangelo, A L AU - Eiden, L E AD - Section of Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03/04/ PY - 1994 DA - 1994 Mar 04 SP - 6823 EP - 6831 VL - 269 IS - 9 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Neuropeptides KW - Nuclear Proteins KW - Peptides KW - RNA, Messenger KW - Colforsin KW - 1F7A44V6OU KW - Galanin KW - 88813-36-9 KW - Cyclic AMP KW - E0399OZS9N KW - Luciferases KW - EC 1.13.12.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Transcription, Genetic -- drug effects KW - Peptide Biosynthesis KW - Cell Nucleus -- metabolism KW - Humans KW - RNA, Messenger -- biosynthesis KW - Mutagenesis, Site-Directed KW - Colforsin -- pharmacology KW - Endothelium, Vascular -- drug effects KW - Molecular Sequence Data KW - Nuclear Proteins -- metabolism KW - Signal Transduction KW - Sequence Deletion KW - Gene Library KW - Second Messenger Systems KW - Endothelium, Vascular -- metabolism KW - HeLa Cells KW - Neuropeptides -- biosynthesis KW - Luciferases -- biosynthesis KW - Cattle KW - Base Sequence KW - Cyclic AMP -- metabolism KW - Consensus Sequence KW - TATA Box KW - RNA, Messenger -- isolation & purification KW - Neuropeptides -- genetics KW - Promoter Regions, Genetic -- drug effects KW - Adrenal Medulla -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Adrenal Medulla -- metabolism KW - Gene Expression Regulation -- drug effects KW - Peptides -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76384602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+a+TPA-responsive+element+mediating+preferential+transactivation+of+the+galanin+gene+promoter+in+chromaffin+cells.&rft.au=Anouar%2C+Y%3BMacArthur%2C+L%3BCohen%2C+J%3BIacangelo%2C+A+L%3BEiden%2C+L+E&rft.aulast=Anouar&rft.aufirst=Y&rft.date=1994-03-04&rft.volume=269&rft.issue=9&rft.spage=6823&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 - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - S68957; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Negative Equity and British Housing in the 1990s: Cause and Effect AN - 918036972; 13500731 AB - This paper is concerned with the emergence in Britain in the early 1990s of a large group of domestic mortgage holders with negative equity (i.e. whose property had fallen below the value of the mortgage advance used to purchase that property). The emergence of negative equity is traced to the conjunction of the long-term trend towards wider home-ownership in Britain and the effects of deregulation of the financial system in the 1980s. Using individual records from a major building society, the temporal, geographical and social distribution of negative equity is assessed. The results suggest that negative equity was far more likely to affect certain social groups living in particular places and that these appear to be the people least well placed to 'help themselves' out of debt. The concluding section attempts to draw out some of the policy conclusions from these findings. JF - Urban Studies AU - Gentle, Christopher AU - Dorling, Daniel AU - Comford, James AD - Centre for Urban and Regional Development Studies & Housing and Society Research Group, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, NEI 7RU, UK Y1 - 1994/03// PY - 1994 DA - Mar 1994 SP - 181 EP - 199 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 USA VL - 31 IS - 2 SN - 0042-0980, 0042-0980 KW - Environment Abstracts KW - British Isles KW - loans KW - deregulation KW - Housing KW - ENA 09:Land Use & Planning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/918036972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urban+Studies&rft.atitle=Negative+Equity+and+British+Housing+in+the+1990s%3A+Cause+and+Effect&rft.au=Gentle%2C+Christopher%3BDorling%2C+Daniel%3BComford%2C+James&rft.aulast=Gentle&rft.aufirst=Christopher&rft.date=1994-03-01&rft.volume=31&rft.issue=2&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Urban+Studies&rft.issn=00420980&rft_id=info:doi/10.1080%2F00420989420080191 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-01-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - loans; Housing; deregulation; British Isles DO - http://dx.doi.org/10.1080/00420989420080191 ER - TY - JOUR T1 - Motor program memory storage in Parkinson's disease patients tested with a delayed response task. AN - 85273167; pmid-8196687 AB - We used a delayed response paradigm to test the hypothesis that the prolonged reaction time in patients with Parkinson's disease (PD) is related to a deficiency in their ability to store a motor program in memory while waiting to move. PD patients, both on and off medication, were compared with age-matched normal subjects during arm movements directed toward a target light. The target light was displayed either during a 3- to 9-s delay or for only 1 s followed by a 2- to 8-s delay before the go signal. At the end of the delay, subjects were required to begin movement rapidly. The reaction time of PD patients was longer than normal and increased slightly when the patients were off medication. The patients had no excessive increase in reaction time with delay in either task compared with the control subjects. We conclude that patients with PD can hold a motor program in memory storage for at least 8 s. JF - Movement Disorders AU - Labutta, R J AU - Miles, R B AU - Sanes, J N AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 218 EP - 222 VL - 9 IS - 2 SN - 0885-3185, 0885-3185 KW - Orientation KW - Human KW - Aged KW - Antiparkinson Agents KW - Mental Recall KW - Memory, Short-Term KW - Parkinson Disease KW - Movement Disorders KW - Adult KW - Middle Age KW - Psychomotor Performance KW - Laterality KW - Attention KW - Male KW - Female KW - Motor Neurons KW - Reaction Time UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273167?accountid=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&rft.atitle=Motor+program+memory+storage+in+Parkinson%27s+disease+patients+tested+with+a+delayed+response+task.&rft.au=Labutta%2C+R+J%3BMiles%2C+R+B%3BSanes%2C+J+N%3BHallett%2C+M&rft.aulast=Labutta&rft.aufirst=R&rft.date=1994-03-01&rft.volume=9&rft.issue=2&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Facial action myoclonus in patients with olivopontocerebellar atrophy. AN - 85271556; pmid-8196688 AB - We studied four patients with familial olivopontocerebellar atrophy (OPCA) who had abnormal twitching of the cheeks and perioral muscles induced by facial movements. With the muscles at rest, electromyographic (EMG) recordings of the orbicularis oris and risorius muscles revealed myokymic discharges in the absence of visible movements. With voluntary contraction, the EMG showed synchronous discharges in the orbicularis oris and risorius muscles ipsilaterally associated with visible twitching. The duration of the EMG bursts was 10 to 75 ms with a frequency of 8 to 25 Hz, which suggested that the abnormal twitching was most consistent with a myoclonic disorder. Because it was induced by activation of the facial muscles, this movement disorder represents a form of action myoclonus. JF - Movement Disorders AU - Lou, J S AU - Valls-Solé J AU - Toro, C AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 223 EP - 226 VL - 9 IS - 2 SN - 0885-3185, 0885-3185 KW - Magnetic Resonance Imaging KW - Myoclonus KW - Fasciculation KW - Human KW - Neurologic Examination KW - Cerebellum KW - Facial Expression KW - Adult KW - Brain Stem KW - Middle Age KW - Case Report KW - Olivopontocerebellar Atrophies KW - Atrophy KW - Facial Muscles KW - Muscle Contraction KW - Laterality KW - Female KW - Male KW - Motor Neurons KW - Electromyography UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85271556?accountid=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&rft.atitle=Facial+action+myoclonus+in+patients+with+olivopontocerebellar+atrophy.&rft.au=Lou%2C+J+S%3BValls-Sol%C3%A9+J%3BToro%2C+C%3BHallett%2C+M&rft.aulast=Lou&rft.aufirst=J&rft.date=1994-03-01&rft.volume=9&rft.issue=2&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Movement+Disorders&rft.issn=08853185&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Gender differences in the normal lateralization of the supratemporal cortex: MRI surface-rendering morphometry of Heschl's gyrus and the planum temporale. AN - 85222280; pmid-8038562 AB - Gender differences in hemispheric asymmetry for language functioning have been reported in the neuropsychological literature. Despite numerous reports of anatomic asymmetries in corresponding cortical regions, the possibility of gender dimorphism in the putative neuroanatomical substrate of language has not been systematically examined in vivo. We assessed asymmetry of the planum temporale (PT), a supratemporal region of auditory association cortex, in 12 normal, right-handed females and 12 age-matched right-handed males with the aid of MRI surface-rendering morphometry. Bilateral areas were also assessed for Heschl's gyrus (HG), a supratemporal region of primary auditory cortex where no asymmetry was anticipated. We found a significant interaction between gender and hemisphere for the PT, with males having significantly larger left versus right PTs. Left-right differences in PT area were not significant among females (10 of 12 males showed leftward lateralization of the PT, vs 5 of 12 females). No main effect of gender was found for total (left + right) PT area, and no asymmetries or gender effects were detected for HG. This finding of gender dimorphism in PT area is consistent with evidence for reduced asymmetry among females in the lateralization of language functions attributable to the supratemporal cortex. The implications for theories about interactions between sex hormones and the development of brain asymmetries are discussed. JF - Cerebral Cortex AU - Kulynych J J AU - Vladar, K AU - Jones, D W AU - Weinberger, D R AD - Clinical Brain Disorders Branch, NIMH Neuroscience Center at St. Elizabeths, Washington, DC 20032. PY - 1994 SP - 107 EP - 118 VL - 4 IS - 2 SN - 1047-3211, 1047-3211 KW - Auditory Cortex KW - Magnetic Resonance Imaging KW - Sex Characteristics KW - Human KW - Adult KW - Temporal Lobe KW - Laterality KW - Female KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85222280?accountid=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=Cerebral+Cortex&rft.atitle=Gender+differences+in+the+normal+lateralization+of+the+supratemporal+cortex%3A+MRI+surface-rendering+morphometry+of+Heschl%27s+gyrus+and+the+planum+temporale.&rft.au=Kulynych+J+J%3BVladar%2C+K%3BJones%2C+D+W%3BWeinberger%2C+D+R&rft.aulast=Kulynych+J+J&rft.aufirst=&rft.date=1994-03-01&rft.volume=4&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Cerebral+Cortex&rft.issn=10473211&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - News from the National Institute on Deafness and Other Communication Disorders. AN - 85192061; pmid-8172291 JF - The American Journal of Otology AU - Snow, J B AD - National Institute on Deafness and other Communication Disorders, Bethesda, Maryland 20892, USA. PY - 1994 SP - 132 EP - 136 VL - 15 IS - 2 SN - 0192-9763, 0192-9763 KW - United States KW - Haemophilus influenzae KW - X Chromosome KW - Human KW - Waardenburg's Syndrome KW - National Institutes of Health (U.S.) KW - Otitis Media KW - Cytomegalovirus Infections KW - Communication Disorders KW - Deafness KW - Research Support UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85192061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Otology&rft.atitle=News+from+the+National+Institute+on+Deafness+and+Other+Communication+Disorders.&rft.au=Snow%2C+J+B&rft.aulast=Snow&rft.aufirst=J&rft.date=1994-03-01&rft.volume=15&rft.issue=2&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Otology&rft.issn=01929763&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Comparison of muscle activation patterns in adductor and abductor spasmodic dysphonia. AN - 85180845; pmid-8122835 AB - Patients with adductor and abductor spasmodic dysphonia were compared with normal controls on speech items particularly difficult for the two patient groups. Intrinsic and extrinsic laryngeal muscles were measured during adduction for voicing and for a glottal stop, and during abduction after a vowel and after a glottal stop. Muscle activity was measured while the patients attempted the speech items, with considerable difficulty, but not during periods of complete voice loss. Muscle activity at rest, activity increases for speech, and percent changes for adduction and abduction did not differ from normal in either patient group. The results demonstrated normal muscle activation levels and changes for speech in the patients, and suggested that symptoms occur when spasmodic bursts intrude on an otherwise normal pattern. JF - The Annals of Otology, Rhinology, and Laryngology AU - Van Pelt F AU - Ludlow, C L AU - Smith, P J AD - Voice and Speech Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD. PY - 1994 SP - 192 EP - 200 VL - 103 IS - 3 SN - 0003-4894, 0003-4894 KW - Analysis of Variance KW - Comparative Study KW - Laryngeal Muscles KW - Vocal Cords KW - Humans KW - Adult KW - Middle Aged KW - Laryngismus KW - Voice Disorders KW - Female KW - Male KW - Phonation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85180845?accountid=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=Comparison+of+muscle+activation+patterns+in+adductor+and+abductor+spasmodic+dysphonia.&rft.au=Van+Pelt+F%3BLudlow%2C+C+L%3BSmith%2C+P+J&rft.aulast=Van+Pelt+F&rft.aufirst=&rft.date=1994-03-01&rft.volume=103&rft.issue=3&rft.spage=192&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.issn=00034894&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Postictal behavior. A clinical and subdural electroencephalographic study. AN - 85163746; pmid-8129636 AB - OBJECTIVE: To examine postictal behaviors after temporal lobe complex partial seizures (CPSs) and to correlate these behavioral phenomena with side of origin and ictal spread pattern. DESIGN: Review language and other behavioral phenomena after seizures defined by subdural electroencephalography. SETTINGS: A surgical epilepsy center. PATIENTS: We studied postictal behavior following 65 CPSs in 18 patients with left hemisphere language dominance using subdural electrode recordings. INTERVENTION: Subdural electrodes. MAIN OUTCOME MEASURES: Language function, affect, orientation, and postictal automatisms. RESULTS: Following the CPS ictal discharge, the mean interval for initial nonreflexive response to an environmental stimulus was 43 seconds (left foci, 57 seconds; right foci, 29 seconds; not significantly) and for first correct verbal response was 219 seconds (left foci, 275 seconds; right foci, 167 seconds; not significant). Impaired comprehension with fluent but unintelligible speech, as well as anomia, occurred after seizures arising from either temporal lobe. All nine seizures followed by global or nonfluent aphasia originated on the left side. Paraphasic errors were significantly more common after left temporal CPSs. Prolonged disorientation for place and flat affect were significantly more common after right temporal CPS. Postictal automatisms were frequent and included rubbing of the face, fumbling and picking hand movements, and repetitive oral movements. CONCLUSIONS: Postictal paraphasias, disorientation for place, and flat affect most likely reflect the functions of the area from which seizures arise but not the areas involved by spread. JF - Archives of Neurology AU - Devinsky, O AU - Kelley, K AU - Yacubian, E M AU - Sato, S AU - Kufta, C V AU - Theodore, W H AU - Porter, R J AD - Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. PY - 1994 SP - 254 EP - 259 VL - 51 IS - 3 SN - 0003-9942, 0003-9942 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85163746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Neurology&rft.atitle=Postictal+behavior.+A+clinical+and+subdural+electroencephalographic+study.&rft.au=Devinsky%2C+O%3BKelley%2C+K%3BYacubian%2C+E+M%3BSato%2C+S%3BKufta%2C+C+V%3BTheodore%2C+W+H%3BPorter%2C+R+J&rft.aulast=Devinsky&rft.aufirst=O&rft.date=1994-03-01&rft.volume=51&rft.issue=3&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=Archives+of+Neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Rodent carcinogenicity bioassay: past, present, and future. AN - 76855712; 7973358 AB - Toxicity/carcinogenicity studies in rodents have played a pivotal role in identifying chemicals that are potentially hazardous to humans. In fact, nearly all of the known human carcinogens are also carcinogenic in 1 or more rodent species. During the past 20 yr the quality and consistency of rodent studies has improved considerably, and much has been learned about mechanisms whereby chemicals initiate or promote the carcinogenic process in rats and mice. The process of identifying chemicals that cause toxicity or carcinogenicity in rodents is quite well established, but the procedures for extrapolating this data for risk management decisions in the protection of human health have lagged far behind. While many would accept the assumptions that genotoxic chemicals that cause cancer in animals pose a cancer risk to humans and that genotoxic chemicals causing cancer at high doses pose a risk at lower doses, there is much less certainty with respect to nongenotoxic chemicals. The confusion about risk extrapolation for nongenotoxic chemicals has often lead to criticism of the hazard identification process for chemicals in general. There is increasing awareness of the complexity of the carcinogenic process that has made species extrapolation and dose extrapolation from rodent studies to humans more complex. Although newer molecular biological techniques and cell kinetic measurements offer exciting possibilities for better risk assessment, it is the combination of well-designed rodent studies with appropriate mechanistic studies that offers the best hope for regulatory decisions based on sound scientific principles. JF - Toxicologic pathology AU - Boorman, G A AU - Maronpot, R R AU - Eustis, S L AD - Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 105 EP - 111 VL - 22 IS - 2 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Animals KW - Mice KW - Risk Assessment KW - Carcinogenicity Tests -- trends KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76855712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Rodent+carcinogenicity+bioassay%3A+past%2C+present%2C+and+future.&rft.au=Boorman%2C+G+A%3BMaronpot%2C+R+R%3BEustis%2C+S+L&rft.aulast=Boorman&rft.aufirst=G&rft.date=1994-03-01&rft.volume=22&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-21 N1 - Date created - 1994-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peer review in carcinogenicity bioassays: uses/abuses. AN - 76840439; 7973361 AB - "Truth is the essence of science," and "peer review" is a key element in assuring the "truth". Peer review is particularly important with regard to diagnostic pathology in bioassays used for regulatory purposes and approval of drugs and medical devices for at least 2 reasons: (a) If a study is designed correctly and conducted properly, the bottom-line results rely almost entirely on pathological interpretations, and (b) diagnostic pathology is a subjective science that relies on the training and experience of the pathologist and therefore is subject to individual bias. "Bias" can be introduced during the collection and preparation of pathological materials, use of inconsistent terminology during the pathology evaluation and interpretation of the results. Peer review can help in reducing this bias. However, peer review is also subject to bias by knowledge of treatment groups, selection of inappropriate slides for review, in the type of question asked of the reviewers, and in the selection of the reviewers. When done correctly, pathology peer review can be an effective and important part of a process to assure the results of a study, but when done improperly it can cloud the issue and have a negative impact on the credibility of the study. JF - Toxicologic pathology AU - McConnell, E E AU - Eustis, S L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 141 EP - 144 VL - 22 IS - 2 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Neoplasms, Experimental -- pathology KW - Carcinogenicity Tests -- standards KW - Peer Review, Research -- standards KW - Carcinogenicity Tests -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76840439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Peer+review+in+carcinogenicity+bioassays%3A+uses%2Fabuses.&rft.au=McConnell%2C+E+E%3BEustis%2C+S+L&rft.aulast=McConnell&rft.aufirst=E&rft.date=1994-03-01&rft.volume=22&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-21 N1 - Date created - 1994-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concurrent approaches to combined chemotherapy and chest radiotherapy for the treatment of patients with limited stage small cell lung cancer. AN - 76721726; 8087521 AB - The addition of chest radiotherapy to combination chemotherapy has been shown to prolong survival of patients with limited stage small cell lung cancer. Treatment of these patients with concurrent etoposide cisplatin and chest radiotherapy has resulted in a median survival of 18-27 months with a 2-year projected actuarial survival of 36-65%. The alternation of etoposide cisplatin (EP) with vincristine, doxorubicin, and cyclophosphamide (VAC) has been associated with prolonged survival in a single trial of patients with limited stage small cell lung cancer treated with combined modality therapy. Timing of the alternation of the two regimens (EP and VAC) in the first, second, or fourth cycle has not been shown to be an important determinant of survival for patients in single arm studies. Three studies evaluating early (within 1 month of starting chemotherapy) versus late (3-4 months after starting chemotherapy) chest radiotherapy in concurrent regimens, have shown early chest radiotherapy is associated with longer survival in one study while the other two show no difference in survival. Further clinical research will continue to define the appropriate ways to combine chemotherapeutic agents and chest radiotherapy to maximize the survival of patients with small cell lung cancer. JF - Lung cancer (Amsterdam, Netherlands) AU - Johnson, B E AD - NCI-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, MD 20889-5105. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - S281 EP - S287 VL - 10 Suppl 1 SN - 0169-5002, 0169-5002 KW - Index Medicus KW - Multicenter Studies as Topic KW - Randomized Controlled Trials as Topic KW - Combined Modality Therapy KW - Radiotherapy Dosage KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic KW - Radiography KW - Actuarial Analysis KW - Survival Analysis KW - Radiotherapy -- adverse effects KW - Carcinoma, Small Cell -- pathology KW - Carcinoma, Small Cell -- therapy KW - Lung Neoplasms -- radiotherapy KW - Carcinoma, Small Cell -- mortality KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- therapy KW - Carcinoma, Small Cell -- diagnostic imaging KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76721726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Concurrent+approaches+to+combined+chemotherapy+and+chest+radiotherapy+for+the+treatment+of+patients+with+limited+stage+small+cell+lung+cancer.&rft.au=Johnson%2C+B+E&rft.aulast=Johnson&rft.aufirst=B&rft.date=1994-03-01&rft.volume=10+Suppl+1&rft.issue=&rft.spage=S281&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-19 N1 - Date created - 1994-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrated clinical and basic studies related to circumventing non-small cell lung cancer drug resistance. AN - 76712875; 8087530 AB - Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium. JF - Lung cancer (Amsterdam, Netherlands) AU - Mulshine, J L AU - Johnson, B E AU - Gazdar, A F AU - Shaw, G L AU - Kramer, B S AU - Mitsudomi, T AU - Minna, J D AU - Pass, H AU - Phelps, R AU - Ghosh, B AD - Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850-3300. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - S73 EP - S81 VL - 10 Suppl 1 SN - 0169-5002, 0169-5002 KW - K-ras KW - p53 KW - ras KW - Antineoplastic Agents KW - 0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Carboplatin KW - BG3F62OND5 KW - Isotretinoin KW - EH28UP18IF KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Clinical Trials, Phase II as Topic KW - Neoplasms, Second Primary KW - Combined Modality Therapy KW - Humans KW - Drug Resistance KW - Carboplatin -- therapeutic use KW - Neoplastic Stem Cells -- drug effects KW - Cisplatin -- administration & dosage KW - Isotretinoin -- therapeutic use KW - Phenotype KW - Cisplatin -- therapeutic use KW - Oncogenes KW - Tumor Cells, Cultured KW - Etoposide -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Chemotherapy, Adjuvant KW - Carcinoma, Non-Small-Cell Lung -- genetics KW - Lung Neoplasms -- drug therapy KW - Lung Neoplasms -- genetics KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76712875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Integrated+clinical+and+basic+studies+related+to+circumventing+non-small+cell+lung+cancer+drug+resistance.&rft.au=Mulshine%2C+J+L%3BJohnson%2C+B+E%3BGazdar%2C+A+F%3BShaw%2C+G+L%3BKramer%2C+B+S%3BMitsudomi%2C+T%3BMinna%2C+J+D%3BPass%2C+H%3BPhelps%2C+R%3BGhosh%2C+B&rft.aulast=Mulshine&rft.aufirst=J&rft.date=1994-03-01&rft.volume=10+Suppl+1&rft.issue=&rft.spage=S73&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-19 N1 - Date created - 1994-10-19 N1 - Date revised - 2017-01-13 N1 - Gene symbol - K-ras; p53; ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [The epidemiological aspects of eye screening in occupational medicine]. TT - Considerazioni epidemiologiche sullo screening oculistico in medicina del lavoro. AN - 76677861; 8072448 AB - The wide-spread use of video display units in many work places has led to an increase in ophthalmologic examinations of the operators. For this reason, instruments for visual test screening (for example Visotest) have become widely used. Nevertheless, the literature does not seem to offer any clarification about the utility of these instruments as epidemiological tools. The costs and benefits of visual screening programmes were estimated in relation to specific visual deficit prevalence in a differently age-structured population. Via epidemiological calculation, it was demonstrated that positive and negative predictive values, which are directly related to deficit prevalence, are more important than sensitivity and specificity calculations. In view of the disorders screened, a visual test with a low positive predictive value is more expensive than one with a low negative predictive value. A visual test for visual deficits screening does not appear to be advisable in young populations, where the true positives/false positives ratio is 1:4, whereas in older populations the ratio is 2:1. JF - La Medicina del lavoro AU - Baldasseroni, A AU - Frosini, R AU - Tartaglia, R AU - Carnevale, F AD - Servizio di Prevenzione, Igiene e Sicurezza nei Luoghi di Lavoro G. Pieraccini, USL 10/D Firenze. PY - 1994 SP - 99 EP - 106 VL - 85 IS - 2 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Cost-Benefit Analysis KW - Adult KW - Prognosis KW - Middle Aged KW - Italy -- epidemiology KW - Vision Tests -- statistics & numerical data KW - Vision Tests -- economics KW - Prevalence KW - Mass Screening -- statistics & numerical data KW - Occupational Diseases -- economics KW - Vision Disorders -- economics KW - Occupational Diseases -- prevention & control KW - Mass Screening -- economics KW - Vision Disorders -- prevention & control KW - Occupational Diseases -- epidemiology KW - Vision Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76677861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BThe+epidemiological+aspects+of+eye+screening+in+occupational+medicine%5D.&rft.au=Baldasseroni%2C+A%3BFrosini%2C+R%3BTartaglia%2C+R%3BCarnevale%2C+F&rft.aulast=Baldasseroni&rft.aufirst=A&rft.date=1994-03-01&rft.volume=85&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-28 N1 - Date created - 1994-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of cardiac flow on gradient recalled echo images of the canine heart. AN - 76677138; 8068531 AB - The effect of coronary flow on the signal intensity of gradient recalled echo (GRE) MR images of the canine heart was evaluated at 4 T. Using a fully instrumented canine model, hyperfusion (local adenosine infusion) and ischemia (local occlusion) were evaluated while coronary blood flow and venous oxygen tension were monitored. These studies demonstrated an increase in GRE signal intensity with increases in coronary blood flow and venous oxygenation. A local occlusion resulted in a small decrease in signal intensity in the affected area of the heart. The dependence of the signal changes on TE and TR indicated that the effects of high flow were associated with changes in the apparent T2 and T1. Both relaxation effects could reflect changes in tissue blood volume associated with the conditions studied. In addition, the apparent T2 changes were consistent with alterations in total tissue deoxyhemoglobin concentration and the changes in apparent T1 were consistent with inflow effects. JF - NMR in biomedicine AU - Balaban, R S AU - Taylor, J F AU - Turner, R AD - Laboratory of Cardiac Energetics, National Heart Lung and Blood Institute, Bethesda, MD 29817. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 89 EP - 95 VL - 7 IS - 1-2 SN - 0952-3480, 0952-3480 KW - Adenosine KW - K72T3FS567 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Signal Processing, Computer-Assisted KW - Perfusion KW - Myocardial Ischemia -- blood KW - Hyperemia -- blood KW - Myocardial Ischemia -- physiopathology KW - Adenosine -- pharmacology KW - Veins KW - Adenosine -- administration & dosage KW - Magnetic Resonance Imaging -- methods KW - Heart Ventricles -- anatomy & histology KW - Oxygen -- blood KW - Dogs KW - Myocardial Ischemia -- chemically induced KW - Hyperemia -- physiopathology KW - Hyperemia -- etiology KW - Coronary Circulation -- physiology KW - Heart -- anatomy & histology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76677138?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NMR+in+biomedicine&rft.atitle=Effect+of+cardiac+flow+on+gradient+recalled+echo+images+of+the+canine+heart.&rft.au=Balaban%2C+R+S%3BTaylor%2C+J+F%3BTurner%2C+R&rft.aulast=Balaban&rft.aufirst=R&rft.date=1994-03-01&rft.volume=7&rft.issue=1-2&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=NMR+in+biomedicine&rft.issn=09523480&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-23 N1 - Date created - 1994-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperthermic sensitization by the radical initiator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). I. In vitro studies. AN - 76674105; 8064185 AB - AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labile azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals might be directly cytotoxic or may react with oxygen to produce potentially cytotoxic alkoxyl and peroxyl radicals. The rate of free radical production as a result of AAPH thermal decomposition increases with increasing temperature. We have evaluated the efficacy of AAPH as a heat sensitizer for Chinese hamster V79 cells by the clonogenic assay. AAPH (50 mM) was not cytotoxic to V79 cells at 37 degrees C for exposures up to 3 h. In contrast, AAPH (50 mM) was found to markedly sensitize cells exposed to 42, 43 and 45 degrees C. For a 75 min exposure to 42 degrees C alone, cell survival was reduced to 9 x 10(-1); however, a 75 min exposure at 42 degrees C+AAPH resulted in survival of 5.5 x 10(-4). For 43 and 45.5 degrees C heating, cell survival was potentiated by AAPH at the 1% survival level by 4.1 and 1.4-fold, respectively. AAPH was also found to sensitize both hypoxic cells and thermotolerant cells. These findings would encourage in vivo evaluation of AAPH (or analogues) as a temperature-dependent heat sensitizer. AAPH represents a new class of heat sensitizers which may have use in unravelling the mechanism(s) of heat killing and may have utility in local hyperthermia treatment. JF - International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group AU - Krishna, M C AU - Dewhirst, M W AU - Friedman, H S AU - Cook, J A AU - DeGraff, W AU - Samuni, A AU - Russo, A AU - Mitchell, J B AD - Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD. PY - 1994 SP - 271 EP - 281 VL - 10 IS - 2 SN - 0265-6736, 0265-6736 KW - Amidines KW - 0 KW - Free Radicals KW - 2,2'-azobis(2-amidinopropane) KW - 7381JDR72F KW - Index Medicus KW - Hot Temperature KW - Animals KW - Cell Survival -- drug effects KW - Humans KW - Cell Hypoxia -- drug effects KW - Neoplasms -- therapy KW - Cell Line KW - Cricetinae KW - Amidines -- pharmacology KW - Hyperthermia, Induced -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76674105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hyperthermia+%3A+the+official+journal+of+European+Society+for+Hyperthermic+Oncology%2C+North+American+Hyperthermia+Group&rft.atitle=Hyperthermic+sensitization+by+the+radical+initiator+2%2C2%27-azobis+%282-amidinopropane%29+dihydrochloride+%28AAPH%29.+I.+In+vitro+studies.&rft.au=Krishna%2C+M+C%3BDewhirst%2C+M+W%3BFriedman%2C+H+S%3BCook%2C+J+A%3BDeGraff%2C+W%3BSamuni%2C+A%3BRusso%2C+A%3BMitchell%2C+J+B&rft.aulast=Krishna&rft.aufirst=M&rft.date=1994-03-01&rft.volume=10&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hyperthermia+%3A+the+official+journal+of+European+Society+for+Hyperthermic+Oncology%2C+North+American+Hyperthermia+Group&rft.issn=02656736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-20 N1 - Date created - 1994-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-Alpha-reductase inhibition and prostate cancer prevention. AN - 76636532; 8049641 AB - Studies of prostate biology support the concept that dihydrotestosterone is the principal androgen responsible for normal and hyperplastic growth of the prostate gland. Cancer is a process of malignant transformation evolving over time, involving cellular growth and division. Therefore, an altered endocrine state, such as suppression of dihydrotestosterone activity, may have an impact on prostate cells inhibiting carcinogenic transformation. In vitro and in vivo preclinical observations support this hypothesis. A placebo-controlled randomized trial using finasteride, an inhibitor of the enzyme that converts testosterone to dihydrotestosterone, is planned. The endpoint of this trial will be reduction of prostate cancer incidence. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Brawley, O W AU - Ford, L G AU - Thompson, I AU - Perlman, J A AU - Kramer, B S AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 177 EP - 182 VL - 3 IS - 2 SN - 1055-9965, 1055-9965 KW - 5-alpha Reductase Inhibitors KW - 0 KW - Dihydrotestosterone KW - 08J2K08A3Y KW - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase KW - EC 1.3.99.5 KW - Index Medicus KW - Cell Transformation, Neoplastic -- pathology KW - Survival Rate KW - Risk Factors KW - Humans KW - Cell Transformation, Neoplastic -- drug effects KW - Prostate -- pathology KW - Dihydrotestosterone -- metabolism KW - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase -- physiology KW - Male KW - Prostatic Neoplasms -- pathology KW - Prostatic Neoplasms -- mortality KW - Neoplasms, Hormone-Dependent -- prevention & control KW - Neoplasms, Hormone-Dependent -- pathology KW - Prostatic Neoplasms -- prevention & control KW - Neoplasms, Hormone-Dependent -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76636532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=5-Alpha-reductase+inhibition+and+prostate+cancer+prevention.&rft.au=Brawley%2C+O+W%3BFord%2C+L+G%3BThompson%2C+I%3BPerlman%2C+J+A%3BKramer%2C+B+S&rft.aulast=Brawley&rft.aufirst=O&rft.date=1994-03-01&rft.volume=3&rft.issue=2&rft.spage=177&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 - 1994-09-08 N1 - Date created - 1994-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of tumour necrosis factor (TNF) in isolated perfusion: results and side effects. The NCI results. AN - 76608588; 8038592 AB - The Surgery Branch of the National Cancer Institute has initiated several clinical trials involving the use of high-dose TNF in isolated limb perfusions. A phase III trial compares the three drug combination of TNF, interferon-gamma (IFN-gamma) and melphalan with a standard melphalan-alone perfusion in a prospective randomized trial. Another protocol escalates the dose of TNF in the perfusate to define the maximally tolerated dose that can be administered in this regional manner. A third protocol adds systemic high-dose interleukin-2 postoperatively to a TNF, IFN, and melphalan limb perfusion for patients with stage IV melanoma with the bulk of the disease in the extremity. This brief review highlights the rationale and study design of these TNF limb perfusion protocols. JF - Melanoma research AU - Fraker, D L AU - Alexander, H R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 27 EP - 29 VL - 4 Suppl 1 SN - 0960-8931, 0960-8931 KW - Interleukin-2 KW - 0 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Extremities KW - Randomized Controlled Trials as Topic KW - Interleukin-2 -- administration & dosage KW - Prospective Studies KW - Dose-Response Relationship, Drug KW - Melphalan -- administration & dosage KW - Humans KW - Clinical Trials as Topic KW - Interferon-gamma -- administration & dosage KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melanoma -- drug therapy KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76608588?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Melanoma+research&rft.atitle=The+use+of+tumour+necrosis+factor+%28TNF%29+in+isolated+perfusion%3A+results+and+side+effects.+The+NCI+results.&rft.au=Fraker%2C+D+L%3BAlexander%2C+H+R&rft.aulast=Fraker&rft.aufirst=D&rft.date=1994-03-01&rft.volume=4+Suppl+1&rft.issue=&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Melanoma+research&rft.issn=09608931&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-23 N1 - Date created - 1994-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of in-transit metastases from cutaneous melanoma by isolation perfusion with tumour necrosis factor-alpha (TNF-alpha), melphalan and interferon-gamma (IFN-gamma). Dose-finding experience at the National Cancer Institute of Milan. AN - 76603042; 8038594 AB - From December 1991 to July 1993, 22 consecutive patients with grade IIIA-IIIAB melanoma underwent isolation perfusion with TNF-alpha (0.5-4 mg), melphalan (10 mg/l perfused limb) and, in the first 12 cases, IFN-gamma (1.5 x 10(6) U). The first series of 12 patients received a total dosage TNF-alpha of 2-4 mg, and the second series of 10 cases received an escalating dosage of TNF-alpha (1.5-1.0-0.5 mg) and no IFN-gamma before or during surgery. The perfusion lasted 90 min and was conducted in mild hyperthermia (39-39.5 degree C muscle temperature). The results of the first series included seven patients in complete remission, four with stable disease and one case not evaluable for local toxicity. Fifty per cent of cases developed a regional relapse from 3 to 4 months after surgery. Presently with a median follow up of 10 months, five patients of this group have no evidence of disease, four are alive with disease, two died from melanoma and one died of complications likely due to treatment (multi-organ failure syndrome). In the second series, the immediate responses included seven patients in complete remission and three in partial remission; with a median follow up of 3 months, two patients developed a regional relapse, respectively, 3 and 5 months after surgery. So far our experience of perfusion with TNF-alpha has not reproduced the data reported by other investigators. Further clinical and biological findings and a longer follow-up period are needed to draw any conclusion, and a decreasing TNF-alpha dose should be carefully evaluated. JF - Melanoma research AU - Vaglini, M AU - Santinami, M AU - Manzi, R AU - Inglese, M G AU - Santoro, N AU - Persiani, L AU - Belli, F AD - Department of Surgical Oncology B, National Cancer Institute, Milan, Italy. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 35 EP - 38 VL - 4 Suppl 1 SN - 0960-8931, 0960-8931 KW - Recombinant Proteins KW - 0 KW - Tumor Necrosis Factor-alpha KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Extremities KW - Melphalan -- administration & dosage KW - Adult KW - Hyperthermia, Induced KW - Interferon-gamma -- administration & dosage KW - Middle Aged KW - Female KW - Male KW - Skin Neoplasms -- drug therapy KW - Neoplastic Cells, Circulating -- pathology KW - Melanoma -- secondary KW - Chemotherapy, Cancer, Regional Perfusion KW - Melanoma -- drug therapy KW - Skin Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Melanoma -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Skin Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76603042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Melanoma+research&rft.atitle=Treatment+of+in-transit+metastases+from+cutaneous+melanoma+by+isolation+perfusion+with+tumour+necrosis+factor-alpha+%28TNF-alpha%29%2C+melphalan+and+interferon-gamma+%28IFN-gamma%29.+Dose-finding+experience+at+the+National+Cancer+Institute+of+Milan.&rft.au=Vaglini%2C+M%3BSantinami%2C+M%3BManzi%2C+R%3BInglese%2C+M+G%3BSantoro%2C+N%3BPersiani%2C+L%3BBelli%2C+F&rft.aulast=Vaglini&rft.aufirst=M&rft.date=1994-03-01&rft.volume=4+Suppl+1&rft.issue=&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Melanoma+research&rft.issn=09608931&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-23 N1 - Date created - 1994-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fetal damage caused by parvoviral infections. AN - 76590567; 8032127 AB - The single-stranded DNA parvoviruses occur in humans and many species of animals. In general, they are species-specific and capable of producing disease at any stage of life. Parvoviruses have a requirement to replicate in cells in a permissive S-phase of DNA mitosis. The infections may be cytolytic to select cell groups resulting in specific developmental defects or may produce more generalized effects such as anemia, pancytopenia, or hemorrhage. The fetus is at particular risk for damage because of the vast number of cells in active mitosis. The teratogenic effects may be severe, often resulting in fetal death. Infections in childhood and adulthood are more frequently mild to subclinical. Some of the teratogenic effects recognized in animal species have been identified in humans. With increased knowledge of parvovirus effects in animals, more pathogenic effects may be related to human parvoviral disease. The need for vaccination, currently used annually in many domestic animal species, continues to be evaluated for humans. JF - Reproductive toxicology (Elmsford, N.Y.) AU - Jordan, E K AU - Sever, J L AD - Animal Health and Care Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 161 EP - 189 VL - 8 IS - 2 SN - 0890-6238, 0890-6238 KW - Index Medicus KW - Animals KW - Humans KW - Gestational Age KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Parvoviridae Infections -- physiopathology KW - Fetal Diseases -- microbiology KW - Parvoviridae Infections -- congenital KW - Pregnancy Complications, Infectious -- physiopathology KW - Congenital Abnormalities -- microbiology KW - Parvoviridae Infections -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76590567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.atitle=Fetal+damage+caused+by+parvoviral+infections.&rft.au=Jordan%2C+E+K%3BSever%2C+J+L&rft.aulast=Jordan&rft.aufirst=E&rft.date=1994-03-01&rft.volume=8&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Reproductive+toxicology+%28Elmsford%2C+N.Y.%29&rft.issn=08906238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-15 N1 - Date created - 1994-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of tumour incidence analyses applicable in single-sacrifice animal experiments. AN - 76589707; 8023043 AB - Monte Carlo methods are used to evaluate the operating characteristics of several trend tests for comparing incidence rates of occult tumours. The candidate tests are applicable in long-term animal experiments that have just one sacrifice time and no information on cause of death. When survival decreases with dose and the tumour is lethal, the tests that do not adjust for survival or that assume tumours are non-lethal behave conservatively, whereas the test that assumes tumours are rapidly lethal rejects the hypothesis of equal incidence rates too frequently. The only test which consistently operates at the correct level is one that specifies a constant difference between the death rates for animals with and without the tumour. Surprisingly, the test that specifies a constant ratio of these death rates often is conservative. Finally, a test based on a simple modification of the unadjusted test, which accounts for differential mortality by scaling down the size of the risk set, performs reasonably well in many cases. Among the tests that operate at the proper level, the constant risk difference test consistently exhibits high power across a wide range of situations. JF - Statistics in medicine AU - Dinse, G E AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. PY - 1994 SP - 689 EP - 708 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Index Medicus KW - Animals KW - Bias (Epidemiology) KW - Likelihood Functions KW - Survival Analysis KW - Proportional Hazards Models KW - Neoplasms, Experimental -- etiology KW - Neoplasms, Experimental -- mortality KW - Incidence KW - Models, Statistical KW - Neoplasms, Experimental -- pathology KW - Monte Carlo Method KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76589707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=A+comparison+of+tumour+incidence+analyses+applicable+in+single-sacrifice+animal+experiments.&rft.au=Dinse%2C+G+E&rft.aulast=Dinse&rft.aufirst=G&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modelling transitional and joint marginal distributions in repeated categorical data. AN - 76589653; 8023029 AB - When a repeated measures endpoint classifies people into several categories, marginal and transitional models provide two distinct approaches for data analysis. Marginal models estimate the probabilities of being in different categories over time. Transitional models estimate the probability of changing between any two given states during follow-up visits. This paper develops transitional and marginal models and applies them to a clinical trial of treatments of opiate addiction. The primary outcome was the presence or absence of opiates in a thrice weekly urine test, administered for 17 weeks. Subjects frequently miss visits, however, and in effect respond in one of three ways to a visit: missing, opiates present or opiates absent. Thus we have three possible states. Our transitional model conditions on the current state and models the transition from state k to one of the other (0, ..., K-1) states using a mutinomial logit model. This model generalizes previous work of Muenz and Rubinstein. Significant covariates in this model are predictive of state changes. Our marginal model views the state at each time point, rather than the transitions, as the primary response. Here we model the probability of being in state k with a multinomial logit model. Correlation within individuals over visits can be handled by applying the approach of Zeger and Liang or the bootstrap. Significant covariates in this model can include more 'global' summaries of a person such as extent of previous opiate use. Both marginal and transitional models are needed to provide a complete description of an individual's behaviour over time since global summaries might not affect transitions. Of particular substantive interest is how the opiate treatments affect both the marginal and transition probabilities. JF - Statistics in medicine AU - Follmann, D AD - Biostatistics Research Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. PY - 1994 SP - 467 EP - 477 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Buprenorphine KW - 40D3SCR4GZ KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Substance Abuse Detection KW - Humans KW - Treatment Outcome KW - Data Interpretation, Statistical KW - Follow-Up Studies KW - Male KW - Female KW - Heroin Dependence -- classification KW - Methadone -- therapeutic use KW - Buprenorphine -- therapeutic use KW - Heroin Dependence -- rehabilitation KW - Models, Statistical KW - Randomized Controlled Trials as Topic -- statistics & numerical data KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76589653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Modelling+transitional+and+joint+marginal+distributions+in+repeated+categorical+data.&rft.au=Follmann%2C+D&rft.aulast=Follmann&rft.aufirst=D&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dosage adjustments in response to monitored plasma concentrations: can unblinded staff adhere to objective criteria? AN - 76583081; 8019586 AB - A randomized, double-blind, placebo-controlled two-period crossover trial was conducted at two centers to evaluate felbamate for treatment of partial seizures in patients receiving concomitant treatment with two standard antiepileptic drugs, phenytoin and carbamazepine. During the pilot study, an interaction was seen; felbamate administration was associated with an approximate 20% increase in plasma phenytoin concentrations. Consequently, the controlled trial was designed to account for this interaction by reducing the phenytoin dosage by approximately 20% during the felbamate treatment period and using matching placebo capsules to maintain the blind. Unblinded staff were to make additional phenytoin dosage adjustments to keep the phenytoin concentrations within 20% of the patient's baseline mean. The data suggest that knowledge of treatment assignment may have influenced decisions regarding dosage adjustments even though there were objective rules for those adjustments. At one center, phenytoin dosages were adjusted at almost twice the rate during the active treatment period as during the placebo treatment period. To avoid potential bias, it is recommended that plasma concentrations be monitored by blinded staff. JF - Journal of biopharmaceutical statistics AU - Sahlroot, J T AU - Pledger, G W AD - Epilepsy Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 91 EP - 100 VL - 4 IS - 1 SN - 1054-3406, 1054-3406 KW - Phenylcarbamates KW - 0 KW - Placebos KW - Propylene Glycols KW - Carbamazepine KW - 33CM23913M KW - Phenytoin KW - 6158TKW0C5 KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Epilepsy -- blood KW - Multicenter Studies as Topic KW - Drug Interactions KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Retrospective Studies KW - Monitoring, Physiologic KW - Epilepsy -- drug therapy KW - Randomized Controlled Trials as Topic -- statistics & numerical data KW - Propylene Glycols -- administration & dosage KW - Attitude of Health Personnel KW - Propylene Glycols -- blood KW - Carbamazepine -- blood KW - Phenytoin -- blood KW - Carbamazepine -- administration & dosage KW - Observer Variation KW - Phenytoin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76583081?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biopharmaceutical+statistics&rft.atitle=Dosage+adjustments+in+response+to+monitored+plasma+concentrations%3A+can+unblinded+staff+adhere+to+objective+criteria%3F&rft.au=Sahlroot%2C+J+T%3BPledger%2C+G+W&rft.aulast=Sahlroot&rft.aufirst=J&rft.date=1994-03-01&rft.volume=4&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Journal+of+biopharmaceutical+statistics&rft.issn=10543406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-02 N1 - Date created - 1994-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A comparison of three approaches to estimate exposure-specific incidence rates from population-based case-control data. AN - 76582204; 8023040 AB - In population-based case-control studies, an attempt is made to identify all incident cases diagnosed in a specified population during a fixed time interval. Assuming that this goal is met allows one to obtain measures of risk other than relative risks. In this paper, we describe three approaches to estimate exposure-specific incidence rates. Approach 1 relies on estimating crude incidence rates of the disease in strata defined, for instance, by age and geographic area, and combining them with relative risk estimates from the case-control data. In approaches 2 and 3, baseline incidence rates and relative risks are estimated jointly. Approach 2 is based on a pseudo-likelihood, while, in approach 3, the problem is regarded as a missing data problem and a full likelihood is maximized. We applied these three approaches to a study of bladder cancer. Our three sets of estimates of exposure-specific incidence rates were in close agreement, while there appeared to be greater precision with approaches 2 and 3. JF - Statistics in medicine AU - Benichou, J AU - Wacholder, S AD - National Cancer Institute, Biostatistics Branch, Rockville, Maryland 20892. PY - 1994 SP - 651 EP - 661 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Index Medicus KW - Urinary Bladder Neoplasms -- etiology KW - Environmental Exposure -- statistics & numerical data KW - Urinary Bladder Neoplasms -- epidemiology KW - Humans KW - Aged KW - Likelihood Functions KW - Population Surveillance KW - Registries KW - Urinary Bladder Neoplasms -- prevention & control KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Environmental Exposure -- adverse effects KW - United States -- epidemiology KW - Female KW - Male KW - Risk KW - Case-Control Studies KW - Incidence KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76582204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=A+comparison+of+three+approaches+to+estimate+exposure-specific+incidence+rates+from+population-based+case-control+data.&rft.au=Benichou%2C+J%3BWacholder%2C+S&rft.aulast=Benichou&rft.aufirst=J&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=651&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sources of bias in studies of time to pregnancy. AN - 76582199; 8023042 AB - Among sexually active couples who are not using contraception, there is considerable heterogeneity in fertility, even among those who eventually achieve pregnancy. The number of menstrual cycles required, measured in integer time, is greatly overdispersed compared to the geometric, suggesting that the per cycle probability of conception varies considerably among couples. Some of this variability may reflect the effect of reproductive toxicants on fertility, and studies of time to pregnancy can be useful in identifying such toxic effects. We describe models for analysing time-to-pregnancy data, and discuss seven sources of bias that can lead the reproductive epidemiologist to spurious conclusions. Certain analytic and design strategies can help protect against some of the pitfalls. JF - Statistics in medicine AU - Weinberg, C R AU - Baird, D D AU - Wilcox, A J AD - National Institute of Environmental Health Sciences, RTP, NC 27709. PY - 1994 SP - 671 EP - 681 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Index Medicus KW - Reference Values KW - Risk Factors KW - Humans KW - Adult KW - Infertility -- epidemiology KW - Infertility -- etiology KW - Male KW - Female KW - Models, Statistical KW - Pregnancy -- statistics & numerical data KW - Bias (Epidemiology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76582199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Sources+of+bias+in+studies+of+time+to+pregnancy.&rft.au=Weinberg%2C+C+R%3BBaird%2C+D+D%3BWilcox%2C+A+J&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=671&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant single-chain immunotoxins against T and B cell leukemias. AN - 76579512; 8025511 AB - Interleukin 2 (IL2) receptors (IL2R's) are found on malignant cells in many human leukemias and lymphomas and are expressed by activated T cells in many autoimmune disorders. Anti-Tac(Fv), a single-chain protein composed of the variable heavy and light domains of the anti-IL2R monoclonal antibody anti-Tac, can be genetically fused to derivatives of Pseudomonas exotoxin (PE) or diphtheria toxin (DT) to form potent immunotoxins. We have shown that anti-Tac(Fv) binds to low affinity IL2R's on fresh chronic lymphocytic leukemia (CLL) and adult T-cell leukemia (ATL) cells and can target either toxin to kill those cells. Anti-Tac(Fv)-PE40, containing the truncated form of PE without its binding domain, was cytotoxic to malignant cells from 8 of 8 ATL patients tested, with IC50's ranging from 0.11 to 5.5 ng/ml. Anti-Tac(Fv)-PE40KDEL, a derivative of anti-Tac(Fv)-PE40 which contains the KDEL carboxyl terminus, was more cytotoxic toward cells from all ATL patients and also killed CLL cells from 8 of 16 patients. DT388-anti-Tac(Fv), containing amino acids 1-388 of DT fused to the amino terminus of anti-Tac(Fv), was less cytotoxic than anti-Tac(Fv)-PE40 on ATL cells from 4 of 5 patients, but was cytotoxic toward CLL cells from 12 of 16 patients. DT388-IL2, where IL2 is substituted for anti-Tac(Fv), is similar to DAB389IL2, an IL2-toxin currently in clinical trials. DT388-IL2 and DAB389IL2 differ by only a few amino acids and have equal cytotoxic activity. DT388-IL2 was cytotoxic toward ATL cells from all patients tested, but usually required much higher concentrations than anti-Tac(Fv)-PE40 and was poorly active against CLL cells. Thus, recombinant toxins containing anti-Tac(Fv) are cytotoxic toward freshly isolated CLL and ATL cells and will be studied further as potential therapy for IL2R-related disorders. JF - Leukemia & lymphoma AU - Kreitman, R J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 1 EP - 10 VL - 13 IS - 1-2 SN - 1042-8194, 1042-8194 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Diphtheria Toxin KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin mu-Chains KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Recombinant Proteins -- biosynthesis KW - Diphtheria Toxin -- toxicity KW - Humans KW - Leukemia-Lymphoma, Adult T-Cell KW - Amino Acid Sequence KW - Recombinant Proteins -- toxicity KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Leukemia, Lymphocytic, Chronic, B-Cell KW - Molecular Sequence Data KW - Diphtheria Toxin -- therapeutic use KW - Exotoxins -- toxicity KW - Exotoxins -- therapeutic use KW - Recombinant Proteins -- therapeutic use KW - Leukemia, T-Cell -- therapy KW - Immunotoxins -- toxicity KW - Immunotoxins -- biosynthesis KW - Bacterial Toxins -- therapeutic use KW - Leukemia, B-Cell -- therapy KW - Immunotoxins -- therapeutic use KW - Bacterial Toxins -- toxicity KW - Receptors, Interleukin-2 -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76579512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia+%26+lymphoma&rft.atitle=Recombinant+single-chain+immunotoxins+against+T+and+B+cell+leukemias.&rft.au=Kreitman%2C+R+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1994-03-01&rft.volume=13&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Leukemia+%26+lymphoma&rft.issn=10428194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-11 N1 - Date created - 1994-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NMDA receptor-mediated excitoprotection of cultured cerebellar granule neurons fails to alter glutamate-induced expression of c-fos and c-jun mRNAs. AN - 76569515; 8015382 AB - Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-D-aspartate (NMDA) induces a state of excitoprotection when measured by subsequent exposure to toxic concentrations of glutamate. This NMDA-induced excitoprotective state is prevented by inhibitors of new RNA and protein synthesis. Since the neurotrophic and excitoprotective effects of NMDA in cerebellar granule neurons may involve changes in the expression of the immediate early genes c-fos and c-jun, we measured c-fos and c-jun mRNAs in cerebellar granule neurons after exposure to either toxic concentrations of glutamate or excitoprotective (subtoxic) concentrations of NMDA. Exposure of cerebellar granule neurons to toxic concentrations of glutamate induced a dramatic increase in c-fos and c-jun mRNAs which was not associated with a corresponding increase in c-fos and c-jun proteins as measured immunocytochemically. However, the increase in c-fos and c-jun mRNAs induced by toxic concentrations of glutamate was not altered by preexposing cerebellar granule neurons to NMDA, suggesting that increased expression of c-fos and c-jun mRNAs is not sufficient for glutamate toxicity of these neurons. Preexposure of cerebellar granule neurons to NMDA for 24 h, which induced a maximal excitoprotective state, resulted in a transient increase in c-fos, and to a lesser degree c-jun, mRNAs similar to that induced by toxic concentrations of glutamate. The induction of c-fos, but not that of c-jun, mRNA both by excitoprotective concentrations of NMDA and by neurotoxic concentrations of glutamate was blocked by the non-competitive NMDA receptor antagonist, MK-801.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Brain research. Molecular brain research AU - Weller, M AU - Montpied, P AU - Paul, S M AD - Section on Molecular Pharmacology, Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 227 EP - 235 VL - 22 IS - 1-4 SN - 0169-328X, 0169-328X KW - Proto-Oncogene Proteins c-fos KW - 0 KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Receptors, N-Methyl-D-Aspartate KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Dizocilpine Maleate -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Cerebellum -- cytology KW - Neurons -- metabolism KW - Proto-Oncogene Proteins c-fos -- genetics KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - RNA, Messenger -- drug effects KW - Neurons -- cytology KW - Proto-Oncogene Proteins c-jun -- genetics KW - RNA, Messenger -- biosynthesis KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76569515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=NMDA+receptor-mediated+excitoprotection+of+cultured+cerebellar+granule+neurons+fails+to+alter+glutamate-induced+expression+of+c-fos+and+c-jun+mRNAs.&rft.au=Weller%2C+M%3BMontpied%2C+P%3BPaul%2C+S+M&rft.aulast=Weller&rft.aufirst=M&rft.date=1994-03-01&rft.volume=22&rft.issue=1-4&rft.spage=227&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 - 1994-07-25 N1 - Date created - 1994-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A multiple decision procedure in clinical trials. AN - 76568195; 8023027 AB - In some multiple treatment arm clinical trials there is an order of preference for the treatments based on secondary considerations like toxicity or cost. In this paper, we consider the case where two or more treatments could have equal prior preference. This formulation includes the problem of comparing several equally preferred experimental treatments to one control, or the comparison of a combination with its components. Our decision procedures will guarantee a high selection probability for the correct treatment(s) when that selection is appropriate. We establish sample size requirements for our decision procedures which can be applied to clinical trials with normal, binomial, or right censored exponential endpoints. JF - Statistics in medicine AU - Chen, T T AU - Simon, R AD - Biometric Research Branch, National Cancer Institute, Bethesda, Maryland 20892. PY - 1994 SP - 431 EP - 446 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Index Medicus KW - Probability KW - Survival Rate KW - Humans KW - Carcinoma, Squamous Cell -- mortality KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- mortality KW - Models, Statistical KW - Radiotherapy, High-Energy -- statistics & numerical data KW - Carcinoma, Squamous Cell -- radiotherapy KW - Randomized Controlled Trials as Topic -- methods KW - Clinical Trials as Topic -- methods KW - Randomized Controlled Trials as Topic -- statistics & numerical data KW - Decision Support Techniques KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76568195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=A+multiple+decision+procedure+in+clinical+trials.&rft.au=Chen%2C+T+T%3BSimon%2C+R&rft.aulast=Chen&rft.aufirst=T&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The utility of large, simple trials in the evaluation of AIDS treatment strategies. AN - 76567788; 7912842 JF - Statistics in medicine AU - Ellenberg, S S AU - Foulkes, M A AD - Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. PY - 1994 SP - 405 EP - 415 VL - 13 IS - 5-7 SN - 0277-6715, 0277-6715 KW - Antiviral Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Zidovudine -- therapeutic use KW - Leukocyte Count -- drug effects KW - Zidovudine -- adverse effects KW - Survival Rate KW - Humans KW - CD4-Positive T-Lymphocytes -- immunology KW - Follow-Up Studies KW - CD4-Positive T-Lymphocytes -- drug effects KW - Bias (Epidemiology) KW - Antiviral Agents -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Acquired Immunodeficiency Syndrome -- immunology KW - HIV Infections -- mortality KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Antiviral Agents -- adverse effects KW - Acquired Immunodeficiency Syndrome -- mortality KW - Clinical Trials as Topic -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76567788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=The+utility+of+large%2C+simple+trials+in+the+evaluation+of+AIDS+treatment+strategies.&rft.au=Ellenberg%2C+S+S%3BFoulkes%2C+M+A&rft.aulast=Ellenberg&rft.aufirst=S&rft.date=1994-03-01&rft.volume=13&rft.issue=5-7&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice. AN - 76567665; 8024534 AB - Exploratory behaviors as well as pharmacological actions of gamma-aminobutyric acidA (GABAA)/benzodiazepine receptor agonists and inverse agonists were characterized in C57BL/6J and A/J strains of mice. C57BL/6J mice displayed higher levels of exploratory behavior than A/J mice in the light in equilibrium with dark exploration model of anxiety and in an open-field test, suggesting that C57BL/6J mice are less "emotional" and more active than A/J mice, respectively. However, C57BL/6J mice were more sensitive than A/J mice to the anxiolytic effects of diazepam in the light in equilibrium with dark exploration model. In contrast, A/J mice were more sensitive than C57BL/6J mice to the convulsant effects of methyl-beta-carboline-3-carboxylate. C57BL/6J mice showed no evidence of acquisition of a passive avoidance task, while A/J readily acquired this memory task at low levels of footshock. C57BL/6J and A/J mice should be useful parental strains in recombinant inbred lines for investigating the genetic determinants of benzodiazepine-sensitive behaviors and sensitivity to drugs acting on the GABAA/benzodiazepine receptor complex. JF - Behavior genetics AU - Mathis, C AU - Paul, S M AU - Crawley, J N AD - Section of Behavioral Neuropharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 171 EP - 180 VL - 24 IS - 2 SN - 0001-8244, 0001-8244 KW - Carbolines KW - 0 KW - Convulsants KW - Receptors, GABA-A KW - beta-carboline-3-carboxylic acid methyl ester KW - I2A008F6YL KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Avoidance Learning -- physiology KW - Convulsants -- pharmacology KW - Diazepam -- pharmacology KW - Avoidance Learning -- drug effects KW - Mice KW - Exploratory Behavior -- drug effects KW - Models, Genetic KW - Seizures -- genetics KW - Exploratory Behavior -- physiology KW - Carbolines -- pharmacology KW - Female KW - Male KW - Receptors, GABA-A -- genetics KW - Mice, Inbred C57BL -- genetics KW - Arousal -- drug effects KW - Arousal -- genetics KW - Mice, Inbred A -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76567665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavior+genetics&rft.atitle=Characterization+of+benzodiazepine-sensitive+behaviors+in+the+A%2FJ+and+C57BL%2F6J+inbred+strains+of+mice.&rft.au=Mathis%2C+C%3BPaul%2C+S+M%3BCrawley%2C+J+N&rft.aulast=Mathis&rft.aufirst=C&rft.date=1994-03-01&rft.volume=24&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Behavior+genetics&rft.issn=00018244&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Nasal toxicity and dosimetry of inhaled xenobiotics: implications for human health. AN - 76563392; 7913439 JF - Environmental health perspectives AU - Boorman, G A Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 318 EP - 319 VL - 102 IS - 3 KW - Xenobiotics KW - 0 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Respiration KW - Humans KW - Nasal Mucosa -- drug effects KW - Models, Biological KW - Xenobiotics -- adverse effects KW - Nasal Cavity -- drug effects KW - Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76563392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Nasal+toxicity+and+dosimetry+of+inhaled+xenobiotics%3A+implications+for+human+health.&rft.au=Boorman%2C+G+A&rft.aulast=Boorman&rft.aufirst=G&rft.date=1994-03-01&rft.volume=102&rft.issue=3&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-16 N1 - Date created - 1994-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping and sequencing of two yeast genes belonging to the ATP-binding cassette superfamily. AN - 76560037; 7912468 AB - ATP-binding cassette (ABC) transporters share significant sequence identity within their ATP-binding domains. Degenerate oligonucleotides based on highly conserved portions of the ATP-binding domain genes were used to clone portions of two members of the ABC gene superfamily from Saccharomyces cerevisiae DNA. These genes were designated MDL1 and MDL2 (for multidrug resistance-like). Each MDL gene is predicted to encode a single set of transmembrane domains and a single ATP-binding domain, thus the MDL gene products are 'half-molecule' ABC proteins. The two genes were mapped to precise regions on chromosomes XII and XVI and show a considerable similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) and peptide transporter (TAP) genes. Preliminary analysis of null mutants constructed by gene replacement has indicated that the MDL genes are not essential for viability of yeast. The sequences have been deposited in the GenBank data library under Accession Numbers L16958 (Locus YSCBCSA) and L16959 (Locus YSCBCSB). JF - Yeast (Chichester, England) AU - Dean, M AU - Allikmets, R AU - Gerrard, B AU - Stewart, C AU - Kistler, A AU - Shafer, B AU - Michaelis, S AU - Strathern, J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 377 EP - 383 VL - 10 IS - 3 SN - 0749-503X, 0749-503X KW - MDL1 KW - MDL2 KW - Bacterial Proteins KW - 0 KW - Carrier Proteins KW - MDL1 protein, S cerevisiae KW - MDL2 protein, S cerevisiae KW - Membrane Glycoproteins KW - P-Glycoprotein KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Base Sequence KW - Bacterial Proteins -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Sequence Analysis, DNA KW - Genome, Fungal KW - Chromosome Mapping KW - Membrane Glycoproteins -- genetics KW - Cloning, Molecular KW - Saccharomyces cerevisiae -- genetics KW - Genes, Fungal -- genetics KW - Carrier Proteins -- genetics KW - ATP-Binding Cassette Transporters UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76560037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=Mapping+and+sequencing+of+two+yeast+genes+belonging+to+the+ATP-binding+cassette+superfamily.&rft.au=Dean%2C+M%3BAllikmets%2C+R%3BGerrard%2C+B%3BStewart%2C+C%3BKistler%2C+A%3BShafer%2C+B%3BMichaelis%2C+S%3BStrathern%2C+J&rft.aulast=Dean&rft.aufirst=M&rft.date=1994-03-01&rft.volume=10&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Yeast+%28Chichester%2C+England%29&rft.issn=0749503X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-25 N1 - Date created - 1994-07-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - MDL1; MDL2 N1 - Genetic sequence - L16959; GENBANK; L16958 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Familial vasculitis: report of 2 families. AN - 76556817; 7911836 AB - We observed systematic vasculitis (polyarteritis nodosa and Wegener's granulomatosis) in several members of 2 different families. Our experience and a review of the literature suggests that genetic factors are important but not sufficient to express clinical features of these diseases. JF - The Journal of rheumatology AU - Rottem, M AU - Cotch, M F AU - Fauci, A S AU - Hoffman, G S AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 561 EP - 563 VL - 21 IS - 3 SN - 0315-162X, 0315-162X KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Pedigree KW - Fatal Outcome KW - Prednisone -- therapeutic use KW - Azathioprine -- therapeutic use KW - Humans KW - Child KW - Kidney Failure, Chronic -- etiology KW - Haplotypes -- genetics KW - Cyclophosphamide -- therapeutic use KW - Adult KW - Middle Aged KW - Female KW - Male KW - Polyarteritis Nodosa -- genetics KW - Granulomatosis with Polyangiitis -- complications KW - Polyarteritis Nodosa -- drug therapy KW - Granulomatosis with Polyangiitis -- genetics KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76556817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=Familial+vasculitis%3A+report+of+2+families.&rft.au=Rottem%2C+M%3BCotch%2C+M+F%3BFauci%2C+A+S%3BHoffman%2C+G+S&rft.aulast=Rottem&rft.aufirst=M&rft.date=1994-03-01&rft.volume=21&rft.issue=3&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-15 N1 - Date created - 1994-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of caramiphen and phencyclidine alone and in combination on behavior in the rat. AN - 76546005; 8208792 AB - Because dextromethorphan (DM) has been shown to inhibit the locomotor stimulant effects of phencyclidine (PCP), this study explored further the possible interaction between drugs acting on DM and PCP receptor sites. Caramiphen, an antitussive that binds with high affinity to the DM site, was injected (IP) alone (15-120 mg/kg) or at two doses (15 or 60 mg/kg) 15 min before a challenge dose of PCP (1.25-20 mg/kg). Caramiphen alone dose-dependently increased ataxia, increased stereotypy, and had no effect on locomotor activity. PCP alone dose-dependently increased ataxia, stereotypy, and locomotor activity, the latter showing an inverted U-shaped function. At both pretreatment doses, caramiphen enhanced locomotor activity and stereotypy when combined with low PCP doses but decreased these behaviors at high PCP doses. Caramiphen produced a dose-dependent additive effect on ataxia when combined with all PCP doses. It was concluded that, although caramiphen, like DM, inhibited the locomotor stimulant effects of selected doses of PCP, that interaction appeared to be due to other behaviors (e.g., ataxia/stereotypy) elicited by caramiphen combined with high doses of PCP. This study underscored the importance of using full dose ranges of PCP when attempting to antagonize its behavioral effects with other drugs. JF - Pharmacology, biochemistry, and behavior AU - Székely, J I AU - Sharpe, L G AU - Katz, J L AD - Psychobiology Section, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 709 EP - 713 VL - 47 IS - 3 SN - 0091-3057, 0091-3057 KW - Cyclopentanes KW - 0 KW - Parasympatholytics KW - caramiphen KW - 97J7NP0XJY KW - Phencyclidine KW - J1DOI7UV76 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Ataxia -- chemically induced KW - Dose-Response Relationship, Drug KW - Stereotyped Behavior -- drug effects KW - Motor Activity -- drug effects KW - Male KW - Behavior, Animal -- drug effects KW - Cyclopentanes -- pharmacology KW - Parasympatholytics -- pharmacology KW - Phencyclidine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76546005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology%2C+biochemistry%2C+and+behavior&rft.atitle=Effects+of+caramiphen+and+phencyclidine+alone+and+in+combination+on+behavior+in+the+rat.&rft.au=Sz%C3%A9kely%2C+J+I%3BSharpe%2C+L+G%3BKatz%2C+J+L&rft.aulast=Sz%C3%A9kely&rft.aufirst=J&rft.date=1994-03-01&rft.volume=47&rft.issue=3&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=Pharmacology%2C+biochemistry%2C+and+behavior&rft.issn=00913057&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-11 N1 - Date created - 1994-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - "Lipomatous" lesions of unknown cellular origin in the liver of B6C3F1 mice. AN - 76532567; 8203079 AB - The gross, microscopic, and ultrastructural features of lipomatous lesions in the liver of B6C3F1 mice are described. The cases were selected from a database of 45,406 male and 45,674 female mice used as treated, control, or vehicle-control animals in the National Cancer Institute's Bioassays or the National Toxicology Program's 2-year carcinogenicity studies. Thirteen hepatic lesions identified from cases within the database were re-evaluated microscopically and selected for further study. These lesions were present in ten males and three females that were between 85 and 113 weeks of age at the time of death. Grossly, the liver lesions were described as white to yellow or red to brown nodules/masses or foci that ranged from 2.0 to 25 mm in diameter. The lesions commonly involved the median and left lateral hepatic lobes. Microscopically, many of the lesions closely resembled lipomas described in the liver of human beings, and they consisted of nonencapsulated mature adipose-like tissue with irregular margins. The majority of the cells that comprised the lipomatous lesions were signet-ring shaped. These cells were positive for lipid as evidenced with oil red-O. The lipid droplets were also present within the hepatocytes that comprised the hepatic plates trapped within or surrounding many of the lipomatous lesions. At the margins of many of the lesions there were spindle-shaped cells that contained small intracytoplasmic lipid vacuoles. These cells were often within a stromal matrix that had focal areas of collagen and mucopolysaccharides, as evidenced by weak staining with Masson's trichrome and periodic acid-Schiff's stains, respectively. There was also disruption of the reticulum fibers in many of the lesions, as noted with a Gomori's reticulum stain. Ultrastructurally, cytoplasmic organelles, such as rough endoplasmic reticulum, free ribosomes and small lipid vacuoles, were present in the spindle-shaped cells, whereas signet-ring-shaped cells had few discernible organelles due to peripheral compression of the cytoplasm by single large vacuoles occupying the cytoplasmic space. The spindle-shaped cells were free of lysosomes. Thin collagen fibers were seen in contact with some of the spindle-shaped cells and were located between these cells and adjacent hepatocytes, or endothelial cells lining sinusoidal capillaries. A distinct basal lamina was not associated with spindle- or signet-ring-shaped cells. Similar lipomatous lesions were not found in other visceral organs. The exact cellular origin of the hepatic lesions described here is not known. JF - Veterinary pathology AU - Dixon, D AU - Yoshitomi, K AU - Boorman, G A AU - Maronpot, R R AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 173 EP - 182 VL - 31 IS - 2 SN - 0300-9858, 0300-9858 KW - Index Medicus KW - Animals KW - Mice KW - Male KW - Female KW - Mice, Inbred Strains KW - Liver Neoplasms -- pathology KW - Lipoma -- etiology KW - Liver Neoplasms -- veterinary KW - Lipoma -- pathology KW - Lipoma -- veterinary KW - Liver Neoplasms -- etiology KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76532567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=%22Lipomatous%22+lesions+of+unknown+cellular+origin+in+the+liver+of+B6C3F1+mice.&rft.au=Dixon%2C+D%3BYoshitomi%2C+K%3BBoorman%2C+G+A%3BMaronpot%2C+R+R&rft.aulast=Dixon&rft.aufirst=D&rft.date=1994-03-01&rft.volume=31&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=03009858&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-dependent antifungal activity and nephrotoxicity of amphotericin B colloidal dispersion in experimental pulmonary aspergillosis. AN - 76524493; 8203848 AB - We investigated the safety and efficacy of amphotericin B colloidal dispersion (ABCD) for the treatment of invasive pulmonary aspergillosis in persistently granulocytopenic rabbits. Treatment groups included ABCD in dosages of 1, 5, and 10 mg/kg/day intravenously or conventional desoxycholate amphotericin B (DAmB) at 1 mg/kg/day intravenously. Antifungal activity was directly related to increasing dosage of ABCD as determined by the concentration of Aspergillus fumigatus organisms in lungs and the frequency of hemorrhagic pulmonary lesions. At 5 and 10 mg/kg/day, there was a significant reduction in the tissue burden of A. fumigatus as measured by percent culture-positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day measured by percent culture-positive lobes and CFU per gram of tissue (P < or = 0.001), whereas at 1 mg/kg/day the tissue burden of A. fumigatus was not significantly different from that in untreated controls. Microbiological clearance was significantly greater at 1 mg of DAmB per kg per day than at 1 mg of ABCD per kg per day (P < or = 0.001). There was no difference in microbiological clearance of bronchoalveolar lavage fluid among the treatment groups as measured by CFU per milliliter. As determined by survival, ABCD at 5.0 mg/kg/day was more effective than DAmB at 1.0 mg/kg/day and ABCD at 10 mg/kg/day. ABCD at 10 mg/kg/day was more nephrotoxic than the lower dosages of ABCD and resulted in higher mortality. Impairment of glomerular filtration developed as a direct function increasing the ABCD dosage (r = 0.77; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Antimicrobial agents and chemotherapy AU - Allende, M C AU - Lee, J W AU - Francis, P AU - Garrett, K AU - Dollenberg, H AU - Berenguer, J AU - Lyman, C A AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 518 EP - 522 VL - 38 IS - 3 SN - 0066-4804, 0066-4804 KW - Colloids KW - 0 KW - Amphotericin B KW - 7XU7A7DROE KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Kidney Function Tests KW - Animals KW - Agranulocytosis -- complications KW - Hemorrhage -- pathology KW - Dose-Response Relationship, Drug KW - Heart -- microbiology KW - Bronchoalveolar Lavage Fluid -- microbiology KW - Rabbits KW - Creatinine -- blood KW - Female KW - Lung -- microbiology KW - Immunosuppression KW - Aspergillosis -- microbiology KW - Lung Diseases, Fungal -- microbiology KW - Kidney Diseases -- pathology KW - Lung Diseases, Fungal -- drug therapy KW - Aspergillosis -- drug therapy KW - Amphotericin B -- administration & dosage KW - Amphotericin B -- pharmacology KW - Kidney Diseases -- chemically induced KW - Amphotericin B -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76524493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Dose-dependent+antifungal+activity+and+nephrotoxicity+of+amphotericin+B+colloidal+dispersion+in+experimental+pulmonary+aspergillosis.&rft.au=Allende%2C+M+C%3BLee%2C+J+W%3BFrancis%2C+P%3BGarrett%2C+K%3BDollenberg%2C+H%3BBerenguer%2C+J%3BLyman%2C+C+A%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Allende&rft.aufirst=M&rft.date=1994-03-01&rft.volume=38&rft.issue=3&rft.spage=518&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-05 N1 - Date created - 1994-07-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Med. 1973 Jan;54(1):6-15 [4345262] Drugs. 1992 Jul;44(1):9-35 [1379913] Sabouraudia. 1984;22(2):163-6 [6729660] Ann N Y Acad Sci. 1985;446:390-402 [3860162] Ann Intern Med. 1986 Jul;105(1):130-1 [3717785] Am J Med. 1986 Aug;81(2):249-54 [3090879] Chest. 1988 Nov;94(5):1008-13 [3180851] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Arch Intern Med. 1988 Nov;148(11):2389-94 [3056312] J Infect Dis. 1989 Apr;159(4):717-24 [2926162] Eur J Epidemiol. 1989 Jun;5(2):131-42 [2670602] Antimicrob Agents Chemother. 1990 Mar;34(3):381-4 [2185689] Semin Respir Infect. 1990 Jun;5(2):111-22 [2247706] J Clin Oncol. 1991 Jan;9(1):77-84 [1845875] Rev Infect Dis. 1990 Nov-Dec;12(6):1147-201 [2267490] Antimicrob Agents Chemother. 1991 Apr;35(4):615-21 [2069367] Antimicrob Agents Chemother. 1991 Jun;35(6):1208-13 [1929263] Antimicrob Agents Chemother. 1991 Sep;35(9):1829-33 [1952853] J Antimicrob Chemother. 1991 Oct;28 Suppl B:63-71 [1778893] Antimicrob Agents Chemother. 1992 Feb;36(2):299-307 [1605595] Ann Intern Med. 1984 Mar;100(3):345-51 [6696356] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators. AN - 76509248; 8195316 AB - To elucidate potential mechanisms of the acute lung injury associated with endotoxemia, we evaluated the effect of intravenously administered endotoxin on the ability of alveolar macrophages isolated by bronchoalveolar lavage from normal subjects to produce inflammatory mediators. Within 1 hr of endotoxin (4 ng/kg body weight) administration, all 12 study subjects developed constitutional symptoms and leukopenia, and within 3 hr, low-grade fever. Resolution of symptoms and fever by 6 hr was accompanied by systemic granulocytosis. Although intravenously administered endotoxin appeared to activate a subset of circulating monocytes, it did not alter the bronchoalveolar lavage cell number, phenotype (95% macrophages), or constitutively expressed high levels of surface HLA-DR and O2-. In contrast, intravenous endotoxin primed the alveolar macrophages for enhanced lipopolysaccharide-induced secretion of interleukin-1 (11.8 to 25.8 U/ml; P = 0.04), tumor necrosis factor-alpha (titer, 6.8 to 13.6; P = 0.20), and prostaglandin E2 (38.4 to 116.3 ng/ml; P = 0.035). These results demonstrate that low-dose intravenous endotoxin primes human alveolar macrophages, which are already differentiated in situ, for enhanced secretion of inflammatory mediators. Such mediators may contribute to the pulmonary changes associated with endotoxemia and acute lung injury. JF - Journal of clinical immunology AU - Smith, P D AU - Suffredini, A F AU - Allen, J B AU - Wahl, L M AU - Parrillo, J E AU - Wahl, S M AD - Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 141 EP - 148 VL - 14 IS - 2 SN - 0271-9142, 0271-9142 KW - Cytokines KW - 0 KW - Endotoxins KW - Lipopolysaccharides KW - Superoxides KW - 11062-77-4 KW - endotoxin, Escherichia coli KW - 67924-63-4 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Fever -- chemically induced KW - Superoxides -- metabolism KW - Lipopolysaccharides -- administration & dosage KW - Injections, Intravenous KW - Leukopenia -- chemically induced KW - Humans KW - Adult KW - Escherichia coli KW - Fluorescent Antibody Technique KW - Bronchoalveolar Lavage Fluid -- cytology KW - Male KW - Female KW - Macrophages, Alveolar -- metabolism KW - Dinoprostone -- biosynthesis KW - Cytokines -- biosynthesis KW - Endotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76509248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology&rft.atitle=Endotoxin+administration+to+humans+primes+alveolar+macrophages+for+increased+production+of+inflammatory+mediators.&rft.au=Smith%2C+P+D%3BSuffredini%2C+A+F%3BAllen%2C+J+B%3BWahl%2C+L+M%3BParrillo%2C+J+E%3BWahl%2C+S+M&rft.aulast=Smith&rft.aufirst=P&rft.date=1994-03-01&rft.volume=14&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+immunology&rft.issn=02719142&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-30 N1 - Date created - 1994-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The association between sniffing inhalants and injecting drugs. AN - 76493049; 8187483 AB - There is evidence that the use of inhalants might prove to be a modifiable risk factor for intravenous (IV) drug use, or possibly an important vulnerability marker. However, this evidence has come from studies using samples of convenience, such as a mixture of psychiatric patients, felons, and their relatives. If there is a link between these two different forms of drug-using behaviors, then a statistical association should be found in epidemiologic studies with rigorous sampling procedures--even after statistical adjustment for plausible confounding variables such as sex, age, socioeconomic status, and the use of drugs such as marijuana. To probe this suspected causal association, we analyzed epidemiologic data from the 1990 National Household Survey on Drug Abuse sponsored by the National Institute on Drug Abuse. The population for this survey consisted of all household residents aged 12 years and older in the conterminous United States, with respondents selected by probability sampling. A total of 9,259 respondents completed the confidential self-report interview conducted by trained interviewers; 192 persons reported a history of injecting drugs for nonmedical reasons (e.g., to get high), and 9,067 reported never injecting drugs. As hypothesized, inhalant use was found to be associated with injecting drugs (relative odds [RO] = 11.8). After adjustment for sex, age, race, socioeconomic status, and use of marijuana, inhalant users still were 5.35 times more likely than nonusers to have injected drugs (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) JF - Comprehensive psychiatry AU - Schütz, C G AU - Chilcoat, H D AU - Anthony, J C AD - Etiology Branch, National Institute on Drug Abuse, Baltimore, MD 21224. PY - 1994 SP - 99 EP - 105 VL - 35 IS - 2 SN - 0010-440X, 0010-440X KW - Anesthetics KW - 0 KW - Solvents KW - Vasodilator Agents KW - Index Medicus KW - Socioeconomic Factors KW - Age Factors KW - Sex Factors KW - Humans KW - Adult KW - Child KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Anesthetics -- administration & dosage KW - Solvents -- administration & dosage KW - Vasodilator Agents -- administration & dosage KW - Cannabis KW - Substance Abuse, Intravenous -- epidemiology KW - Administration, Inhalation KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76493049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+association+between+sniffing+inhalants+and+injecting+drugs.&rft.au=Sch%C3%BCtz%2C+C+G%3BChilcoat%2C+H+D%3BAnthony%2C+J+C&rft.aulast=Sch%C3%BCtz&rft.aufirst=C&rft.date=1994-03-01&rft.volume=35&rft.issue=2&rft.spage=99&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 - 1994-06-17 N1 - Date created - 1994-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of inhibition of O6-alkylguanine-DNA alkyltransferase in rats on carcinogenesis by methylnitrosourea and ethylnitrosourea. AN - 76487026; 8188519 AB - Many alkylating agents are potent carcinogens and there is considerable evidence that the formation of O6-alkylguanine in DNA can lead to mutations and the initiation of neoplastic growth. The repair of O6-methyl- or O6-ethylguanine in DNA is known to be brought about by the action of a protein termed O6-alkylguanine-DNA alkyltransferase. In order to investigate the role of this activity in the carcinogenic action of methylnitrosourea and ethylnitrosourea, O6-benzylguanine, a potent inhibitor of the alkyltransferase, was used. Groups of 20 female F344 rats were treated with the nitrosourea (0.2 mmol) by gavage in 10 weekly doses and a parallel group was also treated with 4 mg of O6-benzylguanine, 2 h prior to each dose of the nitrosourea. This dose of O6-benzylguanine was sufficient to reduce the alkyltransferase activity to zero in the liver for at least 8 h but activity had returned to about 60% of normal within 24 h. Animals were maintained until they became moribund, when they were killed, or until death related to tumors. The median week of death in the animals receiving methylnitrosourea was reduced from 60 wk to 52 wk by co-treatment with O6-benzylguanine. There was a smaller reduction from 55 to 50 wk in the rats receiving ethylnitrosourea. The treatment with O6-benzylguanine caused no significant change in the incidence of the principal tumors induced by the alkylnitrosoureas and there were no liver tumors produced by the combined treatments. These results show that the level of inactivation of alkyltransferase produced by this dose of O6-benzylguanine was not sufficient to greatly alter the potent carcinogenic effect of these doses of alkylnitrosoureas in this system. JF - Japanese journal of cancer research : Gann AU - Lijinsky, W AU - Pegg, A E AU - Anver, M R AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 226 EP - 230 VL - 85 IS - 3 SN - 0910-5050, 0910-5050 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - O(6)-benzylguanine KW - 01KC87F8FE KW - Guanine KW - 5Z93L87A1R KW - Methylnitrosourea KW - 684-93-5 KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Liver -- enzymology KW - Female KW - Ethylnitrosourea -- toxicity KW - Neoplasms, Experimental -- chemically induced KW - Methyltransferases -- antagonists & inhibitors KW - Anticarcinogenic Agents -- pharmacology KW - Methylnitrosourea -- toxicity KW - Guanine -- analogs & derivatives KW - Neoplasms, Experimental -- prevention & control KW - Antineoplastic Agents -- pharmacology KW - Guanine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76487026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Effects+of+inhibition+of+O6-alkylguanine-DNA+alkyltransferase+in+rats+on+carcinogenesis+by+methylnitrosourea+and+ethylnitrosourea.&rft.au=Lijinsky%2C+W%3BPegg%2C+A+E%3BAnver%2C+M+R%3BMoschel%2C+R+C&rft.aulast=Lijinsky&rft.aufirst=W&rft.date=1994-03-01&rft.volume=85&rft.issue=3&rft.spage=226&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-21 N1 - Date created - 1994-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Consumption indicators of alcohol dependence. AN - 76476800; 8173504 AB - This Data Note evaluates various dichotomous measures of alcohol consumption as screeners for past-year alcohol dependence. The analysis is based on data from 22,102 current drinkers interviewed in the 1988 US National Health Interview Survey. The consumption indicators include measures of average daily intake, frequency of heavy drinking, usual quantity and frequency of drinking and various combinations of these measures. The measures based on frequency of heavy drinking are the most strongly correlated with dependence, but none of the consumption indicators have the sensitivity or specificity of screeners based on alcohol-related problems. Most of the consumption items considered in this analysis screen for dependence more successfully among men than among women. JF - Addiction (Abingdon, England) AU - Dawson, D A AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 345 EP - 350 VL - 89 IS - 3 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - United States KW - Cross-Sectional Studies KW - Alcohol Withdrawal Delirium -- classification KW - Psychiatric Status Rating Scales KW - Sex Factors KW - Humans KW - Health Surveys KW - Alcohol Drinking -- adverse effects KW - Incidence KW - Alcoholic Beverages -- statistics & numerical data KW - Alcohol Withdrawal Delirium -- diagnosis KW - Alcohol Drinking -- epidemiology KW - Alcohol Withdrawal Delirium -- epidemiology KW - Male KW - Female KW - Mass Screening KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76476800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Consumption+indicators+of+alcohol+dependence.&rft.au=Dawson%2C+D+A&rft.aulast=Dawson&rft.aufirst=D&rft.date=1994-03-01&rft.volume=89&rft.issue=3&rft.spage=345&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 - 1994-06-08 N1 - Date created - 1994-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta A3/A1-crystallin association: role of the N-terminal arm. AN - 76475972; 8177894 AB - The beta- and gamma-crystallins of the lens form a protein superfamily, the beta gamma-crystallins and have highly conserved two-domain core structures. Whereas gamma-crystallins exist as monomers, the beta-crystallins associate into large aggregates. The N-terminal extensions to the core domains of beta-crystallins are postulated to be essential for their aggregation characteristics. To test this hypothesis, we compared the aggregation properties of a recombinant mouse beta A3/A1-crystallin without its N-terminal extension (r beta A3tr) to a normal recombinant mouse beta A3/A1-crystallin (r beta A3). The identity of the baculo-virus system-expressed recombinant crystallins was confirmed by gel electrophoresis, immunoblots and N-terminal sequence analysis. Circular dichroism measurements indicate that the recombinant crystallins have mostly beta-sheet conformation, similar to normal beta-crystallins. The normal r beta A3 migrates on gel filtration chromatography as a homodimer, whereas the r beta A3tr migrates mostly as a monomer. After relocating the recombinant crystallins with mouse lens soluble extract, r beta A3 migrated with the dimeric beta L2 fractions and to a lesser extent with tetrameric beta L1 fractions. The reassociated r beta A3tr migrated with the trailing edge of the beta L 2 fractions (40 kDa). These results suggest that the N-terminal arm of beta A3/A1-crystallin facilitates dimer formation and is necessary for higher-order associations. JF - Protein engineering AU - Hope, J N AU - Chen, H C AU - Hejtmancik, J F AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 445 EP - 451 VL - 7 IS - 3 SN - 0269-2139, 0269-2139 KW - Crystallins KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - Index Medicus KW - Immunoblotting KW - Baculoviridae -- genetics KW - Animals KW - Protein Structure, Secondary KW - Transfection KW - Molecular Sequence Data KW - Gene Expression KW - Circular Dichroism KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- chemistry KW - Moths KW - Mutagenesis, Insertional KW - Molecular Weight KW - Protein Conformation KW - Crystallins -- chemistry KW - Crystallins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76475972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Beta+A3%2FA1-crystallin+association%3A+role+of+the+N-terminal+arm.&rft.au=Hope%2C+J+N%3BChen%2C+H+C%3BHejtmancik%2C+J+F&rft.aulast=Hope&rft.aufirst=J&rft.date=1994-03-01&rft.volume=7&rft.issue=3&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Associations between bladder cancer risk factors and tumor stage and grade at diagnosis. AN - 76470392; 8172997 AB - Using data on 1,860 bladder cancer cases and 3,934 population-based controls from the National Bladder Cancer Study, we examined associations between suspected bladder cancer risk factors and tumor stage and grade. Employment in a high-risk occupation was associated with the entire clinical spectrum of bladder cancer rather than a particular tumor stage or grade. For example, relative risks (RR) were similar for noninvasive and invasive disease (1.5 and 1.6, respectively). Cigarette smoking also increased risk of the entire clinical spectrum of bladder cancer, but the more advanced the stage, the stronger the effect. For example, relative risks of noninvasive and invasive bladder cancer for current heavy smokers were 3.0 and 5.2, respectively. Cigarette smoking was associated with higher risk of low-grade than high-grade tumors, once stage of disease was taken into account. Compared with whites, nonwhites were at a lower risk of noninvasive bladder cancer (RR = 0.4) but at similar risk of invasive bladder cancer (RR = 1.1), a pattern indicating racial differences in health practices related to bladder cancer detection. History of urinary tract infections and bladder stones was associated with increasing relative risks for advanced tumor stage. Heavy artificial sweetener use was associated with higher-grade, poorly differentiated tumors. Coffee consumption and family history of bladder cancer were not consistently associated with tumor stage or grade. Overall, different clinical presentations of bladder cancer share most suspected bladder cancer risk factors, including employment in a high-risk occupation and cigarette smoking. JF - Epidemiology (Cambridge, Mass.) AU - Sturgeon, S R AU - Hartge, P AU - Silverman, D T AU - Kantor, A F AU - Linehan, W M AU - Lynch, C AU - Hoover, R N AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 218 EP - 225 VL - 5 IS - 2 SN - 1044-3983, 1044-3983 KW - Coffee KW - 0 KW - Saccharin KW - FST467XS7D KW - Index Medicus KW - Educational Status KW - Neoplasm Staging KW - Humans KW - Continental Population Groups KW - Smoking -- adverse effects KW - Occupational Diseases -- complications KW - Aged KW - Urinary Bladder Calculi -- complications KW - Aged, 80 and over KW - Urinary Tract Infections -- complications KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Saccharin -- adverse effects KW - United States -- epidemiology KW - Female KW - Male KW - Urinary Bladder Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- etiology KW - Urinary Bladder Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76470392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+cholera+toxin+by+ADP-ribosylation+factors%3A+20-kDa+guanine+nucleotide-binding+proteins.&rft.au=Moss%2C+J%3BHaun%2C+R+S%3BTsai%2C+S+C%3BWelsh%2C+C+F%3BLee%2C+F+J%3BPrice%2C+S+R%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1994-01-01&rft.volume=237&rft.issue=&rft.spage=44&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 - 1994-06-06 N1 - Date created - 1994-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavior analysis and the search for the origins of hypertension. AN - 76468372; 8169574 AB - Hypertension is a disorder of sodium regulation that develops over time in a context of the interactions of the individual with the environment. Experimental hypertension can be induced in laboratory animals and normotensive humans via increases in sodium intake under conditions of aversive behavioral control. Readiness for avoidance contingencies includes a breathing pattern characterized by subnormal rate and normal tidal volume. Studies with humans have shown that this inhibitory breathing pattern is associated with increased plasma acidity, increased renal sodium reabsorption, increased secretion of digitalis-like hormones that inhibit sodium-pump activity, and increased vasoconstriction and blood pressure. Behavioral research is needed that defines the necessary and sufficient conditions for inhibitory breathing and its role in the development of hypertension. JF - Journal of the experimental analysis of behavior AU - Anderson, D E AD - National Institute on Aging, Baltimore, Maryland. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 255 EP - 261 VL - 61 IS - 2 SN - 0022-5002, 0022-5002 KW - Sodium Chloride, Dietary KW - 0 KW - Index Medicus KW - Animals KW - Conditioning (Psychology) KW - Respiration KW - Dogs KW - Avoidance Learning KW - Sodium Chloride, Dietary -- adverse effects KW - Sodium Chloride, Dietary -- metabolism KW - Hypertension -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76468372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+experimental+analysis+of+behavior&rft.atitle=Behavior+analysis+and+the+search+for+the+origins+of+hypertension.&rft.au=Anderson%2C+D+E&rft.aulast=Anderson&rft.aufirst=D&rft.date=1994-03-01&rft.volume=61&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+experimental+analysis+of+behavior&rft.issn=00225002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Psychosom Med. 1967 Sep-Oct;29(5):408-32 [6059915] Psychophysiology. 1993 Mar;30(2):131-7 [8434076] Am J Physiol. 1969 Jul;217(1):24-9 [4977636] Psychosom Med. 1969 Jul-Aug;31(4):300-9 [4980367] Am J Epidemiol. 1969 Sep;90(3):171-200 [4899564] Science. 1971 May 7;172(3983):595-7 [5555083] Johns Hopkins Med J. 1973 Jan;132(1):16-43 [4682661] J Appl Physiol. 1973 May;34(5):650-4 [4703740] Science. 1973 Oct 12;182(4108):175-7 [4199735] Br J Pharmacol. 1978 Sep;64(1):129-36 [698476] Circ Res. 1980 May;46(5):619-24 [7363411] Am Rev Respir Dis. 1980 Dec;122(6):867-71 [7458060] Clin Sci (Lond). 1981 Nov;61(5):511-9 [7285500] Physiol Rev. 1982 Apr;62(2):347-504 [6461865] Hypertension. 1983 Nov-Dec;5(6):814-20 [6654449] Circ Res. 1985 Jun;56(6):773-88 [2988813] Hypertension. 1985 Jul-Aug;7(4):628-40 [4007994] Physiol Rev. 1985 Jul;65(3):658-759 [2989958] Thorax. 1985 May;40(5):364-70 [4023990] J Cardiovasc Pharmacol. 1986;8 Suppl 5:S23-30 [2427879] Clin Exp Hypertens A. 1987;9(1):125-40 [3581484] Hypertension. 1988 Oct;12(4):457-61 [3169953] Clin Exp Hypertens A. 1988;10 Suppl 1:413-22 [3072127] Hypertension. 1990 Oct;16(4):407-13 [2210808] Hypertension. 1990 Dec;16(6):725-30 [2246039] Hypertension. 1991 Apr;17(4 Suppl):III2-6 [1849502] J Hypertens. 1991 Jun;9(6):499-503 [1653288] J Hypertens. 1991 Oct;9(10):969-75 [1658140] Integr Physiol Behav Sci. 1991 Oct-Dec;26(4):269-81 [1760376] Physiol Rev. 1992 Jan;72(1):231-300 [1731371] Psychosom Med. 1992 Mar-Apr;54(2):231-9 [1565758] Psychophysiology. 1992 Sep;29(5):551-7 [1410184] J Behav Med. 1992 Dec;15(6):573-88 [1484381] Psychosom Med. 1968 Sep-Oct;30(5):Suppl:710-20 [4303378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation, physical activity, and risk of prostate cancer in Shanghai, People's Republic of China. AN - 76462032; 8167260 AB - Based on occupational data for all (n = 264) prostate cancer cases diagnosed during 1980-84 in urban Shanghai and on employment information from the 1982 census, standardized incidence ratios (SIR) were calculated for occupational groups classified by job type and physical activity level. White-collar workers (professionals, government officials, clerical workers, salespersons) had an elevated incidence of prostate cancer, although the excesses were not significant. In addition, when jobs were classified by time spent sitting or energy expenditure, men employed in occupations with low physical activity levels tended to have moderately elevated risks of prostate cancer. Findings from this study in an area with one of the world's lowest incidence rates of prostate cancer add to the accumulating evidence that jobs with a low level of physical activity are associated with an increased prostate-cancer risk. JF - Cancer causes & control : CCC AU - Hsing, A W AU - McLaughlin, J K AU - Zheng, W AU - Gao, Y T AU - Blot, W J AD - National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 136 EP - 140 VL - 5 IS - 2 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Registries KW - Occupational Exposure KW - Risk Factors KW - Humans KW - China -- epidemiology KW - Adult KW - Incidence KW - Employment KW - Posture KW - Energy Metabolism KW - Male KW - Prostatic Neoplasms -- epidemiology KW - Motor Activity KW - Occupations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76462032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Occupation%2C+physical+activity%2C+and+risk+of+prostate+cancer+in+Shanghai%2C+People%27s+Republic+of+China.&rft.au=Hsing%2C+A+W%3BMcLaughlin%2C+J+K%3BZheng%2C+W%3BGao%2C+Y+T%3BBlot%2C+W+J&rft.aulast=Hsing&rft.aufirst=A&rft.date=1994-03-01&rft.volume=5&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radon exposure in residences and lung cancer among women: combined analysis of three studies. AN - 76458870; 8167258 AB - Lung cancer risk in relation to indoor radon was examined in three case-control studies in Stockholm (Sweden), New Jersey (United States), and Shenyang (People's Republic of China). Year-long measurements of radon gas were made in current and past homes of 966 women who developed lung cancer and of 1,158 control women, included in the combined analysis. Nearly 14 percent of the participants were estimated to have a time-weighted, mean, radon concentration in their homes of more than 4 pCi/l (150 Bq/m3) during the period from five to 35 years prior to the date of lung cancer diagnosis (or comparable date for controls). There was a tendency for risk to increase with increasing levels of radon in NJ and Stockholm, but the trends for individual studies and overall were not statistically significant. The estimates of the excess relative risk for indoor exposure per pCi/l were 0.18 (95 percent [CI] = -0.04-0.70) in NJ, 0.06 (CI = -0.05-0.34) in Stockholm, and -0.02 (CI = -infinity-0.03) for Shenyang; these estimates did not differ significantly from each other. The overall excess RR per pCi/l was 0.00 (CI = -0.05-0.07); the confidence limits were sufficiently broad, however, that the overall estimate was still compatible with extrapolations of risks from miners. Cigarette smoking was the predominant cause of lung cancer with the RR significantly elevated in all studies. Within smoking categories, the trend in risk with increasing mean radon concentration was inconsistent. Analyses of data from several studies are complicated by the possibility that there may exist important differences in study bases which might affect results, and which may be controlled only partially through adjustment procedures. Future efforts to combine various residential studies will need to be attentive to the intrinsic limitations of studies to detect low levels of risk as well as the unique uncertainties associated with estimating, accurately, cumulative exposure to indoor radon. JF - Cancer causes & control : CCC AU - Lubin, J H AU - Liang, Z AU - Hrubec, Z AU - Pershagen, G AU - Schoenberg, J B AU - Blot, W J AU - Klotz, J B AU - Xu, Z Y AU - Boice, J D AD - Epidemiology and Biostatistics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 114 EP - 128 VL - 5 IS - 2 SN - 0957-5243, 0957-5243 KW - Air Pollutants, Radioactive KW - 0 KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - Radiation Dosage KW - Humans KW - Aged KW - Smoking -- epidemiology KW - Air Pollution, Indoor -- analysis KW - New Jersey -- epidemiology KW - China -- epidemiology KW - Risk Factors KW - Adult KW - Air Pollutants, Radioactive -- analysis KW - Case-Control Studies KW - Sweden -- epidemiology KW - Middle Aged KW - Female KW - Lung Neoplasms -- epidemiology KW - Housing KW - Radon -- analysis KW - Environmental Exposure KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76458870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Radon+exposure+in+residences+and+lung+cancer+among+women%3A+combined+analysis+of+three+studies.&rft.au=Lubin%2C+J+H%3BLiang%2C+Z%3BHrubec%2C+Z%3BPershagen%2C+G%3BSchoenberg%2C+J+B%3BBlot%2C+W+J%3BKlotz%2C+J+B%3BXu%2C+Z+Y%3BBoice%2C+J+D&rft.aulast=Lubin&rft.aufirst=J&rft.date=1994-03-01&rft.volume=5&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose. AN - 76449583; 8167264 AB - Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the bombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor--age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births--conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early age following exposure may be protective against radiation-related risk. JF - Cancer causes & control : CCC AU - Land, C E AU - Hayakawa, N AU - Machado, S G AU - Yamada, Y AU - Pike, M C AU - Akiba, S AU - Tokunaga, M AD - National Cancer Institute, Bethesda, MD. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 167 EP - 176 VL - 5 IS - 2 SN - 0957-5243, 0957-5243 KW - Index Medicus KW - Parity KW - Age Factors KW - Premenopause KW - Humans KW - Survival KW - Aged KW - Dose-Response Relationship, Radiation KW - Lactation KW - Japan -- epidemiology KW - Postmenopause KW - Risk Factors KW - Maternal Age KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Interviews as Topic KW - Middle Aged KW - Female KW - Radiation Dosage KW - Nuclear Warfare KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76449583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=A+case-control+interview+study+of+breast+cancer+among+Japanese+A-bomb+survivors.+II.+Interactions+with+radiation+dose.&rft.au=Land%2C+C+E%3BHayakawa%2C+N%3BMachado%2C+S+G%3BYamada%2C+Y%3BPike%2C+M+C%3BAkiba%2C+S%3BTokunaga%2C+M&rft.aulast=Land&rft.aufirst=C&rft.date=1994-03-01&rft.volume=5&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses. AN - 76440051; 8155326 AB - In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a protein that couples receptor tyrosine kinases to p21ras. Complex formation between Trk and SHC, SHC tyrosine phosphorylation, and association of SHC with Grb2 were mediated by autophosphorylation at Y490 in Trk [sequence: see text]. To determine the role of SHC and other Trk substrates in NGF signaling, Trk receptors with mutations in Y490 and Y785 (the PLC-gamma 1 association site) were introduced into PC12nnr5 cells. NGF treatment of PC12nnr5 cells expressing Trk with mutations in either substrate-binding site resulted in normal neurite outgrowth and Erk1 activity and tyrosine phosphorylation. However, PC12nnr5 cells expressing Trk with mutations at both sites failed to stably extend neurites and efficiently induce Erk1 activity and tyrosine phosphorylation in response to NGF. We postulate that Trk receptors can activate Erk1 by either SHC- or PLC-gamma 1-dependent signaling pathways. These results suggest a model whereby Trk receptors utilize at least partially redundant signal transduction pathways to mediate NGF responses. JF - Neuron AU - Stephens, R M AU - Loeb, D M AU - Copeland, T D AU - Pawson, T AU - Greene, L A AU - Kaplan, D R AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 691 EP - 705 VL - 12 IS - 3 SN - 0896-6273, 0896-6273 KW - Nerve Growth Factors KW - 0 KW - Proteins KW - Tyrosine KW - 42HK56048U KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Phosphorylation KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Tyrosine -- metabolism KW - PC12 Cells KW - Cricetinae KW - Nerve Growth Factors -- metabolism KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Signal Transduction KW - Proteins -- physiology KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76440051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=Trk+receptors+use+redundant+signal+transduction+pathways+involving+SHC+and+PLC-gamma+1+to+mediate+NGF+responses.&rft.au=Stephens%2C+R+M%3BLoeb%2C+D+M%3BCopeland%2C+T+D%3BPawson%2C+T%3BGreene%2C+L+A%3BKaplan%2C+D+R&rft.aulast=Stephens&rft.aufirst=R&rft.date=1994-03-01&rft.volume=12&rft.issue=3&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-13 N1 - Date created - 1994-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Focal transgene expression associated with papilloma development in v-Ha-ras-transgenic TG.AC mice. AN - 76419760; 7908201 AB - The homozygous transgenic mouse line TG.AC contains a v-Ha-ras transgene and rapidly develops epidermal papillomas in response to either wounding or treatment with tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). The transgenic v-Ha-ras protein product was detected in all papillomas removed from TPA-treated TG.AC mice but not in vehicle- or TPA-treated TG.AC skin without tumors. In situ hybridization demonstrated that focal expression of the transgene was limited to regions of papilloma development and further localized the expression of the transgene message to the epidermal component of the papillomas, with the strongest signal in the basal epidermoid cells. Cellular proliferation, as indicated by immunohistochemical staining for proliferating-cell nuclear antigen (PCNA), was similarly localized primarily to basal epidermoid cells and, to a lesser extent, stratum spinosum cells in all papillomas analyzed. Cells that stained positively for PCNA were much more common in the papillomas than in the surrounding, normal-appearing skin. The focal nature of papilloma development was also evidenced by protein kinase C activity and hyperplasia after TPA treatment. As early as 18 d after the start of TPA treatment, focal hyperplasias associated with the follicular epidermis were observed in TG.AC but not nontransgenic FVB/N skin; these hyperplasias were assumed to be the precursors of the epidermal papillomas. To explain the development of transgene-expressing tumors from apparently transgene-negative, normal-appearing skin, we hypothesize that the papillomas arise from the clonal expansion of focal areas of epidermal cells that overexpress the transgene. We also propose that the TG.AC line is an excellent model for studying very early events in papillomagenesis. JF - Molecular carcinogenesis AU - Hansen, L A AU - Tennant, R AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park 27709. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 143 EP - 154 VL - 9 IS - 3 SN - 0899-1987, 0899-1987 KW - ras KW - Nuclear Proteins KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Protein Kinase C KW - EC 2.7.11.13 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Hyperplasia -- pathology KW - Animals KW - Hyperplasia -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Epidermis -- enzymology KW - Protein Kinase C -- physiology KW - Nuclear Proteins -- metabolism KW - Mice, Transgenic KW - Cell Division KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Papilloma -- pathology KW - Skin Neoplasms -- pathology KW - Papilloma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76419760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Focal+transgene+expression+associated+with+papilloma+development+in+v-Ha-ras-transgenic+TG.AC+mice.&rft.au=Hansen%2C+L+A%3BTennant%2C+R&rft.aulast=Hansen&rft.aufirst=L&rft.date=1994-03-01&rft.volume=9&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-04 N1 - Date created - 1994-05-04 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ras N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection from lethal irradiation by the combination of stem cell factor and tempol. AN - 76417928; 7511822 AB - Cytokines that stimulate growth and differentiation of hematopoietic precursor cells have been used as protectors in vivo against ionizing radiation. Recently, we have shown that the nitroxide tempol is also an effective radiation protector in vivo. The purpose of the present study was to determine if the combination of tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation protection in C57 mice compared with the protection afforded by either agent alone. Mice were exposed to whole-body irradiation and assessed for survival at 30 days after irradiation. No control mice survived doses of more than 9 Gy. Treatment of mice before and after radiation with SCF alone (100 micrograms/kg at -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a radioprotector at 9 Gy (55% survival). The combination of SCF and tempol increased the survival of mice exposed to radiation doses up to 11 Gy (32% survival for the combination vs 4% for SCF alone and 0% for tempol alone; P < 0.001 for the combination vs either agent alone). Lower doses of SCF alone (1 microgram/kg) or tempol alone (275 mg/kg) did not protect mice from radiation. However, the combination of these reduced doses of SCF and tempol protected mice from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly or together were well tolerated by the animals. These data show that SCF and tempol are radiation protectors and that their radioprotective effects are more than additive when the agents are given together. JF - Radiation research AU - Liebmann, J AU - DeLuca, A M AU - Epstein, A AU - Steinberg, S M AU - Morstyn, G AU - Mitchell, J B AD - Radiobiology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 400 EP - 404 VL - 137 IS - 3 SN - 0033-7587, 0033-7587 KW - Cyclic N-Oxides KW - 0 KW - Hematopoietic Cell Growth Factors KW - Radiation-Protective Agents KW - Spin Labels KW - Stem Cell Factor KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Space life sciences KW - Animals KW - Gamma Rays KW - Mice, Inbred C57BL KW - Mice KW - Drug Synergism KW - Female KW - Cyclic N-Oxides -- pharmacology KW - Hematopoietic Cell Growth Factors -- pharmacology KW - Radiation-Protective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76417928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Protection+from+lethal+irradiation+by+the+combination+of+stem+cell+factor+and+tempol.&rft.au=Liebmann%2C+J%3BDeLuca%2C+A+M%3BEpstein%2C+A%3BSteinberg%2C+S+M%3BMorstyn%2C+G%3BMitchell%2C+J+B&rft.aulast=Liebmann&rft.aufirst=J&rft.date=1994-03-01&rft.volume=137&rft.issue=3&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Type II pneumocytes revisited: intracellular membranous systems, surface characteristics, and lamellar body secretion. AN - 76416954; 8145534 AB - Type II pneumocytes, the producers of pulmonary surfactant, have been extensively studied during the last 20 years because of the importance of their metabolism in lung function and integrity. The ultrastructural studies of the 1970s and 1980s have shown that these cells present unique elements. In this work, we used thin-section, freeze-fracture, and fracture-flip electron microscopy techniques to obtain new information on the ultrastructural peculiarities of isolated rat type II pneumocytes, focusing our study on the intracellular membranous systems and their interrelationships and the microanatomy of their plasma membrane during secretory process. In thin-sections of pneumocytes postfixed with osmium tetroxide and potassium ferricyanide, we observed that lamellar bodies (LBs) are usually connected to membranes of the endoplasmic reticulum, and seem to emerge and grow from them. Unusual connections between the endoplasmic reticulum and mitochondria were detected, as well as numerous "bar-like structures" (BLSs), most of them in the early stages of development and often generating from the nuclear membrane. Membranes of the smooth endoplasmic reticulum that closely follow the outlines of mitochondria also appear to be the origin of some BLSs. Possible transition forms, BLS--LB, were also detected, although they were rare. New images of the surface of the pneumocytes and its changes during LB secretion showed a segregation and clearing of membrane particles at the areas of LB extrusion. We propose that LBs can originate directly from membranes of the endoplasmic reticulum or from BLSs. An indirect participation of mitochondria appears possible. The plasma membrane of pneumocytes displays structural changes associated with the secretion of LBs as visualized by a redistribution of intramembrane and surface particles. JF - Laboratory investigation; a journal of technical methods and pathology AU - Risco, C AU - Romero, C AU - Bosch, M A AU - Pinto da Silva, P AD - Biological Carcinogenesis and Development Program, NCI-Frederick Cancer Research and Development Center, Maryland. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 407 EP - 417 VL - 70 IS - 3 SN - 0023-6837, 0023-6837 KW - Pulmonary Surfactants KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Freeze Fracturing KW - Mitochondria -- ultrastructure KW - Endoplasmic Reticulum -- physiology KW - Rats, Wistar KW - Cell Membrane -- ultrastructure KW - Endoplasmic Reticulum -- ultrastructure KW - Male KW - Nuclear Envelope -- ultrastructure KW - Lung -- secretion KW - Lung -- cytology KW - Lung -- ultrastructure KW - Intracellular Membranes -- physiology KW - Pulmonary Surfactants -- secretion KW - Inclusion Bodies -- physiology KW - Intracellular Membranes -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76416954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Type+II+pneumocytes+revisited%3A+intracellular+membranous+systems%2C+surface+characteristics%2C+and+lamellar+body+secretion.&rft.au=Risco%2C+C%3BRomero%2C+C%3BBosch%2C+M+A%3BPinto+da+Silva%2C+P&rft.aulast=Risco&rft.aufirst=C&rft.date=1994-03-01&rft.volume=70&rft.issue=3&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-05 N1 - Date created - 1994-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects on the menstrual cycle of in utero exposure to diethylstilbestrol. AN - 76407801; 8141188 AB - The purpose of this study was to determine the effects of in utero exposure to diethylstilbestrol on the menstrual cycle. This was a prospective cohort study of 198 diethylstilbestrol-exposed women and 162 unexposed controls, recruited from women whose mothers participated in a randomized trial of diethylstilbestrol in pregnancy at the Chicago Lying-In Hospital from 1950 to 1952. Women with severe menstrual abnormality were excluded from the study. Diethylstilbestrol exposure was associated with a statistically significantly decreased duration of menstrual bleeding of approximately one half day and a lower average daily bleeding score (self-reported). We found no evidence for effects of diethylstilbestrol exposure on cycle length or variability of cycle length. Exposure was not related to symptoms of dysmenorrhea. The decreased duration and amount of menstrual bleeding among diethylstilbestrol-exposed women could be due to direct effects on the uterus. The lack of an effect on cycle length and variability appears to indicate that endocrine function is not grossly disturbed in those women studied. JF - American journal of obstetrics and gynecology AU - Hornsby, P P AU - Wilcox, A J AU - Weinberg, C R AU - Herbst, A L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 709 EP - 715 VL - 170 IS - 3 SN - 0002-9378, 0002-9378 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Menstruation Disturbances -- chemically induced KW - Female KW - Pregnancy KW - Diethylstilbestrol -- adverse effects KW - Menstrual Cycle -- drug effects KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76407801?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=Effects+on+the+menstrual+cycle+of+in+utero+exposure+to+diethylstilbestrol.&rft.au=Hornsby%2C+P+P%3BWilcox%2C+A+J%3BWeinberg%2C+C+R%3BHerbst%2C+A+L&rft.aulast=Hornsby&rft.aufirst=P&rft.date=1994-03-01&rft.volume=170&rft.issue=3&rft.spage=709&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids. AN - 76398105; 8132748 AB - High levels of immunoreactive cyclooxygenase (Cox; prostaglandin H synthase) are present in synovia from patients with rheumatoid arthritis (RA). We now show that the recently identified inducible isoform of Cox, Cox-2, is expressed in synovia from patients with RA. To further explore modulation of the Cox isoforms in RA synovial tissues, we examined the expression and modulation of Cox-1 and -2 in rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Immunoprecipitation of in vitro labeled proteins and Western blot analysis demonstrated the presence of both Cox-1 and -2 under basal conditions in freshly explanted rheumatoid synovial tissues. De novo synthesis of Cox-2 polypeptide was enhanced by IL-1 beta or PMA, and dramatically suppressed by dexamethasone (dex). Cox-1 expression, under the same conditions, showed only minor variation. Since mRNA for Cox-2 is highly unstable, we examined the regulation of Cox-2 transcripts in cultured rheumatoid synoviocytes. Under basal conditions both Cox-1 and -2 mRNAs were present at low levels, but Cox-2 mRNA was markedly increased by treatment with IL-1 beta or PMA. dex markedly suppressed the induction of Cox-2 mRNA. In sharp contrast, Cox-1 transcripts were not modulated by IL-1 beta or dex. These data suggest that modulation of Cox-2 expression by IL-1 beta and corticosteroids may be an important component of the inflammatory process in synovial tissues from patients with RA. JF - The Journal of clinical investigation AU - Crofford, L J AU - Wilder, R L AU - Ristimäki, A P AU - Sano, H AU - Remmers, E F AU - Epps, H R AU - Hla, T AD - Inflammatory Joint Diseases Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 1095 EP - 1101 VL - 93 IS - 3 SN - 0021-9738, 0021-9738 KW - Adrenal Cortex Hormones KW - 0 KW - Interleukin-1 KW - Isoenzymes KW - RNA, Messenger KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Cells, Cultured KW - Humans KW - RNA, Messenger -- analysis KW - Precipitin Tests KW - Immunohistochemistry KW - Isoenzymes -- analysis KW - Interleukin-1 -- pharmacology KW - Adrenal Cortex Hormones -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- immunology KW - Synovial Membrane -- enzymology KW - Arthritis, Rheumatoid -- enzymology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76398105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Cyclooxygenase-1+and+-2+expression+in+rheumatoid+synovial+tissues.+Effects+of+interleukin-1+beta%2C+phorbol+ester%2C+and+corticosteroids.&rft.au=Crofford%2C+L+J%3BWilder%2C+R+L%3BRistim%C3%A4ki%2C+A+P%3BSano%2C+H%3BRemmers%2C+E+F%3BEpps%2C+H+R%3BHla%2C+T&rft.aulast=Crofford&rft.aufirst=L&rft.date=1994-03-01&rft.volume=93&rft.issue=3&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-21 N1 - Date created - 1994-04-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Immunol. 1984;2:335-57 [6100476] Ann Rheum Dis. 1983 Feb;42(1):36-9 [6402992] Science. 1987 Oct 23;238(4826):522-4 [2821621] Science. 1987 Oct 23;238(4826):524-6 [2443979] Arthritis Rheum. 1988 Mar;31(3):315-24 [3358796] Lancet. 1988 Sep 24;2(8613):706-9 [2901567] Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459-63 [2845968] Arthritis Rheum. 1989 Jan;32(1):1-9 [2643434] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2374-8 [2538840] J Biol Chem. 1989 Oct 15;264(29):17379-83 [2507542] Biochem Biophys Res Commun. 1989 Nov 15;164(3):1358-65 [2480117] Endocrinology. 1990 Feb;126(2):1223-8 [2153522] Biochim Biophys Acta. 1990 Mar 9;1051(3):310-8 [2310781] J Rheumatol. 1990 Jan;17(1):24-9 [2313668] N Engl J Med. 1990 May 3;322(18):1277-89 [2271017] J Biol Chem. 1990 Jul 5;265(19):10805-8 [1694171] Biochem Pharmacol. 1990 Sep 15;40(6):1307-16 [2119586] J Biol Chem. 1990 Oct 5;265(28):16737-40 [2120205] J Clin Invest. 1990 Oct;86(4):1375-9 [2120289] J Exp Med. 1991 Mar 1;173(3):569-74 [1997647] Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2692-6 [1849272] Biochim Biophys Acta. 1991 May 8;1083(2):121-34 [1903657] J Biol Chem. 1991 Jul 15;266(20):12866-72 [1712772] J Biol Chem. 1991 Dec 5;266(34):23261-7 [1744122] J Clin Invest. 1992 Jan;89(1):97-108 [1729286] Proc Natl Acad Sci U S A. 1992 May 1;89(9):3917-21 [1570314] Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4888-92 [1594589] J Endocrinol. 1992 Jun;133(3):349-55 [1319453] J Rheumatol. 1992 Nov;19(11):1692-6 [1337108] J Biol Chem. 1993 Mar 25;268(9):6610-4 [8454631] Arch Biochem Biophys. 1993 Mar;301(2):439-44 [8460952] Arthritis Rheum. 1992 Jul;35(7):740-4 [1622411] J Biol Chem. 1992 Jul 25;267(21):14547-50 [1634505] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8 [1380156] Biochem Biophys Res Commun. 1992 Sep 16;187(2):1123-7 [1382414] Cell Growth Differ. 1992 Jul;3(7):443-50 [1419907] Arthritis Rheum. 1992 Nov;35(11):1281-8 [1445443] J Biol Chem. 1992 Dec 25;267(36):25934-8 [1464605] Arthritis Rheum. 1974 Sep-Oct;17(5):537-51 [4413366] J Clin Invest. 1975 Nov;56(5):1181-8 [1184744] Proc Natl Acad Sci U S A. 1976 Mar;73(3):945-9 [176663] Proc Natl Acad Sci U S A. 1981 Apr;78(4):2474-7 [6264478] Cell. 1986 Aug 29;46(5):659-67 [3488815] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Subchronic dietary exposure to Aroclor 1254 in rats: accumulation of PCBs in liver, blood, and adipose tissue and its relationship to induction of various hepatic drug-metabolizing enzymes. AN - 76396122; 7510429 AB - Female F344/NCr rats were exposed continuously (7-84 days) or discontinuously (7 days exposure/21 days control diet or 28 days exposure/56 days control diet) to various dietary concentrations (1-100 ppm) of Aroclor 1254. There were dose- and time-dependent increases in PCB levels in liver, blood, and adipose tissue. Following removal of the rats from diet containing Aroclor 1254, there was a relatively rapid decrease in PCB levels, particularly in rats exposed to higher concentrations of Aroclor 1254. In parallel with the alterations in PCB levels observed, the rats showed striking dose- and time-dependent increases in hepatic levels of CYP1A1 and CYP1A2, as determined by various methods [RNA analysis, immunochemical detection, or measurement of the O-dealkylation of methoxyresorufin (CYP1A2) or ethoxyresorufin (CYP1A1)]. In rats removed from the Aroclor 1254 diet, catalytic activity for CYP1A1 as well as RNA levels for both CYP1A1 and CYP1A2 rapidly diminished. In contrast to the high levels of induction of CYP1A1 and CYP1A2 observed, limited induction (< 5-fold) of epoxide hydrolase, quinone oxidoreductase, and aldehyde dehydrogenase was detected, even in rats exposed to the highest concentration of Aroclor (100 ppm) for up to 84 days. Furthermore, induction of these non-CYP hepatic drug-metabolizing genes exhibited distinctly different concentration-response curves. The ratios of hepatic CYP1A1 activity to hepatic PCB burden were similar for rats exposed continuously to Aroclor in the diet for 7, 28, or 84 days, and for rats exposed discontinuously (7 days Aroclor/21 days control diet or 28 days Aroclor/56 days control diet). Thus, hepatic PCB levels alone appeared to be reasonably predictive of CYP1A1 levels under a variety of modes of exposure. When the ratio of CYP1A1 activity to adipose or blood PCB concentration was determined, similar ratios were observed for rats exposed continuously for 7, 28, or 84 days. However, lower ratios were observed for rats discontinuously exposed to Aroclor in the diet. These results have important implications with respect to: (a) employing PCB levels in various tissues to predict biological effects, and (b) determining different concentration-response curves for the various biological effects induced by PCBs. JF - Toxicology and applied pharmacology AU - Dragnev, K H AU - Beebe, L E AU - Jones, C R AU - Fox, S D AU - Thomas, P E AU - Nims, R W AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 111 EP - 122 VL - 125 IS - 1 SN - 0041-008X, 0041-008X KW - Aroclors KW - 0 KW - Carcinogens KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - RNA KW - 63231-63-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Animals KW - Dealkylation KW - Dose-Response Relationship, Drug KW - Oxidoreductases, N-Demethylating -- biosynthesis KW - Aldehyde Dehydrogenase -- biosynthesis KW - Epoxide Hydrolases -- biosynthesis KW - RNA -- biosynthesis KW - Rats KW - Rats, Inbred F344 KW - Base Sequence KW - Adipose Tissue -- metabolism KW - Molecular Sequence Data KW - Enzyme Induction KW - Diet KW - Female KW - RNA -- genetics KW - Oxidoreductases -- biosynthesis KW - Liver -- enzymology KW - Carcinogens -- administration & dosage KW - Polychlorinated Biphenyls -- blood KW - Carcinogens -- toxicity KW - Polychlorinated Biphenyls -- metabolism KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Aroclors -- toxicity KW - Aroclors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76396122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Subchronic+dietary+exposure+to+Aroclor+1254+in+rats%3A+accumulation+of+PCBs+in+liver%2C+blood%2C+and+adipose+tissue+and+its+relationship+to+induction+of+various+hepatic+drug-metabolizing+enzymes.&rft.au=Dragnev%2C+K+H%3BBeebe%2C+L+E%3BJones%2C+C+R%3BFox%2C+S+D%3BThomas%2C+P+E%3BNims%2C+R+W%3BLubet%2C+R+A&rft.aulast=Dragnev&rft.aufirst=K&rft.date=1994-03-01&rft.volume=125&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-08 N1 - Date created - 1994-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of metallothionein gene expression in male Wistar (WF/NCr) rats by treatment with calmodulin inhibitors: potential role of calcium regulatory pathways in metallothionein induction. AN - 76387214; 8128501 AB - Recent reports indicate that calmodulin inhibitors (CIs) can modify cadmium toxicity in rodents. For instance, pretreatment with CIs prevents cadmium-induced testicular damage in mice and substantially reduces such damage in rats, the latter effect coinciding with significant alterations in cadmium distribution. Although the basis of these effects is unclear, it is frequently observed that metal-binding proteins such as metallothionein (MT) are involved in acquired tolerance to cadmium and this could be true of tolerance induced by CIs. Thus, we examined the effects of various CIs on MT gene expression. Treatment of WF/NCr rats with known CIs, including trifluoperazine (TPZ), N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), calmidazolium (CMZ), chlorpromazine (CPZ), and the calcium ionophore, A23187, increased hepatic MT gene expression, as assessed by mRNA levels, in all cases. Furthermore, hepatic MT protein levels were 40 to 180 micrograms MT/g wet wt (g ww) in rats treated with CIs or A23187 compared to control levels of 10 micrograms MT/g ww. Treatment with CPZ and CMZ did not increase renal MT protein after exposure, although increases in renal MT mRNA were observed. However, the CIs TPZ and W7 and the calcium ionophore increased both renal MT protein and MT mRNA levels. In contrast, no increases in testicular MT mRNA or the testicular cadmium binding protein (TCBP) levels were seen with any of the treatments. Treatment with CIs or A23187 produced increases in zinc levels in the liver, but not in the kidneys or testes. These results indicate that CIs, such as TPZ, W7, CMZ, and CPZ, as well as the calcium ionophore A23187, have a marked stimulatory effect on hepatic and renal MT gene expression and that calcium regulatory pathways may play an important role in this induction of MT. JF - Toxicology and applied pharmacology AU - Shiraishi, N AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 97 EP - 103 VL - 125 IS - 1 SN - 0041-008X, 0041-008X KW - Calmodulin KW - 0 KW - Chlorides KW - Imidazoles KW - RNA, Messenger KW - Sulfonamides KW - Cadmium KW - 00BH33GNGH KW - Trifluoperazine KW - 214IZI85K3 KW - Calcimycin KW - 37H9VM9WZL KW - calmidazolium KW - 4R9H38JAWL KW - W 7 KW - 65595-90-6 KW - Metallothionein KW - 9038-94-2 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Chlorpromazine KW - U42B7VYA4P KW - Index Medicus KW - Chlorides -- toxicity KW - Animals KW - Kidney -- metabolism KW - Testis -- metabolism KW - Imidazoles -- pharmacology KW - Trifluoperazine -- pharmacology KW - Kidney -- drug effects KW - Liver -- metabolism KW - Calcimycin -- pharmacology KW - Chlorpromazine -- pharmacology KW - Rats KW - Base Sequence KW - Testis -- drug effects KW - RNA, Messenger -- metabolism KW - Sulfonamides -- pharmacology KW - Liver -- drug effects KW - Rats, Wistar KW - Molecular Sequence Data KW - Cadmium -- toxicity KW - Male KW - Metallothionein -- biosynthesis KW - Calmodulin -- antagonists & inhibitors KW - Metallothionein -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76387214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Enhancement+of+metallothionein+gene+expression+in+male+Wistar+%28WF%2FNCr%29+rats+by+treatment+with+calmodulin+inhibitors%3A+potential+role+of+calcium+regulatory+pathways+in+metallothionein+induction.&rft.au=Shiraishi%2C+N%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1994-03-01&rft.volume=125&rft.issue=1&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-08 N1 - Date created - 1994-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis--thirty-third G. H. A. Clowes Memorial Award Lecture. AN - 76385764; 8118803 AB - The multistage nature of cancer pathogenesis was first defined over 50 years ago by the sequential topical application of chemical agents to mouse skin. Since then, the skin model has provided remarkable insights into the biology, biochemistry, pharmacology, and genetics of carcinogenesis. Discoveries from studies of mouse skin have proved to be landmarks in cancer research including: the binding of carcinogens to DNA; the monoclonal origin of benign and malignant tumors; the powerful tumor-promoting action of phorbol esters; the antipromoting potency of retinoids and steroids; the modifying role of age, caloric intake, and specific dietary constituents on cancer induction; the variable risk for benign tumors to progress to cancer; and the requirement for multiple genetic changes in malignant conversion. Many of these concepts are now widely applied to the interpretation of specific molecular discoveries both in simple experimental systems and in human cancers, but the power of this quantitative, multistage skin carcinogenesis model has made these assessments possible. It has also provided the separation of mechanistically distinct stages in cancer pathogenesis: initiation; promotion; premalignant progression; and malignant conversion. This paper will review our current understanding of the genetic, biological, and biochemical alterations that contribute to the evolution of each of these stages in skin carcinogenesis. These new insights provide an opportunity to replace the traditional operational-based schemata defining the process of carcinogenesis with a working model designed around functional alterations in neoplastic cells. JF - Cancer research AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/03/01/ PY - 1994 DA - 1994 Mar 01 SP - 1178 EP - 1189 VL - 54 IS - 5 SN - 0008-5472, 0008-5472 KW - c-rasHa KW - p53 KW - ras KW - v-rasHa KW - Index Medicus KW - Animals KW - Humans KW - Skin Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- etiology KW - Skin Neoplasms -- etiology KW - Carcinoma, Squamous Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76385764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathogenesis+of+squamous+cell+cancer%3A+lessons+learned+from+studies+of+skin+carcinogenesis--thirty-third+G.+H.+A.+Clowes+Memorial+Award+Lecture.&rft.au=Yuspa%2C+S+H&rft.aulast=Yuspa&rft.aufirst=S&rft.date=1994-03-01&rft.volume=54&rft.issue=5&rft.spage=1178&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 - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-rasHa; p53; ras; v-rasHa N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning of five messenger RNAs differentially expressed in preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to human tissue inhibitor of metalloproteinases-3. AN - 76385720; 8118794 AB - To better understand the molecular mechanism of multistage carcinogenesis, we have attempted to identify putative oncogenes and/or tumor suppressor genes involved in preneoplastic-to-neoplastic progression of mouse epidermal JB6 variants. The JB6 variants consist of P- (promotion resistant), P+ (promotion sensitive), and Tx [transformed; both apoptosis-sensitive (A(s)) and apoptosis-resistant (Ar)] cells, representing progression from early to late stages of carcinogenesis. By using the newly developed differential mRNA display technique, we have isolated five clones from these JB6 variants. The isolated clones were uniquely expressed either in P-/P+ cells or in Tx (A(s)/Ar) cells or showed highly differential expression among the variants. The expression pattern shown by differential mRNA display was confirmed by Northern blot analysis. DNA sequencing followed by computer search against Genbank and EMBL DNA databases indicates that three clones are novel and two have high homology with recorded genes. One of the clones (C1.14), which detects expression in preneoplastic not neoplastic JB6 cells, was used as a probe for complementary DNA library screening. The corresponding gene, named sun for specifically unexpressed in neoplastic JB6 cells, was isolated and sequenced. The longest open reading frame of the sun clone predicts a peptide showing 96% amino acid sequence identity to the recorded sequence of human tissue inhibitor of metalloproteinases-3, one of a family of genes implicated in tumorigenesis and tumor invasion. This is the first report, to our knowledge, of the simultaneous display of mRNAs of four phenotypically distinct cell variants and of the isolation of five clones which may be associated with specific stages of tumor promotion and/or progression and apoptosis. JF - Cancer research AU - Sun, Y AU - Hegamyer, G AU - Colburn, N H AD - Cell Biology Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/03/01/ PY - 1994 DA - 1994 Mar 01 SP - 1139 EP - 1144 VL - 54 IS - 5 SN - 0008-5472, 0008-5472 KW - TIS KW - p53 KW - sun KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - RNA, Messenger KW - Tissue Inhibitor of Metalloproteinase-3 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Sequence Homology, Nucleic Acid KW - Humans KW - Amino Acid Sequence KW - Mice KW - Cloning, Molecular KW - Evaluation Studies as Topic KW - Base Sequence KW - Polymerase Chain Reaction -- methods KW - Databases, Factual KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Sequence Homology, Amino Acid KW - Epithelium -- pathology KW - Skin Neoplasms -- genetics KW - Precancerous Conditions -- genetics KW - Neoplasm Proteins -- genetics KW - Skin Neoplasms -- pathology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76385720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Virological+Methods&rft.atitle=Murine+retroviral+vector+that+induces+long-term+expression+of+HIV-1+envelope+protein&rft.au=Fujita%2C+K%3BMaldarelli%2C+F%3BPurcell%2C+DFJ%3BSilver%2C+J&rft.aulast=Fujita&rft.aufirst=K&rft.date=1994-01-01&rft.volume=50&rft.issue=1-3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TIS; p53; sun N1 - Genetic sequence - Z30970; GENBANK; Z31358; Z31359; Z31361; Z31362; Z31360 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of transformation frequency by exogenous and endogenous growth factors in rat tracheal epithelial cells. AN - 76384398; 8118942 AB - The purpose of our studies was to re-evaluate the rat tracheal epithelial (RTE) transformation system and to identify critical variables that affect the development of enhanced growth variants (EGV). The enhanced growth variant colony, which is a preneoplastic cell variant, is the quantifiable transformation endpoint in RTE cultures. Using a standard protocol the frequency of EGV colony formation was shown to be inversely related to the number of clonogenic cells (CFU) seeded per dish in control cultures as well as in cultures treated with the transforming agent 6-nitrochrysene (6-NC). Experiments showed that the major mechanisms that underlie the CFU density-dependent inhibition of EGV colony formation are depletion of growth factors from and accumulation of autocrine TGF-beta in the media. Thus the cells themselves are creating the selection environment, which allows only the EGVs to survive. The effects of agents such as 6-NC, which increase the frequency of EGV colony formation, are to induce a cellular phenotype that is less susceptible to the selection environment. We showed that TGF-beta-neutralizing antibodies added to the selection media significantly increased EGV colony formation in control cultures but not in 6-NC-exposed cultures. In addition we demonstrated that the development of EGV colonies is much less susceptible to inhibition by (exogenous) TGF-beta in 6-NC-exposed than in control cultures. Thus spontaneous and 6-NC EGV colony formation are distinguishable based on TGF-beta sensitivity. To conduct quantitative cell transformation experiments with RTE cells it is essential that the number of surviving CFU per dish is the same in control and treated cultures. Under the conditions used in the studies described here, 350-500 CFU per culture was found to be the optimum CFU density. Besides 6-NC, agents that have been shown to increase EGV colony frequency under conditions similar to those described here are nitrosamines, NNK, nickel compounds and X-rays. JF - Carcinogenesis AU - Gray, T E AU - Zhu, S J AU - Nettesheim, P AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 549 EP - 555 VL - 15 IS - 3 SN - 0143-3334, 0143-3334 KW - Chrysenes KW - 0 KW - Culture Media, Serum-Free KW - Growth Substances KW - Transforming Growth Factor beta KW - 6-nitrochrysene KW - 82ZK83O33Y KW - Index Medicus KW - Rats KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Rats, Inbred F344 KW - Cell Count -- drug effects KW - Transforming Growth Factor beta -- metabolism KW - Culture Media, Serum-Free -- chemistry KW - Male KW - Cell Transformation, Neoplastic -- pathology KW - Tracheal Neoplasms -- chemically induced KW - Precancerous Conditions -- chemically induced KW - Growth Substances -- pharmacology KW - Cell Transformation, Neoplastic -- metabolism KW - Cell Transformation, Neoplastic -- chemically induced KW - Tracheal Neoplasms -- metabolism KW - Tumor Stem Cell Assay -- methods KW - Tracheal Neoplasms -- pathology KW - Precancerous Conditions -- metabolism KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76384398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+transformation+frequency+by+exogenous+and+endogenous+growth+factors+in+rat+tracheal+epithelial+cells.&rft.au=Gray%2C+T+E%3BZhu%2C+S+J%3BNettesheim%2C+P&rft.aulast=Gray&rft.aufirst=T&rft.date=1994-03-01&rft.volume=15&rft.issue=3&rft.spage=549&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and pharmacokinetic study of recombinant human granulocyte-macrophage colony-stimulating factor given in combination with fluorouracil plus calcium leucovorin in metastatic gastrointestinal adenocarcinoma. AN - 76384079; 8120554 AB - To determine the toxicities and potential for dose escalation of intravenous (IV) bolus fluorouracil (5-FU) given with 500 mg/m2/d leucovorin (LCV) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-seven patients received escalating doses of 5-FU/LCV on days 1 to 5 with subcutaneous GM-CSF either 5 or 10 micrograms/kg/d starting on day 6 or 3 micrograms/kg/d starting on day 1. 5-FU was escalated from 370 mg/m2/d by 15% increments between patient cohorts and within patients according to tolerance. With GM-CSF starting on day 6, dose-limiting toxicity occurred during cycle no. 1 in all three patients entered at 5-FU 490 mg/m2/d. However, individual patients tolerated 5-FU doses up to 644 mg/m2/d. When all cycles were analyzed, grade 3 to 4 mucositis and grade 4 granulocytopenia complicated or = grade 3 mucositis occurred in or = 5 micrograms/kg/d required dose reductions for constitutional toxicity; 3.0 to 3.8 micrograms/kg/d was better tolerated. Venous thrombosis occurred in 17% of patients (concurrent v sequential GM-CSF, 29% v 5%; P2 = .08). The median delivered 5-FU dose-intensity for GM-CSF starting either on day 6 or on day 1 was 615 and 647 mg/m2/wk (P2 = .41), respectively. Pharmacologic exposure to 5-FU increased with higher doses of 5-FU, and concurrent GM-CSF administration did not affect 5-FU clearance. A starting dose of 425 mg/m2/d of 5-FU with LCV on days 1 to 5 could be safely combined with GM-CSF starting either on day 1 or day 6, with further 5-FU dose escalation according to individual tolerance. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Grem, J L AU - McAtee, N AU - Murphy, R F AU - Hamilton, J M AU - Balis, F AU - Steinberg, S AU - Arbuck, S G AU - Setser, A AU - Jordan, E AU - Chen, A AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 560 EP - 568 VL - 12 IS - 3 SN - 0732-183X, 0732-183X KW - Recombinant Proteins KW - 0 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Drug Administration Schedule KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Agranulocytosis -- prevention & control KW - Recombinant Proteins -- therapeutic use KW - Male KW - Female KW - Agranulocytosis -- chemically induced KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Adenocarcinoma -- metabolism KW - Adenocarcinoma -- secondary KW - Gastrointestinal Neoplasms -- drug therapy KW - Gastrointestinal Neoplasms -- pathology KW - Gastrointestinal Neoplasms -- metabolism KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Fluorouracil -- pharmacokinetics KW - Adenocarcinoma -- drug therapy KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76384079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+I+and+pharmacokinetic+study+of+recombinant+human+granulocyte-macrophage+colony-stimulating+factor+given+in+combination+with+fluorouracil+plus+calcium+leucovorin+in+metastatic+gastrointestinal+adenocarcinoma.&rft.au=Grem%2C+J+L%3BMcAtee%2C+N%3BMurphy%2C+R+F%3BHamilton%2C+J+M%3BBalis%2C+F%3BSteinberg%2C+S%3BArbuck%2C+S+G%3BSetser%2C+A%3BJordan%2C+E%3BChen%2C+A&rft.aulast=Grem&rft.aufirst=J&rft.date=1994-03-01&rft.volume=12&rft.issue=3&rft.spage=560&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 - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - LGL-1: a potential triggering molecule on murine NK cells. AN - 76383754; 7509843 AB - Natural killer (NK) cells mediate non-major histocompatibility complex-restricted lysis of tumor cells, lymphokine-activated killing (LAK), antibody-dependent cellular cytotoxicity (ADCC), and reverse ADCC (RADCC). LGL-1+ cells identify a major subset (50%) of murine NK cells. Here we demonstrate that monoclonal antibodies (mAbs) to LGL-1 consistently induce interleukin-2-cultured, and Corynebacterium parvum (in vivo)-activated NK cells to induce RADCC. LGL-1 triggering of activated NK cells coincides with enhanced LGL-1 expression. Testing of murine mAbs to epitopes of CD2 only appears to augment RADCC induced by mAb NK-1.1 on fresh NK cells. Immunoprecipitation of the LGL-1 antigen reveals a highly disulfide-linked 40-kDa homodimer subunit that is N-glycosylated. Therefore, LGL-1 may be similar to other recently characterized NK-associated antigens such as NK-1.1, Ly-49, and NKR-PI. We conclude that although LGL-1 is expressed on "resting" NK cells, enhanced surface expression following activation is usually required for it to act as a signaling molecule. JF - Journal of leukocyte biology AU - Mason, L H AU - Yagita, H AU - Ortaldo, J R AD - Laboratory of Experimental Immunology, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 362 EP - 370 VL - 55 IS - 3 SN - 0741-5400, 0741-5400 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD2 KW - Antigens, Differentiation, T-Lymphocyte KW - Antigens, Surface KW - Epitopes KW - Immunoglobulin Fab Fragments KW - Interleukin-2 KW - Receptors, IgG KW - Receptors, Immunologic KW - Index Medicus KW - Animals KW - Interleukin-2 -- pharmacology KW - Receptors, IgG -- immunology KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Precipitin Tests KW - Antibody-Dependent Cell Cytotoxicity -- physiology KW - Antibodies, Monoclonal -- immunology KW - Receptors, Immunologic -- immunology KW - Receptors, IgG -- analysis KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Flow Cytometry KW - Antigens, Differentiation, T-Lymphocyte -- immunology KW - Drug Synergism KW - Epitopes -- immunology KW - Killer Cells, Natural -- physiology KW - Killer Cells, Natural -- cytology KW - Killer Cells, Natural -- chemistry KW - Antigens, Surface -- physiology KW - Antigens, Surface -- immunology KW - Antigens, Surface -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76383754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cigarette+smoking+and+pancreas+cancer%3A+a+case+-+control+study+based+on+direct+interviews&rft.au=Silverman%2C+D+T%3BDunn%2C+JA%3BHoover%2C+R+N%3BSchiffman%2C+M%3BLillemoe%2C+K+D%3BSchoenberg%2C+J+B%3BBrown%2C+L+M%3BGreenberg%2C+R+S%3BHayes%2C+R+B%3BSwanson%2C+G+M%3BWacholder%2C+S%3BSchwartz%2C+A+G%3BLiff%2C+J+M%3BPottern%2C+L+M&rft.aulast=Silverman&rft.aufirst=D&rft.date=1994-01-01&rft.volume=86&rft.issue=20&rft.spage=1510&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 - 1994-04-05 N1 - Date created - 1994-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-methyl-D-aspartate induces a rapid, reversible, and calcium-dependent intracellular acidosis in cultured fetal rat hippocampal neurons. AN - 76383712; 8120630 AB - The ability of NMDA to alter intracellular pH (pHi) was studied in fetal rat hippocampal neurons and glia using the pH-sensitive fluorescent indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). Brief exposure (60 sec) of hippocampal neurons to NMDA (2.5-250 microM) results in a rapid, and in most cells reversible, reduction in pHi, with full recovery to baseline pHi values taking several minutes following removal of NMDA. In contrast, little or no change in pHi was observed in glial cells exposed to these same concentrations of NMDA. The NMDA-induced acidification of neurons was concentration and time dependent, with an EC50 of 39 microM and Emax (delta pH) of -0.53. More prolonged exposure to NMDA (> or = 10 min) resulted in a more prolonged reduction in pHi values over the ensuing 20 min observation period. The intracellular acidification resulting from NMDA exposure of hippocampal neurons was blocked by the NMDA receptor antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Moreover, removal of extracellular Ca2+ eliminated both the selective NMDA-induced elevation in [Ca2+]i and the reduction in pHi, indicating that Ca2+ influx may be required for the decrease in pHi induced by NMDA receptor activation. Finally, the NMDA-induced reduction in pHi was not significantly attenuated when extracellular [H+] was decreased by increasing extracellular pH to 8.0. The latter suggests that an intracellular source of H+ is responsible for the NMDA-induced reduction in neuronal pHi. The reduction in neuronal pHi induced by NMDA receptor activation may mediate some of the physiological and (or) pathophysiological actions of glutamate. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Irwin, R P AU - Lin, S Z AU - Long, R T AU - Paul, S M AD - Section on Molecular Pharmacology, National Institute of Mental Health, NIH, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 1352 EP - 1357 VL - 14 IS - 3 Pt 1 SN - 0270-6474, 0270-6474 KW - N-Methylaspartate KW - 6384-92-5 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Fetus KW - Animals KW - Neurons -- metabolism KW - Cells, Cultured KW - Calcium -- pharmacology KW - Hydrogen-Ion Concentration -- drug effects KW - N-Methylaspartate -- pharmacology KW - Hippocampus -- metabolism KW - Hippocampus -- cytology KW - Acidosis -- metabolism KW - Acidosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76383712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N-methyl-D-aspartate+induces+a+rapid%2C+reversible%2C+and+calcium-dependent+intracellular+acidosis+in+cultured+fetal+rat+hippocampal+neurons.&rft.au=Irwin%2C+R+P%3BLin%2C+S+Z%3BLong%2C+R+T%3BPaul%2C+S+M&rft.aulast=Irwin&rft.aufirst=R&rft.date=1994-03-01&rft.volume=14&rft.issue=3+Pt+1&rft.spage=1352&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 - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease. AN - 76383155; 7509770 AB - Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease. JF - Hepatology (Baltimore, Md.) AU - Adams, D H AU - Burra, P AU - Hubscher, S G AU - Elias, E AU - Newman, W AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 588 EP - 594 VL - 19 IS - 3 SN - 0270-9139, 0270-9139 KW - Cell Adhesion Molecules KW - 0 KW - E-Selectin KW - Vascular Cell Adhesion Molecule-1 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Portal Vein -- metabolism KW - Liver Circulation KW - Cell Adhesion -- physiology KW - Humans KW - Liver -- metabolism KW - Veins -- metabolism KW - Immunohistochemistry KW - Liver Diseases, Alcoholic -- metabolism KW - Endothelium, Vascular -- metabolism KW - Liver Diseases, Alcoholic -- physiopathology KW - Cell Adhesion Molecules -- metabolism KW - Endothelium, Vascular -- physiopathology KW - Liver Diseases, Alcoholic -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76383155?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Endothelial+activation+and+circulating+vascular+adhesion+molecules+in+alcoholic+liver+disease.&rft.au=Adams%2C+D+H%3BBurra%2C+P%3BHubscher%2C+S+G%3BElias%2C+E%3BNewman%2C+W&rft.aulast=Adams&rft.aufirst=D&rft.date=1994-03-01&rft.volume=19&rft.issue=3&rft.spage=588&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-06 N1 - Date created - 1994-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of cytochrome P-450 in Sigmodon hispidus (cotton rats) exposed to dietary Aroclor 1254. AN - 76382710; 8126756 AB - The induction of immunoreactive cytochrome P-450 protein and associated catalytic activities in 10-wk-old male and female Sigmodon hispidus (cotton rats) exposed for 2 wk to low dietary levels of Aroclor 1254 (0.33, 1.0, 3.3, 10, and 33 ppm), or the prototype P-450 inducers phenobarbital, DDT, clotrimazole, and beta-naphthoflavone was examined. Ethoxy-(ETR), methoxy- (MTR), pentoxy- (PTR), and benzyloxyresorufin (BZR) O-dealkylation activities were significantly increased at 0.33 ppm Aroclor for males and 1.0 ppm for females, when compared to control levels. O-Dealkylation activities peaked at 3.3 ppm for males and 10 ppm for females. ETR and MTR O-dealkylation activities were increased four- to eightfold while PTR and BZR O-dealkylation activities increased only two- to threefold. Liver/body weight ratios also increased, with the maximum ratios observed at the highest Aroclor dose, and were associated with histopathologic hepatocyte lesions. While increases in liver/body weight ratio, immunoreactive CYP2B protein, and BZR O-dealkylation were detected following phenobarbital treatment, no increase in PTR O-dealkylation activity was observed. These results demonstrate that S. hispidus (both males and females) are extremely sensitive to low dietary levels of Aroclor 1254, responding with increases in liver/body weight ratio, immunoreactive P-450 protein, and O-dealkylation activities. The cotton rat would appear to be a sensitive feral target species for detecting exposure to certain environmental contaminants. JF - Journal of toxicology and environmental health AU - Henneman, J R AU - Fox, S D AU - Lubet, R A AU - Ward, J M AU - Nims, R W AD - Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, NCI-FCRDC, MD 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 369 EP - 386 VL - 41 IS - 3 SN - 0098-4108, 0098-4108 KW - Aroclors KW - 0 KW - Carcinogens KW - Xenobiotics KW - Chlorodiphenyl (54% Chlorine) KW - 11097-69-1 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Administration, Oral KW - Animals KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Body Burden KW - Xenobiotics -- toxicity KW - Sigmodontinae KW - Dealkylation -- drug effects KW - Enzyme Induction -- drug effects KW - Body Weight -- drug effects KW - Polychlorinated Biphenyls -- metabolism KW - Female KW - Male KW - Organ Size -- drug effects KW - Liver -- pathology KW - Carcinogens -- administration & dosage KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Aroclors -- toxicity KW - Aroclors -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76382710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Induction+of+cytochrome+P-450+in+Sigmodon+hispidus+%28cotton+rats%29+exposed+to+dietary+Aroclor+1254.&rft.au=Henneman%2C+J+R%3BFox%2C+S+D%3BLubet%2C+R+A%3BWard%2C+J+M%3BNims%2C+R+W&rft.aulast=Henneman&rft.aufirst=J&rft.date=1994-03-01&rft.volume=41&rft.issue=3&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-13 N1 - Date created - 1994-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agranulocytosis. AN - 76381025; 7509883 JF - JAMA AU - Young, N S AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892. PY - 1994 SP - 935 EP - 938 VL - 271 IS - 12 SN - 0098-7484, 0098-7484 KW - Anti-Bacterial Agents KW - 0 KW - Cardiotonic Agents KW - Quinolines KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - vesnarinone KW - 5COW40EV8M KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Abridged Index Medicus KW - Index Medicus KW - Anti-Bacterial Agents -- therapeutic use KW - Heart Failure -- drug therapy KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Incidence KW - Aged KW - Middle Aged KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use KW - Male KW - Female KW - Cardiotonic Agents -- adverse effects KW - Agranulocytosis -- physiopathology KW - Quinolines -- therapeutic use KW - Agranulocytosis -- epidemiology KW - Cardiotonic Agents -- therapeutic use KW - Quinolines -- adverse effects KW - Agranulocytosis -- chemically induced KW - Agranulocytosis -- therapy KW - Agranulocytosis -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76381025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=JAMA&rft.atitle=Agranulocytosis.&rft.au=Young%2C+N+S&rft.aulast=Young&rft.aufirst=N&rft.date=1994-03-01&rft.volume=271&rft.issue=12&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-06 N1 - Date created - 1994-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequential activation of phospholipase-C and -D in agonist-stimulated gonadotrophs. AN - 76380333; 8119185 AB - The contributions of phospholipase-C and -D to diacylglycerol (DG) formation during agonist-induced cell signaling were investigated in rat pituitary cells and alpha T3-1 gonadotrophs. In both cell types, GnRH caused a biphasic increase in DG formation, with an initial spike within 60 sec, followed by a larger and sustained rise to reach a second peak after 15 min of stimulation. Both phases of DG production were temporally correlated with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation, consistent with the dependence of DG formation on phospholipase-C-mediated phosphoinositide hydrolysis. However, the ability of GnRH to stimulate phosphatidylethanol (PEt) in the presence of ethanol suggested that phospholipase-D may also participate in DG formation. Two inhibitors of phospholipase-C-dependent phosphoinositide hydrolysis, U73122 and neomycin sulfate, reduced the PEt as well as the Ins(1,4,5)P3 response to GnRH, indicating that phospholipase-D is activated during phospholipase-C-dependent signaling in pituitary gonadotrophs. The production of both DG and PEt was increased by treatment with the active phorbol ester phorbol 12-myristate 13-acetate (PMA), but not with inactive 4 alpha-phorbol 13-didecanoate, indicating that stimulation of protein kinase-C leads to activation of phospholipase-D. In accord with this, GnRH- and PMA-induced elevations of DG and PEt production were attenuated or abolished in protein kinase-C-depleted cells. In contrast, short and long term stimulation with PMA had no effect on basal inositol phosphate production. Also, GnRH-induced inositol phosphate production was not affected by protein kinase-C depletion. Finally, U73122 and neomycin sulfate did not inhibit PMA-induced PEt formation. These data indicate that GnRH activates a dual phospholipase pathway in a sequential and synchronized manner; phospholipase-C initiates the biphasic increase in Ins(1,4,5)P3 and DG formation, and protein kinase-C mediates the integration of phospholipase-D into the signaling response during the sustained phase of agonist stimulation. JF - Endocrinology AU - Zheng, L AU - Stojilkovic, S S AU - Hunyady, L AU - Krsmanovic, L Z AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 1446 EP - 1454 VL - 134 IS - 3 SN - 0013-7227, 0013-7227 KW - Diglycerides KW - 0 KW - Estrenes KW - Pyrrolidinones KW - 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione KW - 112648-68-7 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase D KW - EC 3.1.4.4 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Inositol 1,4,5-Trisphosphate -- metabolism KW - Calcium -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Estrenes -- pharmacology KW - Gonadotropin-Releasing Hormone -- pharmacology KW - Pyrrolidinones -- pharmacology KW - Female KW - Diglycerides -- metabolism KW - Phospholipase D -- metabolism KW - Pituitary Gland -- metabolism KW - Type C Phospholipases -- metabolism KW - Pituitary Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76380333?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Sequential+activation+of+phospholipase-C+and+-D+in+agonist-stimulated+gonadotrophs.&rft.au=Zheng%2C+L%3BStojilkovic%2C+S+S%3BHunyady%2C+L%3BKrsmanovic%2C+L+Z%3BCatt%2C+K+J&rft.aulast=Zheng&rft.aufirst=L&rft.date=1994-03-01&rft.volume=134&rft.issue=3&rft.spage=1446&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-07 N1 - Date created - 1994-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sap1, a protein that binds to sequences required for mating-type switching, is essential for viability in Schizosaccharomyces pombe. AN - 76373867; 8114737 AB - The pattern of mating-type switching in cell pedigrees of the fission yeast Schizosaccharomyces pombe is dictated by the inheritance of specific DNA chains at the mating-type locus (mat1). The recombination event essential for switching is initiated by a site-specific double-strand break at mat1. The switch-activating protein, Sap1, binds in vitro to a mat1 cis-acting site that was shown earlier to be essential for efficient mating-type switching. We isolated the sap1 gene by using oligonucleotides corresponding to the amino acid sequence of purified Sap1 protein. The sequence of that gene predicted a 30-kDa protein with no significant homology to other canonical DNA-binding protein motifs. To facilitate its biochemical characterization, Sap1 was expressed in Escherichia coli. The protein expressed in bacteria displayed the same DNA-binding specificities as the protein purified from S. pombe. Interestingly, analysis of a sap1 null mutation showed that the gene is essential for growth even in a strain in which mating-type switching is prohibited because of a defect in generation of the double-strand break. Thus, the sap1 gene product implicated in mating-type switching is shown to be essential for cell viability. JF - Molecular and cellular biology AU - Arcangioli, B AU - Copeland, T D AU - Klar, A J AD - Laboratory of Eukaryotic Gene Expression, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 2058 EP - 2065 VL - 14 IS - 3 SN - 0270-7306, 0270-7306 KW - RAD50 KW - Sap1 KW - DNA-Binding Proteins KW - 0 KW - Fungal Proteins KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Sap1 protein, S pombe KW - Schizosaccharomyces pombe Proteins KW - Index Medicus KW - Protein Structure, Secondary KW - Base Sequence KW - Sequence Alignment KW - Oligodeoxyribonucleotides -- chemistry KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Fungal Proteins -- genetics KW - Sequence Homology, Amino Acid KW - RNA, Messenger -- genetics KW - Mutagenesis, Insertional KW - Genes, Mating Type, Fungal KW - Cloning, Molecular KW - Gene Expression Regulation, Fungal KW - Schizosaccharomyces -- genetics KW - Genes, Fungal KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- isolation & purification KW - Schizosaccharomyces -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76373867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sap1%2C+a+protein+that+binds+to+sequences+required+for+mating-type+switching%2C+is+essential+for+viability+in+Schizosaccharomyces+pombe.&rft.au=Arcangioli%2C+B%3BCopeland%2C+T+D%3BKlar%2C+A+J&rft.aulast=Arcangioli&rft.aufirst=B&rft.date=1994-03-01&rft.volume=14&rft.issue=3&rft.spage=2058&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 - 1994-03-25 N1 - Date created - 1994-03-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - RAD50; Sap1 N1 - Genetic sequence - S68941; GENBANK N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] Curr Genet. 1993 Feb;23(2):184-6 [8431959] Nature. 1977 Mar 10;266(5598):172-4 [859590] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Annu Rev Biochem. 1978;47:251-76 [354496] Cell. 1982 Mar;28(3):551-61 [7042099] Nature. 1983 Aug 18-24;304(5927):652-4 [6348555] Methods Enzymol. 1983;101:202-11 [6310324] Virology. 1984 Feb;133(1):137-45 [6322425] EMBO J. 1984 Mar;3(3):603-10 [6325178] Proc Natl Acad Sci U S A. 1984 Jun;81(11):3481-5 [6587363] Annu Rev Biochem. 1984;53:293-321 [6236744] EMBO J. 1985 Jun;4(6):1609-14 [4040853] EMBO J. 1985 Oct;4(10):2627-33 [2996882] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8419-23 [3909145] Science. 1986 Apr 25;232(4749):485-7 [2421409] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5889-93 [3461465] Cell. 1986 Aug 29;46(5):725-31 [3742597] Science. 1986 Oct 17;234(4774):364-8 [2876518] Nature. 1987 Apr 2-8;326(6112):466-70 [3561486] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 [3162770] EMBO J. 1988 May;7(5):1537-47 [2900761] Eur J Biochem. 1989 Feb 1;179(2):359-63 [2645138] EMBO J. 1989 Jan;8(1):269-76 [2714252] Genetics. 1989 May;122(1):47-57 [2659437] EMBO J. 1990 May;9(5):1407-15 [2328720] Methods Enzymol. 1991;194:795-823 [2005825] Genetics. 1991 Mar;127(3):489-96 [2016051] EMBO J. 1991 Oct;10(10):3025-32 [1915277] Nature. 1993 Jan 21;361(6409):271-3 [8423854] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. AN - 76370342; 8113865 AB - Targeted protein toxins are a new class of reagents with the potential for great tumor selectivity and cytotoxic potency. Two such compounds were studied: 1) Tf-CRM107, a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107); and 2) 454A12-rRA, a conjugate of a monoclonal antibody (454A12) to the human Tf receptor and recombinant ricin A chain (rRA). Both compounds are potent and specific in killing human glioblastoma cell lines in vitro. The authors investigated the activity of these reagents administered intratumorally against solid U251 MG human gliomas in vivo. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were randomly assigned to be treated with 100-microliters intratumoral injections of Tf-CRM107 (10 micrograms) or 454A12-rRA (10 micrograms), equimolar doses of CRM107 (4.3 micrograms), 454A12 antibody (7.5 micrograms), or rRA (1.5 micrograms), or phosphate-buffered saline (PBS) every 2 days for a total of four doses. Tumor volume and animal weight were assessed by a blinded observer before each treatment and biweekly for 30 days after initiating therapy. With Tf-CRM107 administration, tumor regression of greater than 95% occurred by Day 14 (p < 0.01) and tumors did not recur by Day 30. Treatment with 454A12-rRA caused a 30% decrease in tumor volume by Day 14 (p < 0.01). Treatment with equimolar doses of the unconjugated targeted protein toxin components CRM107, 454A12, or rRA caused significant U251 MG tumor growth inhibition, but the effects were less potent than the antitumor effects of the conjugates. This study also characterized the dose-response effect of Tf-CRM107 on tumor growth and tumor weight on Day 30. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were treated with 100-microliters intratumoral injections of 10, 1.0, or 0.1 microgram of Tf-CRM107 or PBS every 2 days for a total of four doses. All three doses of Tf-CRM107 significantly inhibited tumor growth by Day 14 (p < 0.01) and at Day 30 (p < 0.05), with a significant dose-response relationship. This study demonstrated in vivo efficacy of the targeted toxins Tf-CRM107 and 454A12-rRA against a human glioma. With intratumoral administration, the effect of Tf-CRM107 was tumor-specific and in some animals curative. Regional therapy with these potent tumor-specific agents using direct intratumoral infusion should limit systemic toxicity and may be efficacious against brain tumors. JF - Journal of neurosurgery AU - Laske, D W AU - Ilercil, O AU - Akbasak, A AU - Youle, R J AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 520 EP - 526 VL - 80 IS - 3 SN - 0022-3085, 0022-3085 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - CRM 107 KW - Diphtheria Toxin KW - Immunotoxins KW - Receptors, Transferrin KW - Recombinant Proteins KW - Ricin KW - 9009-86-3 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Mice, Nude KW - Mice KW - Recombinant Proteins -- administration & dosage KW - Glioma -- drug therapy KW - Ricin -- administration & dosage KW - Immunotoxins -- therapeutic use KW - Bacterial Toxins -- administration & dosage KW - Antibodies, Monoclonal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76370342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Efficacy+of+direct+intratumoral+therapy+with+targeted+protein+toxins+for+solid+human+gliomas+in+nude+mice.&rft.au=Laske%2C+D+W%3BIlercil%2C+O%3BAkbasak%2C+A%3BYoule%2C+R+J%3BOldfield%2C+E+H&rft.aulast=Laske&rft.aufirst=D&rft.date=1994-03-01&rft.volume=80&rft.issue=3&rft.spage=520&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-30 N1 - Date created - 1994-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Function of the cytoplasmic domain of a retroviral transmembrane protein: p15E-p2E cleavage activates the membrane fusion capability of the murine leukemia virus Env protein. AN - 76365103; 8107239 AB - In the murine leukemia viruses (MuLVs), the Env complex is initially cleaved by a cellular protease into gp70SU and pre15ETM. After the virus particle is released from the cell, the C-terminal 16 residues are removed from the cytoplasmic domain of pre15E by the viral protease, yielding the mature p15ETM and p2E. We have investigated the function of this cleavage by generating a Moloney MuLV mutant, termed p2E-, in which the Env coding region terminates at the cleavage site. This mutant synthesizes only the truncated, mature form of TM rather than its extended precursor. When cells expressing this truncated Env protein are cocultivated with NIH 3T3 cells, they induce rapid cell-cell fusion. Thus, the truncated form, which is normally found in virions but not in virus-producing cells, is capable of causing membrane fusion. We conclude that the 16-residue p2E tail inhibits this activity of Env until the virus has left the cell. p2E- virions were found to be infectious, though with a lower specific infectivity than that of the wild type, showing that p2E does not play an essential role in the process of infection. Fusion was also observed with a chimeric p2E- virus in which gp70SU and nearly all of p15ETM are derived from amphotropic, rather than Moloney, MuLV. In a second mutant, an amino acid at the cleavage site was changed. The pre15E protein in this mutant is not cleaved. While the mutant Env complex is incorporated into virions, these particles have a very low specific infectivity. This result suggests that the cleavage event is essential for infectivity, in agreement with the idea that removal of p2E activates the membrane fusion capability of the Env complex. JF - Journal of virology AU - Rein, A AU - Mirro, J AU - Haynes, J G AU - Ernst, S M AU - Nagashima, K AD - Laboratory of Molecular Virology and Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 1773 EP - 1781 VL - 68 IS - 3 SN - 0022-538X, 0022-538X KW - Protein Precursors KW - 0 KW - Retroviridae Proteins KW - Retroviridae Proteins, Oncogenic KW - Viral Envelope Proteins KW - Viral Fusion Proteins KW - Viral Matrix Proteins KW - murine leukemia virus protein p2E KW - p15E protein, Murine leukemia virus KW - Index Medicus KW - Animals KW - Retroviridae Proteins -- metabolism KW - Protein Precursors -- metabolism KW - Retroviridae Proteins -- genetics KW - Viral Fusion Proteins -- metabolism KW - Viral Matrix Proteins -- biosynthesis KW - Protein Precursors -- genetics KW - Viral Fusion Proteins -- isolation & purification KW - Amino Acid Sequence KW - Mice KW - Viral Fusion Proteins -- genetics KW - Virulence KW - Rats KW - Cell Fusion KW - Cells, Cultured KW - Molecular Sequence Data KW - Cytopathogenic Effect, Viral KW - Microscopy, Immunoelectron KW - Retroviridae Proteins, Oncogenic -- biosynthesis KW - Mutation KW - Cricetinae KW - Moloney murine leukemia virus -- pathogenicity KW - Membrane Fusion KW - Viral Envelope Proteins -- biosynthesis KW - Protein Processing, Post-Translational KW - Viral Envelope Proteins -- isolation & purification KW - Moloney murine leukemia virus -- genetics KW - Viral Envelope Proteins -- metabolism KW - Viral Envelope Proteins -- genetics KW - Moloney murine leukemia virus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76365103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Function+of+the+cytoplasmic+domain+of+a+retroviral+transmembrane+protein%3A+p15E-p2E+cleavage+activates+the+membrane+fusion+capability+of+the+murine+leukemia+virus+Env+protein.&rft.au=Rein%2C+A%3BMirro%2C+J%3BHaynes%2C+J+G%3BErnst%2C+S+M%3BNagashima%2C+K&rft.aulast=Rein&rft.aufirst=A&rft.date=1994-03-01&rft.volume=68&rft.issue=3&rft.spage=1773&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 - 1994-03-23 N1 - Date created - 1994-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1971 Feb 19;229(5286):564-6 [4925356] Oncogene. 1988 Dec;3(6):687-9 [2485257] J Virol. 1976 Jul;19(1):19-25 [59816] J Gen Virol. 1977 Jul;36(1):59-74 [886304] J Virol. 1977 Sep;23(3):787-98 [894795] J Virol. 1980 Mar;33(3):983-92 [6154154] Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] Proc Natl Acad Sci U S A. 1981 Oct;78(10):6023-7 [6947213] Virology. 1982 Jul 15;120(1):251-7 [6285602] J Mol Appl Genet. 1982;1(4):327-41 [6286831] Virology. 1983 Feb;125(1):85-98 [6829166] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] J Virol. 1984 Nov;52(2):492-500 [6333515] J Virol. 1985 Mar;53(3):899-907 [3882995] Virology. 1985 Sep;145(2):280-92 [2411050] Virology. 1985 Sep;145(2):335-9 [2992156] Cell. 1987 May 8;49(3):307-19 [3646094] Nature. 1987 Aug 6-12;328(6130):539-43 [3497350] Nature. 1987 Aug 6-12;328(6130):543-7 [3649576] J Virol. 1987 Oct;61(10):2981-8 [3041017] J Virol. 1988 Dec;62(12):4691-6 [2846880] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420-4 [3141927] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8688-92 [2847170] J Virol. 1989 May;63(5):2374-8 [2784836] Adv Virus Res. 1989;36:107-51 [2500008] J Virol. 1989 Oct;63(10):4395-403 [2778881] J Virol. 1989 Nov;63(11):4709-14 [2795718] J Virol. 1990 Feb;64(2):757-66 [2153240] Proc Natl Acad Sci U S A. 1990 Jan;87(2):648-52 [2300552] J Gen Virol. 1990 Apr;71 ( Pt 4):767-73 [2157795] J Virol. 1990 Aug;64(8):3770-8 [2164597] J Med Primatol. 1990;19(3-4):431-7 [2231694] Virology. 1991 Aug;183(2):545-54 [1853560] Virology. 1991 Dec;185(2):710-20 [1962445] J Virol. 1992 Jul;66(7):4220-7 [1602542] J Virol. 1992 Aug;66(8):4748-56 [1629954] Virology. 1992 Aug;189(2):534-46 [1322587] J Virol. 1992 Oct;66(10):6107-16 [1326661] J Virol. 1992 Nov;66(11):6616-25 [1357190] J Virol. 1993 Jan;67(1):213-21 [8416370] J Virol. 1993 Jan;67(1):67-74 [8416389] Virology. 1993 Apr;193(2):545-62 [8460475] J Virol. 1993 May;67(5):2824-31 [8474176] Cell. 1993 May 21;73(4):823-32 [8500173] J Virol. 1993 Sep;67(9):5443-9 [8350405] Virology. 1993 Oct;196(2):557-63 [8372434] Virology. 1993 Nov;197(1):255-64 [8212561] Virology. 1973 Apr;52(2):456-67 [4705382] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eventi alluvionali e frane nell'Italia Nord-Orientale durante il 1992 TT - Flood events and landslides in northeastern Italy during 1992 AN - 51053595; 1996-030801 JF - GEAM. Geoingegneria Ambientale e Mineraria AU - Marchi, L AU - Pasuto, A AU - Silvano, S AU - Tecca, P R Y1 - 1994/03// PY - 1994 DA - March 1994 SP - 31 EP - 38 PB - Associazione Mineraria Subalpina, Torino VL - 31 IS - 1 SN - 1121-9041, 1121-9041 KW - Bolzano Italy KW - geologic hazards KW - Europe KW - atmospheric precipitation KW - northeastern Italy KW - Belluno Italy KW - Italy KW - Southern Europe KW - landslides KW - Veneto Italy KW - mass movements KW - floods KW - Trentino-Alto Adige Italy KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51053595?accountid=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=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.atitle=Eventi+alluvionali+e+frane+nell%27Italia+Nord-Orientale+durante+il+1992&rft.au=Marchi%2C+L%3BPasuto%2C+A%3BSilvano%2C+S%3BTecca%2C+P+R&rft.aulast=Marchi&rft.aufirst=L&rft.date=1994-03-01&rft.volume=31&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=GEAM.+Geoingegneria+Ambientale+e+Mineraria&rft.issn=11219041&rft_id=info:doi/ LA - Italian DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 1996-01-01 N1 - Number of references - 5 N1 - Document feature - illus. incl. 4 tables, sketch maps N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - atmospheric precipitation; Belluno Italy; Bolzano Italy; Europe; floods; geologic hazards; Italy; landslides; mass movements; northeastern Italy; Southern Europe; Trentino-Alto Adige Italy; Veneto Italy ER - TY - JOUR T1 - Cholera toxin-induced Gs alpha down-regulation in neural tissue: studies on the pineal gland. AN - 76520084; 8199855 AB - Cholera toxin (CT) treatment (50 micrograms/ml) was used to down regulate the alpha subunit of the stimulatory guanine nucleotide binding protein (Gs alpha) in pineal glands in organ culture, as has been seen in non-neural tissue. A 15 h treatment reduces Gs alpha by approximately 75% as measured using semi-quantitative Western blot technology. In contrast, this treatment does not alter the abundance of G beta, Gi alpha or Go alpha. This effect on Gs alpha was still apparent following a 36-h washout period. The 48-h CT treatment increased cyclic AMP accumulation 10- to 17-fold but blocked the norepinephrine (NE)-induced increase in cyclic AMP accumulation, presumably reflecting the loss of Gs alpha. This treatment did not, however, inhibit protein synthesis or stimulation of arylalkylamine N-acetyltransferase (NAT) activity produced by treatment with either DB-cyclic AMP (N6,2'-O-dibutyryl adenosine 3',5' monophosphate) or 8 Br-cyclic AMP, stable cyclic AMP derivatives. This indicates that a 48-h CT treatment was not generally toxic. In contrast, this treatment blocked subsequent CT stimulation of NAT. The effects of CT treatment on the adrenergic stimulation of NAT was examined using treatments which selectively produced alpha- or beta-adrenergic stimulation. alpha 1-Adrenergic activation of the pineal gland elevates [Ca2+]i, which potentiates effects of cyclic AMP; in these studies the response to alpha-adrenergic activation was markedly increased in 48 h CT-treated glands, reflecting Ca2+ potentiation of the effects of elevated levels of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Brain research AU - Babila, T AU - Klein, D C AD - Section on Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/28/ PY - 1994 DA - 1994 Feb 28 SP - 151 EP - 156 VL - 638 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Nerve Tissue Proteins KW - 0 KW - Phenylephrine KW - 1WS297W6MV KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Calcimycin KW - 37H9VM9WZL KW - Bucladesine KW - 63X7MBT2LQ KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Isoproterenol KW - L628TT009W KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Norepinephrine -- pharmacology KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Nerve Tissue Proteins -- biosynthesis KW - Calcimycin -- pharmacology KW - Bucladesine -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Arylamine N-Acetyltransferase -- metabolism KW - Isoproterenol -- pharmacology KW - Rats KW - Blotting, Western KW - Kinetics KW - Cyclic AMP -- metabolism KW - Time Factors KW - Organ Culture Techniques KW - Phenylephrine -- pharmacology KW - Pineal Gland -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Cholera Toxin -- pharmacology KW - Pineal Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76520084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cholera+toxin-induced+Gs+alpha+down-regulation+in+neural+tissue%3A+studies+on+the+pineal+gland.&rft.au=Babila%2C+T%3BKlein%2C+D+C&rft.aulast=Babila&rft.aufirst=T&rft.date=1994-02-28&rft.volume=638&rft.issue=1-2&rft.spage=151&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 - 1994-07-07 N1 - Date created - 1994-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Personality-based subtypes of chemically dependent patients. AN - 76431398; 8154690 AB - Jackson's Personality Research Form E (PRF) was administered to a large, heterogeneous group of adult inpatients with diagnoses of alcohol and/or drug dependence. Cluster analysis of PRF factor scores yielded five distinct patient subtypes: hostile-dependent, cooperative-nonreflective, socially uninvolved, impulsive-unsociable, and hostile-overcontrolled. The subtypes differed on two MMPI canonical variables and on self-reported high risk factors for substance usage. Implications of the findings for more appropriate matching of patients to chemical dependency interventions are offered. JF - Annals of the New York Academy of Sciences AU - Allen, J P AU - Fertig, J B AU - Mattson, M E AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1994/02/28/ PY - 1994 DA - 1994 Feb 28 SP - 7 EP - 22 VL - 708 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Sex Factors KW - Humans KW - Religion KW - MMPI KW - Continental Population Groups KW - Adult KW - Personality Inventory KW - Male KW - Female KW - Personality KW - Substance-Related Disorders -- complications KW - Substance-Related Disorders -- psychology KW - Alcoholism -- psychology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76431398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Personality-based+subtypes+of+chemically+dependent+patients.&rft.au=Allen%2C+J+P%3BFertig%2C+J+B%3BMattson%2C+M+E&rft.aulast=Allen&rft.aufirst=J&rft.date=1994-02-28&rft.volume=708&rft.issue=&rft.spage=7&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 - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Research opportunities in typology and genetics of alcoholism. AN - 76431329; 8154682 JF - Annals of the New York Academy of Sciences AU - Gordis, E AU - Allen, J P AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1994/02/28/ PY - 1994 DA - 1994 Feb 28 SP - 214 EP - 217 VL - 708 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - United States KW - Demography KW - Humans KW - National Institutes of Health (U.S.) KW - Alcoholism -- classification KW - Research KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76431329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Research+opportunities+in+typology+and+genetics+of+alcoholism.&rft.au=Gordis%2C+E%3BAllen%2C+J+P&rft.aulast=Gordis&rft.aufirst=E&rft.date=1994-02-28&rft.volume=708&rft.issue=&rft.spage=214&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 - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic adenosine A1 receptor agonist and antagonist: effect on receptor density and N-methyl-D-aspartate induced seizures in mice. AN - 76567234; 8013554 AB - The effect of chronic administration of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. for 9 days with either 1.0 mg/kg CPA or 1.0 mg/kg CPX followed by 2 injection-free days (the washout period) and subsequent administration of a single dose of 60 mg/kg NMDA. As in our previous study, this dose of NMDA caused clonic/tonic seizures resulting in high (60%) mortality within 3 h after injection of the drug. Despite insignificant changes in seizure latency, chronic pretreatment with CPA increased the incidence of clonic/tonic episodes and end-point mortality. Conversely; chronic exposure to CPX completely eliminated clonic/tonic episodes, significantly increased average survival time, and reduced end-point mortality (P < 0.05). The results indicate that chronic treatment with adenosine A1 receptor antagonist may protect against NMDA-evoked seizures to the same degree as previously observed following a single, acute exposure to CPA. Since the density of adenosine receptor binding sites was unchanged after chronic treatment with either CPX or CPA, it is likely that the mechanism behind the observed protection may rest at the level of second messenger systems coupled to adenosine A1 receptors. JF - European journal of pharmacology AU - Von Lubitz, D K AU - Paul, I A AU - Ji, X D AU - Carter, M AU - Jacobson, K A AD - Molecular Recognition Section, NIH/NIDDK, Bethesda, MD 20892. Y1 - 1994/02/21/ PY - 1994 DA - 1994 Feb 21 SP - 95 EP - 99 VL - 253 IS - 1-2 SN - 0014-2999, 0014-2999 KW - Receptors, Purinergic P1 KW - 0 KW - Xanthines KW - N(6)-cyclopentyladenosine KW - 41552-82-3 KW - N-Methylaspartate KW - 6384-92-5 KW - 1,3-dipropyl-8-cyclopentylxanthine KW - 9PTP4FOI9E KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Injections, Subcutaneous KW - Motor Activity -- drug effects KW - Mice KW - Male KW - Binding Sites KW - Seizures -- chemically induced KW - Adenosine -- pharmacology KW - Adenosine -- administration & dosage KW - Receptors, Purinergic P1 -- drug effects KW - Xanthines -- administration & dosage KW - N-Methylaspartate -- pharmacology KW - Adenosine -- analogs & derivatives KW - Xanthines -- metabolism KW - Seizures -- drug therapy KW - Receptors, Purinergic P1 -- metabolism KW - Xanthines -- pharmacology KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76567234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+adenosine+A1+receptor+agonist+and+antagonist%3A+effect+on+receptor+density+and+N-methyl-D-aspartate+induced+seizures+in+mice.&rft.au=Von+Lubitz%2C+D+K%3BPaul%2C+I+A%3BJi%2C+X+D%3BCarter%2C+M%3BJacobson%2C+K+A&rft.aulast=Von+Lubitz&rft.aufirst=D&rft.date=1994-02-21&rft.volume=253&rft.issue=1-2&rft.spage=95&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 - 1994-07-26 N1 - Date created - 1994-07-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurotrauma. 1992 May;9 Suppl 2:S563-77 [1613814] Trends Pharmacol Sci. 1992 Dec;13(12):439-45 [1293870] Brain Res Bull. 1991 Jul;27(1):101-4 [1933421] J Neurochem. 1991 Feb;56(2):644-50 [1671090] Trends Pharmacol Sci. 1988 Jun;9(6):193-4 [3073553] Epilepsia. 1985 Sep-Oct;26(5):480-7 [4043018] Adv Neurol. 1986;44:857-77 [3706027] Brain Res. 1986 Jun 25;376(2):382-6 [3015342] Neurosci Lett. 1986 Jun 30;67(3):334-8 [2426636] Neuropharmacology. 1985 Aug;24(8):761-6 [3018616] Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):59-63 [3574492] J Clin Invest. 1988 Jul;82(1):242-7 [3392208] Life Sci. 1991;49(20):1435-53 [1943450] Brain Res. 1993 May 28;612(1-2):271-7 [8330205] Cell Mol Neurobiol. 1993 Jun;13(3):247-61 [8242688] Eur J Pharmacol. 1993 Nov 16;249(3):265-70 [8287913] Eur J Pharmacol. 1993 Nov 16;249(3):271-80 [8287914] Am J Physiol. 1963 Feb;204:317-22 [13971060] Neurosci Lett. 1984 May 18;46(3):317-22 [6738923] Eur J Pharmacol. 1978 Jun 1;49(3):305-8 [658145] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proximal and distal effects of sequence context on ultraviolet mutational hotspots in a shuttle vector replicated in xeroderma cells. AN - 76365747; 8107135 AB - Hotspots are a standard feature of mutational spectra induced by mutagens in a variety of marker genes. While it is generally believed that sequence context exerts an important influence on hotspot location, direct experimental evidence is quite limited. We have studied ultraviolet mutagenesis in a suppressor tRNA marker gene (supF) carried in a mammalian shuttle vector and replicated in Xeroderma pigmentosum cells in culture. We have now constructed a small family of functional variant suppressor tRNA marker gene which differ from one another by one or two nucleotide changes. UV mutational spectra were generated for each variant gene. We found that the change of a dipyrimidine from 5' TC to 5' CC eliminated a strong mutational hotspot. In addition a single base change in the supF gene was accompanied by the appearance of a new hotspot eight bases away. Finally, another single base change suppressed a major hotspot 48 bases away. Polymerase stop assays on the UV modified marker genes were used to measure the frequency and distribution of photoproducts. The differences in hotspot patterns could not be explained by differences in modification patterns. These results indicate that a change in sequence context can directly influence the probability of mutagenesis at specific sites. JF - Journal of molecular biology AU - Parris, C N AU - Levy, D D AU - Jessee, J AU - Seidman, M M AD - Laboratory of Molecular Carcinogenesis, NCI, Bethesda, MD 20892. Y1 - 1994/02/18/ PY - 1994 DA - 1994 Feb 18 SP - 491 EP - 502 VL - 236 IS - 2 SN - 0022-2836, 0022-2836 KW - supF KW - Genetic Markers KW - 0 KW - DNA KW - 9007-49-2 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Xeroderma Pigmentosum KW - Ultraviolet Rays KW - Base Sequence KW - RNA, Transfer -- genetics KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - Suppression, Genetic KW - Nucleic Acid Conformation KW - DNA Replication KW - Genetic Vectors KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76365747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Proximal+and+distal+effects+of+sequence+context+on+ultraviolet+mutational+hotspots+in+a+shuttle+vector+replicated+in+xeroderma+cells.&rft.au=Parris%2C+C+N%3BLevy%2C+D+D%3BJessee%2C+J%3BSeidman%2C+M+M&rft.aulast=Parris&rft.aufirst=C&rft.date=1994-02-18&rft.volume=236&rft.issue=2&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-23 N1 - Date created - 1994-03-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - supF N1 - Genetic sequence - U14594; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overexpressed protein kinase C-delta and -epsilon subtypes in NIH 3T3 cells exhibit differential subcellular localization and differential regulation of sodium-dependent phosphate uptake. AN - 76360883; 8106444 AB - To examine the biological properties of protein kinase C (PKC)-delta and -epsilon NIH 3T3 cells were stably transfected with metallothionein-based expression vectors that overexpressed these isoforms. In addition to their inducibility by Zn2+, the protein levels of these two PKC subtypes, but not that of endogenous PKC-alpha, increased with increasing cell density. An unexpected role for Mg2+ in the subcellular localization of PKC-delta was found. This isoenzyme was predominantly membrane-associated when cell fractionation was carried out in the absence of Mg2+ but cytosolic when the fractionation was performed in the presence of 10 mM Mg2+. In contrast, the predominant localization of cytosolic PKC-alpha and of membrane-associated PKC-epsilon was not influenced by Mg2+. In vivo and in vitro studies of [3H]phorbol 12,13-dibutyrate binding in the overexpressing cell lines confirmed the cytosolic localization of PKC-alpha, the membrane-associated state of PKC-epsilon, and the presence of PKC-delta at both locations. Readdition of serum for 5 min to serum-starved, quiescent cell lines initiated the redistribution of PKC-alpha to the particulate fraction, while the location of PKC-delta and PKC-epsilon was not affected. Zn(2+)-induced overexpression of PKC-delta- and PKC-epsilon-stimulated sodium-dependent phosphate uptake. Overexpression of PKC-delta caused an increase in the Vmax of Na+/P(i) uptake, while overexpression of PKC-epsilon resulted in a decrease in Km for orthophosphate. A further stimulation of Na+/P(i) uptake in the overexpressing cells could be achieved by phorbol ester activation of endogenous PKC-alpha. These results suggest that each of the three PKC isotypes contribute to the regulation of sodium-dependent phosphate uptake, but through distinct mechanisms. JF - The Journal of biological chemistry AU - Lehel, C AU - Olah, Z AU - Mischak, H AU - Mushinski, J F AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/18/ PY - 1994 DA - 1994 Feb 18 SP - 4761 EP - 4766 VL - 269 IS - 7 SN - 0021-9258, 0021-9258 KW - Isoenzymes KW - 0 KW - Phosphates KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Sodium KW - 9NEZ333N27 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Zinc KW - J41CSQ7QDS KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression -- drug effects KW - 3T3 Cells KW - Animals KW - Electrophoresis, Polyacrylamide Gel KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Cell Division -- drug effects KW - Mice KW - Protein Binding KW - Biological Transport -- drug effects KW - Zinc -- pharmacology KW - Blotting, Western KW - Transfection KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Induction KW - Subcellular Fractions -- enzymology KW - Protein Kinase C -- metabolism KW - Phosphates -- metabolism KW - Protein Kinase C -- analysis KW - Isoenzymes -- analysis KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- biosynthesis KW - Isoenzymes -- metabolism KW - Sodium -- pharmacology KW - Sodium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76360883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Overexpressed+protein+kinase+C-delta+and+-epsilon+subtypes+in+NIH+3T3+cells+exhibit+differential+subcellular+localization+and+differential+regulation+of+sodium-dependent+phosphate+uptake.&rft.au=Lehel%2C+C%3BOlah%2C+Z%3BMischak%2C+H%3BMushinski%2C+J+F%3BAnderson%2C+W+B&rft.aulast=Lehel&rft.aufirst=C&rft.date=1994-02-18&rft.volume=269&rft.issue=7&rft.spage=4761&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 - 1994-03-22 N1 - Date created - 1994-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A sequence-specific, single-strand binding protein activates the far upstream element of c-myc and defines a new DNA-binding motif. AN - 76383768; 8125259 AB - The far upstream element (FUSE) of the human c-myc proto-oncogene stimulates expression in undifferentiated cells. A FUSE-binding protein (FBP) is present in undifferentiated but not differentiated cells. Peptide sequences from the purified protein allowed cloning of cDNAs encoding FBP. Expression of FBP mRNA declined upon differentiation, suggesting transcriptional regulation of FBP. Features in the FBP cDNA suggest that FBP is also regulated by RNA processing, translation, and post-translational mechanisms. Both cellular and recombinant FBP form sequence-specific complexes with a single strand of FUSE. Transfection of FBP into human leukemia cells stimulated c-myc-promoter-driven expression from a reporter plasmid in a FUSE-dependent manner. Deletion and insertion mutagenesis of FBP defined a novel single-strand DNA-binding domain. Analysis of the primary and predicted secondary structure of the amino acid sequence reveals four copies of a reiterated unit comprised of a 30-residue direct repeat and an amphipathic alpha-helix separated by an 18- to 21-residue spacer. The third and fourth copies of this repeat-helix unit constitute the minimum single-stranded DNA-binding domain. To determine whether the FUSE site, in vivo, possesses single-strand conformation, and therefore could be bound by FBP, cells were treated with potassium permanganate (KMnO4) to modify unpaired bases. Modification of genomic DNA in vivo revealed hyperreactivity associated with single-stranded DNA in the FUSE sequence and protection on the strand that binds FBP in vitro. The role of single-stranded DNA and single-strand binding proteins in c-myc regulation is discussed. JF - Genes & development AU - Duncan, R AU - Bazar, L AU - Michelotti, G AU - Tomonaga, T AU - Krutzsch, H AU - Avigan, M AU - Levens, D AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/15/ PY - 1994 DA - 1994 Feb 15 SP - 465 EP - 480 VL - 8 IS - 4 SN - 0890-9369, 0890-9369 KW - c-myc KW - DNA, Complementary KW - 0 KW - DNA, Single-Stranded KW - DNA-Binding Proteins KW - Index Medicus KW - DNA, Single-Stranded -- metabolism KW - Protein Structure, Secondary KW - Promoter Regions, Genetic KW - Base Sequence KW - DNA, Complementary -- genetics KW - Humans KW - Molecular Sequence Data KW - Cell Differentiation -- genetics KW - Gene Expression Regulation KW - Amino Acid Sequence KW - Repetitive Sequences, Nucleic Acid KW - Cell Line KW - Mutagenesis KW - Genes, myc KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76383768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=A+sequence-specific%2C+single-strand+binding+protein+activates+the+far+upstream+element+of+c-myc+and+defines+a+new+DNA-binding+motif.&rft.au=Duncan%2C+R%3BBazar%2C+L%3BMichelotti%2C+G%3BTomonaga%2C+T%3BKrutzsch%2C+H%3BAvigan%2C+M%3BLevens%2C+D&rft.aulast=Duncan&rft.aufirst=R&rft.date=1994-02-15&rft.volume=8&rft.issue=4&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-08 N1 - Date created - 1994-04-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-myc N1 - Genetic sequence - U05040; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of RNA-binding proteins in mammalian cells by DNA-damaging agents. AN - 76361181; 7509078 AB - A technique to detect RNA-binding proteins (RBP) involving hybridization of RNA probe to proteins transferred to a membrane was used to study RBP in different mammalian cells and in cells after genotoxic stress. With this approach, up to 13 proteins of different sizes were detected in crude nuclear extracts by using a viral RNA probe consisting of the trans-activation-responsive (TAR) element of human immunodeficiency virus type 1 (HIV-1). The TAR RNA probe contains a stem-loop structure found in nascent HIV-1 transcripts. A G+C-rich probe with similar structure also bound to many of these RBP. Only a 102-kDa protein strongly bound to other RNA probes lacking this structure, while a probe with an A+U-rich stem-loop structure fail to bind most RBP, thus indicating a RNA secondary structure preference. The expression of these RBP varied substantially in nine different human and hamster cell lines, with no detectable RBP in two human myeloid lines. Evidence for induction of these RBP was found in six of seven lines after treatment with DNA-damaging agents; UV radiation was the most effective agent. In Chinese hamster ovary cells, which showed the strongest response, all five RBP present in untreated cells rapidly increased in activity after UV irradiation, and eight additional RBP were detected. The induction of these RBP by DNA-damaging agents indicates one or more possible roles for these proteins in the cellular response to genotoxic stress and in viral activation after such stress. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Carrier, F AU - Gatignol, A AU - Hollander, M C AU - Jeang, K T AU - Fornace, A J AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1994/02/15/ PY - 1994 DA - 1994 Feb 15 SP - 1554 EP - 1558 VL - 91 IS - 4 SN - 0027-8424, 0027-8424 KW - Nuclear Proteins KW - 0 KW - RNA-Binding Proteins KW - RNA KW - 63231-63-0 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Ultraviolet Rays KW - Gamma Rays KW - Humans KW - Xeroderma Pigmentosum -- metabolism KW - Protein Binding KW - Methyl Methanesulfonate -- pharmacology KW - RNA -- metabolism KW - CHO Cells -- radiation effects KW - Nuclear Proteins -- metabolism KW - Species Specificity KW - Cell Line KW - Cricetinae KW - DNA Damage -- physiology KW - RNA-Binding Proteins -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76361181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+RNA-binding+proteins+in+mammalian+cells+by+DNA-damaging+agents.&rft.au=Carrier%2C+F%3BGatignol%2C+A%3BHollander%2C+M+C%3BJeang%2C+K+T%3BFornace%2C+A+J&rft.aulast=Carrier&rft.aufirst=F&rft.date=1994-02-15&rft.volume=91&rft.issue=4&rft.spage=1554&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 - 1994-03-22 N1 - Date created - 1994-03-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Rev Physiol Biochem Pharmacol. 1992;119:187-223 [1604153] J Virol. 1992 Jul;66(7):4065-72 [1602533] Mol Cell Biol. 1993 Apr;13(4):2193-202 [8455607] Cell. 1993 Jun 4;73(5):837-40 [8500177] Nature. 1988 May 5;333(6168):78-81 [3129661] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8800-4 [3194391] Proc Natl Acad Sci U S A. 1989 Feb;86(4):1163-7 [2919165] Cell. 1989 Oct 20;59(2):273-82 [2478293] Proc Natl Acad Sci U S A. 1989 Oct;86(20):7828-32 [2510154] Proc Natl Acad Sci U S A. 1990 May;87(9):3624-8 [2333305] Mol Biol Rep. 1990;14(2-3):151-5 [1694559] J Clin Invest. 1990 Oct;86(4):1369-74 [2120288] J Virol. 1991 Feb;65(2):632-40 [1702840] New Biol. 1990 May;2(5):479-86 [1981148] Science. 1991 Mar 29;251(5001):1597-600 [2011739] New Biol. 1991 Sep;3(9):825-33 [1931825] Genes Dev. 1991 Nov;5(11):2128-40 [1936997] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9712-6 [1719538] Genes Dev. 1991 Dec;5(12B):2508-20 [1752441] Cell. 1991 Dec 20;67(6):1041-6 [1722140] J Virol. 1992 Mar;66(3):1688-94 [1738206] Mol Cell Biol. 1992 Apr;12(4):1856-63 [1312672] Virology. 1992 May;188(1):47-56 [1373554] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):517-21 [8421684] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. AN - 76354183; 8313377 AB - Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal tissues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host. The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well. JF - Cancer research AU - Samid, D AU - Ram, Z AU - Hudgins, W R AU - Shack, S AU - Liu, L AU - Walbridge, S AU - Oldfield, E H AU - Myers, C E AD - Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/15/ PY - 1994 DA - 1994 Feb 15 SP - 891 EP - 895 VL - 54 IS - 4 SN - 0008-5472, 0008-5472 KW - Phenylacetates KW - 0 KW - phenylacetic acid KW - ER5I1W795A KW - Mevalonic Acid KW - S5UOB36OCZ KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Tumor Cells, Cultured KW - Humans KW - Mevalonic Acid -- metabolism KW - Mice, Nude KW - Mice KW - Female KW - Protein Prenylation KW - Brain Neoplasms -- pathology KW - Glioma -- pathology KW - Phenylacetates -- pharmacology KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Phenylketonurias -- pathology KW - Brain -- pathology KW - Brain -- drug effects KW - Phenylacetates -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76354183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Selective+activity+of+phenylacetate+against+malignant+gliomas%3A+resemblance+to+fetal+brain+damage+in+phenylketonuria.&rft.au=Samid%2C+D%3BRam%2C+Z%3BHudgins%2C+W+R%3BShack%2C+S%3BLiu%2C+L%3BWalbridge%2C+S%3BOldfield%2C+E+H%3BMyers%2C+C+E&rft.aulast=Samid&rft.aufirst=D&rft.date=1994-02-15&rft.volume=54&rft.issue=4&rft.spage=891&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 - 1994-03-24 N1 - Date created - 1994-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors. AN - 76353059; 8313365 AB - Cytochrome P450 (CYP) enzymes expressed in human lung can metabolize a variety of xenobiotics, drugs, and endogenous compounds. Metabolism of these substrates may lead to their detoxification or activation and may affect the homeostasis of the lung, its susceptibility to disease, response to therapy, and clinical prognosis. We analyzed the expression of CYP2B7, CYP4B1, and NADPH-cytochrome P450 oxidoreductase (OR) mRNAs in normal lung controls, normal lung from lung cancer patients, and lung tumors using the sensitive technique of RNase protection. The mRNAs of CYP2B7, CYP4B1, and OR were detected in all the normal and a majority of neoplastic tissues. The three mRNAs were quantified and found at an average ratio of 0.89, 4.03, and 0.88% relative to actin mRNA in normal lung, respectively. There was no correlation between the levels of expression of the three mRNAs and the histological diagnosis of tumors. The amounts of each of the three mRNAs varied considerably between patients, but analysis of frequency distribution of the levels of CYP2B7 and CYP4B1 mRNAs did not present evidence for genetic polymorphism as a possible source of the observed interindividual variability. Levels of expression of the two P450 mRNAs were reduced (2.3- and 2.4-fold) in the neoplasms compared to normal lung. The level of OR mRNA expression was uniform with no significant differences between normal and neoplastic tissues, and its interindividual variability was the lowest amongst the three mRNAs studied. All mRNAs had increased interindividual variability in neoplastic tissues. Analysis of the patients' smoking histories and the level of CYP2B7, CYP4B1, and OR mRNAs revealed no evidence for their induction by compounds present in cigarette smoke. This study identifies and characterizes lung and lung tumor mRNAs encoding enzymes that may participate in the metabolism of xenobiotics in humans. JF - Cancer research AU - Czerwinski, M AU - McLemore, T L AU - Gelboin, H V AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/02/15/ PY - 1994 DA - 1994 Feb 15 SP - 1085 EP - 1091 VL - 54 IS - 4 SN - 0008-5472, 0008-5472 KW - RNA, Messenger KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - Index Medicus KW - Liver -- enzymology KW - Tumor Cells, Cultured KW - Humans KW - Smoking -- metabolism KW - Enzyme Induction KW - NADPH-Ferrihemoprotein Reductase -- genetics KW - Lung Neoplasms -- enzymology KW - Cytochrome P-450 Enzyme System -- genetics KW - RNA, Messenger -- analysis KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Lung -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76353059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantification+of+CYP2B7%2C+CYP4B1%2C+and+CYPOR+messenger+RNAs+in+normal+human+lung+and+lung+tumors.&rft.au=Czerwinski%2C+M%3BMcLemore%2C+T+L%3BGelboin%2C+H+V%3BGonzalez%2C+F+J&rft.aulast=Czerwinski&rft.aufirst=M&rft.date=1994-02-15&rft.volume=54&rft.issue=4&rft.spage=1085&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 - 1994-03-24 N1 - Date created - 1994-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An Escherichia coli RNA polymerase defective in transcription due to its overproduction of abortive initiation products. AN - 76362906; 7508986 AB - One of the potential regulatory steps in procaryotic transcription is promoter clearance, a transition step in transcription initiation at which an RNA polymerase (RNAP) switches from the initial transcribing stage to the elongation stage. The biological significance of promoter clearance and the role of RNAP in this process are not understood. One approach to address these questions is to study mutant RNAPs that have altered promoter clearance. Because the antibiotic rifampicin inhibits transcription by preventing an initial transcribing complex from entering the elongation mode, mutant RNAPs which confer rifampicin (Rifr) are likely to be altered in promoter clearance. To test this hypothesis, we studied the effects of Rifr RNAPs on the pyrBI promoter, which is subject to control of promoter clearance in response to the availability of UTP. Two Rifr alleles that carry a different altered amino acid residue at position 529 of the beta subunit appeared to be defective in transcription from the pyrBI promoter in vivo. Biochemical analysis of one of these mutant RNAPs, RpoB3401 with a R529C change in the beta subunit, showed that it overproduces aborted initiation products from the pyrBI promoter and thus is defective in promoter clearance leading to reduced productive initiation. The severity of overproducing the aborted initiation products is an inverse function of the UTP concentration indicating that RpoB3401 has reduced affinity for UTP and thus is subject to a high Km barrier during promoter clearance. The defect of RpoB3401 in abortive initiation in vitro could account fully for its reduced initiation activity in vivo demonstrating the biological significance of abortive synthesis in transcription initiation. Our results indicate that at least part of the "rif region" is important for the process of abortive initiation and that promoter clearance can be regulated in part by modulating the Km of RNAP for nucleotides during initiation. The mutant enzyme is not altered in stuttering RNA synthesis at the pyrBI promoter, previously observed with wild-type RNAP. Our results also show that the mechanisms underlying the two non-productive initiation events (abortive synthesis and stuttering synthesis) at the pyrBI promoter are distinct. JF - Journal of molecular biology AU - Jin, D J AU - Turnbough, C L AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02/11/ PY - 1994 DA - 1994 Feb 11 SP - 72 EP - 80 VL - 236 IS - 1 SN - 0022-2836, 0022-2836 KW - pyrB KW - pyrI KW - RNA, Bacterial KW - 0 KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Rifampin -- toxicity KW - Gene Expression Regulation, Bacterial KW - Regulatory Sequences, Nucleic Acid KW - Base Sequence KW - beta-Galactosidase -- metabolism KW - RNA, Bacterial -- biosynthesis KW - Kinetics KW - Drug Resistance, Microbial -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Templates, Genetic KW - beta-Galactosidase -- biosynthesis KW - Promoter Regions, Genetic KW - DNA-Directed RNA Polymerases -- metabolism KW - Operon KW - Escherichia coli -- drug effects KW - Escherichia coli -- genetics KW - Transcription, Genetic KW - Escherichia coli -- enzymology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76362906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=An+Escherichia+coli+RNA+polymerase+defective+in+transcription+due+to+its+overproduction+of+abortive+initiation+products.&rft.au=Jin%2C+D+J%3BTurnbough%2C+C+L&rft.aulast=Jin&rft.aufirst=D&rft.date=1994-02-11&rft.volume=236&rft.issue=1&rft.spage=72&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - pyrB; pyrI N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacteriophage lambda N-dependent transcription antitermination. Competition for an RNA site may regulate antitermination. AN - 76356438; 8107107 AB - Bacteriophage lambda controls the expression of its early genes in a temporal manner by a series of transcription termination and antitermination events. This antitermination requires the lambda N protein as well as host proteins called Nus, and cis-acting sites called nut. Following transcription of the nut site, N and Nus proteins bind to the nut RNA and modify the transcription complex to a termination-resistant form. The nut site is a composite of at least two components; one is the boxB hairpin structure which interacts with N. The other is boxA, a nine-nucleotide sequence upstream of boxB. To understand more about the formation of the antitermination complex, we have characterized the effect of point mutations in and deletions of boxA on antitermination. Point mutations in boxA were found to either enhance or reduce N-mediated antitermination. Several boxA deletions, on the other hand, had little effect on antitermination other than to eliminate the requirement for the NusB host protein. To explain these observations, we propose that at least two factors compete to interact with boxA, NusB and an inhibitor of the antitermination reaction. In addition, we propose that NusB is required to prevent the inhibitor from binding at boxA. The results with various nusB and boxA mutations can be explained by this model of competition between NusB and an inhibitor for boxA RNA. JF - Journal of molecular biology AU - Patterson, T A AU - Zhang, Z AU - Baker, T AU - Johnson, L L AU - Friedman, D I AU - Court, D L AD - Laboratory of Chromosome Biology, NCI-Frederick Cancer Research and Development Center, MD 21702. Y1 - 1994/02/11/ PY - 1994 DA - 1994 Feb 11 SP - 217 EP - 228 VL - 236 IS - 1 SN - 0022-2836, 0022-2836 KW - boxA KW - cro KW - nusA KW - nusB KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - N protein, Bacteriophage lambda KW - NusB protein, E coli KW - Peptide Elongation Factors KW - RNA, Viral KW - Transcription Factors KW - Transcriptional Elongation Factors KW - Viral Regulatory and Accessory Proteins KW - nusA protein, E coli KW - Index Medicus KW - Protein Biosynthesis KW - Escherichia coli -- metabolism KW - Genes, Bacterial KW - Bacterial Proteins -- biosynthesis KW - Transcription Factors -- metabolism KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Transcription Factors -- biosynthesis KW - Mutagenesis KW - Genotype KW - Base Sequence KW - Kinetics KW - RNA, Viral -- chemistry KW - Molecular Sequence Data KW - Suppression, Genetic KW - RNA, Viral -- metabolism KW - Gene Expression Regulation, Viral KW - Bacteriophage lambda -- genetics KW - Bacteriophage lambda -- metabolism KW - Viral Regulatory and Accessory Proteins -- metabolism KW - Transcription, Genetic KW - Genes, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76356438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Bacteriophage+lambda+N-dependent+transcription+antitermination.+Competition+for+an+RNA+site+may+regulate+antitermination.&rft.au=Patterson%2C+T+A%3BZhang%2C+Z%3BBaker%2C+T%3BJohnson%2C+L+L%3BFriedman%2C+D+I%3BCourt%2C+D+L&rft.aulast=Patterson&rft.aufirst=T&rft.date=1994-02-11&rft.volume=236&rft.issue=1&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - boxA; cro; nusA; nusB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The footprint of chromosomal proteins HMG-14 and HMG-17 on chromatin subunits. AN - 76353463; 8107104 AB - The position of chromosomal proteins HMG-14 and HMG-17 in nucleosome cores and in chromatosomes lacking linker histones has been mapped by hydroxyl radical footprinting. Both the nucleosome core and the H1/H5 depleted chromatosome can specifically bind two molecules of HMG-14/-17. The path of HMG-14 on the surface of chromatin subunits is indistinguishable from that of HMG-17. The bound HMGs protect the DNA from hydroxyl radical cleavage 25 base-pairs from the end of the DNA in nucleosome cores and in each of the two major grooves of the DNA flanking the nucleosomal dyad axis. Thus, in both cores and H1/H5-depleted chromatosomes the proteins bridge two adjacent DNA strands on the surface of the particles. The sites occupied by HMG near the end of the chromatosome-length particles are distinct from those occupied by the H1/H5 linker histones. In the region of the dyad axis the binding sites of HMGs overlap those of the linker histones. The placement of HMG-14/-17 near the nucleosomal dyad axis raises the possibility that interactions between histone H1 and HMGs may affect the transcriptional potential of chromatin. JF - Journal of molecular biology AU - Alfonso, P J AU - Crippa, M P AU - Hayes, J J AU - Bustin, M AD - Laboratory of Molecular Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02/11/ PY - 1994 DA - 1994 Feb 11 SP - 189 EP - 198 VL - 236 IS - 1 SN - 0022-2836, 0022-2836 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Nucleosomes KW - Recombinant Proteins KW - Hydroxyl Radical KW - 3352-57-6 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Models, Structural KW - DNA -- metabolism KW - Humans KW - Nucleosomes -- metabolism KW - Amino Acid Sequence KW - Erythrocytes -- metabolism KW - Nucleic Acid Conformation KW - Binding Sites KW - Chickens KW - Recombinant Proteins -- metabolism KW - Nucleosomes -- ultrastructure KW - Molecular Sequence Data KW - DNA -- chemistry KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - High Mobility Group Proteins -- chemistry KW - Chromatin -- metabolism KW - High Mobility Group Proteins -- metabolism KW - Chromatin -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76353463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=The+footprint+of+chromosomal+proteins+HMG-14+and+HMG-17+on+chromatin+subunits.&rft.au=Alfonso%2C+P+J%3BCrippa%2C+M+P%3BHayes%2C+J+J%3BBustin%2C+M&rft.aulast=Alfonso&rft.aufirst=P&rft.date=1994-02-11&rft.volume=236&rft.issue=1&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Mol Biol 1994 Jun 10;239(3):436 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of cysteine 78 in fluorosulfonylbenzoyladenosine inactivation of rat liver S-adenosylhomocysteine hydrolase. AN - 76349919; 8307967 AB - Inactivation of rat liver S-adenosylhomocysteine hydrolase by the site-directed reagent 5'-p-fluorosulfonylbenzoyladenosine (FSBA) is associated with the formation of a disulfide bond between Cys-78 and Cys-112 (Takata, Y., and Fujioka, M. (1984) Biochemistry 23, 4357-4362; Gomi, T., Ogawa, H., and Fujioka, M. (1986) J. Biol. Chem. 261, 13422-13425). To characterize the inactivation mechanism more precisely, the properties of four hydrolase proteins mutated at Cys-78 or Cys-112 were compared to those of the wild-type enzyme. When Cys-78 was mutated to either a serine or an alanine, proteins with greatly reduced enzymatic activity were obtained, large effects on kinetic constants were observed, and enzymatic activity was not affected by incubation with FSBA. When Cys-112 was mutated to either a serine or an alanine, the activity was similar to the wild-type protein, only small changes in the kinetic constants were observed, and the enzyme was inactivated more rapidly upon incubation with FSBA. FSBA inactivation of the C112A mutant protein was accompanied by the formation of a disulfide between Cys-78 and Cys-52. The data indicate that FSBA initially reacts with Cys-78 and that Cys-78 has an important role in the structure of the enzyme. JF - The Journal of biological chemistry AU - Aksamit, R R AU - Backlund, P S AU - Moos, M AU - Caryk, T AU - Gomi, T AU - Ogawa, H AU - Fujioka, M AU - Cantoni, G L AD - Laboratory of General and Comparative Biochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/11/ PY - 1994 DA - 1994 Feb 11 SP - 4084 EP - 4091 VL - 269 IS - 6 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Recombinant Proteins KW - 5'-(4-fluorosulfonylbenzoyl)adenosine KW - 78859-42-4 KW - Hydrolases KW - EC 3.- KW - Adenosylhomocysteinase KW - EC 3.3.1.1 KW - Chymotrypsin KW - EC 3.4.21.1 KW - Adenosine KW - K72T3FS567 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Chymotrypsin -- pharmacology KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Rats KW - Base Sequence KW - Kinetics KW - In Vitro Techniques KW - Molecular Sequence Data KW - DNA Primers -- chemistry KW - Cysteine -- chemistry KW - Adenosine -- pharmacology KW - Adenosine -- analogs & derivatives KW - Hydrolases -- chemistry KW - Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76349919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+role+of+cysteine+78+in+fluorosulfonylbenzoyladenosine+inactivation+of+rat+liver+S-adenosylhomocysteine+hydrolase.&rft.au=Aksamit%2C+R+R%3BBacklund%2C+P+S%3BMoos%2C+M%3BCaryk%2C+T%3BGomi%2C+T%3BOgawa%2C+H%3BFujioka%2C+M%3BCantoni%2C+G+L&rft.aulast=Aksamit&rft.aufirst=R&rft.date=1994-02-11&rft.volume=269&rft.issue=6&rft.spage=4084&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 - 1994-03-17 N1 - Date created - 1994-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An activating mutation in ARF1 stabilizes coatomer binding to Golgi membranes. AN - 76359227; 8106346 AB - The Ras-related protein ADP-ribosylation factor 1 (ARF1) is a low molecular weight GTP binding protein, which in its GTP state supports the binding of coatomer, a cytosolic coat protein complex, to Golgi membranes. To create an "active" ARF, we constructed a point mutation in ARF1, Q71I, which was predicted to slow the rate of GTP hydrolysis. We demonstrate that Q71I, in contrast to wild type ARF1, exhibits a 2-3-fold increase in the half-life of ARF-GTP and is able to promote stable coatomer binding to Golgi membranes in the presence of GTP in vitro. Additionally, Q71I is able to support the binding of a significant amount of coatomer to membranes in the absence of added nucleotides, effectively bypassing the brefeldin A (BFA)-sensitive exchange activity. Furthermore, transfection of cells with Q71I, but not ARF1, renders the Golgi association of coatomer resistant to the effects of BFA in vivo. These observations provide compelling evidence that ARF1 is a necessary GTP binding protein that regulates the reversible binding of coat proteins to Golgi membranes and that the effects of BFA on this process in living cells must be a consequence of BFA's inhibition of guanine nucleotide exchange onto ARF1. JF - The Journal of biological chemistry AU - Teal, S B AU - Hsu, V W AU - Peters, P J AU - Klausner, R D AU - Donaldson, J G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02/04/ PY - 1994 DA - 1994 Feb 04 SP - 3135 EP - 3138 VL - 269 IS - 5 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Coatomer Protein KW - Cyclopentanes KW - Membrane Proteins KW - Protein Synthesis Inhibitors KW - Recombinant Proteins KW - Brefeldin A KW - 20350-15-6 KW - Guanosine Triphosphate KW - 86-01-1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factor 1 KW - EC 3.6.5.2 KW - ADP-Ribosylation Factors KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Liver -- metabolism KW - Drug Resistance KW - Protein Binding KW - Cloning, Molecular KW - Guanosine Triphosphate -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Cyclopentanes -- pharmacology KW - Protein Synthesis Inhibitors -- pharmacology KW - Recombinant Proteins -- metabolism KW - Kinetics KW - CHO Cells KW - Cricetinae KW - GTP-Binding Proteins -- biosynthesis KW - Carrier Proteins -- metabolism KW - Membrane Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- isolation & purification KW - Point Mutation KW - Golgi Apparatus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76359227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+activating+mutation+in+ARF1+stabilizes+coatomer+binding+to+Golgi+membranes.&rft.au=Teal%2C+S+B%3BHsu%2C+V+W%3BPeters%2C+P+J%3BKlausner%2C+R+D%3BDonaldson%2C+J+G&rft.aulast=Teal&rft.aufirst=S&rft.date=1994-02-04&rft.volume=269&rft.issue=5&rft.spage=3135&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 - 1994-03-18 N1 - Date created - 1994-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substituted O6-benzylguanine derivatives and their inactivation of human O6-alkylguanine-DNA alkyltransferase. AN - 76355411; 8308861 AB - Several new O6-benzylguanine analogs bearing increasingly bulky substituent groups on the benzene ring or at position 9 were tested for their ability to inactivate the human DNA repair protein, O6-alkylguanine-DNA alkyltransferase. Substitution on the benzene ring was well tolerated although activity varied considerably with structural changes in groups attached to position 9. For this site, activity was preserved with large or small lipophilic groups while introduction of non-carbohydrate polar groups generally reduced activity regardless of their size. JF - Journal of medicinal chemistry AU - Chae, M Y AU - McDougall, M G AU - Dolan, M E AU - Swenn, K AU - Pegg, A E AU - Moschel, R C AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702. Y1 - 1994/02/04/ PY - 1994 DA - 1994 Feb 04 SP - 342 EP - 347 VL - 37 IS - 3 SN - 0022-2623, 0022-2623 KW - O(6)-benzylguanine KW - 01KC87F8FE KW - Guanine KW - 5Z93L87A1R KW - Methyltransferases KW - EC 2.1.1.- KW - O(6)-Methylguanine-DNA Methyltransferase KW - EC 2.1.1.63 KW - Index Medicus KW - Molecular Structure KW - Tumor Cells, Cultured KW - Humans KW - Structure-Activity Relationship KW - Colonic Neoplasms -- enzymology KW - Methyltransferases -- antagonists & inhibitors KW - Guanine -- chemistry KW - Guanine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76355411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substituted+O6-benzylguanine+derivatives+and+their+inactivation+of+human+O6-alkylguanine-DNA+alkyltransferase.&rft.au=Chae%2C+M+Y%3BMcDougall%2C+M+G%3BDolan%2C+M+E%3BSwenn%2C+K%3BPegg%2C+A+E%3BMoschel%2C+R+C&rft.aulast=Chae&rft.aufirst=M&rft.date=1994-02-04&rft.volume=37&rft.issue=3&rft.spage=342&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 - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Viral interactions with the p53 gene in human cancer: NCI workshop. AN - 76330217; 7904309 JF - Journal of the National Cancer Institute AU - Wong, M AU - Gruber, J Y1 - 1994/02/02/ PY - 1994 DA - 1994 Feb 02 SP - 177 EP - 182 VL - 86 IS - 3 KW - p53 KW - Oncogene Proteins, Viral KW - 0 KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Genes, p53 -- physiology KW - Oncogene Proteins, Viral -- physiology KW - Neoplasms -- microbiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76330217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Viral+interactions+with+the+p53+gene+in+human+cancer%3A+NCI+workshop.&rft.au=Wong%2C+M%3BGruber%2C+J&rft.aulast=Wong&rft.aufirst=M&rft.date=1994-02-02&rft.volume=86&rft.issue=3&rft.spage=177&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 - 1994-02-16 N1 - Date created - 1994-02-16 N1 - Date revised - 2017-01-13 N1 - Gene symbol - p53 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Construction of a cDNA library from microdissected guinea pig crista ampullaris. AN - 85163580; pmid-8157507 AB - Poly(A) RNA was isolated from microdissected guinea pig crista ampullaris epithelium and converted into cDNA with RNase H- murine leukemia virus reverse transcriptase. After size fractionation, the cDNA was directionally ligated into the vector pSPORT 1 and the plasmids electroporated into E. coli. The library was found to have 1.6 x 10(7) independent colonies with 5% of the colonies lacking an insert. Thirty randomly selected colonies were checked for inserts and the average insert size was 833 base pairs with a range of 400 to 2300 base pairs. The library was screened with a beta-actin guinea pig cDNA probe and 0.16% of the colonies contained an insert hybridizing to the probe. JF - Hearing Research AU - Wilcox, E R AU - Fex, J AD - Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892. PY - 1994 SP - 65 EP - 66 VL - 73 IS - 1 SN - 0378-5955, 0378-5955 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85163580?accountid=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=Construction+of+a+cDNA+library+from+microdissected+guinea+pig+crista+ampullaris.&rft.au=Wilcox%2C+E+R%3BFex%2C+J&rft.aulast=Wilcox&rft.aufirst=E&rft.date=1994-02-01&rft.volume=73&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Hearing+Research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Infectivity of titered doses of simian immunodeficiency virus clone E11S inoculated intravenously into rhesus macaques (Macaca mulatta). AN - 76828008; 7966238 AB - The macaque infectious dose (MID) of a single-cell clone of simian immunodeficiency virus isolated from a pig-tailed macaque (SIV/Mne clone E11S) was determined in rhesus macaques (Macaca mulatta). Twenty-one macaques were inoculated with 10-fold dilutions of the virus stock (three or four animals per dose). The virologic and clinical status of these animals was monitored for 26 weeks. The 25% MID (MID25) occurred at a 10(5)-fold dilution of the viral stock. JF - Journal of medical primatology AU - Benveniste, R E AU - Roodman, S T AU - Hill, R W AU - Knott, W B AU - Ribas, J L AU - Lewis, M G AU - Eddy, G A AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21702-1201. PY - 1994 SP - 83 EP - 88 VL - 23 IS - 2-3 SN - 0047-2565, 0047-2565 KW - Antibodies, Viral KW - 0 KW - DNA Primers KW - Index Medicus KW - AIDS/HIV KW - Simian Acquired Immunodeficiency Syndrome -- immunology KW - Sensitivity and Specificity KW - Antibodies, Viral -- blood KW - Immunoblotting KW - Animals KW - Base Sequence KW - Simian Acquired Immunodeficiency Syndrome -- physiopathology KW - Polymerase Chain Reaction -- methods KW - Macaca nemestrina KW - Molecular Sequence Data KW - Simian Immunodeficiency Virus -- isolation & purification KW - Simian Immunodeficiency Virus -- pathogenicity KW - Macaca mulatta -- virology KW - Simian Immunodeficiency Virus -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76828008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+primatology&rft.atitle=Infectivity+of+titered+doses+of+simian+immunodeficiency+virus+clone+E11S+inoculated+intravenously+into+rhesus+macaques+%28Macaca+mulatta%29.&rft.au=Benveniste%2C+R+E%3BRoodman%2C+S+T%3BHill%2C+R+W%3BKnott%2C+W+B%3BRibas%2C+J+L%3BLewis%2C+M+G%3BEddy%2C+G+A&rft.aulast=Benveniste&rft.aufirst=R&rft.date=1994-02-01&rft.volume=23&rft.issue=2-3&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+primatology&rft.issn=00472565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-16 N1 - Date created - 1994-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [125I]CGP 42112 reveals a non-angiotensin II binding site in 1-methyl-4-phenylpyridine (MPP+)-induced brain injury. AN - 76808853; 7954664 AB - 1. Intracerebral injection of the oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridine (MPP+), into the substantia nigra of adult rats resulted in a lesion at the injection site. 2. Using autoradiography, we localized specific [125I]CGP 42112 binding that was not recognized by angiotensin II or angiotensin II AT1 or AT2 receptor-selective ligands. 3. Our results suggest that [125I]CGP 42112 may be binding to activated microglia that appear at the lesion site. JF - Cellular and molecular neurobiology AU - Viswanathan, M AU - de Oliveira, A M AU - Wu, R M AU - Chiueh, C C AU - Saavedra, J M AD - Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 99 EP - 104 VL - 14 IS - 1 SN - 0272-4340, 0272-4340 KW - Angiotensin Receptor Antagonists KW - 0 KW - Biphenyl Compounds KW - Imidazoles KW - Iodine Radioisotopes KW - Oligopeptides KW - Receptors, Angiotensin KW - Tetrazoles KW - Angiotensin II KW - 11128-99-7 KW - CGP 42112A KW - 127060-75-7 KW - Losartan KW - JMS50MPO89 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - Animals KW - Imidazoles -- pharmacology KW - Receptors, Angiotensin -- metabolism KW - Substantia Nigra -- drug effects KW - Biphenyl Compounds -- pharmacology KW - Autoradiography KW - Binding Sites KW - Substantia Nigra -- metabolism KW - Rats KW - Tetrazoles -- pharmacology KW - Rats, Sprague-Dawley KW - Substantia Nigra -- pathology KW - Male KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - Brain -- pathology KW - Brain -- drug effects KW - Oligopeptides -- metabolism KW - Brain -- metabolism KW - Brain Injuries -- chemically induced KW - Angiotensin II -- pharmacology KW - Brain Injuries -- metabolism KW - Angiotensin II -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76808853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=%5B125I%5DCGP+42112+reveals+a+non-angiotensin+II+binding+site+in+1-methyl-4-phenylpyridine+%28MPP%2B%29-induced+brain+injury.&rft.au=Viswanathan%2C+M%3Bde+Oliveira%2C+A+M%3BWu%2C+R+M%3BChiueh%2C+C+C%3BSaavedra%2C+J+M&rft.aulast=Viswanathan&rft.aufirst=M&rft.date=1994-02-01&rft.volume=14&rft.issue=1&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-25 N1 - Date created - 1994-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of immunotoxins. AN - 76706086; 8086044 AB - Immunotoxins are being tested for the therapy of systemic cancer and brain tumors. Neurotoxicity has been dose limiting for several of these antibody conjugates given systemically. We review the animal and clinical data related to the neurotoxicity of immunotoxins in attempt to understand the molecular basis for the unexpected neural involvement and to prevent or minimize this toxicity in future clinical trials. JF - Molecular and chemical neuropathology AU - Ilercil, O AU - Laske, D W AU - Walbridge, S AU - Muaszko, K AU - Oldfield, E H AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892. PY - 1994 SP - 379 EP - 386 VL - 21 IS - 2-3 SN - 1044-7393, 1044-7393 KW - Immunotoxins KW - 0 KW - Index Medicus KW - Animals KW - Brain Neoplasms -- therapy KW - Tumor Cells, Cultured KW - Humans KW - Clinical Trials as Topic KW - Neoplasms -- therapy KW - Female KW - Immunotoxins -- toxicity KW - Central Nervous System -- drug effects KW - Immunotoxins -- therapeutic use KW - Central Nervous System -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76706086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+chemical+neuropathology&rft.atitle=Neurotoxicity+of+immunotoxins.&rft.au=Ilercil%2C+O%3BLaske%2C+D+W%3BWalbridge%2C+S%3BMuaszko%2C+K%3BOldfield%2C+E+H%3BYoule%2C+R+J&rft.aulast=Ilercil&rft.aufirst=O&rft.date=1994-02-01&rft.volume=21&rft.issue=2-3&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Molecular+and+chemical+neuropathology&rft.issn=10447393&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-10-17 N1 - Date created - 1994-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of hepatocellular carcinoma in nonhuman primates by the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline. AN - 76598613; 8033850 AB - The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was evaluated for carcinogenic effects in macaques, primarily cynomolgus monkeys. IQ was administered by gavage five times a week at doses of 10 or 20 mg/kg. IQ induced hepatocellular carcinoma in 55% of the animals at the low dose and in 95% of the animals at 20 mg/kg. The average latent period at the high dose level was 43 months and that at the low dose was 60 months. Generally, the tumor nodules exhibited a well- to moderately well-differentiated hepatocellular carcinoma, and a trabecular pattern was most frequently seen. Pulmonary metastases were also found in several of the monkeys. Thus, IQ is a potent carcinogen in nonhuman primates and is a potential carcinogen for humans. JF - Environmental health perspectives AU - Adamson, R H AU - Takayama, S AU - Sugimura, T AU - Thorgeirsson, U P AD - Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 190 EP - 193 VL - 102 IS - 2 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Macaca mulatta KW - Male KW - Female KW - Quinolines -- toxicity KW - Food Contamination KW - Mutagens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76598613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+hepatocellular+carcinoma+in+nonhuman+primates+by+the+food+mutagen+2-amino-3-methylimidazo%5B4%2C5-f%5Dquinoline.&rft.au=Adamson%2C+R+H%3BTakayama%2C+S%3BSugimura%2C+T%3BThorgeirsson%2C+U+P&rft.aulast=Adamson&rft.aufirst=R&rft.date=1994-02-01&rft.volume=102&rft.issue=2&rft.spage=190&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-17 N1 - Date created - 1994-08-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Carcinogenesis. 1988 Jan;9(1):71-3 [3335050] Carcinogenesis. 1984 Jul;5(7):921-4 [6733854] Gan. 1984 Jun;75(6):467-70 [6468834] Jpn J Cancer Res. 1985 Jul;76(7):570-6 [3928552] Environ Health Perspect. 1994 Feb;102(2):194-9 [8033851] Jpn J Cancer Res. 1990 Jan;81(1):10-4 [1691162] Mutat Res. 1991 Mar-Apr;259(3-4):399-410 [2017219] Carcinogenesis. 1991 Aug;12(8):1503-6 [1860171] Comment In: Environ Health Perspect. 1994 Feb;102(2):138-9 [8033833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates. AN - 76592450; 8033851 AB - The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights, and no abnormalities were observed upon gross inspection of the hearts. Microscopically, focal myocardial lesions were observed in 8 of 10 monkeys dosed with IQ. Light microscopic abnormalities included myocyte necrosis with or without chronic inflammatory infiltrates, interstitial fibrosis with myocyte hypertrophy or atrophy, and vasculitis. Electron microscopic findings included disruption of the mitochondrial architecture (i.e., mitochondrial swelling and clearing of matrix densities), myofibrillar loss, disorganization of the normal alignment of sarcomeres, and occasional myocytes showing nuclear hypertrophy or peripheral clumping of the nuclear chromatin. There was some correlation between the cumulative dose of IQ and the extent of the myocardial abnormalities. These findings suggest that chronic exposure to IQ can lead to myocardial damage in monkeys. Although focal and not associated with clinical evidence of heart failure, these abnormalities may represent the initial stages of IQ-induced toxic cardiomyopathy. JF - Environmental health perspectives AU - Thorgeirsson, U P AU - Farb, A AU - Virmani, R AU - Adamson, R H AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 194 EP - 199 VL - 102 IS - 2 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - Index Medicus KW - Animals KW - Necrosis KW - Macaca fascicularis KW - Myocardium -- pathology KW - Fibrosis KW - Cardiomegaly -- chemically induced KW - Macaca mulatta KW - Male KW - Female KW - Organ Size -- drug effects KW - Quinolines -- toxicity KW - Heart Diseases -- chemically induced KW - Carcinogens -- toxicity KW - Heart Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76592450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cardiac+damage+induced+by+2-amino-3-methyl-imidazo%5B4%2C5-f%5Dquinoline+in+nonhuman+primates.&rft.au=Thorgeirsson%2C+U+P%3BFarb%2C+A%3BVirmani%2C+R%3BAdamson%2C+R+H&rft.aulast=Thorgeirsson&rft.aufirst=U&rft.date=1994-02-01&rft.volume=102&rft.issue=2&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-17 N1 - Date created - 1994-08-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Circulation. 1968 May;37(5):854-64 [5646867] Am Heart J. 1965 Jun;69:766-79 [14296642] Ann Intern Med. 1974 Feb;80(2):249-59 [4590654] Lancet. 1976 Jan 10;1(7950):58-62 [54581] Am Heart J. 1976 Jun;91(6):792-7 [132114] Cancer Treat Rev. 1976 Sep;3(3):111-20 [822941] Ann Intern Med. 1978 Feb;88(2):168-75 [626445] Am J Med. 1978 Nov;65(5):823-32 [707541] Pharmacology. 1980;20(1):9-14 [6769133] Cancer Res. 1981 Mar;41(3):1006-10 [7459847] Arch Intern Med. 1981 May;141(6):758-63 [7235784] Cancer Res. 1983 Dec;43(12 Pt 1):5768-74 [6416669] Food Chem Toxicol. 1983 Oct;21(5):641-3 [6686192] Carcinogenesis. 1984 Jul;5(7):921-4 [6733854] Carcinogenesis. 1988 Mar;9(3):411-8 [3162208] Arch Pathol Lab Med. 1989 Aug;113(8):842-5 [2757483] Jpn J Cancer Res. 1990 Jan;81(1):10-4 [1691162] Mutat Res. 1991 Mar-Apr;259(3-4):205-17 [2017208] Lab Invest. 1991 Aug;65(2):228-36 [1715447] Ann Intern Med. 1992 Feb 15;116(4):311-3 [1733387] Gan. 1984 Jun;75(6):467-70 [6468834] Science. 1984 Oct 26;226(4673):466-8 [6093249] Mutat Res. 1985 Jun-Jul;150(1-2):33-41 [3889618] Environ Health Perspect. 1985 Oct;62:19-30 [4085422] N Engl J Med. 1987 Jan 22;316(4):191-3 [3796692] Arch Pathol Lab Med. 1987 Oct;111(10):953-6 [2957973] Arch Pathol Lab Med. 1988 Mar;112(3):225-30 [3278699] Biochemistry. 1992 Oct 13;31(40):9513-9 [1390733] J Natl Cancer Inst. 1992 Oct 21;84(20):1587-92 [1404452] Cancer Res. 1993 Apr 1;53(7):1583-9 [8453627] Environ Health Perspect. 1994 Feb;102(2):190-3 [8033850] Comment In: Environ Health Perspect. 1994 Feb;102(2):138-9 [8033833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report. AN - 76575474; 8021534 AB - We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac. JF - Journal of pain and symptom management AU - De Conno, F AU - Zecca, E AU - Martini, C AU - Ripamonti, C AU - Caraceni, A AU - Saita, L AD - Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 119 EP - 121 VL - 9 IS - 2 SN - 0885-3924, 0885-3924 KW - Analgesics KW - 0 KW - Tolmetin KW - D8K2JPN18B KW - Ketorolac KW - YZI5105V0L KW - Index Medicus KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Time Factors KW - Infusions, Parenteral KW - Male KW - Female KW - Pain, Intractable -- drug therapy KW - Neoplasms -- complications KW - Tolmetin -- adverse effects KW - Analgesics -- administration & dosage KW - Analgesics -- adverse effects KW - Tolmetin -- analogs & derivatives KW - Tolmetin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76575474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pain+and+symptom+management&rft.atitle=Tolerability+of+ketorolac+administered+via+continuous+subcutaneous+infusion+for+cancer+pain%3A+a+preliminary+report.&rft.au=De+Conno%2C+F%3BZecca%2C+E%3BMartini%2C+C%3BRipamonti%2C+C%3BCaraceni%2C+A%3BSaita%2C+L&rft.aulast=De+Conno&rft.aufirst=F&rft.date=1994-02-01&rft.volume=9&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Journal+of+pain+and+symptom+management&rft.issn=08853924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-04 N1 - Date created - 1994-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental profiles of ornithine decarboxylase activity in the hippocampus, neocortex and cerebellum: modulation following lead exposure. AN - 76552149; 8010157 AB - Ornithine decarboxylase (ODC) is a growth-associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead-acetate (Pb2+ prenatally (gestational day 13 to birth), postnatally (PND 1-15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb2+ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb2+ resulted in prolonged stimulations of ODC activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb2+ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb(2+)-induced modulations of ODC activity suggest that polyamine-dependent processes may play a significant role in the manifestation of Pb(2+)-induced neurotoxicity dependent upon developmental factors at specific exposure periods. JF - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience AU - Zawia, N H AU - Evers, L B AU - Harry, G J AD - Laboratory of Integrative Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27707. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 25 EP - 30 VL - 12 IS - 1 SN - 0736-5748, 0736-5748 KW - Lead KW - 2P299V784P KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals, Newborn KW - Animals KW - Fetus -- metabolism KW - Male KW - Female KW - Prenatal Exposure Delayed Effects KW - Pregnancy KW - Ornithine Decarboxylase -- metabolism KW - Aging -- metabolism KW - Cerebellum -- growth & development KW - Hippocampus -- growth & development KW - Cerebral Cortex -- enzymology KW - Cerebral Cortex -- growth & development KW - Hippocampus -- enzymology KW - Lead -- pharmacology KW - Cerebellum -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76552149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Strategy+and+planning+for+chemopreventive+drug+development%3A+clinical+development+plans.+Chemoprevention+Branch+and+Agent+Development+Committee.+National+Cancer+Institute.&rft.au=Kelloff%2C+G+J%3BCrowell%2C+J+A%3BBoone%2C+C+W%3BSteele%2C+V+E%3BLubet%2C+R+A%3BGreenwald%2C+P%3BAlberts%2C+D+S%3BCovey%2C+J+M%3BDoody%2C+L+A%3BKnapp%2C+G+G&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1994-01-01&rft.volume=20&rft.issue=&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-21 N1 - Date created - 1994-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pulmonary toxicity to intratracheally administered indium trichloride in Fischer 344 rats. AN - 76548325; 8005375 AB - The use of indium by the semiconductor industry has risen sharply in recent years with the discovery that the electrical properties of compounds such as indium phosphide and indium arsenide are better than those of silicon. However, relatively little is known about its potential to induce lung damage. These studies examined the effect of indium trichloride (InCl3) on the lung. To examine the disposition and removal of InCl3 from the lung, groups of female Fischer 344 rats received a single intratracheal dose of 1.3 mg In/kg as InCl3 and were euthanized after 1, 2, 4, 7, 14, 28, and 56 days at which time lung samples were analyzed for metal content. Furthermore, the histology, hydroxyproline levels, and bronchoalveolar lavage (BAL) fluid cellularity of the lung were studied. In addition, the effect of 0.00016, 0.00325, 0.065, and 1.3 mg In/kg on inflammatory response and BAL fluid cellularity was compared. While a dose as low as 0.00325 mg In/kg was capable of initiating an influx of inflammatory cells, instillation of 1.3 mg In/kg resulted in an inflammatory response that was still evident 56 days later. After 28 days, the lung weight of the InCl3-treated animals was 2.5 times greater than that of the controls. The total cell number in the BAL fluid of the treated animals after 28 days was 32 times higher than that in the control rats. Sixty-seven percent of these cells were granulocytes. Compared to the controls, the hydroxyproline content of the lungs from the InCl3-treated animals were two-fold greater after 28 and 56 days. Furthermore, the levels of fibronectin and TNF alpha present in the BAL fluid of InCl3-treated rats increased sharply during the first 24 hr and remained elevated 56 days later. These data and the histological examination of the lung following InCl3 treatment suggest that InCl3 is capable of causing severe lung damage and the development of fibrosis. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Blazka, M E AU - Dixon, D AU - Haskins, E AU - Rosenthal, G J AD - Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 231 EP - 239 VL - 22 IS - 2 SN - 0272-0590, 0272-0590 KW - Fibronectins KW - 0 KW - Tumor Necrosis Factor-alpha KW - Indium KW - 045A6V3VFX KW - indium trichloride KW - 31JB8MKF8Z KW - Hydroxyproline KW - RMB44WO89X KW - Index Medicus KW - Animals KW - Intubation, Intratracheal KW - Fibronectins -- metabolism KW - Spectrophotometry, Atomic KW - Lung -- metabolism KW - Lung -- pathology KW - Rats KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Lung -- drug effects KW - Tumor Necrosis Factor-alpha -- metabolism KW - Bronchoalveolar Lavage Fluid -- cytology KW - Female KW - Hydroxyproline -- metabolism KW - Organ Size -- drug effects KW - Lung Diseases -- chemically induced KW - Indium -- toxicity KW - Lung Diseases -- pathology KW - Indium -- pharmacokinetics KW - Indium -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76548325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Pulmonary+toxicity+to+intratracheally+administered+indium+trichloride+in+Fischer+344+rats.&rft.au=Blazka%2C+M+E%3BDixon%2C+D%3BHaskins%2C+E%3BRosenthal%2C+G+J&rft.aulast=Blazka&rft.aufirst=M&rft.date=1994-02-01&rft.volume=22&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-20 N1 - Date created - 1994-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 1462V mutation in the human CYP1A1 gene: lack of correlation with either the Msp I 1.9 kb (M2) allele or CYP1A1 inducibility in a three-generation family of east Mediterranean descent. AN - 76547634; 7516235 AB - A 15-member three-generation family of Eastern Mediterranean descent was previously studied, and an association between CYP1A1 (cytochrome P1450, benzo[a]pyrene hydroxylase) inducibility and a CYP1A1 3'-polymorphism (the Msp I 1.9 kb allele) was reported (Petersen et al., Am J Hum Genet 1991:48, 720-725). Here we have re-examined the original DNA (and in some cases, newly prepared DNA from freshly drawn blood) from these same individuals, in order to assess the association between CYP1A1 inducibility and both the CYP1A1 gene Msp I RFLP polymorphism and the CYP1A1 gene A-->G polymorphism at codon 462. This latter nucleotide change results in an altered amino acid (462Ile-->Val), which is purported to increase CYP1A1 enzyme activity and mutagenicity towards benzo[a]pyrene about two-fold among Japanese. Among the 15 members of this three-generation family examined, no absolute correlation was observed between the 1462V genotype and either the Msp I 1.9 kb allele or the CYP1A1 inducibility phenotype. We also found no absolute correlation between the Msp I 1.9 kb allele and the CYP1A1 inducibility phenotype. JF - Pharmacogenetics AU - Wedlund, P J AU - Kimura, S AU - Gonzalez, F J AU - Nebert, D W AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 21 EP - 26 VL - 4 IS - 1 SN - 0960-314X, 0960-314X KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Benzopyrene Hydroxylase KW - EC 1.14.14.- KW - Deoxyribonuclease HpaII KW - EC 3.1.21.- KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - Index Medicus KW - Pedigree KW - Alleles KW - Genome, Human KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Enzyme Induction KW - Mediterranean Sea KW - Male KW - Female KW - Deoxyribonucleases, Type II Site-Specific -- metabolism KW - Benzopyrene Hydroxylase -- genetics KW - Gene Expression Regulation, Enzymologic KW - Cytochrome P-450 Enzyme System -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76547634?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=1462V+mutation+in+the+human+CYP1A1+gene%3A+lack+of+correlation+with+either+the+Msp+I+1.9+kb+%28M2%29+allele+or+CYP1A1+inducibility+in+a+three-generation+family+of+east+Mediterranean+descent.&rft.au=Wedlund%2C+P+J%3BKimura%2C+S%3BGonzalez%2C+F+J%3BNebert%2C+D+W&rft.aulast=Wedlund&rft.aufirst=P&rft.date=1994-02-01&rft.volume=4&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-19 N1 - Date created - 1994-07-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin A in epithelial differentiation and skin carcinogenesis. AN - 76526974; 8202282 JF - Nutrition reviews AU - De Luca, L M AU - Darwiche, N AU - Celli, G AU - Kosa, K AU - Jones, C AU - Ross, S AU - Chen, L C AD - Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - S45 EP - S52 VL - 52 IS - 2 Pt 2 SN - 0029-6643, 0029-6643 KW - Receptors, Retinoic Acid KW - 0 KW - Vitamin A KW - 11103-57-4 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Receptors, Retinoic Acid -- physiology KW - Animals KW - Humans KW - Epithelium -- physiology KW - Tretinoin -- metabolism KW - Skin Neoplasms -- etiology KW - Vitamin A -- physiology KW - Vitamin A Deficiency -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76526974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+reviews&rft.atitle=Vitamin+A+in+epithelial+differentiation+and+skin+carcinogenesis.&rft.au=De+Luca%2C+L+M%3BDarwiche%2C+N%3BCelli%2C+G%3BKosa%2C+K%3BJones%2C+C%3BRoss%2C+S%3BChen%2C+L+C&rft.aulast=De+Luca&rft.aufirst=L&rft.date=1994-02-01&rft.volume=52&rft.issue=2+Pt+2&rft.spage=S45&rft.isbn=&rft.btitle=&rft.title=Nutrition+reviews&rft.issn=00296643&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-01 N1 - Date created - 1994-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebrospinal fluid oxytocin concentration in schizophrenic patients does not differ from control subjects and is not changed by neuroleptic medication. AN - 76506811; 7910756 AB - Cerebrospinal fluid (CSF) oxytocin concentrations in 20 neuroleptic-treated schizophrenic patients, 31 neuroleptic-withdrawn schizophrenic patients, and 15 normal control subjects were compared. Neither within-subject comparisons of CSF oxytocin concentration measurements made during neuroleptic treatment and withdrawal (n = 11), nor comparison of the combined neuroleptic-withdrawn and neuroleptic-treated patient group (n = 40) with control subjects (n = 15) differed significantly, suggesting that CSF oxytocin concentration is not altered in schizophrenia. JF - Schizophrenia research AU - Glovinsky, D AU - Kalogeras, K T AU - Kirch, D G AU - Suddath, R AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Center at Saint Elizabeths, Washington, DC 20032. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 273 EP - 276 VL - 11 IS - 3 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Oxytocin KW - 50-56-6 KW - Index Medicus KW - Reference Values KW - Substance Withdrawal Syndrome -- diagnosis KW - Humans KW - Adult KW - Substance Withdrawal Syndrome -- cerebrospinal fluid KW - Male KW - Female KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Schizophrenia -- cerebrospinal fluid KW - Oxytocin -- cerebrospinal fluid KW - Antipsychotic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76506811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Cerebrospinal+fluid+oxytocin+concentration+in+schizophrenic+patients+does+not+differ+from+control+subjects+and+is+not+changed+by+neuroleptic+medication.&rft.au=Glovinsky%2C+D%3BKalogeras%2C+K+T%3BKirch%2C+D+G%3BSuddath%2C+R%3BWyatt%2C+R+J&rft.aulast=Glovinsky&rft.aufirst=D&rft.date=1994-02-01&rft.volume=11&rft.issue=3&rft.spage=273&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-27 N1 - Date created - 1994-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An examination of the alcohol consumption and peptic ulcer association--results of a national survey. AN - 76503680; 8198212 AB - Excessive alcohol consumption causes damages to the stomach or duodenum by impairing the integrity of the mucosal barrier. The aim of this study was to estimate the association between alcohol consumption and peptic ulcer, utilizing a large representative sample of the U.S. population, while controlling for cigarette smoking and major sociodemographic variables. Results indicated that alcohol consumption only minimally increased the odds of peptic ulcer. Thus, this study offers little support for the association between ethanol intake and peptic ulcer. JF - Alcoholism, clinical and experimental research AU - Chou, S P AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 149 EP - 153 VL - 18 IS - 1 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Cross-Sectional Studies KW - Alcoholism -- epidemiology KW - Risk Factors KW - Adult KW - Incidence KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Alcoholism -- complications KW - Female KW - Male KW - Alcohol Drinking -- adverse effects KW - Peptic Ulcer -- etiology KW - Alcohol Drinking -- epidemiology KW - Peptic Ulcer -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76503680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=An+examination+of+the+alcohol+consumption+and+peptic+ulcer+association--results+of+a+national+survey.&rft.au=Chou%2C+S+P&rft.aulast=Chou&rft.aufirst=S&rft.date=1994-02-01&rft.volume=18&rft.issue=1&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-30 N1 - Date created - 1994-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mouse selenocysteine tRNA([Ser]Sec) gene (Trsp) and its localization on chromosome 7. AN - 76502853; 8188307 JF - Genomics AU - Ohama, T AU - Choi, I S AU - Hatfield, D L AU - Johnson, K R AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 595 EP - 596 VL - 19 IS - 3 SN - 0888-7543, 0888-7543 KW - TRSP KW - Trsp KW - Genetic Markers KW - 0 KW - RNA, Transfer, Amino Acid-Specific KW - tRNA, selenocysteine- KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Hybridization, Genetic KW - Humans KW - Chromosome Mapping KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Crosses, Genetic KW - Species Specificity KW - Muridae -- genetics KW - Female KW - Male KW - Gene Library KW - Genes KW - Mice -- genetics KW - RNA, Transfer, Amino Acid-Specific -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76502853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Mouse+selenocysteine+tRNA%28%5BSer%5DSec%29+gene+%28Trsp%29+and+its+localization+on+chromosome+7.&rft.au=Ohama%2C+T%3BChoi%2C+I+S%3BHatfield%2C+D+L%3BJohnson%2C+K+R&rft.aulast=Ohama&rft.aufirst=T&rft.date=1994-02-01&rft.volume=19&rft.issue=3&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-20 N1 - Date created - 1994-06-20 N1 - Date revised - 2017-01-13 N1 - Gene symbol - TRSP; Trsp N1 - Genetic sequence - L22019; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia. AN - 76501262; 7910755 AB - Patients with schizophrenia appear to have abnormalities in both brain structures and information processing. Several recent reports have suggested that correlations exist between such measures. We examined the volume of several brain regions using magnetic resonance imaging (MRI), and also assessed both information processing, using brain event-related potentials (ERPs), and clinical symptomatology in sixteen medicated patients with schizophrenia. Subjects were tested using auditory and visual discrimination tasks. From the ERPs elicited by stimuli presented with relative probabilities of 0.1, the N100, N200, and P300 components were identified and measured. All subjects also had MRI scans that included 12 contiguous coronal sections, each 1 cm thick. From these scans, the following structures were identified and the volume or area quantified: third ventricle, lateral ventricles (partial), amygdala and hippocampus (one slice), partial brain volume (in one slice through the parietal lobe), and total prefrontal and temporal lobe gray and white matter in both cortical regions. Significant correlations were found between hippocampal area and the amplitude of the auditory and visual N200, and between the right hippocampus and the visual P300. Lower but significant correlations were seen between auditory P300 and measures of left temporal lobe structures. Auditory P300 amplitude correlated inversely with positive symptoms of schizophrenia. These preliminary results suggest that the ERP abnormalities in patients with schizophrenia are associated with temporal lobe pathology. JF - Schizophrenia research AU - Egan, M F AU - Duncan, C C AU - Suddath, R L AU - Kirch, D G AU - Mirsky, A F AU - Wyatt, R J AD - Neuropsychiatry Branch, National Institute of Mental Health, Neuroscience Research Center, St. Elizabeths, Washington, DC 20032. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 259 EP - 271 VL - 11 IS - 3 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Reaction Time -- drug effects KW - Reference Values KW - Cerebral Cortex -- drug effects KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Evoked Potentials, Auditory -- drug effects KW - Evoked Potentials, Visual -- physiology KW - Reaction Time -- physiology KW - Hippocampus -- drug effects KW - Cerebral Cortex -- physiopathology KW - Brain Mapping KW - Evoked Potentials, Visual -- drug effects KW - Psychiatric Status Rating Scales KW - Cerebral Cortex -- pathology KW - Adult KW - Hippocampus -- physiopathology KW - Hippocampus -- pathology KW - Antipsychotic Agents -- adverse effects KW - Male KW - Female KW - Evoked Potentials, Auditory -- physiology KW - Neurocognitive Disorders -- psychology KW - Arousal -- physiology KW - Schizophrenia -- diagnosis KW - Electroencephalography -- drug effects KW - Neurocognitive Disorders -- drug therapy KW - Schizophrenia -- physiopathology KW - Temporal Lobe -- pathology KW - Neurocognitive Disorders -- diagnosis KW - Temporal Lobe -- drug effects KW - Arousal -- drug effects KW - Schizophrenic Psychology KW - Attention -- physiology KW - Schizophrenia -- drug therapy KW - Attention -- drug effects KW - Temporal Lobe -- physiopathology KW - Neurocognitive Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76501262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry.+Supplement&rft.atitle=Surrogate+endpoint+biomarkers+for+phase+II+cancer+chemoprevention+trials.&rft.au=Kelloff%2C+G+J%3BBoone%2C+C+W%3BCrowell%2C+J+A%3BSteele%2C+V+E%3BLubet%2C+R%3BDoody%2C+L+A&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1994-01-01&rft.volume=19&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry.+Supplement&rft.issn=07331959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-27 N1 - Date created - 1994-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-tumor efficacy of glutaminase-copper-ATP combination in mice bearing Ehrlich ascites carcinoma. AN - 76486792; 8186431 AB - Glutaminase is a hematotoxic anti-tumor agent, and copper-ATP complex (Cu-ATP) is both anti-neoplastic and hematostimulatory. Combination chemotherapy with these two agents has been performed in mice bearing Ehrlich ascites carcinoma, to elucidate whether this could result in augmented tumor inhibition with reduced hematotoxicity. Glutaminase-Cu-ATP combination (glutaminase 250 IU/kg per day intraperitoneally for 10 days and Cu-ATP 2.5 mg/kg per day intraperitoneally for 10 days) was observed to be more effective in inhibiting tumor growth and in increasing the life span of the tumor hosts, compared with the individual efficacies of these two agents. Moreover, addition of Cu-ATP successfully prevented the hematotoxic effects of glutaminase in normal and in tumor-bearing animals. Thus glutaminase in combination with Cu-ATP holds promise for an effective cancer chemotherapeutic regimen. JF - Anti-cancer drugs AU - Pal, S AU - Maity, P AD - Department of Cell Biology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 57 EP - 63 VL - 5 IS - 1 SN - 0959-4973, 0959-4973 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - RNA, Neoplasm KW - Copper KW - 789U1901C5 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Glutaminase KW - EC 3.5.1.2 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Neoplasm Proteins -- biosynthesis KW - Animals KW - Bone Marrow -- pathology KW - Liver -- enzymology KW - Copper -- administration & dosage KW - Spleen -- pathology KW - Glutaminase -- administration & dosage KW - Mice KW - Cell Nucleus -- drug effects KW - Neoplasm Transplantation KW - Adenosine Triphosphate -- administration & dosage KW - Glutaminase -- metabolism KW - Spleen -- drug effects KW - Colony-Forming Units Assay KW - Drug Synergism KW - Bone Marrow -- drug effects KW - DNA, Neoplasm -- biosynthesis KW - Male KW - Blood Cell Count -- drug effects KW - Carcinoma, Ehrlich Tumor -- metabolism KW - Carcinoma, Ehrlich Tumor -- pathology KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76486792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Carbohydrate+Chemistry&rft.atitle=Synthesis+of+the+methyl+alpha+-glycoside+of+the+intracatenary+disaccharide+repeating+unit+of+the+O-polysaccharide+of+Vibrio+cholerae+O%3A1.+A+comparison+of+two+assembly+strategies&rft.au=Gotoh%2C+M%3BKovac%2C+P&rft.aulast=Gotoh&rft.aufirst=M&rft.date=1994-01-01&rft.volume=13&rft.issue=8&rft.spage=1193&rft.isbn=&rft.btitle=&rft.title=Journal+of+Carbohydrate+Chemistry&rft.issn=07328303&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-23 N1 - Date created - 1994-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Manic-depressive (bipolar) disorder: the course in light of a prospective ten-year follow-up of 131 patients. AN - 76485750; 8178659 AB - For a five-year period, 131 bipolar patients were followed every 6 months; for the next 5 years, they were followed yearly. Each patient was interviewed in a systematic way that gave information about episodes, hospitalizations, cycle lengths and the presence of alcoholism. Women and men were not significantly different in the number of follow-up manic or depressive episodes or hospitalizations. Chronicity from index episode to the end of the 10-year follow-up was uncommon (4%). Alcoholism, which was common in these patients, showed a great diminution at the end of 10 years. Contrary to expectation, cycle lengths showed no systematic decrease in length over the follow-up. In this naturalistic study, treatment intensity was not related to decreasing episodes or to changes in cycle length. The number of episodes in the first 5 years of follow-up was not correlated with the number of episodes in the last 5 years. Cycle lengths in the first 5 years of follow-up were similar in length to the last 5 years of follow-up. A family history of mania in these bipolar patients was associated with more episodes in follow-up than if such a family history were absent. The patients whose alcoholism predated the onset of their affective illness were less likely to have episodes in the follow-up than the patients in whom affective illness predated the onset of the alcoholism. JF - Acta psychiatrica Scandinavica AU - Winokur, G AU - Coryell, W AU - Akiskal, H S AU - Endicott, J AU - Keller, M AU - Mueller, T AD - US National Institute of Mental Health, Collaborative Program on Psychobiology of Depression, Bethesda, Maryland. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 102 EP - 110 VL - 89 IS - 2 SN - 0001-690X, 0001-690X KW - Index Medicus KW - Alcoholism -- rehabilitation KW - Alcoholism -- diagnosis KW - Humans KW - Alcoholism -- genetics KW - Recurrence KW - Comorbidity KW - Patient Readmission KW - Prospective Studies KW - Risk Factors KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Bipolar Disorder -- diagnosis KW - Bipolar Disorder -- genetics KW - Bipolar Disorder -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76485750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+psychiatrica+Scandinavica&rft.atitle=Manic-depressive+%28bipolar%29+disorder%3A+the+course+in+light+of+a+prospective+ten-year+follow-up+of+131+patients.&rft.au=Winokur%2C+G%3BCoryell%2C+W%3BAkiskal%2C+H+S%3BEndicott%2C+J%3BKeller%2C+M%3BMueller%2C+T&rft.aulast=Winokur&rft.aufirst=G&rft.date=1994-02-01&rft.volume=89&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Acta+psychiatrica+Scandinavica&rft.issn=0001690X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-09 N1 - Date created - 1994-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Acta Psychiatr Scand. 1995 Nov;92(5):398 [8619346] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do the benefits of nicotine help beat the addiction rap? AN - 76475306; 8173474 JF - Addiction (Abingdon, England) AU - Henningfield, J E AD - Clinical Pharmacology Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 135 EP - 6; discussion 144-6 VL - 89 IS - 2 SN - 0965-2140, 0965-2140 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Self Administration KW - Cognition -- drug effects KW - Arousal -- drug effects KW - Humans KW - Nicotine -- adverse effects KW - Smoking Cessation -- methods KW - Nicotine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76475306?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biological+Chemistry&rft.atitle=Importance+of+the+region+around+lysine+196+for+catalytic+activity+of+adenylyl+cyclase+from+Escherichia+coli&rft.au=Amin%2C+N%3BPeterkofsky%2C+A&rft.aulast=Amin&rft.aufirst=N&rft.date=1994-01-01&rft.volume=269&rft.issue=49&rft.spage=31094&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 completed - 1994-06-08 N1 - Date created - 1994-06-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Addiction. 1993 May;88(5):589-90 [8043039] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promotion of hepatocellular foci and adenomas by di(2-ethylhexyl) phthalate and phenobarbital in C3H/HeNCr mice following exposure to N-nitrosodiethylamine at 15 days of age. AN - 76450434; 8167465 AB - Previous studies have shown that phenobarbital (PB), as well as another known liver tumor promoter, alpha-hexachlorocyclohexane (HCH), inhibits hepatic tumor formation in infant N-nitrosodiethylamine (NDEA)-initiated C57BL/6 x C3H/He (B6C3F1) male mice. These inconsistencies in detecting PB and HCH as tumor promoters have raised important questions on the mechanism of tumor promotion in mice, as well as the reliability of the infant B6C3F1 mouse as an initiation model in two-stage carcinogenesis experiments. Therefore, in an effort to avoid the inconsistencies associated with the B6C3F1 mouse, the present study evaluated the ability of two known hepatic liver tumor promoters, di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, and phenobarbital (PB), a barbiturate, to promote hepatocellular tumorigenesis in mice of the C3H/HeNCr strain initiated during infancy. At 15 days of age, male and female C3H/HeNCr mice received either a single ip injection of NDEA (5 micrograms/g body weight) or saline. At weaning (4 weeks of age), mice were divided into 3 groups and treated with either DEHP in the diet (12,000 ppm), PB in the drinking water (500 ppm), or control drinking water and diet for 24 weeks. All mice were killed at 28 weeks of age and the number and size of hepatic foci and adenomas were evaluated. Mice exposed to NDEA+DEHP or NDEA+PB showed significant increases in the number and size of hepatic tumors compared to those receiving NDEA alone. DEHP treatment in males yielded larger adenomas than those seen in PB-treated males.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Weghorst, C M AU - Devor, D E AU - Henneman, J R AU - Ward, J M AD - Laboratory of Comparative Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 423 EP - 431 VL - 45 IS - 7 SN - 0940-2993, 0940-2993 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Mice, Inbred C3H KW - Incidence KW - Disease Models, Animal KW - Mice KW - Male KW - Female KW - Diethylnitrosamine -- toxicity KW - Liver Neoplasms -- pathology KW - Diethylhexyl Phthalate -- toxicity KW - Liver Neoplasms -- chemically induced KW - Liver Neoplasms -- epidemiology KW - Adenoma, Liver Cell -- pathology KW - Adenoma, Liver Cell -- chemically induced KW - Phenobarbital -- toxicity KW - Adenoma, Liver Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76450434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Promotion+of+hepatocellular+foci+and+adenomas+by+di%282-ethylhexyl%29+phthalate+and+phenobarbital+in+C3H%2FHeNCr+mice+following+exposure+to+N-nitrosodiethylamine+at+15+days+of+age.&rft.au=Weghorst%2C+C+M%3BDevor%2C+D+E%3BHenneman%2C+J+R%3BWard%2C+J+M&rft.aulast=Weghorst&rft.aufirst=C&rft.date=1994-02-01&rft.volume=45&rft.issue=7&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-02 N1 - Date created - 1994-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Potassium permanganate can be used for degrading hazardous compounds. AN - 76438914; 8160606 AB - Solutions of potassium permanganate in 3 M sulfuric acid, 1 M sodium hydroxide solution, and water can be used to degrade hazardous compounds. Excess oxidant can be removed by using sodium metabisulfite. Manganese, a carcinogen and mutagen, can be removed from the final reaction mixtures by making these mixtures strongly basic. Aqueous dilution causes the soluble potassium sulfate to dissolve while still allowing the insoluble manganese compounds to be removed by filtration and so reduces the weight of precipitate. In all cases the amount of manganese left in the filtrates was less than 2 ppm and the reaction mixtures were nonmutagenic. When ethanol was used as a test compound, degradation was much more rapid when the solvent was 3 M sulfuric acid or 1 M sodium hydroxide solution than when the solvent was water. However, the variation of the rate of reaction with pH depends on the nature of the substrate. Thus the effectiveness of the various methods may vary for other substrates. Potassium permanganate in sulfuric acid was used to degrade four polycyclic heterocyclic hydrocarbons. Destruction was greater than 99.9% and the final reaction mixtures contained no more than 0.5 ppm manganese and were not mutagenic. By modifying the work-up procedures to remove manganese from the final reaction mixture, procedures previously developed for degrading hazardous compounds can still be employed. JF - American Industrial Hygiene Association journal AU - Lunn, G AU - Sansone, E B AU - De Méo, M AU - Laget, M AU - Castegnaro, M AD - PRI/DynCorp, Environmental Control and Research Program, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 167 EP - 171 VL - 55 IS - 2 SN - 0002-8894, 0002-8894 KW - Drug Combinations KW - 0 KW - Hazardous Substances KW - Hazardous Waste KW - Polycyclic Compounds KW - Sulfuric Acids KW - Potassium Permanganate KW - 00OT1QX5U4 KW - Manganese KW - 42Z2K6ZL8P KW - Sodium Hydroxide KW - 55X04QC32I KW - sulfuric acid KW - O40UQP6WCF KW - Index Medicus KW - Chemistry, Physical KW - Hydrogen-Ion Concentration KW - Manganese -- chemistry KW - Chemical Phenomena KW - Refuse Disposal KW - Polycyclic Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76438914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Industrial+Hygiene+Association+journal&rft.atitle=Potassium+permanganate+can+be+used+for+degrading+hazardous+compounds.&rft.au=Lunn%2C+G%3BSansone%2C+E+B%3BDe+M%C3%A9o%2C+M%3BLaget%2C+M%3BCastegnaro%2C+M&rft.aulast=Lunn&rft.aufirst=G&rft.date=1994-02-01&rft.volume=55&rft.issue=2&rft.spage=167&rft.isbn=&rft.btitle=&rft.title=American+Industrial+Hygiene+Association+journal&rft.issn=00028894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-13 N1 - Date created - 1994-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleotide excision repair genes involved in xeroderma pigmentosum. AN - 76423313; 8144390 JF - Japanese journal of cancer research : Gann AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 VL - 85 IS - 2 SN - 0910-5050, 0910-5050 KW - ERCC KW - NER KW - XPA KW - XPB KW - XPC KW - XPD KW - XPG KW - Nucleotides KW - 0 KW - DNA KW - 9007-49-2 KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Nucleotides -- metabolism KW - Animals KW - Humans KW - DNA Helicases -- genetics KW - Genetic Predisposition to Disease KW - DNA -- biosynthesis KW - DNA Repair -- genetics KW - Genes KW - Xeroderma Pigmentosum -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76423313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Japanese+journal+of+cancer+research+%3A+Gann&rft.atitle=Nucleotide+excision+repair+genes+involved+in+xeroderma+pigmentosum.&rft.au=Kraemer%2C+K+H&rft.aulast=Kraemer&rft.aufirst=K&rft.date=1994-02-01&rft.volume=85&rft.issue=2&rft.spage=inside+front+cover&rft.isbn=&rft.btitle=&rft.title=Japanese+journal+of+cancer+research+%3A+Gann&rft.issn=09105050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-03 N1 - Date created - 1994-05-03 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ERCC; NER; XPA; XPB; XPC; XPD; XPG N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of NaCl entry into Necturus gallbladder epithelium by protein kinase C. AN - 76421487; 8141267 AB - The role of protein kinase C in the regulation of the mode of NaCl entry into Necturus gallbladder epithelial cells was determined from the rate and magnitude of ouabain-induced cell swelling in the presence of inhibitors. Stimulation of protein kinase C by phorbol ester increased the rate of cell swelling from the control value of 2.9% to 4.7%/min and caused the predominant apical membrane transport mechanism for NaCl to switch from bumetanide-sensitive Na-Cl cotransport to amiloride-sensitive parallel exchange. Na-Cl cotransport could be restored as the predominant mode of NaCl entry by treatment of stimulated tissues with the kinase inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and calphostin C. Therefore the mechanism of NaCl transport across the apical membrane can be controlled by the activity of protein kinase C. JF - The American journal of physiology AU - Dausch, R AU - Spring, K R AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - C531 EP - C535 VL - 266 IS - 2 Pt 1 SN - 0002-9513, 0002-9513 KW - Bumetanide KW - 0Y2S3XUQ5H KW - Sodium Chloride KW - 451W47IQ8X KW - Ouabain KW - 5ACL011P69 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Bumetanide -- pharmacology KW - Animals KW - Necturus maculosus KW - Epithelial Cells KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Epithelium -- metabolism KW - Ouabain -- pharmacology KW - Epithelium -- drug effects KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Gallbladder -- cytology KW - Gallbladder -- metabolism KW - Sodium Chloride -- metabolism KW - Gallbladder -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76421487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Regulation+of+NaCl+entry+into+Necturus+gallbladder+epithelium+by+protein+kinase+C.&rft.au=Dausch%2C+R%3BSpring%2C+K+R&rft.aulast=Dausch&rft.aufirst=R&rft.date=1994-02-01&rft.volume=266&rft.issue=2+Pt+1&rft.spage=C531&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-28 N1 - Date created - 1994-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection. AN - 76380820; 7907174 AB - Zidovudine and didanosine are both beneficial for the treatment of human immunodeficiency virus (HIV) infection in children. Because disease progression and toxicity often limit their long-term use as single agents, new approaches to using nucleoside analogues are necessary to improve current antiretroviral therapy. We conducted a phase I-II study to evaluate the tolerance, pharmacokinetics, and antiviral activity of the combination of zidovudine and didanosine in children with HIV infection. Sixty-eight children who were either previously untreated or who had manifested hematologic toxicity on full-dose zidovudine were enrolled. Eight dose combinations were studied in the previously untreated children, with doses of zidovudine ranging from 90 to 180 mg/m2 every 6 hours and doses of didanosine ranging from 90 to 180 mg/m2 every 12 hours. Fifty-four previously untreated HIV-infected children were enrolled in this part of the study, of whom 49 remained in the study for a minimum of 24 weeks. For children with previous zidovudine-related hematologic toxicity, three dose levels with zidovudine at 60 mg/m2 every 6 hours orally and didanosine ranging from 90 to 180 mg/m2 every 12 hours orally were used. A total of 14 children were enrolled in this part of the study, and 12 remained on therapy for at least 24 weeks. No evidence of new or enhanced toxicity was observed in either group. After 24 weeks, the median CD4 cell count for all patients increased from 331 to 556 cells/mm3 (P = .01). For the previously untreated group, the median increase in CD4 counts was from 386 to 726 cells/mm3 (P = .003). The median p24 antigen concentration (in those with a detectable level at baseline) decreased from 95 to < 31 pg/mL (p < .001). The geometric mean titer of HIV in plasma decreased from 83.1 to 2.7 tissue culture infectious doses/mL (P = .001). The combination of zidovudine and didanosine was well-tolerated at doses as high as those used in single agent therapy. Potent in vivo antiviral activity was observed. Combination therapy with nucleoside analogues may be an important approach to optimizing the use of these agents in the treatment of HIV infection. JF - Pediatrics AU - Husson, R N AU - Mueller, B U AU - Farley, M AU - Woods, L AU - Kovacs, A AU - Goldsmith, J C AU - Ono, J AU - Lewis, L L AU - Balis, F M AU - Brouwers, P AD - Pediatric Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 316 EP - 322 VL - 93 IS - 2 SN - 0031-4005, 0031-4005 KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Infant KW - Drug Therapy, Combination KW - Leukocyte Count -- drug effects KW - Drug Administration Schedule KW - Humans KW - Adult KW - Treatment Outcome KW - Child KW - Adolescent KW - Male KW - Female KW - CD4-Positive T-Lymphocytes KW - Child, Preschool KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - Zidovudine -- adverse effects KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - Zidovudine -- administration & dosage KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76380820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biological+Chemistry&rft.atitle=Slippage+synthesis+at+the+galP2+promoter+of+Escherichia+coli+and+its+regulation+by+UTP+concentration+and+cAMP-cAMP+receptor+protein&rft.au=Jin%2C+Ding+Jun&rft.aulast=Jin&rft.aufirst=Ding&rft.date=1994-01-01&rft.volume=269&rft.issue=25&rft.spage=17221&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 completed - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiotoxicity of heterocyclic amine food mutagens in cultured myocytes and in rats. AN - 76375402; 8122265 AB - Cooked meat contains a number of mutagenic/carcinogenic heterocyclic amines, including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP). We recently observed that monkeys treated with IQ showed myocyte degeneration and mitochondrial changes. Thus, it was of interest to develop models to investigate heterocyclic amine cardiotoxicity. Primary cultures of fetal rat myocytes were exposed to the activated forms of the carcinogens (N-OH-IQ and N-OH-PhIP). LDH leakage increased in proportion to the carcinogen dose but was significantly greater in cells exposed to N-OH-IQ than that in cells exposed to N-OH-PhIP. Electron microscopy revealed that treated cells had swollen and irregular mitochondria and fewer organelles. However, DNA adducts, assessed using the 32P-postlabeling method, were significantly higher in myocytes exposed to N-OH-PhIP than in cells exposed to N-OH-IQ. The toxic effects of heterocyclic amines were also evaluated in rats given IQ or PhIP (100 mg/kg, po 10 doses over 2 weeks). Light microscopic and ultrastructural cardiac abnormalities were present in seven of eight rats exposed to IQ or PhIP. Whereas control animals had a normal cardiac morphology, carcinogen-treated animals had foci of chronic inflammation with myocyte necrosis, myofibrillar dissolution and disarray, and dilation of T-tubules. These results suggest that, in addition to being carcinogenic, food mutagens may play a role in cardiac degeneration. JF - Toxicology and applied pharmacology AU - Davis, C D AU - Farb, A AU - Thorgeirsson, S S AU - Virmani, R AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 201 EP - 211 VL - 124 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - DNA, Mitochondrial KW - Imidazoles KW - Mutagens KW - Quinolines KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Animals KW - Myocardium -- pathology KW - Myocardium -- ultrastructure KW - Autoradiography KW - Rats KW - Animals, Newborn KW - Rats, Inbred F344 KW - DNA, Mitochondrial -- drug effects KW - Cells, Cultured KW - Body Weight -- drug effects KW - L-Lactate Dehydrogenase -- metabolism KW - Male KW - Organ Size -- drug effects KW - Quinolines -- toxicity KW - Imidazoles -- toxicity KW - Food Contamination KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Heart -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76375402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Cardiotoxicity+of+heterocyclic+amine+food+mutagens+in+cultured+myocytes+and+in+rats.&rft.au=Davis%2C+C+D%3BFarb%2C+A%3BThorgeirsson%2C+S+S%3BVirmani%2C+R%3BSnyderwine%2C+E+G&rft.aulast=Davis&rft.aufirst=C&rft.date=1994-02-01&rft.volume=124&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-06 N1 - Date created - 1994-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of self-reported injection frequencies for past 30 days and 6 months among intravenous drug users. AN - 76372421; 8113828 AB - In this study we compared two parallel self-reported measures that now are being used to assess the recent frequency of intravenous drug use. This study sample consisted of 926 HIV seronegative drug users recruited for participation in HIV research. During a standard interview with each drug user, we first asked about injections in the past 30 days, and then about injections in the past 6 months. The correlation between reports on the past 6 months and the past 30 days was appreciable when all injections were considered (Spearman correlation coefficient rho = 0.78). It increased when the sample was restricted to subjects who reported injections in the past month (rho = 0.88). This restriction resulted in a 15% reduction of the sample size, since 137 participants reported drug use in the previous 6 months but not in the previous 30 days. Concordance tended to be slightly higher for reported frequencies of heroin injections than for cocaine injections, and for men as compared to women. The observed levels of concordance indicate that in many instances both approaches can yield comparable results. Nevertheless the choice of 30 days recall vs 6 months recall must rest upon the specific research questions of each investigation. JF - Journal of clinical epidemiology AU - Schütz, C G AU - Vlahov, D AU - Anthony, J C AU - Graham, N M AD - Etiology Branch, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 191 EP - 195 VL - 47 IS - 2 SN - 0895-4356, 0895-4356 KW - Heroin KW - 70D95007SX KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - AIDS/HIV KW - Sex Factors KW - Humans KW - Adult KW - Follow-Up Studies KW - Longitudinal Studies KW - HIV Seronegativity KW - Male KW - Injections, Intravenous -- statistics & numerical data KW - Female KW - Substance Abuse, Intravenous -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76372421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+epidemiology&rft.atitle=Comparison+of+self-reported+injection+frequencies+for+past+30+days+and+6+months+among+intravenous+drug+users.&rft.au=Sch%C3%BCtz%2C+C+G%3BVlahov%2C+D%3BAnthony%2C+J+C%3BGraham%2C+N+M&rft.aulast=Sch%C3%BCtz&rft.aufirst=C&rft.date=1994-02-01&rft.volume=47&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure. AN - 76361438; 8111462 AB - Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed. JF - Occupational and environmental medicine AU - Dosemeci, M AU - McLaughlin, J K AU - Chen, J Q AU - Hearl, F AU - McCawley, M AU - Wu, Z AU - Chen, R G AU - Peng, K L AU - Chen, A L AU - Rexing, S H AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 136 EP - 138 VL - 51 IS - 2 SN - 1351-0711, 1351-0711 KW - Dust KW - 0 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Retrospective Studies KW - Case-Control Studies KW - Silicosis -- etiology KW - Male KW - Occupational Exposure KW - Lung Neoplasms -- etiology KW - Silicon Dioxide -- administration & dosage KW - Occupational Diseases -- etiology KW - Dust -- adverse effects KW - Silicon Dioxide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76361438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Indirect+validation+of+a+retrospective+method+of+exposure+assessment+used+in+a+nested+case-control+study+of+lung+cancer+and+silica+exposure.&rft.au=Dosemeci%2C+M%3BMcLaughlin%2C+J+K%3BChen%2C+J+Q%3BHearl%2C+F%3BMcCawley%2C+M%3BWu%2C+Z%3BChen%2C+R+G%3BPeng%2C+K+L%3BChen%2C+A+L%3BRexing%2C+S+H&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1994-02-01&rft.volume=51&rft.issue=2&rft.spage=136&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-31 N1 - Date created - 1994-03-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Scand J Work Environ Health. 1982 Mar;8(1):24-8 [7134919] Am J Epidemiol. 1983 Oct;118(4):583-91 [6637985] Br J Ind Med. 1985 Aug;42(8):563-4 [4016009] Am J Epidemiol. 1986 Mar;123(3):481-9 [3946394] Br J Ind Med. 1986 Oct;43(10):667-76 [3778837] J Occup Med. 1987 Feb;29(2):136-41 [3819894] J Occup Med. 1987 Apr;29(4):361-3 [3495651] Br J Ind Med. 1987 Oct;44(10):702-10 [3118933] J Occup Med. 1987 Oct;29(10):795-800 [3681489] Am J Ind Med. 1987;12(5):551-62 [3687951] Br J Ind Med. 1988 Jan;45(1):29-32 [3342185] Am J Epidemiol. 1988 Aug;128(2):343-51 [3256301] Am J Ind Med. 1988;14(6):703-13 [3232688] Med Lav. 1988 Sep-Oct;79(5):363-7 [3252127] Int J Epidemiol. 1989 Sep;18(3):674-9 [2807673] Am J Epidemiol. 1989 Dec;130(6):1236-46 [2589314] Scand J Work Environ Health. 1989 Dec;15(6):424-9 [2617258] Scand J Work Environ Health. 1990 Aug;16(4):284-8 [2389136] Am J Ind Med. 1991;19(4):523-30 [2035550] Am J Ind Med. 1992;21(1):125-32 [1553981] Am J Ind Med. 1992;21(1):53-63 [1553986] Br J Ind Med. 1992 Mar;49(3):167-71 [1313281] Am J Epidemiol. 1992 Mar 1;135(5):564-70 [1570822] Chest. 1992 Aug;102(2):402-7 [1643922] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors. AN - 76359656; 8109904 AB - Felbamate is a promising new antiepileptic drug whose mechanism of action is unknown. In whole-cell voltage clamp recordings from cultured rat hippocampal neurons, clinically relevant concentrations of felbamate (0.1-3 mM) inhibited N-methyl-D-aspartate (NMDA) responses and potentiated gamma-aminobutyric acid (GABA) responses. Single-channel recordings indicated that the effect on NMDA responses occurred via a channel blocking mechanism. Felbamate is the first anticonvulsant drug with dual actions on excitatory (NMDA) and inhibitory (GABA) brain mechanisms. This unique combination of effects could account for felbamate's broad spectrum of anticonvulsant activity in animal seizure models and its distinctive clinical efficacy and safety profile. JF - Annals of neurology AU - Rho, J M AU - Donevan, S D AU - Rogawski, M A AD - Neuronal Excitability Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 229 EP - 234 VL - 35 IS - 2 SN - 0364-5134, 0364-5134 KW - Anticonvulsants KW - 0 KW - Phenylcarbamates KW - Propylene Glycols KW - Receptors, GABA KW - N-Methylaspartate KW - 6384-92-5 KW - felbamate KW - X72RBB02N8 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Hippocampus -- metabolism KW - Drug Synergism KW - Hippocampus -- drug effects KW - Propylene Glycols -- pharmacology KW - Receptors, GABA -- drug effects KW - Anticonvulsants -- pharmacology KW - Receptors, GABA -- metabolism KW - N-Methylaspartate -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76359656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Mechanism+of+action+of+the+anticonvulsant+felbamate%3A+opposing+effects+on+N-methyl-D-aspartate+and+gamma-aminobutyric+acidA+receptors.&rft.au=Rho%2C+J+M%3BDonevan%2C+S+D%3BRogawski%2C+M+A&rft.aulast=Rho&rft.aufirst=J&rft.date=1994-02-01&rft.volume=176&rft.issue=10&rft.spage=2922&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 - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Neurol. 1994 Oct;36(4):677-8 [7944305] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of unilamellar liposomal amphotericin B in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: the potential role of bronchoalveolar D-mannitol and serum galactomannan as markers of infection. AN - 76354030; 8106769 AB - A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. D-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, D-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits. JF - The Journal of infectious diseases AU - Francis, P AU - Lee, J W AU - Hoffman, A AU - Peter, J AU - Francesconi, A AU - Bacher, J AU - Shelhamer, J AU - Pizzo, P A AU - Walsh, T J AD - Infectious Diseases Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 356 EP - 368 VL - 169 IS - 2 SN - 0022-1899, 0022-1899 KW - Antigens, Fungal KW - 0 KW - Biomarkers KW - Liposomes KW - Mannans KW - galactomannan KW - 11078-30-1 KW - Mannitol KW - 3OWL53L36A KW - Amphotericin B KW - 7XU7A7DROE KW - Ergosterol KW - Z30RAY509F KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Aspergillus fumigatus -- pathogenicity KW - Mannans -- blood KW - Rabbits KW - Opportunistic Infections -- drug therapy KW - Life Tables KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Antigens, Fungal -- analysis KW - Survival Analysis KW - Kidney Diseases -- chemically induced KW - Lung Diseases -- drug therapy KW - Aspergillosis -- microbiology KW - Agranulocytosis -- complications KW - Aspergillosis -- blood KW - Aspergillosis -- drug therapy KW - Lung Diseases -- microbiology KW - Amphotericin B -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76354030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Efficacy+of+unilamellar+liposomal+amphotericin+B+in+treatment+of+pulmonary+aspergillosis+in+persistently+granulocytopenic+rabbits%3A+the+potential+role+of+bronchoalveolar+D-mannitol+and+serum+galactomannan+as+markers+of+infection.&rft.au=Francis%2C+P%3BLee%2C+J+W%3BHoffman%2C+A%3BPeter%2C+J%3BFrancesconi%2C+A%3BBacher%2C+J%3BShelhamer%2C+J%3BPizzo%2C+P+A%3BWalsh%2C+T+J&rft.aulast=Francis&rft.aufirst=P&rft.date=1994-02-01&rft.volume=169&rft.issue=2&rft.spage=356&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-23 N1 - Date created - 1994-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of hepatocarcinogenesis and induction of specific cytochrome P450-dependent monooxygenase activities by the barbiturates allobarbital, aprobarbital, pentobarbital, secobarbital and 5-phenyl- and 5-ethylbarbituric acids. AN - 76352766; 8313534 AB - To test predictions that barbiturates which are long-acting sedatives and/or strong inducers of CYP2B-mediated monooxygenase activities would be effective promoters of hepatocarcinogenesis, a series of clinically-useful barbiturates and structural analogs were tested for ability to promote hepatocellular carcinogenesis in male F344/NCr rats initiated with N-nitrosodiethylamine and for efficacy as inducers of CYP2B activity in non-initiated rats of the same sex and strain. The barbiturates were administered in the diet at concentrations equimolar to 500 p.p.m. of the known liver tumor promoter phenobarbital, which served as the positive control for this study. Phenobarbital, which has the longest duration of sedative action of this series of compounds, caused the greatest induction of CYP2B activity, and displayed strong liver tumor promoting effects. Allobarbital and aprobarbital, two intermediate-duration sedatives, were found to promote hepatocarcinogenesis, with allobarbital proving to be as effective as phenobarbital in this respect and aprobarbital being somewhat weaker as a promoter. These intermediate-duration sedatives were each relatively weak CYP2B-type inducers, causing approximately 25% of the induction displayed by phenobarbital. The nonsedatives, 5-phenyl- and 5-ethyl-barbituric acids, were essentially inactive as CYP2B-type inducers and were also found to be relatively inactive as promoters of hepatocarcinogenesis. Of the shorter-duration sedatives, pentobarbital was found to promote, and was relatively effective as a CYP2B-type inducer, while secobarbital showed little or no promoting activity and was less effective as an inducer of CYP2B activities. Pentobarbital thus proved an important exception to our hypothesis that only long-acting sedative barbiturates would promote hepatocarcinogenesis. Although both the durations of sedative action and the degrees of CYP2B-type induction exhibited by these compounds correlate with a quantitative parameter for liver tumor-promoting activity (relative promotion index), neither parameter appears to be sufficient, by itself, as a predictor of promoting activity for rat liver. JF - Carcinogenesis AU - Rice, J M AU - Diwan, B A AU - Hu, H AU - Ward, J M AU - Nims, R W AU - Lubet, R A AD - Laboratory of Comparative Carcinogenesis, Program Resources, Inc./DynCorp, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 395 EP - 402 VL - 15 IS - 2 SN - 0143-3334, 0143-3334 KW - Barbiturates KW - 0 KW - Carcinogens KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxygenases KW - EC 1.13.- KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Neoplasms, Experimental -- chemically induced KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Enzyme Induction KW - Male KW - Organ Size -- drug effects KW - Carcinogens -- pharmacology KW - Oxygenases -- biosynthesis KW - Liver Neoplasms, Experimental -- pathology KW - Barbiturates -- pharmacology KW - Liver Neoplasms, Experimental -- enzymology KW - Liver Neoplasms, Experimental -- chemically induced KW - Cytochrome P-450 Enzyme System -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76352766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhancement+of+hepatocarcinogenesis+and+induction+of+specific+cytochrome+P450-dependent+monooxygenase+activities+by+the+barbiturates+allobarbital%2C+aprobarbital%2C+pentobarbital%2C+secobarbital+and+5-phenyl-+and+5-ethylbarbituric+acids.&rft.au=Rice%2C+J+M%3BDiwan%2C+B+A%3BHu%2C+H%3BWard%2C+J+M%3BNims%2C+R+W%3BLubet%2C+R+A&rft.aulast=Rice&rft.aufirst=J&rft.date=1994-02-01&rft.volume=15&rft.issue=2&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-22 N1 - Date created - 1994-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cells of Th2 cytokine phenotype prevent LPS-induced lethality during murine graft-versus-host reaction. Regulation of cytokines and CD8+ lymphoid engraftment. AN - 76351598; 7905495 AB - A murine parent-into-F1 graft-vs-host reaction (GVHR) model that utilizes LPS to induce lethality was used to evaluate the in vivo regulatory role of donor cells of Th2 cytokine phenotype. Transfer of B6 spleen cells into B6C3F1 hosts was lethal when LPS endotoxin (15 micrograms) was administered on day 7 after cell transfer. Parental cells of Th2 cytokine phenotype were generated by treating B6 mice in vivo with a combination of IL-2 and IL-4 or with high dose IL-2. The CD4-enriched population from these cytokine-treated mice expressed and secreted increased levels of IL-4 and IL-10, with concomitantly decreased IL-2 and IFN-gamma. Cell mixing experiments (parental spleen cells+parental CD4-enriched. Th2-type cells) demonstrated that the Th2-type cells protected F1 hosts from LPS-induced lethality. These mice were analyzed to study possible mechanisms by which this protection was mediated. Compared with mice undergoing LPS-induced lethality during GVHR, Th2-protected mice had: 1) lower levels of donor CD8+ lymphoid engraftment, 2) in vivo suppression of IFN-gamma mRNA, 3) in vivo augmentation of IL-4 mRNA, and 4) a reduction in serum TNF-alpha. We thus conclude that donor cells of Th2 cytokine phenotype prevent LPS-induced, TNF-alpha-mediated lethality during GVHR, and that this protection is associated with regulation of both cellular- and cytokine-mediated events. As a result, we propose that cells of Th2 cytokine phenotype may represent a novel approach for establishing allogeneic lymphoid engraftment without lethal graft-vs-host disease. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Fowler, D H AU - Kurasawa, K AU - Husebekk, A AU - Cohen, P A AU - Gress, R E AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/02/01/ PY - 1994 DA - 1994 Feb 01 SP - 1004 EP - 1013 VL - 152 IS - 3 SN - 0022-1767, 0022-1767 KW - Antigens, CD8 KW - 0 KW - Cytokines KW - Lipopolysaccharides KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Immunity, Cellular KW - Antigens, CD8 -- analysis KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Gene Expression KW - Mice KW - Tumor Necrosis Factor-alpha -- metabolism KW - RNA, Messenger -- genetics KW - Graft vs Host Reaction -- immunology KW - Cytokines -- pharmacology KW - T-Lymphocyte Subsets -- immunology KW - Lipopolysaccharides -- toxicity KW - Cytokines -- physiology KW - CD4-Positive T-Lymphocytes -- immunology KW - T-Lymphocytes, Helper-Inducer -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76351598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Cells+of+Th2+cytokine+phenotype+prevent+LPS-induced+lethality+during+murine+graft-versus-host+reaction.+Regulation+of+cytokines+and+CD8%2B+lymphoid+engraftment.&rft.au=Fowler%2C+D+H%3BKurasawa%2C+K%3BHusebekk%2C+A%3BCohen%2C+P+A%3BGress%2C+R+E&rft.aulast=Fowler&rft.aufirst=D&rft.date=1994-02-01&rft.volume=152&rft.issue=3&rft.spage=1004&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-09 N1 - Date created - 1994-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced metallothionein gene expression is associated with protection from cadmium-induced genotoxicity in cultured rat liver cells. AN - 76349815; 8301701 AB - Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that appear to play an important role in the cellular defense system against cadmium toxicity. Although substantial evidence exists demonstrating a reduction in cadmium toxicity concomitant with MT induction, little is known about the possible effects of stimulation of MT synthesis on cadmium-induced genotoxicity. Thus, the alkaline elution technique was used to assess single-strand DNA damage (SSD) in TRL-1215 cells, a liver-derived cell line shown to have inducible MT gene expression. The SSD accumulated over a 2-h time period in a time-dependent manner following exposure to 500 microM CdCl2. Low-concentration cadmium pretreatment (10 microM CdCl2, 24 h) provided protection against the genotoxicity of high-concentration cadmium (500 microM CdCl2, 2 h). A 2-h exposure to 500 microM CdCl2 had no effect on viability, as assessed using a tetrazolium-dye based assay, in cells from either the pretreated or nonpretreated group. Metallothionein was induced in a time-dependent manner by low-concentration cadmium pretreatment: Exposure for 24 and 48 h resulted in 3.3- and 6.4-fold increases, respectively. In addition, a 24-h exposure to low-concentration cadmium resulted in an increase in MT-I gene expression. Cadmium accumulation was 2.6-fold greater in low-concentration cadmium-pretreated cells as compared to nonpretreated cells. These data demonstrate that low-concentration cadmium pretreatment provides protection against cadmium-induced single-strand DNA damage and support the hypothesis that this protection is due to stimulation of MT gene expression. JF - Journal of toxicology and environmental health AU - Coogan, T P AU - Bare, R M AU - Bjornson, E J AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 233 EP - 245 VL - 41 IS - 2 SN - 0098-4108, 0098-4108 KW - Cadmium KW - 00BH33GNGH KW - DNA KW - 9007-49-2 KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cells, Cultured KW - Time Factors KW - Cadmium -- pharmacology KW - Liver -- cytology KW - Metallothionein -- biosynthesis KW - Liver -- drug effects KW - DNA Damage KW - Metallothionein -- drug effects KW - Cadmium -- toxicity KW - Metallothionein -- genetics KW - Gene Expression Regulation -- drug effects KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76349815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health&rft.atitle=Enhanced+metallothionein+gene+expression+is+associated+with+protection+from+cadmium-induced+genotoxicity+in+cultured+rat+liver+cells.&rft.au=Coogan%2C+T+P%3BBare%2C+R+M%3BBjornson%2C+E+J%3BWaalkes%2C+M+P&rft.aulast=Coogan&rft.aufirst=T&rft.date=1994-02-01&rft.volume=41&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health&rft.issn=00984108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-10 N1 - Date created - 1994-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biodistribution and preclinical radioimmunotherapy studies using radiolanthanide-labeled immunoconjugates. AN - 76345197; 8306291 AB - Lutetium-177 (177Lu), samarium-153 (153Sm), and yttrium-90 (90Y) are members of the family of elements known as lanthanides or rare earths. Monoclonal antibody CC49, a murine immunoglobulin (Ig) G1, which is reactive with the tumor-associated antigen TAG-72, previously has been shown to react with a wide range of human carcinomas. The authors review here the comparative biodistributions of CC49 IgG and F(ab')2 fragments labeled with 177Lu, 153Sm, and 90Y using the bifunctional chelating agent PA-DOTA. The authors also review the results of a biodistribution study comparing iodine-125-labeled and 177Lu-labeled CC49 sFv, and the use of 177Lu-CC+9 IgG in an experimental therapy model. Chelation and conjugations gave similar yields, and the labeled proteins showed similar retention of immunoreactivity regardless of the isotope used for both IgG and F(ab')2. Biodistribution data obtained in athymic mice bearing LS-174T human colon carcinoma xenografts likewise showed no differences among the three radioisotopes for both IgG and F(ab')2. Femur uptake of radioactivity was lower than previously reported for other radiolanthanide immunoconjugates. Different metabolic patterns were observed for radioiodinated versus radiometal-labeled sFv, particularly in the kidney, where localization of the latter was increased dramatically. 177Lu-CC49 was found to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50 microCi. Elimination of established tumors was demonstrated over the observation period (77 days) using single administrations of 200 or 350 microCi. Dose fractionation experiments revealed that the mice tolerated 750 microCi (3 x 250 microCi, given weekly), whereas > 50% of the mice died after receiving a single administration of approximately 500 microCi. In isotype-matched control experiments, a large differential in the therapeutic effects was observed between 177Lu-labeled control antibody and CC49. JF - Cancer AU - Schott, M E AU - Schlom, J AU - Siler, K AU - Milenic, D E AU - Eggensperger, D AU - Colcher, D AU - Cheng, R AU - Kruper, W J AU - Fordyce, W AU - Goeckeler, W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02/01/ PY - 1994 DA - 1994 Feb 01 SP - 993 EP - 998 VL - 73 IS - 3 Suppl SN - 0008-543X, 0008-543X KW - Aniline Compounds KW - 0 KW - Antibodies, Monoclonal KW - Antigens, Neoplasm KW - Glycoproteins KW - Heterocyclic Compounds KW - Immunotoxins KW - Iodine Radioisotopes KW - Metals, Rare Earth KW - Radioisotopes KW - Yttrium Radioisotopes KW - tumor-associated antigen 72 KW - 4-aminophenylethyl-1,4,7,10-tetraazacyclodecane-N,N',N'',N'''-tetraacetic acid KW - 130707-75-4 KW - Samarium KW - 42OD65L39F KW - Lutetium KW - 5H0DOZ21UJ KW - Abridged Index Medicus KW - Index Medicus KW - Yttrium Radioisotopes -- therapeutic use KW - Animals KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Mice KW - Mice, Nude KW - Tissue Distribution KW - Lutetium -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use KW - Neoplasm Transplantation KW - Transplantation, Heterologous KW - Colonic Neoplasms -- metabolism KW - Samarium -- therapeutic use KW - Iodine Radioisotopes -- metabolism KW - Glycoproteins -- immunology KW - Radioimmunotherapy KW - Radioisotopes -- metabolism KW - Glycoproteins -- metabolism KW - Radioisotopes -- therapeutic use KW - Antigens, Neoplasm -- metabolism KW - Antigens, Neoplasm -- immunology KW - Metals, Rare Earth -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76345197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Biodistribution+and+preclinical+radioimmunotherapy+studies+using+radiolanthanide-labeled+immunoconjugates.&rft.au=Schott%2C+M+E%3BSchlom%2C+J%3BSiler%2C+K%3BMilenic%2C+D+E%3BEggensperger%2C+D%3BColcher%2C+D%3BCheng%2C+R%3BKruper%2C+W+J%3BFordyce%2C+W%3BGoeckeler%2C+W&rft.aulast=Schott&rft.aufirst=M&rft.date=1994-02-01&rft.volume=73&rft.issue=3+Suppl&rft.spage=993&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-14 N1 - Date created - 1994-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of an antitumor ribonuclease to Purkinje neurons. AN - 76342618; 8301353 AB - Purkinje cell toxicity is one of the characteristic features of the Gordon phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and tremor that may lead to death (Gordon, 1933). Two members of the RNase superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP (eosinophil cationic protein), cause the Gordon phenomenon when injected intraventricularly into guinea pigs or rabbits. We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The neurotoxic activity of onconase correlates with ribonuclease activity. Onconase modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity of the native enzyme displays a similar decrease in ability to cause the Gordon phenomenon. In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon. A comparison of the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three pancreatic RNA substrates demonstrates that onconase is orders of magnitude less active enzymatically than EDN and RNase A. Thus, another member of the RNase superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Newton, D L AU - Walbridge, S AU - Mikulski, S M AU - Ardelt, W AU - Shogen, K AU - Ackerman, S J AU - Rybak, S M AU - Youle, R J AD - Biochemistry Section, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 538 EP - 544 VL - 14 IS - 2 SN - 0270-6474, 0270-6474 KW - Antineoplastic Agents KW - 0 KW - Blood Proteins KW - Egg Proteins KW - Eosinophil Granule Proteins KW - Neurotoxins KW - Eosinophil-Derived Neurotoxin KW - EC 3.1.- KW - Ribonucleases KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Humans KW - Rabbits KW - Amino Acid Sequence KW - Cerebral Ventricles -- drug effects KW - Injections, Intraventricular KW - Injections, Spinal KW - Spinal Cord -- drug effects KW - Cerebral Ventricles -- physiology KW - Molecular Sequence Data KW - Spinal Cord -- physiology KW - Sequence Homology, Amino Acid KW - Female KW - Ribonucleases -- toxicity KW - Purkinje Cells -- pathology KW - Egg Proteins -- administration & dosage KW - Ribonucleases -- chemistry KW - Ribonuclease, Pancreatic -- toxicity KW - Blood Proteins -- chemistry KW - Neurotoxins -- toxicity KW - Blood Proteins -- administration & dosage KW - Blood Proteins -- toxicity KW - Purkinje Cells -- drug effects KW - Egg Proteins -- chemistry KW - Neurotoxins -- administration & dosage KW - Ribonucleases -- administration & dosage KW - Antineoplastic Agents -- toxicity KW - Ribonuclease, Pancreatic -- administration & dosage KW - Egg Proteins -- toxicity KW - Neurotoxins -- chemistry KW - Ribonuclease, Pancreatic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76342618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicity+of+an+antitumor+ribonuclease+to+Purkinje+neurons.&rft.au=Newton%2C+D+L%3BWalbridge%2C+S%3BMikulski%2C+S+M%3BArdelt%2C+W%3BShogen%2C+K%3BAckerman%2C+S+J%3BRybak%2C+S+M%3BYoule%2C+R+J&rft.aulast=Newton&rft.aufirst=D&rft.date=1994-02-01&rft.volume=14&rft.issue=2&rft.spage=538&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 - 1994-03-10 N1 - Date created - 1994-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel cis-acting element controlling the rat CYP2D5 gene and requiring cooperativity between C/EBP beta and an Sp1 factor. AN - 76340696; 8289814 AB - The rat CYP2D5 gene encodes a cytochrome P450 and is expressed in liver cells. Its expression commences a few days after birth, and maximal mRNA levels are achieved when animals reach puberty. Transfection and DNA binding studies were performed to investigate the mechanism controlling developmentally programmed, liver-specific expression of CYP2D5. Transfection studies using a series of CYP2D5 upstream DNA chloramphenicol acetyltransferase gene fusion constructs identified a segment of DNA between nucleotides -55 and -156 that conferred transcriptional activity in HepG2 cells. Activity was markedly increased by cotransfection with a vector expressing C/EBP beta but was unaffected by vectors producing other liver-enriched transcription factors (C/EBP alpha, HNF-1 alpha, and DBP). DNase I footprinting revealed a region protected by both HepG2 and liver cell nuclear extracts between nucleotides -83 and -112. This region displayed some sequence similarity to the Sp1 consensus sequence and was able to bind the Sp1 protein, as assessed by a gel mobility shift assay. The role of Sp1 in CYP2D5 transcription was confirmed by trans activation of the 2D5-CAT construct in Drosophila melanogaster cells by using an Sp1 expression vector. C/EBP beta alone was unable to directly bind the -83 to -112 region of the promoter but was able to produce a ternary complex when combined with HepG2 nuclear extracts or recombinant human Sp1. C/EBP alpha was unable to substitute for C/EBP beta in forming this ternary complex. A poor C/EBP binding site is present adjacent to the Sp1 site, and mutagenesis of this site abolished formation of the ternary complex with the CYP2D5 regulatory region. These result establish that two transcription factors can work in conjunction, possibly by protein-protein interaction, to activate the CYP2D5 gene. JF - Molecular and cellular biology AU - Lee, Y H AU - Yano, M AU - Liu, S Y AU - Matsunaga, E AU - Johnson, P F AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 1383 EP - 1394 VL - 14 IS - 2 SN - 0270-7306, 0270-7306 KW - CYP2C6 KW - CYP2D KW - CYP2D3 KW - CYP2D5 KW - CYP2E1 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Oligodeoxyribonucleotides KW - RNA, Messenger KW - Sp1 Transcription Factor KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Index Medicus KW - Aging -- metabolism KW - Animals KW - Chloramphenicol O-Acetyltransferase -- biosynthesis KW - Humans KW - DNA -- analysis KW - Gene Expression KW - Transcription, Genetic KW - Chloramphenicol O-Acetyltransferase -- analysis KW - RNA, Messenger -- biosynthesis KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Transfection KW - Restriction Mapping KW - Drosophila melanogaster KW - Molecular Sequence Data KW - Cell Line KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Cytochrome P-450 Enzyme System -- genetics KW - Sp1 Transcription Factor -- metabolism KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Nuclear Proteins -- metabolism KW - Rats -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76340696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+toxicology+%3A+JAT&rft.atitle=Toxicity+of+diethanolamine.+1.+Drinking+water+and+topical+application+exposures+in+F344+rats.&rft.au=Melnick%2C+R+L%3BMahler%2C+J%3BBucher%2C+J+R%3BThompson%2C+M%3BHejtmancik%2C+M%3BRyan%2C+M+J%3BMezza%2C+L+E&rft.aulast=Melnick&rft.aufirst=R&rft.date=1994-01-01&rft.volume=14&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+toxicology+%3A+JAT&rft.issn=0260437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-24 N1 - Date created - 1994-02-24 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP2C6; CYP2D; CYP2D3; CYP2D5; CYP2E1 N1 - SuppNotes - Cited By: EMBO J. 1993 Sep;12(9):3551-8 [8253080] Pharmacogenetics. 1993 Feb;3(1):51-7 [8387380] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Cell. 1986 Dec 5;47(5):767-76 [3779841] Cell. 1987 Jan 16;48(1):79-89 [3024847] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Cell. 1987 Aug 14;50(4):627-38 [3607880] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413-7 [2823261] Genes Dev. 1987 Apr;1(2):133-46 [2824279] Cell. 1988 Oct 7;55(1):125-33 [3139301] Genes Dev. 1988 Aug;2(8):957-74 [3169549] Mol Cell Biol. 1989 Apr;9(4):1415-25 [2786140] J Mol Evol. 1990 Feb;30(2):155-69 [2107330] Crit Rev Biochem Mol Biol. 1990;25(2):97-153 [2183970] Mol Cell Biol. 1990 Jun;10(6):2757-64 [2111442] Mol Cell Biol. 1990 Sep;10(9):4495-505 [2388615] DNA Cell Biol. 1990 Jul-Aug;9(6):443-52 [2206401] Cell. 1990 Oct 5;63(1):155-65 [2170018] Science. 1991 Jan 18;251(4991):288-92 [1987644] Environ Health Perspect. 1990 Aug;88:13-25 [2272308] Genes Dev. 1991 Apr;5(4):670-82 [2010091] Genes Dev. 1991 Sep;5(9):1553-67 [1884998] Clin Pharmacol Ther. 1991 Sep;50(3):233-8 [1680592] J Clin Invest. 1992 Jan;89(1):223-33 [1729273] Xenobiotica. 1991 Dec;21(12):1621-31 [1785207] Biochem J. 1992 Feb 1;281 ( Pt 3):577-92 [1536639] Biochem Pharmacol. 1992 Feb 4;43(3):393-401 [1311577] Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2145-9 [1372436] Mol Cell Biol. 1992 Jun;12(6):2847-54 [1588973] Keio J Med. 1992 Jun;41(2):68-75 [1619850] Virology. 1973 Apr;52(2):456-67 [4705382] Proteins. 1992 Feb;12(2):101-4 [1603798] EMBO J. 1992 Oct;11(10):3663-71 [1356762] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9759-63 [1329106] J Biol Chem. 1993 Mar 25;268(9):6567-74 [8454627] Nucleic Acids Res. 1993 Apr 11;21(7):1527-32 [8479902] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endothelin-1 receptor binding and cellular signal transduction in cultured human brain endothelial cells. AN - 76340173; 8294922 AB - The kinetic properties of endothelin-1 (ET-1) binding sites and the production of inositol phosphates (IPs; IP1, IP2, IP3), cyclic AMP, thromboxane B2, and prostaglandin F2 alpha induced by various endothelins (ET-1, ET-2, ET-3, and sarafotoxin S6b) were examined in endothelial cells derived from human brain microvessels (HBECs). The presence of both high- and low-affinity binding sites for ET-1 with KD1 = 122 pM and KD2 = 31 nM, and Bmax1 = 124 fmol/mg of protein and Bmax2 = 909 fmol/mg of protein, respectively, was demonstrated on intact HBECs. ET-1 dose-dependently stimulated IP accumulation with EC50 (IP3) = 0.79 nM, whereas ET-3 was ineffective. The order of potency for displacing ET-1 from high-affinity binding sites (ET-1 > ET-2 > sarafotoxin S6b > ET-3) correlated exponentially with the ability of respective ligands to induce IP3 formation. ET-1-induced IP3 formation by HBEC was inhibited by the ETA receptor antagonist, BQ123. The protein kinase C activator phorbol myristate ester dose-dependently inhibited the ET-1-stimulated production of IPs, whereas pertussis toxin was ineffective. Cyclic AMP production by HBECs was enhanced by both phorbol myristate ester and ET-1, and potentiated by combined treatment with ET-1 and phorbol myristate ester. Data indicate that protein kinase C plays a role in regulating the ET-1-induced activation of phospholipase C, whereas interaction of different messenger systems may regulate ET-1-induced accumulation of cyclic AMP. ET-1 also stimulated endothelial prostaglandin F2 alpha production, suggesting that activation of phospholipase A2 is most likely secondary to IP3-mediated intracellular calcium mobilization because both ET-1-induced IP3 and prostaglandin F2 alpha were inhibited by BQ123. These findings are the first demonstration of ET-1 (ETA-type) receptors linked to phospholipase C and phospholipase A2 activation in HBECs. JF - Journal of neurochemistry AU - Stanimirovic, D B AU - Yamamoto, T AU - Uematsu, S AU - Spatz, M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 592 EP - 601 VL - 62 IS - 2 SN - 0022-3042, 0022-3042 KW - Endothelin Receptor Antagonists KW - 0 KW - Endothelins KW - Inositol Phosphates KW - Peptides, Cyclic KW - Receptors, Endothelin KW - Virulence Factors, Bordetella KW - Dinoprost KW - B7IN85G1HY KW - Cyclic AMP KW - E0399OZS9N KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - cyclo(Trp-Asp-Pro-Val-Leu) KW - S2A8YZM151 KW - Index Medicus KW - Virulence Factors, Bordetella -- pharmacology KW - Endothelins -- pharmacology KW - Cyclic AMP -- biosynthesis KW - Dinoprost -- biosynthesis KW - Inositol Phosphates -- metabolism KW - Cells, Cultured KW - Humans KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Capillaries -- metabolism KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Brain -- blood supply KW - Brain -- metabolism KW - Signal Transduction KW - Receptors, Endothelin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76340173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Endothelin-1+receptor+binding+and+cellular+signal+transduction+in+cultured+human+brain+endothelial+cells.&rft.au=Stanimirovic%2C+D+B%3BYamamoto%2C+T%3BUematsu%2C+S%3BSpatz%2C+M&rft.aulast=Stanimirovic&rft.aufirst=D&rft.date=1994-02-01&rft.volume=62&rft.issue=2&rft.spage=592&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-02 N1 - Date created - 1994-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ontogeny of kainate-induced gene expression in rat hippocampus. AN - 76340037; 8294905 AB - The ontogeny of kainate induction of AP-1 mRNAs, proteins, and DNA binding activities was examined in the rat hippocampus. In addition, kainate induction of preproenkephalin and preprodynorphin mRNAs was examined; these genes have been shown to be induced by kainate and have been suggested to be targets of AP-1 regulation in adult rat hippocampus. Despite producing seizures at postnatal day (P) 7, kainate failed to induce AP-1 or opiate gene expression and did not increase AP-1 DNA binding activity at this age. Basal levels of AP-1 and opiate mRNAs were low in P7 hippocampus. Basal levels of c-jun protein and AP-1 DNA binding activity were elevated in the P7 hippocampus, to values greater than induced levels in adult hippocampus. Furthermore, AP-1 DNA binding in P7 hippocampal nuclear extract was unaffected by antibodies against fos-related antigens, in contrast to hippocampal extracts from the older rats examined. At P14, induction of AP-1 and preproenkephalin (but not preprodynorphin) mRNAs was observed with kainate treatment, but the time course for inductions was delayed relative to kainate inductions in the adult hippocampus. At P21, responses to kainate were similar to the adult response. Unlike in adult hippocampus, seizure activity caused by kainate treatment does not increase the transcription factor and opioid peptide gene expression in the hippocampi of P7 rats. JF - Journal of neurochemistry AU - Pennypacker, K R AU - McMillian, M K AU - Douglass, J AU - Hong, J S AD - Laboratory of Integrative Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 438 EP - 444 VL - 62 IS - 2 SN - 0022-3042, 0022-3042 KW - DNA-Binding Proteins KW - 0 KW - Endorphins KW - Molecular Probes KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Transcription Factors KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Seizures -- physiopathology KW - Endorphins -- genetics KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Transcription Factors -- genetics KW - Rats KW - Animals, Newborn KW - Rats, Inbred F344 KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Seizures -- genetics KW - Molecular Sequence Data KW - Proto-Oncogene Proteins c-jun -- genetics KW - Male KW - DNA-Binding Proteins -- metabolism KW - Gene Expression -- drug effects KW - Kainic Acid -- pharmacology KW - Hippocampus -- physiology KW - Hippocampus -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76340037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Ontogeny+of+kainate-induced+gene+expression+in+rat+hippocampus.&rft.au=Pennypacker%2C+K+R%3BMcMillian%2C+M+K%3BDouglass%2C+J%3BHong%2C+J+S&rft.aulast=Pennypacker&rft.aufirst=K&rft.date=1994-02-01&rft.volume=62&rft.issue=2&rft.spage=438&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-02 N1 - Date created - 1994-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: evidence for a role of protease in the early phase. AN - 76332488; 8289379 AB - The antiviral activities of two substrate-based inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, UK-88,947 and Ro 31-8959, were studied in acute infections. H9 and HeLaCD4-LTR/beta-gal cells were infected either with HIV-1IIIB or a replication-defective virus, HIV-gpt(HXB-2). Both inhibitors were capable of blocking early steps of HIV-1 replication if added to cells prior to infection. Partial inhibition was also obtained by addition of inhibitor at the time of or as late as 15 min after infection. The inhibitors were ineffective if added 30 min postinfection. The inhibitory effects were studied by cDNA analysis with PCR followed by Southern blot hybridization and by infectivity assays allowing quantitation of HIV-1 in a single cycle of replication. When UK-88,947-treated H9 cells were coinfected with HIV-1 and human T-cell leukemia virus type I only the replication of HIV-1 was inhibited, demonstrating viral specificity. Pretreating the infectious virus stocks with the inhibitors also prevented replication, indicating that the inhibitors block the action of the viral protease and not a cellular protease. A panel of primer sets was used to analyze cDNA from cell lysates by PCR amplification at 4 and 18 h postinfection. Four hours after infection, viral specific cDNA was detected with all of the four primer pairs used: R/U5, nef/U3, 5' gag, and long terminal repeat (LTR)/gag. However, after 18 h, only the R/U5 and nef/U3 primer pairs and not the 5' gag or LTR/gag primer pair were able to allow amplification of cDNA. The results suggest a crucial role of HIV-1 protease in the early phase of viral replication. Although it is not clear what early steps are affected by the protease, it is likely that the target is the NC protein, as referred from our previous reports of the in situ cleavage of the nucleocapsid (NC) protein by the viral protease inside lentiviral capsids. The results suggest that it is not the inhibition of initiation and progression of reverse transcription but the stability of full-size unintegrated cDNA which is affected in the presence of protease inhibitors. Alternatively, the cleavage of the NC protein may be required for the proper formation of preintegration complex and/or for its transport to the nucleus. JF - Journal of virology AU - Nagy, K AU - Young, M AU - Baboonian, C AU - Merson, J AU - Whittle, P AU - Oroszlan, S AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 757 EP - 765 VL - 68 IS - 2 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - DNA, Complementary KW - HIV Protease Inhibitors KW - Isoquinolines KW - Oligopeptides KW - Quinolines KW - UK 88947 KW - 137015-76-0 KW - Saquinavir KW - L3JE09KZ2F KW - Index Medicus KW - AIDS/HIV KW - Sensitivity and Specificity KW - Polymerase Chain Reaction KW - Base Sequence KW - Dose-Response Relationship, Drug KW - Humans KW - Molecular Sequence Data KW - Genome, Viral KW - Time Factors KW - DNA, Complementary -- biosynthesis KW - Cell Line KW - Isoquinolines -- pharmacology KW - Quinolines -- pharmacology KW - Virus Replication -- drug effects KW - HIV Protease Inhibitors -- pharmacology KW - HIV-1 -- growth & development KW - Oligopeptides -- pharmacology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76332488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antiviral+activity+of+human+immunodeficiency+virus+type+1+protease+inhibitors+in+a+single+cycle+of+infection%3A+evidence+for+a+role+of+protease+in+the+early+phase.&rft.au=O%27Brien%2C+T+R%3BBusch%2C+M+P%3BDonegan%2C+E%3BWard%2C+J+W%3BWong%2C+L%3BSamson%2C+S+M%3BPerkins%2C+HA%3BAltman%2C+R%3BStoneburner%2C+R+L%3BHolmberg%2C+S+D&rft.aulast=O%27Brien&rft.aufirst=T&rft.date=1994-01-01&rft.volume=7&rft.issue=7&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=JAIDS+Journal+of+Acquired+Immune+Deficiency+Syndromes&rft.issn=08949255&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1981 Dec 24;294(5843):770-1 [6275274] J Clin Microbiol. 1992 Apr;30(4):905-10 [1572977] Science. 1983 Dec 9;222(4628):1125-7 [6316502] Nucleic Acids Res. 1993 Feb 25;21(4):831-9 [8383840] Biochemistry. 1993 Apr 6;32(13):3347-53 [8384879] J Virol. 1993 Jul;67(7):4027-36 [8510214] J Virol. 1993 Jul;67(7):4050-5 [8510215] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] Annu Rev Biochem. 1993;62:543-85 [8352596] J Virol. 1993 Oct;67(10):6159-69 [8371356] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9721-4 [7692451] J Enzyme Inhib. 1992;6(1):65-98 [1285304] Science. 1984 May 4;224(4648):497-500 [6200935] Cell. 1989 Mar 24;56(6):911-3 [2647305] J Virol. 1989 Apr;63(4):1558-68 [2926863] Biochem Biophys Res Commun. 1989 Apr 28;160(2):486-94 [2541703] Genes Dev. 1989 Apr;3(4):469-78 [2721960] J Virol. 1989 Sep;63(9):3708-13 [2760980] Nature. 1990 Jan 4;343(6253):90-2 [1688646] J Biol Chem. 1992 Jun 15;267(17):11769-76 [1376311] J Virol. 1992 Aug;66(8):5087-91 [1378515] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618-22 [6304725] Science. 1990 Jan 26;247(4941):454-6 [2405486] Science. 1990 Apr 20;248(4953):358-61 [2183354] Virology. 1990 May;176(1):184-94 [2184575] Cell. 1990 Apr 20;61(2):213-22 [2331748] J Clin Microbiol. 1990 Jul;28(7):1560-4 [2380380] Curr Top Microbiol Immunol. 1990;157:153-85 [2203608] J Virol. 1990 Nov;64(11):5270-6 [2214018] Virology. 1991 Mar;181(1):55-61 [1704660] Mol Cell Biol. 1991 Mar;11(3):1419-30 [1847499] J Virol. 1991 Apr;65(4):1910-5 [2002549] Oncogene. 1991 Mar;6(3):491-3 [1707154] J Med Chem. 1991 Aug;34(8):2305-14 [1875332] Biochem Biophys Res Commun. 1991 Aug 30;179(1):17-24 [1652947] Protein Eng. 1991 Aug;4(6):695-700 [1658777] J Virol. 1992 Mar;66(3):1717-25 [1371173] J Virol. 1992 Mar;66(3):1737-45 [1310774] J Virol. 1992 Apr;66(4):2232-9 [1548759] J Virol. 1992 Apr;66(4):2547-50 [1548779] J Virol. 1993 Feb;67(2):623-31 [8380458] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the NH2-terminal glycosylation sites of the insulin receptor alpha-subunit. AN - 76331519; 8288048 AB - The insulin receptor is synthesized as a single chain of 190 kiloDaltons, which is processed to disulfide-linked mature alpha- and beta- subunits, containing N- and O-linked oligosaccharides and fatty acids. Previously (Collier E, Carpentier J-L, Beitz L, Caro LHP, Taylor SI, Gorden P: Biochemistry 32:7818-23, 1993), site directed mutagenesis of the asparagine in the first four sites of N-linked glycosylation to glutamine resulted in a receptor that was retained in the endoplasmic reticulum and not processed past the proreceptor form. In this study, mutation of these sites individually and in various combinations is studied. Mutation in the first or second glycosylation site does not significantly impair processing of the receptor; the receptor is found on the cell surface and binds insulin normally. If both the first and second sites are mutated, a significant reduction occurs in the amount of receptor found on the cell surface and in insulin binding. There is some processing of the receptor in cells expressing this mutant compared with the four-part mutant. If only the third and fourth sites are mutated, processing is impaired less than in the mutant with the first and second sites mutated. However, the amount of receptor found on the cell surface is less than in the mutant of only the first or only the second site. In all of these glycosylation mutants, the amount of receptor on the cell surface correlates with the level of 125I-labeled insulin binding on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Diabetes AU - Caro, L H AU - Ohali, A AU - Gorden, P AU - Collier, E AD - Diabetes Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 240 EP - 246 VL - 43 IS - 2 SN - 0012-1797, 0012-1797 KW - Insulin KW - 0 KW - Macromolecular Substances KW - Peptide Fragments KW - Glutamine KW - 0RH81L854J KW - Asparagine KW - 7006-34-0 KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Trypsin KW - EC 3.4.21.4 KW - Abridged Index Medicus KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Peptide Mapping KW - Humans KW - Peptide Fragments -- isolation & purification KW - Insulin -- metabolism KW - Mice KW - Glycosylation KW - Chromatography, High Pressure Liquid KW - Binding Sites KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Restriction Mapping KW - Cell Membrane -- metabolism KW - DNA Mutational Analysis KW - Receptor, Insulin -- biosynthesis KW - Receptor, Insulin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76331519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Mutational+analysis+of+the+NH2-terminal+glycosylation+sites+of+the+insulin+receptor+alpha-subunit.&rft.au=Caro%2C+L+H%3BOhali%2C+A%3BGorden%2C+P%3BCollier%2C+E&rft.aulast=Caro&rft.aufirst=L&rft.date=1994-02-01&rft.volume=43&rft.issue=2&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. AN - 76330384; 7904313 AB - The antifungal agent ketoconazole was found to overcome resistance to vinblastine and doxorubicin in multidrug resistant KB-V1 cells in vitro. These cells are several hundred-fold more resistant than the parental cell line KB-3-1. Ketoconazole had little or no effect on the parental KB-3-1 cells. The concentrations used to overcome drug resistance in vitro have already been safely used in vivo for treatment of fungal infections and in the monotherapy of hormone independent prostate carcinomas to block adrenal androgen production. Because of a possible beneficial effect of a combination of ketoconazole and a chemotherapeutic drug in multidrug resistant cancers, we examined a panel of 11 prostate carcinoma tissues for the expression of the MDR1 gene by an RNA-PCR assay. MDR1 expression was detectable, albeit at low levels, in 8 of the 11 tumors, suggesting a possible role of this gene in the drug resistance of prostate carcinomas. Our data suggest that ketoconazole might be useful in overcoming multidrug resistance in concentrations that are achievable in humans. JF - The Journal of urology AU - Siegsmund, M J AU - Cardarelli, C AU - Aksentijevich, I AU - Sugimoto, Y AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Molecular Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/02// PY - 1994 DA - February 1994 SP - 485 EP - 491 VL - 151 IS - 2 SN - 0022-5347, 0022-5347 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA, Messenger KW - Rhodamines KW - Vinblastine KW - 5V9KLZ54CY KW - Doxorubicin KW - 80168379AG KW - Ketoconazole KW - R9400W927I KW - Abridged Index Medicus KW - Index Medicus KW - Vinblastine -- pharmacology KW - Doxorubicin -- pharmacology KW - Humans KW - Prostatic Neoplasms -- genetics KW - Drug Resistance KW - Drug Synergism KW - RNA, Messenger -- biosynthesis KW - Male KW - Rhodamines -- pharmacokinetics KW - Membrane Glycoproteins -- drug effects KW - KB Cells -- physiology KW - Carrier Proteins -- drug effects KW - Carrier Proteins -- genetics KW - KB Cells -- drug effects KW - Ketoconazole -- pharmacology KW - KB Cells -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76330384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+urology&rft.atitle=Ketoconazole+effectively+reverses+multidrug+resistance+in+highly+resistant+KB+cells.&rft.au=Siegsmund%2C+M+J%3BCardarelli%2C+C%3BAksentijevich%2C+I%3BSugimoto%2C+Y%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Siegsmund&rft.aufirst=M&rft.date=1994-02-01&rft.volume=151&rft.issue=2&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-15 N1 - Date created - 1994-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The origin of human immunodeficiency virus type-1 rev gene. An evolutionary hypothesis. AN - 76353048; 8307167 AB - The Rev protein of human immunodeficiency virus type-1 is an RNA-binding posttranscriptional transregulator encoded by an accessory gene that is distinct from retroviral oncogenes and whose origin is unclear. We hypothesize that the rev gene was generated by duplication of a viral RNA segment having a secondary-structure that evolved into the Rev-responsive element (RRE). This hypothesis is based on the following findings. First, accumulated data on functional mapping of Rev, Tat, and the transmembrane protein of Env suggested that the major coding exon of rev should have been inserted into the transmembrane region of env during the course of its evolution. Experiments with equine infectious anemia virus, another complex retrovirus, also indicate that a large portion of rev is located within the dispensable transmembrane region of env. Second, base usage analysis suggests the same origin for rev and RRE. Our hypothesis may provide a new insight into the evolutionary aspect of RNA-binding transactivators. JF - FEBS letters AU - Kubota, S AU - Oroszlan, S AU - Hatanaka, M AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research and Development Center, MD 21702-1201. Y1 - 1994/01/31/ PY - 1994 DA - 1994 Jan 31 SP - 118 EP - 121 VL - 338 IS - 2 SN - 0014-5793, 0014-5793 KW - rev KW - DNA, Viral KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - DNA, Viral -- chemistry KW - Molecular Sequence Data KW - Models, Biological KW - HIV-1 -- genetics KW - Biological Evolution KW - Genes, rev UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76353048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=The+origin+of+human+immunodeficiency+virus+type-1+rev+gene.+An+evolutionary+hypothesis.&rft.au=Kubota%2C+S%3BOroszlan%2C+S%3BHatanaka%2C+M&rft.aulast=Kubota&rft.aufirst=S&rft.date=1994-01-31&rft.volume=338&rft.issue=2&rft.spage=118&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 - 1994-03-15 N1 - Date created - 1994-03-15 N1 - Date revised - 2017-01-13 N1 - Gene symbol - rev N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytostatic and cytotoxic activity of sex steroids against human leukemia cell lines. AN - 76426900; 8149350 AB - We investigated effects of sex steroids and analogs (estradiol, DES, norgestrel, progesterone, medroxyprogesterone, and testosterone) on the proliferation and survival of 10 human leukemia/lymphoma cell lines (HL-60, K562, U937, CEM, KG-1, Jurkat, U266, H929, PA and SUNHL). Micromolar concentrations of sex steroids exerted cytostatic and cytotoxic effects on all cell lines tested, irrespective of their sensitivity to glucocorticoids. The order of potency of sex hormones was: DES > progesterone > or = medroxyprogesterone > testosterone > estradiol >> norgestrel. For progesterone and estradiol, cytostatic effects can be achieved at lower concentrations than cytotoxic effects. The most potent agent, DES, exerted half maximal cytotoxic activity at a median concentration of 4 microM (for 10 leukemia cell lines). Our results provide a basis for the potential therapeutic use of estrogens and progestins in glucocorticoid-resistant leukemias and lymphomas. JF - Cancer letters AU - Blagosklonny, M V AU - Neckers, L M AD - Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, MD 20892. Y1 - 1994/01/30/ PY - 1994 DA - 1994 Jan 30 SP - 81 EP - 86 VL - 76 IS - 2-3 SN - 0304-3835, 0304-3835 KW - Androgens KW - 0 KW - Antineoplastic Agents KW - Estrogens KW - Glucocorticoids KW - Gonadal Steroid Hormones KW - Steroids KW - Tetrazolium Salts KW - Thiazoles KW - Progesterone KW - 4G7DS2Q64Y KW - Diethylstilbestrol KW - 731DCA35BT KW - thiazolyl blue KW - EUY85H477I KW - Index Medicus KW - Progesterone -- toxicity KW - Glucocorticoids -- toxicity KW - Diethylstilbestrol -- toxicity KW - Humans KW - Progesterone -- pharmacology KW - Androgens -- pharmacology KW - Estrogens -- toxicity KW - Glucocorticoids -- pharmacology KW - Tumor Cells, Cultured KW - Estrogens -- pharmacology KW - Diethylstilbestrol -- pharmacology KW - Androgens -- toxicity KW - Leukemia -- drug therapy KW - Gonadal Steroid Hormones -- pharmacology KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Antineoplastic Agents -- toxicity KW - Steroids -- pharmacology KW - Steroids -- toxicity KW - Gonadal Steroid Hormones -- toxicity KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76426900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Cytostatic+and+cytotoxic+activity+of+sex+steroids+against+human+leukemia+cell+lines.&rft.au=Blagosklonny%2C+M+V%3BNeckers%2C+L+M&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1994-01-30&rft.volume=76&rft.issue=2-3&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-06 N1 - Date created - 1994-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies. AN - 76379914; 8122051 AB - This article describes how genetic components of disease susceptibility can be evaluated in case-control studies, where cases and controls are sampled independently from the population at large. Subjects are assumed unrelated, in contrast to studies of familial aggregation and linkage. The logistic model can be used to test collapsibility over phenotypes or genotypes, and to estimate interactions between environmental and genetic factors. Such interactions provide an example of a context where non-hierarchical models make sense biologically. Also, if the exposure and genetic categories occur independently and the disease is rare, then analyses based only on cases are valid, and offer better precision for estimating gene-environment interactions than those based on the full data. JF - Statistics in medicine AU - Piegorsch, W W AU - Weinberg, C R AU - Taylor, J A AD - Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01/30/ PY - 1994 DA - 1994 Jan 30 SP - 153 EP - 162 VL - 13 IS - 2 SN - 0277-6715, 0277-6715 KW - Biomarkers KW - 0 KW - Genetic Markers KW - Index Medicus KW - Occupational Exposure KW - Carcinoma, Squamous Cell -- etiology KW - Odds Ratio KW - Humans KW - Smoking -- adverse effects KW - Genotype KW - Phenotype KW - Lung Neoplasms -- etiology KW - Biomarkers -- analysis KW - Risk Factors KW - Environmental Exposure KW - Family KW - Logistic Models KW - Case-Control Studies KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76379914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Non-hierarchical+logistic+models+and+case-only+designs+for+assessing+susceptibility+in+population-based+case-control+studies.&rft.au=Piegorsch%2C+W+W%3BWeinberg%2C+C+R%3BTaylor%2C+J+A&rft.aulast=Piegorsch&rft.aufirst=W&rft.date=1994-01-30&rft.volume=13&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Statistics+in+medicine&rft.issn=02776715&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-04 N1 - Date created - 1994-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tyrosine phosphorylation of protein kinase C-delta in response to its activation. AN - 76340813; 7507923 AB - Retroviral vectors containing five different protein kinase C (PKC) isoenzymes (alpha, delta, epsilon, eta, zeta) were expressed in 32D hematopoietic cells and NIH-3T3 fibroblasts. In an effort to investigate signaling events regulated by PKC activation, we analyzed whether tyrosine phosphorylation of cellular proteins would occur after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of the various transfectants. While no detectable tyrosine-specific phosphorylation was observed after treatment of the majority of the transfectants, pronounced TPA-dependent tyrosine phosphorylation of an 82-kDa protein was detected in the 32D/PKC-delta and NIH-3T3/PKC-delta lines. Interestingly, the 82-kDa substrate proved to be PKC-delta itself. Tyrosine phosphorylation of purified PKC-delta by src family or receptor tyrosine kinases in vitro enhanced PKC-delta activity, suggesting that tyrosine phosphorylation of PKC-delta may positively affect its function. JF - The Journal of biological chemistry AU - Li, W AU - Mischak, H AU - Yu, J C AU - Wang, L M AU - Mushinski, J F AU - Heidaran, M A AU - Pierce, J H AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/01/28/ PY - 1994 DA - 1994 Jan 28 SP - 2349 EP - 2352 VL - 269 IS - 4 SN - 0021-9258, 0021-9258 KW - Interleukin-3 KW - 0 KW - Isoenzymes KW - Phosphopeptides KW - Phosphoproteins KW - Recombinant Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Receptor Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Genes, src KW - Recombinant Proteins -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme Activation KW - Interleukin-3 -- pharmacology KW - Amino Acid Sequence KW - Mice KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Phosphopeptides -- chemistry KW - Molecular Weight KW - Recombinant Proteins -- isolation & purification KW - Phosphopeptides -- isolation & purification KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Substrate Specificity KW - Protein Kinase C -- metabolism KW - Isoenzymes -- isolation & purification KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- isolation & purification KW - Protein Kinase C -- biosynthesis KW - Tyrosine -- analogs & derivatives KW - Phosphoproteins -- isolation & purification KW - Isoenzymes -- metabolism KW - Tyrosine -- analysis KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76340813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tyrosine+phosphorylation+of+protein+kinase+C-delta+in+response+to+its+activation.&rft.au=Li%2C+W%3BMischak%2C+H%3BYu%2C+J+C%3BWang%2C+L+M%3BMushinski%2C+J+F%3BHeidaran%2C+M+A%3BPierce%2C+J+H&rft.aulast=Li&rft.aufirst=W&rft.date=1994-01-28&rft.volume=269&rft.issue=4&rft.spage=2349&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 - 1994-03-04 N1 - Date created - 1994-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. AN - 76343325; 8294408 AB - A thiol-specific antioxidant enzyme (TSA), which provides protection against the inactivation of other enzymes by the thiol/Fe(III)/oxygen system, was previously isolated and cloned. We investigated the mechanism by which TSA protects biomolecules from oxidative damage caused by the thiol-containing oxidation system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Thiyl radicals from dithiothreitol (.DTT) were produced by horseradish peroxidase/H2O2 under aerobic and anaerobic conditions and by the Fe(III)/oxygen system. The formation of DMPO-.DTT radical adducts were inhibited by TSA regardless of the thiyl radical-generating conditions used. The active mutant C170S also quenched the signals of the radical adduct, whereas the inactive mutant C47S did not exert any effect. It was also found that C170S has a higher rate at the initial stage of the reaction than that of the native enzyme, although C170S failed to remove DMPO-.DTT radical adducts completely. These results indicate that only active TSA can catalyze the removal of thiyl radicals, and cysteine 47 is required for this activity. In addition, thiyl radicals react with oxygen to generate unidentified thiylperoxy species. Fe.EDTA reacts with this species to generate a reactive radical that can abstract hydrogen atom from ethanol to produce a hydroxyethyl radical. This reactive thiyl-oxygen radical is believed to be responsible for causing deleterious effects on biomolecules. Together, our data indicate that TSA protects biomolecules from oxidative damage by catalyzing the removal of thiyl radicals before they generate more reactive radicals. However, presently we cannot rule out the possibility that TSA can also use other thiol-containing species as substrates. JF - The Journal of biological chemistry AU - Yim, M B AU - Chae, H Z AU - Rhee, S G AU - Chock, P B AU - Stadtman, E R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01/21/ PY - 1994 DA - 1994 Jan 21 SP - 1621 EP - 1626 VL - 269 IS - 3 SN - 0021-9258, 0021-9258 KW - Antioxidants KW - 0 KW - Cyclic N-Oxides KW - Fungal Proteins KW - Oxidants KW - Recombinant Proteins KW - Spin Labels KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Peroxidases KW - Peroxiredoxins KW - EC 1.11.1.15 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Recombinant Proteins -- metabolism KW - Oxygen -- pharmacology KW - Kinetics KW - Electron Spin Resonance Spectroscopy KW - Models, Theoretical KW - Mathematics KW - Horseradish Peroxidase -- metabolism KW - Fungal Proteins -- metabolism KW - Antioxidants -- metabolism KW - Oxidants -- toxicity KW - Fungal Proteins -- biosynthesis KW - Antioxidants -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76343325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Antimicrobial+Agents&rft.atitle=Treatment+and+developmental+therapeutics+of+Mycobacterium+tuberculosis+infections&rft.au=St.+Georgiev%2C+V&rft.aulast=St.+Georgiev&rft.aufirst=V&rft.date=1994-01-01&rft.volume=4&rft.issue=3&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Antimicrobial+Agents&rft.issn=09248579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-25 N1 - Date created - 1994-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mispair-, site-, and strand-specific error rates during simian virus 40 origin-dependent replication in vitro with excess deoxythymidine triphosphate. AN - 76341596; 8294419 AB - We have measured the fidelity of leading and lagging strand DNA replication in HeLa cell extracts. Providing an excess of one dNTP in reactions induces replication errors consistent with misincorporation of that dNTP. With excess dTTP, both substitutions and single-nucleotide frameshifts are induced. Error distribution is nonrandom; reproducible hot spots for a substitution and a frameshift error are observed. Measurements with two vectors having the origin of replication on opposite sides of the mutational target demonstrate that error rates for G.dTTP and C.dTTP mispairs depend on whether the strand is replicated as the leading or lagging strand. Also, the two hot spots are only observed in one origin-target orientation. Replication reactions reconstituted from two fractions derived from extracts are 3-fold less accurate, but the error specificity with excess dTTP is similar to that with extracts. This suggests that the processes responsible for the nonrandom error rates are not lost as a result of fractionation. Furthermore, the reconstituted system is devoid of mismatch repair activity. Thus, mismatch repair is not responsible for the mispair-, site-, and strand-specific differences observed. JF - The Journal of biological chemistry AU - Roberts, J D AU - Izuta, S AU - Thomas, D C AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/01/21/ PY - 1994 DA - 1994 Jan 21 SP - 1711 EP - 1717 VL - 269 IS - 3 SN - 0021-9258, 0021-9258 KW - lacZ KW - DNA, Viral KW - 0 KW - Deoxyribonucleotides KW - Nucleic Acid Heteroduplexes KW - Oligodeoxyribonucleotides KW - Thymine Nucleotides KW - beta-Galactosidase KW - EC 3.2.1.23 KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Index Medicus KW - Viral Plaque Assay KW - HeLa Cells KW - Humans KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Mutagenesis KW - Frameshift Mutation KW - Base Sequence KW - Nucleic Acid Heteroduplexes -- metabolism KW - Transfection KW - Genetic Vectors KW - Restriction Mapping KW - Deoxyribonucleotides -- metabolism KW - Genetic Complementation Test KW - Molecular Sequence Data KW - beta-Galactosidase -- biosynthesis KW - DNA, Viral -- biosynthesis KW - DNA Repair KW - Thymine Nucleotides -- metabolism KW - Simian virus 40 -- genetics KW - Simian virus 40 -- metabolism KW - DNA, Viral -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76341596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mispair-%2C+site-%2C+and+strand-specific+error+rates+during+simian+virus+40+origin-dependent+replication+in+vitro+with+excess+deoxythymidine+triphosphate.&rft.au=Roberts%2C+J+D%3BIzuta%2C+S%3BThomas%2C+D+C%3BKunkel%2C+T+A&rft.aulast=Roberts&rft.aufirst=J&rft.date=1994-01-21&rft.volume=269&rft.issue=3&rft.spage=1711&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 - 1994-02-25 N1 - Date created - 1994-02-25 N1 - Date revised - 2017-01-13 N1 - Gene symbol - lacZ N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential regulation of protein kinase C isozymes by bryostatin 1 and phorbol 12-myristate 13-acetate in NIH 3T3 fibroblasts. AN - 76339902; 8294465 AB - Bryostatin 1 and phorbol 12-myristate 13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in many systems bryostatin 1 induces only a subset of the responses to PMA and blocks those which it does not induce. We report here that in NIH 3T3 fibroblasts PMA showed similar potencies for translocating PKC isozymes alpha, delta, and epsilon to the Triton X-100-soluble and -insoluble fractions and for the down-regulation of the three isozymes. Bryostatin 1 was slightly was more potent than PMA for down-regulating it. Bryostatin 1 was markedly more potent than PMA for translocating PKC delta but showed a biphasic dose-response curve for down-regulating this isozyme. 1-10 nM bryostatin 1 down-regulated PKC delta to a similar extent as PMA; lower (10-100 pM) or, unexpectedly, higher (100 nM to 1 microM) doses of bryostatin 1 caused either no or reduced down-regulation. Moreover, these high (100 nM to 1 microM) doses of bryostatin 1 inhibited the down-regulation of PKC delta by 1 microM PMA when coapplied. Bryostatin 1 caused translocation of PKC epsilon with slightly higher potency than PKC delta, but there was no protection of this isozyme at any of the doses examined. Bryostatin 1 induced a long-term increase in c-Jun level. The dose-response curve for bryostatin 1 was biphasic, with maximal induction at 1-10 nM bryostatin 1, coincident with the maximal down-regulation of PKC delta. We conclude that bryostatin 1 showed substantially different regulation for PKC alpha, PKC delta, and PKC epsilon, whereas PMA distinguished only weakly between these isozymes. JF - The Journal of biological chemistry AU - Szallasi, Z AU - Smith, C B AU - Pettit, G R AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/01/21/ PY - 1994 DA - 1994 Jan 21 SP - 2118 EP - 2124 VL - 269 IS - 3 SN - 0021-9258, 0021-9258 KW - Bryostatins KW - 0 KW - Isoenzymes KW - Lactones KW - Macrolides KW - Mitogens KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mitogens -- pharmacology KW - Animals KW - 3T3 Cells KW - Fibroblasts -- enzymology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Enzyme Activation KW - Kinetics KW - Enzyme Induction KW - Mice KW - Isoenzymes -- isolation & purification KW - Isoenzymes -- biosynthesis KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- isolation & purification KW - Protein Kinase C -- biosynthesis KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76339902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+regulation+of+protein+kinase+C+isozymes+by+bryostatin+1+and+phorbol+12-myristate+13-acetate+in+NIH+3T3+fibroblasts.&rft.au=Szallasi%2C+Z%3BSmith%2C+C+B%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=Z&rft.date=1994-01-21&rft.volume=269&rft.issue=3&rft.spage=2118&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 - 1994-02-25 N1 - Date created - 1994-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. AN - 76335594; 8277546 AB - To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene. Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants. Patients and controls from clinical and epidemiologic collections in the United States and Europe. A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taql site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white. Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups. We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia. No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia. JF - JAMA AU - Gejman, P V AU - Ram, A AU - Gelernter, J AU - Friedman, E AU - Cao, Q AU - Pickar, D AU - Blum, K AU - Noble, E P AU - Kranzler, H R AU - O'Malley, S AD - Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Md. 20892. Y1 - 1994/01/19/ PY - 1994 DA - 1994 Jan 19 SP - 204 EP - 208 VL - 271 IS - 3 SN - 0098-7484, 0098-7484 KW - DRD2 KW - Receptors, Dopamine D2 KW - 0 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Genes KW - Electrophoresis -- methods KW - Exons KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - DNA -- analysis KW - Receptors, Dopamine D2 -- genetics KW - Schizophrenia -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76335594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=No+structural+mutation+in+the+dopamine+D2+receptor+gene+in+alcoholism+or+schizophrenia.+Analysis+using+denaturing+gradient+gel+electrophoresis.&rft.au=Gejman%2C+P+V%3BRam%2C+A%3BGelernter%2C+J%3BFriedman%2C+E%3BCao%2C+Q%3BPickar%2C+D%3BBlum%2C+K%3BNoble%2C+E+P%3BKranzler%2C+H+R%3BO%27Malley%2C+S&rft.aulast=Gejman&rft.aufirst=P&rft.date=1994-01-19&rft.volume=271&rft.issue=3&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Gene symbol - DRD2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reconstitution of the biosynthetic pathway of selenocysteine tRNAs in Xenopus oocytes. AN - 76331646; 8286391 AB - Selenocysteine is cotranslationally introduced into a growing polypeptide in response to certain UGA codons in selenoprotein mRNAs. The biosynthesis of this amino acid initiates by aminoacylation of specific tRNAs (designated tRNA([Ser]Sec)) with serine and subsequent conversion of the serine moiety to selenocysteine. The resulting selenocysteyl-tRNA then donates selenocysteine to protein. In most higher vertebrate cells and tissues examined, multiple selenocysteine isoacceptors have been described. Two of these have been determined to differ by only a single modified residue in the wobble position of the anticodon. In addition, the steady-state levels and relative distributions of these isoacceptors have been shown to be influenced by the presence of selenium. In order to gain a better understanding of the relationship between these tRNAs and how they are regulated, both the Xenopus selenocysteine tRNA gene and an in vitro synthesized RNA have each been injected into Xenopus oocytes and their maturation analyzed. In this system, selenium enhanced RNA stability and altered the distribution of isoacceptors that differ by a single ribose methylation. Interestingly, the biosynthesis of one of these modified nucleosides (5-methylcarboxymethyl-2'-O-methyluridine), which has been identified only in the wobble position of selenocysteine tRNA, also occurs in oocytes. Examination of the modified residues in both the naturally occurring Xenopus selenocysteine tRNA and the products generated from exogenous templates in oocytes demonstrated the faithful reconstruction of the biosynthetic pathway for these tRNAs. JF - Biochemistry AU - Choi, I S AU - Diamond, A M AU - Crain, P F AU - Kolker, J D AU - McCloskey, J A AU - Hatfield, D L AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01/18/ PY - 1994 DA - 1994 Jan 18 SP - 601 EP - 605 VL - 33 IS - 2 SN - 0006-2960, 0006-2960 KW - RNA, Transfer, Amino Acid-Specific KW - 0 KW - RNA, Transfer, Amino Acyl KW - selenocysteinyl-tRNA KW - tRNA, selenocysteine- KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Xenopus laevis KW - Drug Stability KW - Animals KW - Base Sequence KW - Gene Transfer Techniques KW - Selenium -- pharmacology KW - Molecular Sequence Data KW - RNA, Transfer, Amino Acid-Specific -- metabolism KW - Microinjections KW - Plasmids KW - Female KW - Oocytes -- metabolism KW - RNA, Transfer, Amino Acyl -- biosynthesis KW - RNA, Transfer, Amino Acyl -- genetics KW - RNA, Transfer, Amino Acyl -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76331646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reconstitution+of+the+biosynthetic+pathway+of+selenocysteine+tRNAs+in+Xenopus+oocytes.&rft.au=Choi%2C+I+S%3BDiamond%2C+A+M%3BCrain%2C+P+F%3BKolker%2C+J+D%3BMcCloskey%2C+J+A%3BHatfield%2C+D+L&rft.aulast=Choi&rft.aufirst=I&rft.date=1994-01-18&rft.volume=33&rft.issue=2&rft.spage=601&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Series: 'Current issues in mutagenesis and carcinogenesis.' No. 43. Mutations among the living and the undead. AN - 76331477; 7506376 JF - Mutation research AU - Burkhart, J G AU - Malling, H V AD - Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01/16/ PY - 1994 DA - 1994 Jan 16 SP - 315 EP - 320 VL - 304 IS - 2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Index Medicus KW - Animals KW - Spermatozoa -- drug effects KW - Cell Death KW - Mutagens -- toxicity KW - Mice KW - Germ-Line Mutation KW - Cell Cycle KW - Male KW - DNA Replication KW - Mice, Transgenic -- genetics KW - Mutagenicity Tests -- standards KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76331477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Series%3A+%27Current+issues+in+mutagenesis+and+carcinogenesis.%27+No.+43.+Mutations+among+the+living+and+the+undead.&rft.au=Burkhart%2C+J+G%3BMalling%2C+H+V&rft.aulast=Burkhart&rft.aufirst=J&rft.date=1994-01-16&rft.volume=304&rft.issue=2&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Series: 'Current issues in mutagenesis and carcinogenesis.' No. 42. Strategies and philosophies of genotoxicity testing: what is the question? AN - 76330357; 7506375 AB - A number of statements concerning the uses and effectiveness of in vitro and in vivo genetic toxicity tests have recently been made. Certain of these statements are examined using genetic toxicity and carcinogenicity data available in the literature. JF - Mutation research AU - Zeiger, E AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01/16/ PY - 1994 DA - 1994 Jan 16 SP - 309 EP - 314 VL - 304 IS - 2 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Animals KW - Micronucleus Tests KW - Reproducibility of Results KW - Mammals KW - Humans KW - Salmonella typhimurium -- drug effects KW - Predictive Value of Tests KW - Salmonella typhimurium -- genetics KW - False Positive Reactions KW - Mutagenicity Tests -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76330357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Series%3A+%27Current+issues+in+mutagenesis+and+carcinogenesis.%27+No.+42.+Strategies+and+philosophies+of+genotoxicity+testing%3A+what+is+the+question%3F&rft.au=Zeiger%2C+E&rft.aulast=Zeiger&rft.aufirst=E&rft.date=1994-01-16&rft.volume=304&rft.issue=2&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mutat Res. 1994 Jul 1;308(1):111-2 [7516480] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NotI linking clones as a tool for joining physical and genetic maps of the human genome. AN - 76485867; 8188261 AB - To study the connection among NotI linking clones, CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These NotI linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps and used for generating a long-range NotI map of the human genome. A majority (about 90%) of these clones contain transcribed sequences, as detected by Northern blot hybridization, providing an efficient link between physical and functional (genetic) maps. The GenBank nucleotide database was searched with sequences from these NotI linking clones. For many clones, homology was found to human and other vertebrate genes. About 20 clones contained various repeats in their sequences and may represent microsatellite loci. Most of these NotI linking clones therefore represent evolutionarily conserved DNA fragments and also can be used for comparative genome mapping of other mammalian species. In addition, approximately 20% of all sequenced human CpG island-containing genes and more than 12% of all well-characterized human genes were found to possess NotI restriction sites. This is at least 2-5 times more than has been previously estimated and suggests that NotI sites have a much stronger association with genes. JF - Genomics AU - Allikmets, R L AU - Kashuba, V I AU - Pettersson, B AU - Gizatullin, R AU - Lebedeva, T AU - Kholodnyuk, I D AU - Bannikov, V M AU - Petrov, N AU - Zakharyev, V M AU - Winberg, G AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland 21702. Y1 - 1994/01/15/ PY - 1994 DA - 1994 Jan 15 SP - 303 EP - 309 VL - 19 IS - 2 SN - 0888-7543, 0888-7543 KW - DNA KW - 9007-49-2 KW - Deoxyribonucleases, Type II Site-Specific KW - EC 3.1.21.4 KW - GCGGCCGC-specific type II deoxyribonucleases KW - Index Medicus KW - Animals KW - Vertebrates -- genetics KW - Base Composition KW - Sequence Homology, Nucleic Acid KW - Humans KW - Gene Expression KW - In Situ Hybridization, Fluorescence KW - Base Sequence KW - Chromosomes, Human, Pair 3 KW - Sequence Alignment KW - DNA -- genetics KW - Molecular Sequence Data KW - Species Specificity KW - Gene Library KW - Genome, Human KW - Chromosome Mapping -- methods KW - Cloning, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76485867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=NotI+linking+clones+as+a+tool+for+joining+physical+and+genetic+maps+of+the+human+genome.&rft.au=Allikmets%2C+R+L%3BKashuba%2C+V+I%3BPettersson%2C+B%3BGizatullin%2C+R%3BLebedeva%2C+T%3BKholodnyuk%2C+I+D%3BBannikov%2C+V+M%3BPetrov%2C+N%3BZakharyev%2C+V+M%3BWinberg%2C+G&rft.aulast=Allikmets&rft.aufirst=R&rft.date=1994-01-15&rft.volume=19&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-20 N1 - Date created - 1994-06-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - Z22423; GENBANK; Z22270; Z22446; Z22462; Z22409; Z22264; Z22444; Z22265; Z22477; Z22279; Z22376; Z22241; Z22344; Z22240; Z22346; Z22345; Z22395; Z22323; Z22414; Z22326; Z22301 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan. AN - 76342878; 8293417 AB - Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation. From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature). Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6). The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment. JF - Cancer AU - Vaglini, M AU - Belli, F AU - Ammatuna, M AU - Inglese, M G AU - Manzi, R AU - Prada, A AU - Persiani, L AU - Santinami, M AU - Santoro, N AU - Cascinelli, N AD - Department of Surgical Oncology B, National Cancer Institute, Milan, Italy. Y1 - 1994/01/15/ PY - 1994 DA - 1994 Jan 15 SP - 483 EP - 492 VL - 73 IS - 2 SN - 0008-543X, 0008-543X KW - Tumor Necrosis Factor-alpha KW - 0 KW - Interferon-gamma KW - 82115-62-6 KW - Melphalan KW - Q41OR9510P KW - Abridged Index Medicus KW - Index Medicus KW - Skin Neoplasms -- drug therapy KW - Humans KW - Chemotherapy, Cancer, Regional Perfusion KW - Carcinoma -- drug therapy KW - Melanoma -- drug therapy KW - Adult KW - Aged KW - Pilot Projects KW - Middle Aged KW - Sarcoma -- drug therapy KW - Male KW - Female KW - Leg KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melphalan -- administration & dosage KW - Interferon-gamma -- administration & dosage KW - Soft Tissue Neoplasms -- drug therapy KW - Arm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76342878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment+of+primary+or+relapsing+limb+cancer+by+isolation+perfusion+with+high-dose+alpha-tumor+necrosis+factor%2C+gamma-interferon%2C+and+melphalan.&rft.au=Vaglini%2C+M%3BBelli%2C+F%3BAmmatuna%2C+M%3BInglese%2C+M+G%3BManzi%2C+R%3BPrada%2C+A%3BPersiani%2C+L%3BSantinami%2C+M%3BSantoro%2C+N%3BCascinelli%2C+N&rft.aulast=Vaglini&rft.aufirst=M&rft.date=1994-01-15&rft.volume=73&rft.issue=2&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-25 N1 - Date created - 1994-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma. AN - 76330354; 8286741 AB - Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin composed of the variable domains of the monoclonal antibody anti-Tac, which binds to the p55 subunit of the interleukin-2 receptor (IL-2R), and a truncated form of Pseudomonas exotoxin (PE), which does not bind to the PE receptor (Chaudhary et al, Nature 339:394, 1989). Whereas its cytotoxic activity toward autoimmune and malignant target cells has been established, its efficacy in vivo remains unknown. To establish an animal model, we produced ATAC-4 cells by transfecting the gene encoding the low-affinity IL-2R (p55) into A431 epidermoid carcinoma cells. ATAC-4 cells contained low-affinity IL-2Rs (2 x 10(5)/cell) and formed tumors in nude mice. In tissue culture, protein synthesis in ATAC-4 cells was inhibited 50% (IC50) at 0.06 ng/mL (0.9 pmol/L) of anti-Tac(Fv)-PE40. IC50s for the derivatives anti-Tac(Fv)-PE38, which is missing PE amino acids 365-380, and anti-Tac(Fv)-PE38KDEL, which contains the same deletion plus the KDEL carboxyl terminus, were 0.04 and 0.025 ng/mL, respectively. All the agents produced complete tumor regressions in ATAC-4 tumor-bearing mice and anti-Tac(Fv)-PE38KDEL had significant antitumor activity at 1% of the LD50. The dose limiting toxicity of anti-Tac(Fv)-PE38KDEL was from hemorrhagic liver necrosis, which was observed at approximately 55% of the LD50. JF - Blood AU - Kreitman, R J AU - Bailon, P AU - Chaudhary, V K AU - FitzGerald, D J AU - Pastan, I AD - Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/15/ PY - 1994 DA - 1994 Jan 15 SP - 426 EP - 434 VL - 83 IS - 2 SN - 0006-4971, 0006-4971 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Transplantation, Heterologous KW - Mice KW - Recombinant Proteins -- therapeutic use KW - Female KW - Receptors, Interleukin-2 -- analysis KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76330354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+immunotoxins+containing+anti-Tac%28Fv%29+and+derivatives+of+Pseudomonas+exotoxin+produce+complete+regression+in+mice+of+an+interleukin-2+receptor-expressing+human+carcinoma.&rft.au=Kreitman%2C+R+J%3BBailon%2C+P%3BChaudhary%2C+V+K%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1994-01-15&rft.volume=83&rft.issue=2&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-23 N1 - Date created - 1994-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reciprocal expression of cell-cell coupling and voltage-dependent Na current during embryogenesis of rat telencephalon. AN - 76388664; 8131265 AB - Using whole-cell patch-clamp techniques in situ (whole-tissue and tissue slices), we have studied two aspects of rat telencephalic cell development during the period of embryogenesis starting at E12. The first aspect was related to junctional coupling as revealed by low input resistance, intercellular dye spread and pharmacologic blockade. Coupling appeared to decrease with time, both in extent and occurrence. The second aspect dealt with cell excitability as revealed by voltage-dependent Na current (INa) expression. Immature action potentials and their underlying INaS were present in a small proportion of E12 cells. These currents were blocked 36% and 78% by 10(-7) M and 10(-6) M tetrodotoxin (TTX), respectively. From then onward, INaS got larger and more prevalent while no obvious changes in kinetics were observed. At E21, INaS were abolished by 10(-7) M TTX and channel density apparently was sufficient to support overshooting yet still immature action potentials. JF - Brain research. Developmental brain research AU - Mienville, J M AU - Lange, G D AU - Barker, J L AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/14/ PY - 1994 DA - 1994 Jan 14 SP - 89 EP - 95 VL - 77 IS - 1 SN - 0165-3806, 0165-3806 KW - Sodium Channels KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Index Medicus KW - Rats KW - Animals KW - Electrophysiology KW - Tetrodotoxin -- pharmacology KW - Embryo, Mammalian -- physiology KW - Telencephalon -- embryology KW - Embryonic and Fetal Development KW - Embryo, Mammalian -- cytology KW - Sodium Channels -- physiology KW - Cell Communication KW - Sodium Channels -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76388664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=Reciprocal+expression+of+cell-cell+coupling+and+voltage-dependent+Na+current+during+embryogenesis+of+rat+telencephalon.&rft.au=Mienville%2C+J+M%3BLange%2C+G+D%3BBarker%2C+J+L&rft.aulast=Mienville&rft.aufirst=J&rft.date=1994-01-14&rft.volume=77&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Immunogenetics&rft.issn=00937711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-19 N1 - Date created - 1994-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electrostatic activation of rat phenylalanine hydroxylase. AN - 76342613; 7904815 AB - The conversion of phenylalanine to tyrosine is accelerated approximately five fold by phosphorylation of the enzyme which catalyzes this step, phenylalanine hydroxylase. To gain a clearer understanding of the mechanism of this activation, we have applied site-directed mutagenesis to specifically modify a clone of the hydroxylase at the phosphorylation site, the serine at position 16. We converted this serine residue to alanine and to glutamic acid. The wild-type and mutant proteins were purified and the activation states of the enzymes were examined with respect to the single phosphorylation site at position 16. Substitution of Ser16 with a negatively charged Glu residue resulted in activation of the enzyme, whereas substitution with an uncharged Ala residue did not. These results indicate that activation of the native enzyme by phosphorylation is due to the introduction of a negative charge, and suggest involvement of electrostatic interactions. JF - Biochemical and biophysical research communications AU - Citron, B A AU - Davis, M D AU - Kaufman, S AD - Laboratory of Neurochemistry, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/14/ PY - 1994 DA - 1994 Jan 14 SP - 174 EP - 180 VL - 198 IS - 1 SN - 0006-291X, 0006-291X KW - Glutamates KW - 0 KW - Recombinant Proteins KW - Glutamic Acid KW - 3KX376GY7L KW - Serine KW - 452VLY9402 KW - DNA KW - 9007-49-2 KW - Phenylalanine Hydroxylase KW - EC 1.14.16.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Enzyme Activation KW - DNA -- metabolism KW - Amino Acid Sequence KW - Plasmids KW - Rats KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Polymerase Chain Reaction KW - Base Sequence KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Restriction Mapping KW - Molecular Sequence Data KW - Electrochemistry KW - Phenylalanine Hydroxylase -- isolation & purification KW - Phenylalanine Hydroxylase -- biosynthesis KW - Phenylalanine Hydroxylase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76342613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Electrostatic+activation+of+rat+phenylalanine+hydroxylase.&rft.au=Citron%2C+B+A%3BDavis%2C+M+D%3BKaufman%2C+S&rft.aulast=Citron&rft.aufirst=B&rft.date=1994-01-14&rft.volume=198&rft.issue=1&rft.spage=174&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 - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro evidence for involvement of CoA thioesters in peroxisome proliferation and hypolipidaemia. AN - 76348019; 7906145 AB - The mechanisms of peroxisomal induction and hypolipidaemia caused by treatment with peroxisome proliferators, such as nafenopin and clofibrate, remain to be elucidated. Proposed mechanisms include receptor-mediated processes or adaptations resulting from disruption of hepatic lipid metabolism. The latter mechanism was investigated in a series of in vitro studies. Incubation of primary rat hepatocytes with various carboxyl-containing compounds revealed no clear common factor which imparted potency as a peroxisomal inducer. Inhibitors of fatty acyl-CoA synthetase, norepinephrine and desulpho-CoA, however, decreased the level of peroxisomal induction by nafenopin in rat hepatocytes, suggesting that activation of carboxyl-containing compounds to their CoA thioesters may be a necessary step in initiating peroxisome proliferation. Coenzyme A thioesters of nafenopin, clofibric acid and other carboxyl-containing chemicals were synthesised and found to inhibit the activity of acetyl-CoA carboxylase to varying degrees. The CoA thioester of nafenopin was the most potent inhibitor among this group (Ki = 1.45 x 10(-5) M), but weaker than palmitoyl-CoA (Ki = 2.22 x 10(-6) M), the feedback inhibitor of acetyl-CoA carboxylase. Hypolipidaemia caused by treatment with peroxisome proliferators may, therefore, be related to inhibition of fatty-acid synthesis by the corresponding CoA thioester derivative. JF - Biochimica et biophysica acta AU - Tomaszewski, K E AU - Melnick, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01/13/ PY - 1994 DA - 1994 Jan 13 SP - 118 EP - 124 VL - 1220 IS - 2 SN - 0006-3002, 0006-3002 KW - Acyl Coenzyme A KW - 0 KW - Anticholesteremic Agents KW - Esters KW - Fatty Acids KW - Nafenopin KW - 093W78U96W KW - clofibric acid-coenzyme A KW - 104732-21-0 KW - nafenopin-coenzyme A KW - 112195-81-0 KW - Clofibric Acid KW - 53PF01Q249 KW - desulfo-coenzyme A KW - 5863-40-1 KW - Acetyl-CoA Carboxylase KW - EC 6.4.1.2 KW - Coenzyme A KW - SAA04E81UX KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Animals KW - Coenzyme A -- pharmacology KW - Norepinephrine -- pharmacology KW - Fatty Acids -- biosynthesis KW - Acetyl-CoA Carboxylase -- antagonists & inhibitors KW - Clofibric Acid -- pharmacology KW - Nafenopin -- pharmacology KW - Acyl Coenzyme A -- pharmacology KW - Acetyl-CoA Carboxylase -- metabolism KW - Esters -- pharmacology KW - Nafenopin -- analogs & derivatives KW - Liver -- metabolism KW - Anticholesteremic Agents -- pharmacology KW - Microbodies -- drug effects KW - Clofibric Acid -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76348019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=In+vitro+evidence+for+involvement+of+CoA+thioesters+in+peroxisome+proliferation+and+hypolipidaemia.&rft.au=Tomaszewski%2C+K+E%3BMelnick%2C+R+L&rft.aulast=Tomaszewski&rft.aufirst=K&rft.date=1994-01-13&rft.volume=1220&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-21 N1 - Date created - 1994-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutation hotspot in radon-associated lung cancer. AN - 76328667; 7903781 AB - Mutations in gene p53 are the most common defects in lung cancer and may be a pathway through which environmental carcinogens initiate cancer. We investigated p53 mutations in lung cancers from uranium miners with high radon exposure. 16 (31%) of 52 large-cell and squamous-cell cancers from miners contained the same AGG to ATG transversion at codon 249, including cancers from 3 or 5 miners who had never smoked. This specific mutation has been reported in only 1 of 241 published p53 mutations from lung cancers. The codon 249 mutation may be a marker for radon-induced lung cancer. JF - Lancet (London, England) AU - Taylor, J A AU - Watson, M A AU - Devereux, T R AU - Michels, R Y AU - Saccomanno, G AU - Anderson, M AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1994/01/08/ PY - 1994 DA - 1994 Jan 08 SP - 86 EP - 87 VL - 343 IS - 8889 SN - 0140-6736, 0140-6736 KW - Codon KW - 0 KW - Uranium KW - 4OC371KSTK KW - Radon KW - Q74S4N8N1G KW - Abridged Index Medicus KW - Index Medicus KW - Exons -- genetics KW - Codon -- genetics KW - Humans KW - Case-Control Studies KW - Mining KW - Occupational Diseases -- genetics KW - Lung Neoplasms -- etiology KW - Genes, p53 -- radiation effects KW - Neoplasms, Radiation-Induced -- etiology KW - Occupational Diseases -- etiology KW - Lung Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- genetics KW - Radon -- adverse effects KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76328667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=p53+mutation+hotspot+in+radon-associated+lung+cancer.&rft.au=Taylor%2C+J+A%3BWatson%2C+M+A%3BDevereux%2C+T+R%3BMichels%2C+R+Y%3BSaccomanno%2C+G%3BAnderson%2C+M&rft.aulast=Taylor&rft.aufirst=J&rft.date=1994-01-08&rft.volume=343&rft.issue=8889&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-31 N1 - Date created - 1994-01-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 1994 Mar 26;343(8900):795 [7907754] Lancet. 1994 May 7;343(8906):1158-9 [7910245] Lancet. 1995 Jul 8;346(8967):121 [7603194] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secretion from rat basophilic RBL-2H3 cells is associated with diphosphorylation of myosin light chains by myosin light chain kinase as well as phosphorylation by protein kinase C. AN - 76332936; 8276847 AB - The phosphorylation of myosin light chains and heavy chains by protein kinase C is known to be temporally correlated with Ca(2+)-dependent secretion of granules from RBL-2H3 cells (Ludowyke, R. I., Peleg, I., Beaven, M. A., and Adelstein, R. S. (1989) J. Biol. Chem. 264, 12492-12501). We now report that whereas myosin light chains are predominantly monophosphorylated by the Ca2+/calmodulin-dependent myosin light chain kinase at serine 19 in unstimulated cells, stimulation of RBL-2H3 cells with antigen or other stimulants causes additional phosphorylation of myosin light chains by myosin light chain kinase at threonine 18, as well as by protein kinase C at serine 1 or serine 2. This diphosphorylation at serine 19 and threonine 18 by myosin light chain kinase and the monophosphorylation by protein kinase C is correlated with the rate and extent of degranulation. Secretion occurs whenever phosphorylation by both enzymes is stimulated by antigen or by the combination of low concentrations of A23187 (50 nM) and phorbol 12-myristate 13-acetate (20 nM). These phosphorylations appear to be closely associated with exocytosis in RBL-2H3 cells. Thus, phosphorylation, as well as secretion, can be blocked by the kinase inhibitors KT5926 and ML-7. More specifically, phorbol ester alone induces phosphorylation of myosin light chains by protein kinase C exclusively, but fails to induce secretion until accompanied by low concentrations of A23187, which activates myosin light chain kinase. Conversely, selective suppression of phosphorylation by protein kinase C (with Ro31-7549 in antigen-stimulated cells) suppresses degranulation, thereby indicating a requirement for protein kinase C. JF - The Journal of biological chemistry AU - Choi, O H AU - Adelstein, R S AU - Beaven, M A AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01/07/ PY - 1994 DA - 1994 Jan 07 SP - 536 EP - 541 VL - 269 IS - 1 SN - 0021-9258, 0021-9258 KW - Alkaloids KW - 0 KW - Antigens KW - Carbazoles KW - Indoles KW - Maleimides KW - Ro 31-7549 KW - 125313-65-7 KW - KT 5926 KW - 126643-38-7 KW - Calcimycin KW - 37H9VM9WZL KW - Egtazic Acid KW - 526U7A2651 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Myosin-Light-Chain Kinase KW - EC 2.7.11.18 KW - Myosins KW - EC 3.6.4.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Antigens -- pharmacology KW - Animals KW - Phosphorylation KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Alkaloids -- pharmacology KW - Indoles -- pharmacology KW - Calcimycin -- pharmacology KW - Egtazic Acid -- pharmacology KW - Maleimides -- pharmacology KW - Protein Kinase C -- metabolism KW - Myosins -- metabolism KW - Myosin-Light-Chain Kinase -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Basophils -- secretion KW - Basophils -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76332936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Secretion+from+rat+basophilic+RBL-2H3+cells+is+associated+with+diphosphorylation+of+myosin+light+chains+by+myosin+light+chain+kinase+as+well+as+phosphorylation+by+protein+kinase+C.&rft.au=Choi%2C+O+H%3BAdelstein%2C+R+S%3BBeaven%2C+M+A&rft.aulast=Choi&rft.aufirst=O&rft.date=1994-01-07&rft.volume=269&rft.issue=1&rft.spage=536&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 - 1994-02-08 N1 - Date created - 1994-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and DNA-sequence selectivity of a series of mono- and difunctional 9-aminoacridine nitrogen mustards. AN - 76332697; 8289202 AB - The aim of this work was to identify nitrogen mustards that would react selectively with DNA, particularly in G-rich regions. A series of mono- and difunctional nitrogen mustards was synthesized in which the (2-chloroethyl)amino functions were connected to the N9 of 9-aminoacridine by way of a spacer chain consisting of two to six methylene units. The length of the spacer chain connecting the alkylating and putative DNA-intercalating groups was found to affect the preference for the alkylation of different guanine-N7 positions in a DNA sequence. All of the compounds reacted preferentially at G's that are followed by G as do most other types of nitrogen mustards, but the degree of selectivity was greater. The compounds reacted at much lower concentrations than were required for comparable reaction by mechlorethamine (HN2), consistent with initial noncovalent binding to DNA prior to guanine-N7 alkylation. The degree of DNA-sequence selectivity increased as the spacer-chain length decreased below four methylene units. Most strikingly, long spacer compounds reacted strongly at 5'-GT-3' sequences, whereas this reaction was almost completely suppressed when the spacer length was reduced to two or three methylenes. Mono- and difunctional compounds of a given spacer length showed no consistent difference in DNA-sequence preference. JF - Journal of medicinal chemistry AU - Kohn, K W AU - Orr, A AU - O'Connor, P M AU - Guziec, L J AU - Guziec, F S AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1994/01/07/ PY - 1994 DA - 1994 Jan 07 SP - 67 EP - 72 VL - 37 IS - 1 SN - 0022-2623, 0022-2623 KW - Acridines KW - 0 KW - Intercalating Agents KW - Nitrogen Mustard Compounds KW - Mechlorethamine KW - 50D9XSG0VR KW - Guanine KW - 5Z93L87A1R KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Molecular Structure KW - Mechlorethamine -- metabolism KW - Base Sequence KW - Tumor Cells, Cultured KW - Mechlorethamine -- chemistry KW - Humans KW - Colonic Neoplasms -- drug therapy KW - Molecular Sequence Data KW - Guanine -- metabolism KW - Binding Sites KW - Alkylation KW - Intercalating Agents -- therapeutic use KW - Intercalating Agents -- metabolism KW - Acridines -- therapeutic use KW - Nitrogen Mustard Compounds -- therapeutic use KW - Nitrogen Mustard Compounds -- chemical synthesis KW - DNA -- metabolism KW - DNA -- chemistry KW - Acridines -- chemical synthesis KW - Intercalating Agents -- chemical synthesis KW - Acridines -- metabolism KW - Nitrogen Mustard Compounds -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76332697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+DNA-sequence+selectivity+of+a+series+of+mono-+and+difunctional+9-aminoacridine+nitrogen+mustards.&rft.au=Kohn%2C+K+W%3BOrr%2C+A%3BO%27Connor%2C+P+M%3BGuziec%2C+L+J%3BGuziec%2C+F+S&rft.aulast=Kohn&rft.aufirst=K&rft.date=1994-01-07&rft.volume=37&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 - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood. AN - 76331509; 8258885 AB - To evaluate human immunodeficiency virus (HIV) type 1-specific cellular immune responses in HIV-seronegative health care workers with occupational high-risk exposures to HIV-infected (HIV-positive) patients. Peripheral blood mononuclear cells (PBMCs) were obtained after occupational exposures to HIV, and PBMCs from health care workers exposed to HIV-negative patients served as controls. The PBMCs were stimulated in vitro with HIV envelope synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay. The HIV antibody status was determined by standard enzyme-linked immunosorbent assays. Exposed individuals were also evaluated for HIV proviral DNA by polymerase chain reaction techniques. The PBMCs from eight health care workers with high-risk exposures and nine control health care workers were studied. The PBMCs from all individuals showed strong IL-2 production to control antigens, indicating intact T-helper function. Interleukin 2 production to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals, but in only one of the nine health care workers exposed to HIV-negative body fluids (P < .008). None of the HIV-exposed health care workers became infected as determined by negative HIV antibody and polymerase chain reaction analysis after follow-up evaluation that ranged from 8 to 64 weeks. Human immunodeficiency virus-specific T-helper activity was detected in six (75%) of eight HIV-negative health care workers with exposure to HIV-positive body fluids. Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the exposure and was lost in individuals followed up for 8 to 64 weeks. Three health care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without evidence of subsequent infection appears to result in activation of cellular immunity without activation of antibody production. JF - JAMA AU - Clerici, M AU - Levin, J M AU - Kessler, H A AU - Harris, A AU - Berzofsky, J A AU - Landay, A L AU - Shearer, G M AD - National Cancer Institute, National Institutes of Health, Experimental Immunology Branch, Bethesda, MD 20892. Y1 - 1994/01/05/ PY - 1994 DA - 1994 Jan 05 SP - 42 EP - 46 VL - 271 IS - 1 SN - 0098-7484, 0098-7484 KW - DNA, Viral KW - 0 KW - HIV Antibodies KW - Interleukin-2 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Infectious Disease Transmission, Patient-to-Professional KW - Interleukin-2 -- biosynthesis KW - Chicago KW - Polymerase Chain Reaction KW - Interleukin-2 -- blood KW - Hospitals, University KW - Immunity, Cellular KW - HIV Antibodies -- blood KW - DNA, Viral -- analysis KW - Adult KW - Blood-Borne Pathogens KW - Enzyme-Linked Immunosorbent Assay KW - Middle Aged KW - HIV Antibodies -- biosynthesis KW - Male KW - Female KW - Occupational Exposure KW - HIV-1 -- immunology KW - HIV Infections -- transmission KW - HIV-1 -- isolation & purification KW - HIV Infections -- immunology KW - Health Personnel KW - HIV Seronegativity -- immunology KW - T-Lymphocytes, Helper-Inducer -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76331509?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=HIV-specific+T-helper+activity+in+seronegative+health+care+workers+exposed+to+contaminated+blood.&rft.au=Clerici%2C+M%3BLevin%2C+J+M%3BKessler%2C+H+A%3BHarris%2C+A%3BBerzofsky%2C+J+A%3BLanday%2C+A+L%3BShearer%2C+G+M&rft.aulast=Clerici&rft.aufirst=M&rft.date=1994-01-05&rft.volume=271&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-01-14 N1 - Date created - 1994-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I trial of recombinant human macrophage colony-stimulating factor administered by continuous intravenous infusion in patients with metastatic cancer. AN - 76327522; 8271281 AB - Macrophage colony-stimulating factor is a bone marrow-derived glycoprotein that can stimulate monocytes and macrophages, resulting in production of factors involved in immune response. In vitro and in vivo preclinical studies in animals have demonstrated that recombinant human macrophage colony-stimulating factor (rHuM-CSF) can have antitumor activity. A phase I clinical trial was undertaken to evaluate the toxicity, pharmacokinetics, and immunologic effects of rHuM-CSF given by continuous intravenous infusion in patients with cancer. Eighteen patients with metastatic solid tumors refractory to conventional therapy were treated with rHuM-CSF. Twelve patients received two 14-day cycles of rHuM-CSF by continuous infusion, with a 2-week interval. Dose escalation levels were 50, 100, and 150 micrograms/kg over 24 hours. Consecutive cohorts of three to six patients were planned at each dose level. Six patients received a modified regimen of four 7-day periods of infusion at 100 micrograms/kg over 24 hours, with 1-week intervals. Dose-limiting toxicity was grade 4 thrombocytopenia at a dose of 150 micrograms/kg over 24 hours in two patients receiving the 2-week regimen. Platelet count nadirs and concomitant monocytosis were seen on days 7-9, but recovery occurred during the treatment period. Macrophage colony-stimulating factor serum levels were maximal on day 1 and returned to near baseline on day 7 of infusion. Patients treated with four 7-day infusions had no treatment-limiting thrombocytopenia. There were no cumulative effects on platelet or monocyte counts or significant constitutional symptoms. Subclinical conjunctival injection was noted in five of 10 patients receiving screening ophthalmologic evaluation. Grade 2 episcleritis was diagnosed in one patient, and asymptomatic perilimbal and retinal hemorrhages were seen in two. Two patients developed sepsis caused by the intravenous line, which required cessation of therapy. No objective responses were documented. The maximum tolerated dose of rHuM-CSF given by continuous intravenous infusion for 14 days was 100 micrograms/kg over 24 hours, with rapidly reversible, dose-limiting thrombocytopenia at 150 micrograms/kg over 24 hours. A regimen alternating weekly cycles of infusion avoids dose-limiting toxicity and allows long-term treatment. The regimen of repeated 7-day infusions may be useful for future studies evaluating rHuM-CSF-activated monocytes in therapy for long-term infectious diseases or in investigation of new modes of cancer therapy using rHuM-CSF in conjunction with a tumor-specific antibody. JF - Journal of the National Cancer Institute AU - Cole, D J AU - Sanda, M G AU - Yang, J C AU - Schwartzentruber, D J AU - Weber, J AU - Ettinghausen, S E AU - Pockaj, B A AU - Kim, H I AU - Levin, R D AU - Pogrebniak, H W AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/05/ PY - 1994 DA - 1994 Jan 05 SP - 39 EP - 45 VL - 86 IS - 1 SN - 0027-8874, 0027-8874 KW - Recombinant Proteins KW - 0 KW - Macrophage Colony-Stimulating Factor KW - 81627-83-0 KW - Index Medicus KW - Infusions, Intravenous KW - Humans KW - Aged KW - Platelet Count -- drug effects KW - Leukocyte Count -- drug effects KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Monocytes -- drug effects KW - Middle Aged KW - Female KW - Male KW - Recombinant Proteins -- therapeutic use KW - Neoplasms -- drug therapy KW - Macrophage Colony-Stimulating Factor -- administration & dosage KW - Macrophage Colony-Stimulating Factor -- therapeutic use KW - Macrophage Colony-Stimulating Factor -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76327522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phase+I+trial+of+recombinant+human+macrophage+colony-stimulating+factor+administered+by+continuous+intravenous+infusion+in+patients+with+metastatic+cancer.&rft.au=Cole%2C+D+J%3BSanda%2C+M+G%3BYang%2C+J+C%3BSchwartzentruber%2C+D+J%3BWeber%2C+J%3BEttinghausen%2C+S+E%3BPockaj%2C+B+A%3BKim%2C+H+I%3BLevin%2C+R+D%3BPogrebniak%2C+H+W&rft.aulast=Cole&rft.aufirst=D&rft.date=1994-01-05&rft.volume=86&rft.issue=1&rft.spage=39&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 - 1994-02-02 N1 - Date created - 1994-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. AN - 76325640; 7505830 AB - Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 micrograms/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer. JF - Journal of the National Cancer Institute AU - Kohn, E C AU - Sarosy, G AU - Bicher, A AU - Link, C AU - Christian, M AU - Steinberg, S M AU - Rothenberg, M AU - Adamo, D O AU - Davis, P AU - Ognibene, F P AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/05/ PY - 1994 DA - 1994 Jan 05 SP - 18 EP - 24 VL - 86 IS - 1 SN - 0027-8874, 0027-8874 KW - Platinum Compounds KW - 0 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Drug Administration Schedule KW - Prospective Studies KW - Humans KW - Adult KW - Treatment Outcome KW - Drug Resistance KW - Aged KW - Middle Aged KW - Platinum Compounds -- therapeutic use KW - Neoplasm Recurrence, Local KW - Female KW - Survival Analysis KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Bone Marrow Diseases -- prevention & control KW - Bone Marrow Diseases -- chemically induced KW - Carcinoma -- drug therapy KW - Paclitaxel -- therapeutic use KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76325640?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-intense+taxol%3A+high+response+rate+in+patients+with+platinum-resistant+recurrent+ovarian+cancer.&rft.au=Kohn%2C+E+C%3BSarosy%2C+G%3BBicher%2C+A%3BLink%2C+C%3BChristian%2C+M%3BSteinberg%2C+S+M%3BRothenberg%2C+M%3BAdamo%2C+D+O%3BDavis%2C+P%3BOgnibene%2C+F+P&rft.aulast=Kohn&rft.aufirst=E&rft.date=1994-01-05&rft.volume=86&rft.issue=1&rft.spage=18&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 - 1994-02-02 N1 - Date created - 1994-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. AN - 76334735; 7506410 AB - In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expression in U1 cells as measured by accumulation of steady-state mRNAs and production of reverse transcriptase activity. The HIV inductive effect of IL-1 was blocked by transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies directed to the type 1, but not to the type 2, cell surface receptor for IL-1; the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not induce activation of the transcription activating factor NF-kappa B above the constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor antagonist effectively blocked IL-1-mediated direct and synergistic inductive effects on virus production. Thus, IL-1 may be an important mediator of HIV expression, and blocking of IL-1 expression and/or its effects may have a potential therapeutic role in the inhibition of HIV expression in infected individuals. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Poli, G AU - Kinter, A L AU - Fauci, A S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/04/ PY - 1994 DA - 1994 Jan 04 SP - 108 EP - 112 VL - 91 IS - 1 SN - 0027-8424, 0027-8424 KW - IL1RN protein, human KW - 0 KW - Interleukin 1 Receptor Antagonist Protein KW - Interleukin-1 KW - Interleukin-6 KW - NF-kappa B KW - Oligonucleotide Probes KW - RNA, Messenger KW - Receptors, Interleukin-1 KW - Sialoglycoproteins KW - Transforming Growth Factor beta KW - Tumor Necrosis Factor-alpha KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Index Medicus KW - AIDS/HIV KW - Transforming Growth Factor beta -- pharmacology KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Gene Expression Regulation, Viral -- drug effects KW - RNA-Directed DNA Polymerase -- metabolism KW - RNA, Messenger -- genetics KW - Base Sequence KW - Sialoglycoproteins -- pharmacology KW - Tumor Cells, Cultured KW - Virus Replication -- drug effects KW - In Vitro Techniques KW - Molecular Sequence Data KW - Oligonucleotide Probes -- chemistry KW - Receptors, Interleukin-1 -- physiology KW - Drug Synergism KW - NF-kappa B -- metabolism KW - Interleukin-1 -- pharmacology KW - HIV-1 -- growth & development KW - Interleukin-6 -- pharmacology KW - HIV-1 -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76334735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interleukin+1+induces+expression+of+the+human+immunodeficiency+virus+alone+and+in+synergy+with+interleukin+6+in+chronically+infected+U1+cells%3A+inhibition+of+inductive+effects+by+the+interleukin+1+receptor+antagonist.&rft.au=Wahba%2C+Z+Z%3BMiller%3BWaalkes%2C+M+P&rft.aulast=Wahba&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=13&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Human+%26+Experimental+Toxicology&rft.issn=01445952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-04 N1 - Date created - 1994-02-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6155-9 [8327496] FEBS Lett. 1992 Jun 15;304(2-3):261-4 [1535600] Clin Exp Immunol. 1985 Oct;62(1):136-42 [2998656] Science. 1987 Nov 6;238(4828):800-2 [3313729] J Virol. 1988 Jan;62(1):139-47 [3257102] Science. 1988 Feb 5;239(4840):617-22 [3277274] J Immunol. 1989 Jan 15;142(2):431-8 [2463307] Clin Immunol Immunopathol. 1989 Mar;50(3):374-84 [2492910] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336-40 [2494664] J Neuroimmunol. 1989 Jul;23(2):109-16 [2656753] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974-8 [2762307] J Virol. 1989 Oct;63(10):4404-8 [2789293] Biochem Biophys Res Commun. 1989 Dec 15;165(2):715-21 [2480782] Proc Natl Acad Sci U S A. 1990 Jan;87(2):782-5 [2300561] AIDS Res Hum Retroviruses. 1992 Apr;8(4):487-93 [1599755] J Clin Invest. 1992 Apr;89(4):1154-60 [1556179] J Immunol. 1992 Aug 15;149(4):1462-9 [1500725] Pathobiology. 1992;60(4):246-51 [1388722] Clin Exp Immunol. 1993 Jan;91(1):30-6 [8419083] J Biol Chem. 1993 Feb 5;268(4):2513-24 [8428929] Int Rev Cytol. 1993;143:1-62 [8449662] Nature. 1993 Mar 25;362(6418):355-8 [8455722] Nature. 1993 Mar 25;362(6418):359-62 [8096068] Immunol Today. 1990 Jun;11(6):217-23 [2191685] J Exp Med. 1990 Jul 1;172(1):151-8 [2193094] J Clin Invest. 1990 Jul;86(1):148-59 [2114424] Nature. 1990 Dec 6;348(6301):550-2 [2147233] J Exp Med. 1991 Mar 1;173(3):589-97 [1705278] Br J Dermatol. 1990 Oct;123(4):487-92 [2095180] Res Virol. 1991 Mar-Jun;142(2-3):197-204 [1716776] J Immunol. 1991 Oct 1;147(7):2290-4 [1680914] Cytokine. 1991 Sep;3(5):372-9 [1751774] J Immunol. 1992 Feb 15;148(4):1222-9 [1371135] Immunol Today. 1991 Nov;12(11):404-10 [1838480] Science. 1993 Jul 23;261(5120):472-5 [8332913] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Limitations of electromyography and magnetic stimulation for assessing laryngeal muscle control. AN - 85184476; pmid-8291855 AB - The development of new phonosurgical techniques has increased the level of interest in the field of neurolaryngology. This field requires valid techniques for determining if muscle activation is normal. Laryngeal electromyography is being used more frequently to assess muscle innervation and synkinesis. Further, magnetic stimulation has been introduced as a noninvasive technique for nerve stimulation. Technical limitations that affect the clinical utility of both these techniques are reviewed: 1) difficulties obtaining selective and accurate electromyographic laryngeal muscle recordings, 2) normal variation in movement and muscle activation patterns within and between normal individuals when producing the same speech syllables, and 3) variation in laryngeal muscle response latencies between and within normal subjects during peripheral magnetic stimulation. Given the normal variation in laryngeal electromyography and magnetic stimulation response latencies, these techniques may not yet be reliable or accurate for assessing reinnervation or synkinesis following recurrent laryngeal nerve injury. JF - The Annals of Otology, Rhinology, and Laryngology AU - Ludlow, Christy L AU - Yeh, J AU - Cohen, L G AU - Van Pelt F AU - Rhew, K AU - Hallett, M AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke PY - 1994 SP - 16 EP - 27 VL - 103 IS - 1 SN - 0003-4894, 0003-4894 KW - Laryngeal Nerves KW - Laryngeal Muscles KW - Vocal Cords KW - Humans KW - Adult KW - Electromagnetics KW - Electric Stimulation KW - Speech KW - Female KW - Male KW - Electromyography UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85184476?accountid=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=Limitations+of+electromyography+and+magnetic+stimulation+for+assessing+laryngeal+muscle+control.&rft.au=Ludlow%2C+Christy+L%3BYeh%2C+J%3BCohen%2C+L+G%3BVan+Pelt+F%3BRhew%2C+K%3BHallett%2C+M&rft.aulast=Ludlow&rft.aufirst=Christy&rft.date=1994-01-01&rft.volume=103&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+Otology%2C+Rhinology%2C+and+Laryngology&rft.issn=00034894&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Modulation of developmental cerebellar ornithine decarboxylase activity by lead-acetate. AN - 77807947; 7715861 AB - The developing brain is particularly susceptible to the neurotoxic effects of lead exposure. The ontological profile of ornithine decarboxylase (ODC) activity in the cerebellum was examined following lactational exposure of rats to 0.2% lead acetate (Pb). Relative to controls, Pb-exposure induced ODC activity levels in a transient manner with a 50% increase at postnatal day (PND) 6, a 20% increase at PND 9, returning to control basal levels by PND 15. These effects were seen at exposure levels of Pb that did not alter the normal growth and body weight of either the lactating dam or the developing pups. Basal cerebellar ODC activity in homogenates was increased with addition of low concentrations of Pb acetate (0.01 microM and 0.1 microM), while concentrations of 1 microM or greater were inhibitory. The effects of Pb acetate on tissue ODC activity in vitro were not mimicked by the addition of calcium chloride. Unlike tissue ODC activity, incubation of these metals with a pure ODC protein preparation exhibited fluctuations in ODC activity possibly due to the ionic interactions of Pb or calcium chloride. Calcium homeostatic mechanisms appeared to be unchanged with Pb exposure, at this dose, in that neither 45Ca-uptake (both mitochondrial and microsomal) nor synaptosomal Ca(2+)-ATPase activity was altered. These data suggest that alterations in ODC activity may be indicative of subtle toxicant induced perturbations during early development. Although the precise mechanism by which Pb may induce ODC activity in developing tissue is unknown, our results suggest that Pb may specifically alter ODC activity via cytosolic interactions. JF - Neurotoxicology AU - Zawia, N H AU - Evers, L B AU - Kodavanti, P R AU - Harry, G J AD - Lab of Integrated Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27707, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 903 EP - 911 VL - 15 IS - 4 SN - 0161-813X, 0161-813X KW - Lead KW - 2P299V784P KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Age Factors KW - Dose-Response Relationship, Drug KW - Cerebellum KW - Mitochondria -- metabolism KW - Calcium -- pharmacology KW - Ornithine Decarboxylase -- drug effects KW - Lead -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77807947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Modulation+of+developmental+cerebellar+ornithine+decarboxylase+activity+by+lead-acetate.&rft.au=Zawia%2C+N+H%3BEvers%2C+L+B%3BKodavanti%2C+P+R%3BHarry%2C+G+J&rft.aulast=Zawia&rft.aufirst=N&rft.date=1994-01-01&rft.volume=15&rft.issue=4&rft.spage=903&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-05-17 N1 - Date created - 1995-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of the effects of three cardioactive agents on the electrical activity from embryonic chick heart cell aggregates: TTX, ACh, and E-4031. AN - 77802019; 7892502 JF - Progress in biophysics and molecular biology AU - Clay, J R AU - Kristof, A S AU - Shenasa, J AU - Brochu, R M AU - Shrier, A AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 185 EP - 202 VL - 62 IS - 3 SN - 0079-6107, 0079-6107 KW - Anti-Arrhythmia Agents KW - 0 KW - Piperidines KW - Pyridines KW - Sulfanilamides KW - E 4031 KW - 113558-89-7 KW - Tetrodotoxin KW - 4368-28-9 KW - risotilide KW - 46Z36VJE7H KW - Acetylcholine KW - N9YNS0M02X KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- metabolism KW - Myocardium -- cytology KW - Animals KW - Patch-Clamp Techniques KW - Cells, Cultured KW - Chick Embryo KW - Sulfanilamides -- pharmacology KW - Myocardial Contraction -- drug effects KW - Action Potentials -- drug effects KW - Models, Biological KW - Cell Aggregation KW - Piperidines -- pharmacology KW - Heart -- physiology KW - Heart -- drug effects KW - Acetylcholine -- pharmacology KW - Heart -- embryology KW - Tetrodotoxin -- pharmacology KW - Pyridines -- pharmacology KW - Anti-Arrhythmia Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77802019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biophysics+and+molecular+biology&rft.atitle=A+review+of+the+effects+of+three+cardioactive+agents+on+the+electrical+activity+from+embryonic+chick+heart+cell+aggregates%3A+TTX%2C+ACh%2C+and+E-4031.&rft.au=Clay%2C+J+R%3BKristof%2C+A+S%3BShenasa%2C+J%3BBrochu%2C+R+M%3BShrier%2C+A&rft.aulast=Clay&rft.aufirst=J&rft.date=1994-01-01&rft.volume=62&rft.issue=3&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Progress+in+biophysics+and+molecular+biology&rft.issn=00796107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-04-20 N1 - Date created - 1995-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Childhood-onset schizophrenia: an NIMH study in progress. AN - 77786356; 7701277 AB - An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism "spectrum" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia. JF - Schizophrenia bulletin AU - Gordon, C T AU - Frazier, J A AU - McKenna, K AU - Giedd, J AU - Zametkin, A AU - Zahn, T AU - Hommer, D AU - Hong, W AU - Kaysen, D AU - Albus, K E AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 697 EP - 712 VL - 20 IS - 4 SN - 0586-7614, 0586-7614 KW - Clozapine KW - J60AR2IKIC KW - Haloperidol KW - J6292F8L3D KW - Index Medicus KW - United States KW - Haloperidol -- adverse effects KW - Reaction Time -- drug effects KW - Haloperidol -- therapeutic use KW - Double-Blind Method KW - Humans KW - Brain -- drug effects KW - National Institute of Mental Health (U.S.) KW - Diagnostic Imaging KW - Child KW - Clozapine -- adverse effects KW - Pursuit, Smooth -- drug effects KW - Reaction Time -- physiology KW - Brain -- physiopathology KW - Brain Mapping KW - Clozapine -- therapeutic use KW - Pursuit, Smooth -- physiology KW - Follow-Up Studies KW - Neuropsychological Tests KW - Adolescent KW - Male KW - Female KW - Schizophrenia, Childhood -- diagnosis KW - Schizophrenia, Childhood -- physiopathology KW - Schizophrenia, Childhood -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77786356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Block+of+HIV-1+infection+by+a+combination+of+antisense+tat+RNA+and+TAR+decoys%3A+A+strategy+for+control+of+HIV-1&rft.au=Chang%2C+Hsiao-Kuey%3BGendelman%2C+R%3BLisziewicz%2C+J%3BGallo%2C+R+C%3BEnsoli%2C+B&rft.aulast=Chang&rft.aufirst=Hsiao-Kuey&rft.date=1994-01-01&rft.volume=1&rft.issue=3&rft.spage=208&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 - 1995-05-03 N1 - Date created - 1995-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health policy aspects of lipid nutrition and early development. AN - 77769410; 7871832 JF - World review of nutrition and dietetics AU - Salem, N AU - Pawlosky, R J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Md. Y1 - 1994 PY - 1994 DA - 1994 SP - 46 EP - 51 VL - 75 SN - 0084-2230, 0084-2230 KW - Dietary Fats, Unsaturated KW - 0 KW - Fatty Acids KW - Plant Oils KW - Index Medicus KW - Retina -- metabolism KW - Animals KW - Plant Oils -- administration & dosage KW - Cats KW - Alcoholism -- metabolism KW - Retina -- growth & development KW - Brain -- metabolism KW - Female KW - Brain -- growth & development KW - Pregnancy KW - Fatty Acids -- metabolism KW - Growth KW - Dietary Fats, Unsaturated -- administration & dosage KW - Embryonic and Fetal Development KW - Nutrition Policy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77769410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+review+of+nutrition+and+dietetics&rft.atitle=Health+policy+aspects+of+lipid+nutrition+and+early+development.&rft.au=Salem%2C+N%3BPawlosky%2C+R+J&rft.aulast=Salem&rft.aufirst=N&rft.date=1994-01-01&rft.volume=75&rft.issue=&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=World+review+of+nutrition+and+dietetics&rft.issn=00842230&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-24 N1 - Date created - 1995-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intraventricular administration of galanin does not affect behaviors associated with locus coeruleus activation in rats. AN - 77728232; 7531843 AB - The 29 amino acid peptide galanin (GAL) coexists with norepinephrine in rat locus coeruleus (LC) neurons to a remarkably high degree. The effects of central administration of GAL were examined in three behavioral paradigms that putatively involve increases in the activity of LC neurons. GAL did not affect behavioral signs associated with naloxone-precipitated withdrawal in rats treated chronically with morphine, a condition in which the firing rate of LC neurons is dramatically increased, although the behavioral signs of withdrawal were abolished by clonidine. Foot shock induced freezing behavior was similarly unaffected by either dose of GAL but was significantly diminished by clonidine and the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF. GAL did not influence the decrease in exploratory activity in a novel open field induced by idazoxan. The behavioral activity of the peptide and route of administration were confirmed in a feeding paradigm. Doses of GAL that were inactive in the three paradigms were active in stimulating intake of a palatable food to a similar degree as clonidine-stimulated intake. These results suggest that intraventricularly administered GAL may not influence behaviors thought to be mediated by activation of neurons in the LC. JF - Peptides AU - Holmes, P V AU - Koprivica, V AU - Chough, E AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892-1380. Y1 - 1994 PY - 1994 DA - 1994 SP - 1303 EP - 1308 VL - 15 IS - 7 SN - 0196-9781, 0196-9781 KW - Peptides KW - 0 KW - Galanin KW - 88813-36-9 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Norepinephrine -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Substance Withdrawal Syndrome -- drug therapy KW - Motor Activity -- drug effects KW - Male KW - Injections, Intraventricular KW - Behavior, Animal -- drug effects KW - Locus Coeruleus -- drug effects KW - Peptides -- administration & dosage KW - Behavior, Animal -- physiology KW - Peptides -- physiology KW - Locus Coeruleus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77728232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.atitle=Development+of+human+lymphocyte-engrafted+SCID+mice+as+a+model+for+immunotoxicity+assessment.&rft.au=Pollock%2C+P+L%3BGermolec%2C+D+R%3BComment%2C+C+E%3BRosenthal%2C+G+J%3BLuster%2C+M+I&rft.aulast=Pollock&rft.aufirst=P&rft.date=1994-01-01&rft.volume=22&rft.issue=1&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=Fundamental+and+applied+toxicology+%3A+official+journal+of+the+Society+of+Toxicology&rft.issn=02720590&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-03-16 N1 - Date created - 1995-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The antidepressant response to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate. AN - 77714978; 7831449 AB - Standard tricyclic antidepressant (TCA) treatment usually entails response latencies of 2 to 4 weeks. To accelerate the antidepressant response, methylphenidate (MPH) was administered together with standard antidepressants in an open label trial. Twenty inpatients (9 females, 11 males) met DSM-III-R criteria for major depressive episode (15 unipolar and 2 bipolar), depression NOS (n = 2), or Research Diagnostic Criteria for schizoaffective illness, depressed type (n = 1). Following evaluation for depression, patients received an open-label oral MPH stimulation trial (MST), in 1 or 2 dosages of 5 to 15 mg at 0900 and 1000 hours. Twenty patients with positive MST response were treated with TCAs combined with MPH (5-15 mg/d). Therapeutic response was defined as 50 percent decline in the Hamilton Rating Scale for Depression. Six of 20 (30%) patients responded after 1 week of combination TCA-MPH, and 10 of 16 (63%) after 2 weeks. Adverse effects of the combination treatment included: dizziness and orthostatic blood pressure changes (n = 3), dry mouth (n = 3), increased anxiety (n = 3), and hypomania (n = 1). The severity of adverse effects required cessation of the MPH in 3 patients. Elevated self-ratings of anxiety were associated with lack of improvement after both 1 and 2 weeks. Adjunctive MPH appears to accelerate response to tricyclics in this systematically conducted open trial, and adverse effects of the TCA-MPH combination were usually tolerable. Positive response on the MST may be predictive of beneficial therapeutic outcome, especially in depressed patients without high anxiety levels.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Psychopharmacology bulletin AU - Gwirtsman, H E AU - Szuba, M P AU - Toren, L AU - Feist, M AD - Mood, Anxiety, and Personality Disorders Research Branch, DCTR, NIMH, Rockville, MD 20857. Y1 - 1994 PY - 1994 DA - 1994 SP - 157 EP - 164 VL - 30 IS - 2 SN - 0048-5764, 0048-5764 KW - Antidepressive Agents, Tricyclic KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Drug Synergism KW - Male KW - Female KW - Depressive Disorder -- psychology KW - Antidepressive Agents, Tricyclic -- therapeutic use KW - Methylphenidate -- therapeutic use KW - Depressive Disorder -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77714978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bulletin&rft.atitle=The+antidepressant+response+to+tricyclics+in+major+depressives+is+accelerated+with+adjunctive+use+of+methylphenidate.&rft.au=Gwirtsman%2C+H+E%3BSzuba%2C+M+P%3BToren%2C+L%3BFeist%2C+M&rft.aulast=Gwirtsman&rft.aufirst=H&rft.date=1994-01-01&rft.volume=30&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology+bulletin&rft.issn=00485764&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biology and structure of the zona pellucida: a target for immunocontraception. AN - 77684534; 7831483 AB - Although reversible interference of sperm-egg interactions with pharmacological agents has not yet been achieved, animal models have provided increasing evidence that immunological reagents directed against mammalian gametes can effectively inhibit fertilization. One potential target of immunocontraception is the zona pellucida, an extracellular matrix that surrounds the growing oocyte and ovulated egg. Recent advances in our knowledge of the biosynthesis and molecular biology of the zona pellucida have provided much information useful in the rational design of immunocontraceptive vaccines. There remain, however, major obstacles to using immunological reagents to prevent fertilization, including potential toxic side effects, the lack of adequate delivery systems and the possibility of incomplete reversibility. This review summarizes current understanding of the production of the zona pellucida during folliculogenesis, the structure of the conserved proteins and genes in the zona pellucida, and the progress made in the development of immunocontraceptive strategies that focus on this oocyte-specific structure. JF - Reproduction, fertility, and development AU - Epifano, O AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, NIDDK National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 319 EP - 330 VL - 6 IS - 3 SN - 1031-3613, 1031-3613 KW - ZP1 KW - ZP2 KW - ZP3 KW - Antibodies, Anti-Idiotypic KW - 0 KW - Egg Proteins KW - Membrane Glycoproteins KW - Receptors, Cell Surface KW - Zona Pellucida Glycoproteins KW - Index Medicus KW - Animals KW - Ovarian Follicle -- physiology KW - Sperm-Ovum Interactions KW - Humans KW - Antibodies, Anti-Idiotypic -- administration & dosage KW - Mice KW - Male KW - Immunization KW - Female KW - Zona Pellucida -- physiology KW - Zona Pellucida -- chemistry KW - Membrane Glycoproteins -- biosynthesis KW - Membrane Glycoproteins -- physiology KW - Egg Proteins -- genetics KW - Egg Proteins -- biosynthesis KW - Contraception, Immunologic -- methods KW - Zona Pellucida -- immunology KW - Egg Proteins -- pharmacology KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77684534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproduction%2C+fertility%2C+and+development&rft.atitle=Biology+and+structure+of+the+zona+pellucida%3A+a+target+for+immunocontraception.&rft.au=Epifano%2C+O%3BDean%2C+J&rft.aulast=Epifano&rft.aufirst=O&rft.date=1994-01-01&rft.volume=6&rft.issue=3&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Reproduction%2C+fertility%2C+and+development&rft.issn=10313613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-02-23 N1 - Date created - 1995-02-23 N1 - Date revised - 2017-01-13 N1 - Gene symbol - ZP1; ZP2; ZP3 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Summary of critiques from the drug abuse epidemiology and prevention research review committee. AN - 77132372; 8742556 JF - NIDA research monograph AU - Crider, R AU - Friedenberg, E AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 155 EP - 169 VL - 139 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Minority Groups KW - Humans KW - Ethics, Medical KW - Data Interpretation, Statistical KW - Budgets KW - Sex Distribution KW - Male KW - Female KW - Peer Review, Research KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77132372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Summary+of+critiques+from+the+drug+abuse+epidemiology+and+prevention+research+review+committee.&rft.au=Crider%2C+R%3BFriedenberg%2C+E&rft.aulast=Crider&rft.aufirst=R&rft.date=1994-01-01&rft.volume=139&rft.issue=&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Issues in drug abuse prevention intervention research with African Americans. AN - 77131485; 8742557 JF - NIDA research monograph AU - Beatty, L A AD - Prevention Research Branch, Division of Epidemiology and Prevention Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 171 EP - 201 VL - 139 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Socioeconomic Factors KW - Risk Factors KW - Humans KW - Cultural Diversity KW - United States -- epidemiology KW - African Americans KW - Substance-Related Disorders -- ethnology KW - Research Design KW - Substance-Related Disorders -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77131485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Issues+in+drug+abuse+prevention+intervention+research+with+African+Americans.&rft.au=Beatty%2C+L+A&rft.aulast=Beatty&rft.aufirst=L&rft.date=1994-01-01&rft.volume=139&rft.issue=&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention intervention research: focus and perspective. AN - 77130703; 8742549 JF - NIDA research monograph AU - Cázares, A AD - Prevention Research Branch Division of Epidemiology and Prevention Research National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 5 EP - 35 VL - 139 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Risk Factors KW - Humans KW - Outcome and Process Assessment (Health Care) KW - Forecasting KW - Child KW - Adolescent KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- ethnology KW - Research Design KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77130703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Prevention+intervention+research%3A+focus+and+perspective.&rft.au=C%C3%A1zares%2C+A&rft.aulast=C%C3%A1zares&rft.aufirst=A&rft.date=1994-01-01&rft.volume=139&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic communities and treatment research. AN - 77125747; 8742603 JF - NIDA research monograph AU - Tims, F M AU - Jainchill, N AU - De Leon, G AD - Division of Clinical Research, National Institute on Drug Abuse, Rockville, MD 20867, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 1 EP - 15 VL - 144 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - United States KW - Humans KW - Substance-Related Disorders -- therapy KW - Research Design -- trends KW - Therapeutic Community UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77125747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Therapeutic+communities+and+treatment+research.&rft.au=Tims%2C+F+M%3BJainchill%2C+N%3BDe+Leon%2C+G&rft.aulast=Tims&rft.aufirst=F&rft.date=1994-01-01&rft.volume=144&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Therapeutic community research and practice: recommendations. AN - 77125693; 8742616 JF - NIDA research monograph AU - Tims, F M AU - De Leon, G AU - Jainchill, N AD - Division of Clinical Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 280 EP - 286 VL - 144 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - Humans KW - Practice Guidelines as Topic KW - Therapeutic Community KW - Substance-Related Disorders -- rehabilitation KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77125693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Therapeutic+community+research+and+practice%3A+recommendations.&rft.au=Tims%2C+F+M%3BDe+Leon%2C+G%3BJainchill%2C+N&rft.aulast=Tims&rft.aufirst=F&rft.date=1994-01-01&rft.volume=144&rft.issue=&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurobiological mechanisms underlying the acquisition and expression of incentive motivation by cocaine-associated stimuli: relationship to craving. AN - 77124196; 8742813 JF - NIDA research monograph AU - Pert, A AD - National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 163 EP - 190 VL - 145 SN - 1046-9516, 1046-9516 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Feeding Behavior -- physiology KW - Neurobiology KW - Humans KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Motivation KW - Conditioning, Operant -- physiology KW - Substance-Related Disorders -- drug therapy KW - Substance Withdrawal Syndrome -- drug therapy KW - Cocaine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77124196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Neurobiological+mechanisms+underlying+the+acquisition+and+expression+of+incentive+motivation+by+cocaine-associated+stimuli%3A+relationship+to+craving.&rft.au=Pert%2C+A&rft.aulast=Pert&rft.aufirst=A&rft.date=1994-01-01&rft.volume=145&rft.issue=&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-09-18 N1 - Date created - 1996-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug abuse research accomplishments and opportunities: a report from the national perspective. AN - 77124091; 8722448 JF - NIDA research monograph AU - Millstein, R A AD - National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 11 EP - 22 VL - 140 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - United States KW - Animals KW - Humans KW - National Institutes of Health (U.S.) KW - Research -- trends KW - Substance-Related Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77124091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Drug+abuse+research+accomplishments+and+opportunities%3A+a+report+from+the+national+perspective.&rft.au=Millstein%2C+R+A&rft.aulast=Millstein&rft.aufirst=R&rft.date=1994-01-01&rft.volume=140&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-12 N1 - Date created - 1996-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug use and HIV risk among gay and bisexual men: an overview. AN - 77123430; 8742593 JF - NIDA research monograph AU - Battjes, R J AD - Division of Clinical Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 82 EP - 87 VL - 143 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - AIDS/HIV KW - Risk-Taking KW - Humans KW - Substance Abuse, Intravenous -- epidemiology KW - Male KW - Homosexuality, Male KW - HIV Infections -- transmission KW - Bisexuality KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77123430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Drug+use+and+HIV+risk+among+gay+and+bisexual+men%3A+an+overview.&rft.au=Battjes%2C+R+J&rft.aulast=Battjes&rft.aufirst=R&rft.date=1994-01-01&rft.volume=143&rft.issue=&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological evaluation of compounds for their physical dependence potential and abuse liability. XVII. Drug Evaluation Committee of the College on Problems of Drug Dependence, Inc. (1993). AN - 77123014; 8722465 JF - NIDA research monograph AU - Jacobson, A E AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 179 EP - 195 VL - 140 SN - 1046-9516, 1046-9516 KW - Narcotics KW - 0 KW - Receptors, Opioid KW - Index Medicus KW - Animals KW - Self Administration KW - Receptors, Opioid -- metabolism KW - Receptors, Opioid -- drug effects KW - Pain Measurement -- drug effects KW - Drug Evaluation, Preclinical KW - Narcotics -- toxicity KW - Substance-Related Disorders KW - Narcotics -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77123014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Biological+evaluation+of+compounds+for+their+physical+dependence+potential+and+abuse+liability.+XVII.+Drug+Evaluation+Committee+of+the+College+on+Problems+of+Drug+Dependence%2C+Inc.+%281993%29.&rft.au=Jacobson%2C+A+E&rft.aulast=Jacobson&rft.aufirst=A&rft.date=1994-01-01&rft.volume=140&rft.issue=&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-11-12 N1 - Date created - 1996-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV risk in drug-using adolescents. AN - 77122651; 8742596 JF - NIDA research monograph AU - Smeriglio, V L AD - Division of Clinical Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 132 EP - 134 VL - 143 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - AIDS/HIV KW - Risk KW - Humans KW - Adolescent KW - United States -- epidemiology KW - Substance-Related Disorders -- psychology KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77122651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=HIV+risk+in+drug-using+adolescents.&rft.au=Smeriglio%2C+V+L&rft.aulast=Smeriglio&rft.aufirst=V&rft.date=1994-01-01&rft.volume=143&rft.issue=&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are hallucinogens psychoheuristic? AN - 77121763; 8742793 AB - The author argues in this chapter for a reconsideration of the perception of hallucinogens as being only toxic, damaging, and therefore strictly condemnable for being abused. The author advocates that hallucinogens be viewed as powerful psychoheuristic tools that, in combination with other necessary conceptual (such as holarchic theory) and laboratory tools (such as PET scan or MRI), may help solve a major mystery of nature: the workings of human brains and minds. JF - NIDA research monograph AU - Szára, S AD - Biomedical Research Branch, National Institute on Drug Abuse, Kensington, MD 20895, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 33 EP - 51 VL - 146 SN - 1046-9516, 1046-9516 KW - Hallucinogens KW - 0 KW - Index Medicus KW - History of medicine KW - Behavior -- drug effects KW - Animals KW - History, 20th Century KW - Humans KW - Behavior, Animal KW - Hallucinogens -- pharmacology KW - Hallucinogens -- history KW - Hallucinogens -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77121763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Are+hallucinogens+psychoheuristic%3F&rft.au=Sz%C3%A1ra%2C+S&rft.aulast=Sz%C3%A1ra&rft.aufirst=S&rft.date=1994-01-01&rft.volume=146&rft.issue=&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-25 N1 - Date created - 1996-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV risk behaviors of heterosexual male drug users. AN - 77121709; 8742587 JF - NIDA research monograph AU - Needle, R H AD - Division of Clinical Research, National Institute on Drug Abuse, Rockville, MD 20857, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 5 EP - 8 VL - 143 SN - 1046-9516, 1046-9516 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - United States -- epidemiology KW - Male KW - Sexual Behavior KW - Risk-Taking KW - HIV Infections -- transmission KW - Substance Abuse, Intravenous -- epidemiology KW - HIV Infections -- psychology KW - HIV Infections -- epidemiology KW - Substance Abuse, Intravenous -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77121709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=HIV+risk+behaviors+of+heterosexual+male+drug+users.&rft.au=Needle%2C+R+H&rft.aulast=Needle&rft.aufirst=R&rft.date=1994-01-01&rft.volume=143&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1996-10-02 N1 - Date created - 1996-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humanized immunotoxins. AN - 77117000; 7584480 JF - Therapeutic immunology AU - Gadina, M AU - Newton, D L AU - Rybak, S M AU - Wu, Y N AU - Youle, R J AD - Biochemistry Section, NINDS, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 59 EP - 64 VL - 1 IS - 1 SN - 0967-0149, 0967-0149 KW - Immunotoxins KW - 0 KW - Recombinant Fusion Proteins KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Ribonucleases -- toxicity KW - Humans KW - Eosinophils -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77117000?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapeutic+immunology&rft.atitle=Humanized+immunotoxins.&rft.au=Gadina%2C+M%3BNewton%2C+D+L%3BRybak%2C+S+M%3BWu%2C+Y+N%3BYoule%2C+R+J&rft.aulast=Gadina&rft.aufirst=M&rft.date=1994-01-01&rft.volume=1&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Therapeutic+immunology&rft.issn=09670149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-12-12 N1 - Date created - 1995-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Positron emission tomography in studies of drug abuse. AN - 77105156; 7603540 JF - NIDA research monograph AU - London, E D AD - Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 15 EP - 24 VL - 138 SN - 1046-9516, 1046-9516 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Nuclear Medicine KW - Humans KW - Glucose -- metabolism KW - Tomography, Emission-Computed KW - Brain -- metabolism KW - Substance-Related Disorders -- metabolism KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77105156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NIDA+research+monograph&rft.atitle=Positron+emission+tomography+in+studies+of+drug+abuse.&rft.au=London%2C+E+D&rft.aulast=London&rft.aufirst=E&rft.date=1994-01-01&rft.volume=138&rft.issue=&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=NIDA+research+monograph&rft.issn=10469516&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-08-10 N1 - Date created - 1995-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced cytotoxicity with interleukin-1 alpha and 5-fluorouracil in HCT116 colon cancer cells. AN - 77100962; 7787251 AB - Recombinant human interleukin-1 alpha (rIL-1 alpha), at concentrations that were not growth-inhibitory when given alone (100-10,000 U/ml), enhanced the growth inhibition resulting from a 72-h fluorouracil (FUra) exposure in HCT116 colon cancer cells. Median-effect analysis of clonogenic assays indicated that rIL-1 alpha, given 24 h prior to and following a 24-h exposure to FUra, increased lethality in a more than additive fashion. rIL-1 alpha did not appear to significantly affect [3H]-FUra metabolism, total [3H]-FUra-RNA incorporation or RNA retention after drug removal, inhibition of thymidylate synthase, or thymidine triphosphate pool depletion. During continuous exposure to rIL-1 alpha, transient stimulation of RNA and DNA synthesis was observed at 72 h, with a return to normal by 96 h. A 24-h exposure to 10 microM FUra altered the elution profile of newly synthesized DNA as monitored by pH step alkaline elution. An accumulation of lower-MW single-stranded DNA species was noted with FUra compared to control, accompanied by a significantly decreased proportion of DNA retained on the polycarbonate filter: 10% retained vs. 32% for control (P = 0.01). A 48-h exposure to rIL-1 alpha alone did not affect the elution profile of nascent DNA species, nor did it enhance the effects of FUra. Although FUra did not appreciably affect pulse [3H]-uridine incorporation into RNA for the initial 8-24 h of FUra exposure, progressive inhibition of net RNA synthesis was observed thereafter. FUra prevented the stimulatory effect of rIL-1 alpha on RNA synthesis, and net RNA synthesis was significantly inhibited (by 64-79% after 72 and 96 h) with the combination compared to rIL-1 alpha alone. Continuous exposure to 10 microM thymidine did not rescue cells from the lethality of FUra alone or the combination of FUra plus rIL-1 alpha, suggesting that depletion of deoxythymidine triphosphate as a consequence of thymidylate synthase inhibition was not the most important component of FUra toxicity. In contrast, 1 mM uridine provided partial protection against the toxicity of FUra alone or with rIL-1 alpha. Although uridine did not affect FUra metabolism, it decreased FUra-RNA incorporation by 42-60%, presumably as a consequence of the 2-fold expansion of UTP pools. [125I]-rIL-1 alpha binding was nonspecific; with a 24-h exposure, however, internalized [125I]-rIL-1 alpha exceeded cell surface-bound material by 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Oncology research AU - Geoffroy, F J AU - Allegra, C J AU - Sinha, B AU - Grem, J L AD - Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20889-5101, USA. Y1 - 1994 PY - 1994 DA - 1994 SP - 581 EP - 591 VL - 6 IS - 12 SN - 0965-0407, 0965-0407 KW - DNA, Neoplasm KW - 0 KW - Interleukin-1 KW - Prodrugs KW - RNA, Neoplasm KW - Receptors, Interleukin-1 KW - Recombinant Proteins KW - Thymine Nucleotides KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Fluorouracil KW - U3P01618RT KW - Uridine Triphosphate KW - UT0S826Z60 KW - Thymidine KW - VC2W18DGKR KW - Uridine KW - WHI7HQ7H85 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Thymine Nucleotides -- metabolism KW - Humans KW - Cell Division -- drug effects KW - Uridine Triphosphate -- metabolism KW - Biotransformation -- drug effects KW - Thymidine -- pharmacology KW - Recombinant Proteins -- toxicity KW - Tumor Cells, Cultured KW - Uridine -- pharmacology KW - Receptors, Interleukin-1 -- metabolism KW - Drug Synergism KW - DNA, Neoplasm -- biosynthesis KW - Tumor Stem Cell Assay KW - Prodrugs -- toxicity KW - Fluorouracil -- toxicity KW - Colonic Neoplasms -- drug therapy KW - Fluorouracil -- metabolism KW - Interleukin-1 -- toxicity KW - Colonic Neoplasms -- pathology KW - Prodrugs -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/77100962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+research&rft.atitle=Enhanced+cytotoxicity+with+interleukin-1+alpha+and+5-fluorouracil+in+HCT116+colon+cancer+cells.&rft.au=Geoffroy%2C+F+J%3BAllegra%2C+C+J%3BSinha%2C+B%3BGrem%2C+J+L&rft.aulast=Geoffroy&rft.aufirst=F&rft.date=1994-01-01&rft.volume=6&rft.issue=12&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Oncology+research&rft.issn=09650407&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-07-24 N1 - Date created - 1995-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of cocaine on P3B in cocaine abusers. AN - 76897586; 7800160 AB - Little is known about the effects of cocaine on cognitive tasks. Event-related potentials (ERP) were recorded in 7 cocaine abusers during the performance of the auditory oddball task before and after the intravenous injections of saline and cocaine (60-80 mg). The P3B and slow wave components of the ERP were significantly larger 60-210 min after the cocaine than after the placebo injection. The results suggest that cocaine abusers have difficulty in maintaining optimal stimulus processing during extended testing. Cocaine blocks this decrement in stimulus processing. JF - Neuropsychobiology AU - Herning, R I AU - Glover, B J AU - Guo, X AD - Molecular Neuropsychiatry Section, National Institutes of Health, National Institute on Drug Abuse, Baltimore, Md 21224. Y1 - 1994 PY - 1994 DA - 1994 SP - 132 EP - 142 VL - 30 IS - 2-3 SN - 0302-282X, 0302-282X KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Reaction Time -- drug effects KW - Cerebral Cortex -- drug effects KW - Infusions, Intravenous KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Substance Abuse, Intravenous -- rehabilitation KW - Humans KW - Adult KW - Substance Abuse, Intravenous -- physiopathology KW - Reaction Time -- physiology KW - Male KW - Cerebral Cortex -- physiopathology KW - Substance-Related Disorders -- physiopathology KW - Arousal -- drug effects KW - Evoked Potentials, Auditory -- drug effects KW - Arousal -- physiology KW - Electroencephalography -- drug effects KW - Attention -- physiology KW - Attention -- drug effects KW - Substance-Related Disorders -- rehabilitation KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76897586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropsychobiology&rft.atitle=Effects+of+cocaine+on+P3B+in+cocaine+abusers.&rft.au=Herning%2C+R+I%3BGlover%2C+B+J%3BGuo%2C+X&rft.aulast=Herning&rft.aufirst=R&rft.date=1994-01-01&rft.volume=30&rft.issue=2-3&rft.spage=132&rft.isbn=&rft.btitle=&rft.title=Neuropsychobiology&rft.issn=0302282X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-25 N1 - Date created - 1995-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of DNA adduct levels in human placenta from polychlorinated biphenyl exposed women and smokers in which CYP 1A1 levels are similarly elevated. AN - 76882047; 7992230 AB - Previous studies demonstrated that cigarette smoking is associated with high elevations in levels of both cytochrome P450 1A1 (CYP1A1) and DNA adducts in human placenta. To date, the identity of the smoking related DNA adducts is not known. The DNA adducts identified in placenta of smokers could result from chemicals present in cigarette smoke, substances formed by CYP 1A1 metabolic activation of endogenous compounds, noncigarette related exposures or a combination of these processes. Exposure to contaminated rice oil containing large doses of polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) also resulted in massive elevation of CYP 1A1 in human placenta but formation of DNA adducts directly from this exposure has not previously been reported. The purpose for comparing the two populations was to test the hypothesis that if CYP 1A1 induction results in the metabolic activation of endogenous compounds, then DNA adducts should also be present in PCB/PCDF exposed tissues exhibiting high CYP 1A1 activity and some of the adducts detected in the placental DNA from smokers may be identified as those derived from the metabolic activation of endogenous compounds. To test this hypothesis, we measured DNA adducts using 32P-postlabeling to analyze placental DNA from women exposed to PCB/PCDF and from cigarette smokers where levels of CYP 1A1 were similarly elevated. There was no evidence of DNA adducts among specimens obtained from PCB/PCDF exposed individuals. These data suggest that CYP 1A1 induction alone (in the absence of cigarette smoking) does not induce the formation of DNA adducts detectable by this approach, and that smoking related adducts are not a consequence of CYP 1A1 induction mediated activation of endogenous compounds or xenobiotics other than cigarette smoke. JF - Teratogenesis, carcinogenesis, and mutagenesis AU - Gallagher, J E AU - Everson, R B AU - Lewtas, J AU - George, M AU - Lucier, G W AD - Health Effects Research Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1994 PY - 1994 DA - 1994 SP - 183 EP - 192 VL - 14 IS - 4 SN - 0270-3211, 0270-3211 KW - Benzofurans KW - 0 KW - Dibenzofurans, Polychlorinated KW - Isoenzymes KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Index Medicus KW - Enzyme Induction -- drug effects KW - Humans KW - Environmental Exposure KW - Female KW - Benzofurans -- toxicity KW - Benzofurans -- metabolism KW - Pregnancy KW - Aryl Hydrocarbon Hydroxylases -- biosynthesis KW - Polychlorinated Biphenyls -- toxicity KW - Isoenzymes -- biosynthesis KW - DNA -- metabolism KW - Smoking -- metabolism KW - Polychlorinated Biphenyls -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Placenta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76882047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.atitle=Comparison+of+DNA+adduct+levels+in+human+placenta+from+polychlorinated+biphenyl+exposed+women+and+smokers+in+which+CYP+1A1+levels+are+similarly+elevated.&rft.au=Gallagher%2C+J+E%3BEverson%2C+R+B%3BLewtas%2C+J%3BGeorge%2C+M%3BLucier%2C+G+W&rft.aulast=Gallagher&rft.aufirst=J&rft.date=1994-01-01&rft.volume=14&rft.issue=4&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Teratogenesis%2C+carcinogenesis%2C+and+mutagenesis&rft.issn=02703211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1995-01-06 N1 - Date created - 1995-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model of effects of TCDD on expression of rat liver proteins. AN - 76853234; 7972248 JF - Progress in clinical and biological research AU - Kohn, M C AU - Portier, C J AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 211 EP - 222 VL - 387 SN - 0361-7742, 0361-7742 KW - Estrogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Receptors, Estrogen KW - Transforming Growth Factor alpha KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Rats KW - Animals KW - Receptors, Estrogen -- drug effects KW - Receptor, Epidermal Growth Factor -- metabolism KW - Receptors, Aryl Hydrocarbon -- physiology KW - DNA Damage KW - Neoplasms -- chemically induced KW - Receptors, Estrogen -- metabolism KW - Estrogens -- physiology KW - Male KW - Female KW - Oxidoreductases -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Transforming Growth Factor alpha -- biosynthesis KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - Models, Biological KW - Oxidoreductases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76853234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+and+biological+research&rft.atitle=A+model+of+effects+of+TCDD+on+expression+of+rat+liver+proteins.&rft.au=Kohn%2C+M+C%3BPortier%2C+C+J&rft.aulast=Kohn&rft.aufirst=M&rft.date=1994-01-01&rft.volume=387&rft.issue=&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-response and risk assessment considerations for receptor-mediated effects: case study with a TCDD hepatic tumor promotion model. AN - 76853194; 7972245 JF - Progress in clinical and biological research AU - Sewall, C H AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994 PY - 1994 DA - 1994 SP - 155 EP - 171 VL - 387 SN - 0361-7742, 0361-7742 KW - CYP 1A1 KW - CYP 1A2 KW - Polychlorinated Dibenzodioxins KW - 0 KW - Receptors, Aryl Hydrocarbon KW - Thyrotropin KW - 9002-71-5 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Glucuronosyltransferase -- genetics KW - Thyrotropin -- secretion KW - Cytochrome P-450 Enzyme System -- genetics KW - Dose-Response Relationship, Drug KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Models, Biological KW - Risk Assessment KW - Receptor, Epidermal Growth Factor -- biosynthesis KW - Rats KW - Glucuronosyltransferase -- biosynthesis KW - Oxidoreductases -- genetics KW - Receptor, Epidermal Growth Factor -- genetics KW - Enzyme Induction -- drug effects KW - Signal Transduction KW - Female KW - Oxidoreductases -- biosynthesis KW - Receptors, Aryl Hydrocarbon -- drug effects KW - Receptors, Aryl Hydrocarbon -- physiology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76853194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+and+biological+research&rft.atitle=Dose-response+and+risk+assessment+considerations+for+receptor-mediated+effects%3A+case+study+with+a+TCDD+hepatic+tumor+promotion+model.&rft.au=Sewall%2C+C+H%3BLucier%2C+G+W&rft.aulast=Sewall&rft.aufirst=C&rft.date=1994-01-01&rft.volume=387&rft.issue=&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Gene symbol - CYP 1A1; CYP 1A2 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C in signal transduction and carcinogenesis. AN - 76850553; 7972255 JF - Progress in clinical and biological research AU - Blumberg, P M AU - Acs, G AU - Areces, L B AU - Kazanietz, M G AU - Lewin, N E AU - Szallasi, Z AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 3 EP - 19 VL - 387 SN - 0361-7742, 0361-7742 KW - Bryostatins KW - 0 KW - Carcinogens KW - Isoenzymes KW - Lactones KW - Macrolides KW - Phorbol Esters KW - Receptors, Cell Surface KW - bryostatin 1 KW - 37O2X55Y9E KW - prostratin KW - 60857-08-1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Carcinogens -- pharmacology KW - Humans KW - Mice KW - Phorbol Esters -- toxicity KW - Protein Binding KW - Structure-Activity Relationship KW - Lactones -- pharmacology KW - Phorbol Esters -- pharmacology KW - Isoenzymes -- physiology KW - Skin Neoplasms -- chemically induced KW - Enzyme Activation -- drug effects KW - Mice, Inbred C3H KW - Receptors, Cell Surface -- physiology KW - Protein Kinase C -- physiology KW - Signal Transduction KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76850553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+and+biological+research&rft.atitle=Protein+kinase+C+in+signal+transduction+and+carcinogenesis.&rft.au=Blumberg%2C+P+M%3BAcs%2C+G%3BAreces%2C+L+B%3BKazanietz%2C+M+G%3BLewin%2C+N+E%3BSzallasi%2C+Z&rft.aulast=Blumberg&rft.aufirst=P&rft.date=1994-01-01&rft.volume=387&rft.issue=&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Progress+in+clinical+and+biological+research&rft.issn=03617742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-12-29 N1 - Date created - 1994-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using sequence homology to analyze the structure and function of voltage-gated ion channel proteins. AN - 76781352; 7524164 AB - Molecular modeling and mutagenesis analysis of voltage-gated channels have succeeded in identifying much of the topology of the proteins and in identifying which sequential segments are involved in functional mechanisms such as activation gating, inactivation gating, ion selectivity, and ligand binding. Efforts are currently underway to use these methods to model the protein structure and functional mechanisms more precisely. The experimental and theoretical efforts are dependent to a considerable extent upon information obtained by comparing homologous sequences. Although the fine details of models developed in this manner are unlikely to be as correct as models developed from x-ray crystallography and NMR, they still may contribute substantially to our understanding of the structure and function of these important proteins. JF - Society of General Physiologists series AU - Guy, H R AU - Durell, S R AD - Laboratory of Mathematical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 197 EP - 212 VL - 49 SN - 0094-7733, 0094-7733 KW - Ion Channels KW - 0 KW - Index Medicus KW - Animals KW - Models, Genetic KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Electrophysiology KW - Sequence Homology, Amino Acid KW - Structure-Activity Relationship KW - Ion Channel Gating KW - Ion Channels -- physiology KW - Ion Channels -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76781352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Society+of+General+Physiologists+series&rft.atitle=Using+sequence+homology+to+analyze+the+structure+and+function+of+voltage-gated+ion+channel+proteins.&rft.au=Guy%2C+H+R%3BDurell%2C+S+R&rft.aulast=Guy&rft.aufirst=H&rft.date=1994-01-01&rft.volume=49&rft.issue=&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Society+of+General+Physiologists+series&rft.issn=00947733&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-21 N1 - Date created - 1994-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biological actions of cholecystokinin. AN - 76780363; 7937354 AB - Cholecystokinin (CCK) has emerged as an important mammalian neuropeptide, localized in peripheral organs and in the central nervous system. This review presents an overview of the molecular aspects of CCK peptides and CCK receptors, the anatomical distribution of CCK, the neurophysiological actions of CCK, release of CCK and effects of CCK on release of other neurotransmitters, and the actions of CCK on digestion, feeding, cardiovascular function, respiratory function, neurotoxicity and seizures, cancer cell proliferation, analgesia, sleep, sexual and reproductive behaviors, memory, anxiety, and dopamine-mediated exploratory and rewarded behaviors. Human clinical studies of CCK in feeding disorders and panic disorders are described. New findings are presented on potent, nonpeptide CCK antagonists, selective for the two CCK receptor subtypes, which demonstrate that endogenous CCK has biologically important effects on physiology and behavior. JF - Peptides AU - Crawley, J N AU - Corwin, R L AD - Section on Behavioral Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 731 EP - 755 VL - 15 IS - 4 SN - 0196-9781, 0196-9781 KW - DNA, Complementary KW - 0 KW - Neurotransmitter Agents KW - Receptors, Cholecystokinin KW - Cholecystokinin KW - 9011-97-6 KW - Index Medicus KW - Receptors, Cholecystokinin -- genetics KW - Animals KW - Neurotransmitter Agents -- metabolism KW - DNA, Complementary -- genetics KW - Humans KW - Receptors, Cholecystokinin -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Receptors, Cholecystokinin -- drug effects KW - Digestion -- physiology KW - Behavior, Animal -- physiology KW - Behavior -- physiology KW - Cholecystokinin -- physiology KW - Cholecystokinin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76780363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Biological+actions+of+cholecystokinin.&rft.au=Crawley%2C+J+N%3BCorwin%2C+R+L&rft.aulast=Crawley&rft.aufirst=J&rft.date=1994-01-01&rft.volume=15&rft.issue=4&rft.spage=731&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-22 N1 - Date created - 1994-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of fibrosarcoma induction on copper and ceruloplasmin concentration in different organs of the host. AN - 76766899; 7935989 AB - The copper content and ceruloplasmin activity were determined in mice bearing benzo(a)pyrene induced fibrosarcoma. The copper level and ceruloplasmin activity in different organs of fibrosarcomatous mice varied when compared to their controls. Significant changes in copper and ceruloplasmin concentration were observed in the liver and tumor tissue of host mice bearing fibrosarcoma compared to controls. Disturbed copper metabolism at the hepatic level may account for the hypercupremia observed during malignancy. JF - Neoplasma AU - Chakravarty, P K AU - Ghosh, A AU - Chowdhury, J R AD - Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 187 EP - 189 VL - 41 IS - 3 SN - 0028-2685, 0028-2685 KW - Copper KW - 789U1901C5 KW - Ceruloplasmin KW - EC 1.16.3.1 KW - Index Medicus KW - Mice, Inbred A KW - Animals KW - Kidney -- metabolism KW - Spleen -- metabolism KW - Liver -- metabolism KW - Bone Marrow -- metabolism KW - Mice KW - Brain -- metabolism KW - Myocardium -- metabolism KW - Fibrosarcoma -- metabolism KW - Fibrosarcoma -- chemically induced KW - Copper -- metabolism KW - Ceruloplasmin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76766899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+fibrosarcoma+induction+on+copper+and+ceruloplasmin+concentration+in+different+organs+of+the+host.&rft.au=Chakravarty%2C+P+K%3BGhosh%2C+A%3BChowdhury%2C+J+R&rft.aulast=Chakravarty&rft.aufirst=P&rft.date=1994-01-01&rft.volume=41&rft.issue=3&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-17 N1 - Date created - 1994-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3-Aminobenzamide delays rejoining of DNA strand breaks in gamma-irradiated lymphocytes from patients with breast cancer and not cervical cancer. AN - 76765376; 7935983 AB - An inhibitor of poly(ADP-ribose) polymerase is 3-aminobenzamide (3AB), treatment by which normally results in the decreased levels of rejoining of DNA single strand breaks. We have studied the effect of 3AB in gamma-irradiation induced damage and the subsequent repair of DNA along with the corresponding changes in poly (ADP-ribose) polymerase activity in lymphocytes of patients with the cancer of breast and uterine cervix. The presence or absence of 3AB prior to gamma-irradiation did not influence the extent of DNA damage. On the other hand, single strand breaks rejoining in breast cancer cases was found to be slower as compared to that of cervical cancer cases and normal individuals. The relative ADP-ribosylation in the presence of 3AB was much lower in the breast cancer cases as compared to normal but there was no significant change in the cervical cancer cases. Overall the maximum relative ADP-ribosylation was slower in the presence of 3AB. This suggests that the lower activity of poly (ADP-ribose) polymerase in breast cancer cases might delay the first phase of single strand breaks (SSBs) rejoining. JF - Neoplasma AU - Mukhopadhyay, D AU - Anant, S AU - Mukherji, S AD - Department of Biophysics, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 151 EP - 157 VL - 41 IS - 3 SN - 0028-2685, 0028-2685 KW - Benzamides KW - 0 KW - DNA, Neoplasm KW - Poly(ADP-ribose) Polymerase Inhibitors KW - Radiation-Sensitizing Agents KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Ribose KW - 681HV46001 KW - 3-aminobenzamide KW - 8J365YF1YH KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Index Medicus KW - Reference Values KW - Humans KW - Ribose -- metabolism KW - Adult KW - Aged KW - Middle Aged KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Female KW - Adenosine Diphosphate -- metabolism KW - DNA, Neoplasm -- radiation effects KW - Uterine Cervical Neoplasms -- enzymology KW - DNA, Neoplasm -- blood KW - DNA Damage KW - Lymphocytes -- radiation effects KW - Lymphocytes -- physiology KW - Radiation-Sensitizing Agents -- toxicity KW - Breast Neoplasms -- enzymology KW - Benzamides -- toxicity KW - Lymphocytes -- drug effects KW - Breast Neoplasms -- blood KW - Uterine Cervical Neoplasms -- blood KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76765376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=3-Aminobenzamide+delays+rejoining+of+DNA+strand+breaks+in+gamma-irradiated+lymphocytes+from+patients+with+breast+cancer+and+not+cervical+cancer.&rft.au=Mukhopadhyay%2C+D%3BAnant%2C+S%3BMukherji%2C+S&rft.aulast=Mukhopadhyay&rft.aufirst=D&rft.date=1994-01-01&rft.volume=41&rft.issue=3&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-11-17 N1 - Date created - 1994-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Soy intake and cancer risk: a review of the in vitro and in vivo data. AN - 76664746; 8058523 AB - International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of cancer cells, with IC50 values ranging from 5 to 40 microM (1-10 micrograms/ml). Of the 26 animal studies of experimental carcinogenesis in which diets containing soy or soybean isoflavones were employed, 17 (65%) reported protective effects. No studies reported soy intake increased tumor development. The epidemiological data are also inconsistent, although consumption of nonfermented soy products, such as soymilk and tofu, tended to be either protective or not associated with cancer risk; however, no consistent pattern was evident with the fermented soy products, such as miso. Protective effects were observed for both hormone- and nonhormone-related cancers. While a definitive statement that soy reduces cancer risk cannot be made at this time, there is sufficient evidence of a protective effect to warrant continued investigation. JF - Nutrition and cancer AU - Messina, M J AU - Persky, V AU - Setchell, K D AU - Barnes, S AD - National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1994 PY - 1994 DA - 1994 SP - 113 EP - 131 VL - 21 IS - 2 SN - 0163-5581, 0163-5581 KW - Isoflavones KW - 0 KW - Genistein KW - DH2M523P0H KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Space life sciences KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Animals KW - Tumor Cells, Cultured KW - Risk Factors KW - Humans KW - Signal Transduction -- drug effects KW - Neoplasms, Experimental -- prevention & control KW - Isoflavones -- pharmacology KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Soybeans UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76664746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Soy+intake+and+cancer+risk%3A+a+review+of+the+in+vitro+and+in+vivo+data.&rft.au=Messina%2C+M+J%3BPersky%2C+V%3BSetchell%2C+K+D%3BBarnes%2C+S&rft.aulast=Messina&rft.aufirst=M&rft.date=1994-01-01&rft.volume=21&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-09-13 N1 - Date created - 1994-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of cholera toxin by ADP-ribosylation factors. AN - 76646340; 8057933 JF - Methods in enzymology AU - Moss, J AU - Tsai, S C AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 640 EP - 647 VL - 235 SN - 0076-6879, 0076-6879 KW - Detergents KW - 0 KW - Phospholipids KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Agmatine KW - 70J407ZL5Q KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - NAD+ Nucleosidase KW - EC 3.2.2.5 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Agmatine -- metabolism KW - NAD+ Nucleosidase -- metabolism KW - Enzyme Activation KW - Phospholipids -- metabolism KW - Molecular Sequence Data KW - Carbohydrate Sequence KW - Allosteric Regulation KW - Adenosine Diphosphate Ribose -- metabolism KW - GTP-Binding Proteins -- classification KW - Poly(ADP-ribose) Polymerases -- chemistry KW - GTP-Binding Proteins -- physiology KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cholera Toxin -- chemistry KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76646340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+cholera+toxin+by+ADP-ribosylation+factors.&rft.au=Moss%2C+J%3BTsai%2C+S+C%3BVaughan%2C+M&rft.aulast=Moss&rft.aufirst=J&rft.date=1994-01-01&rft.volume=235&rft.issue=&rft.spage=640&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 - 1994-09-09 N1 - Date created - 1994-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Children of substance abusers: the life experiences of children of opiate addicts in methadone maintenance. AN - 76633019; 8042601 AB - We interviewed 70 substance abusers in methadone maintenance treatment regarding the life experiences of their 188 children. Sixty-four percent of the mothers reported using psychoactive drugs during their pregnancies. Eighty percent of parents reported an arrest during the time the child was growing up, 34% reported receiving treatment for an emotional disorder, and 14% were hospitalized. Four percent of the parents reported that their children had been placed in adoptive care, 9% in foster care, and 1% had a child in a group home. Forty-one percent of the parents reported that at least one of their children repeated a grade in school, 19% were involved in truancy, and 30% had been suspended from school. Twenty percent of parents reported their children's involvement with the law, and 17% reported drug or alcohol use. Problems with the law correlated highly with 1) being held back a grade, 2) truancy, 3) suspension from school, 4) expulsion from school, and 5) treatment for alcohol or drug abuse. JF - The American journal of drug and alcohol abuse AU - Kolar, A F AU - Brown, B S AU - Haertzen, C A AU - Michaelson, B S AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1994 PY - 1994 DA - 1994 SP - 159 EP - 171 VL - 20 IS - 2 SN - 0095-2990, 0095-2990 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Family Characteristics KW - Child Abuse, Sexual -- epidemiology KW - Child Abuse -- psychology KW - Child Abuse -- statistics & numerical data KW - Depressive Disorder -- psychology KW - Humans KW - Child KW - Antisocial Personality Disorder -- psychology KW - Depressive Disorder -- epidemiology KW - Child Abuse, Sexual -- psychology KW - Adult KW - Personality Assessment KW - Adolescent KW - Male KW - Learning Disorders -- epidemiology KW - Learning Disorders -- psychology KW - Pregnancy KW - Child, Preschool KW - Socioeconomic Factors KW - Antisocial Personality Disorder -- epidemiology KW - Cross-Sectional Studies KW - Bipolar Disorder -- epidemiology KW - Life Change Events KW - Child Behavior Disorders -- psychology KW - Bipolar Disorder -- psychology KW - Incidence KW - Maryland -- epidemiology KW - Child Behavior Disorders -- epidemiology KW - Female KW - Prenatal Exposure Delayed Effects KW - Opioid-Related Disorders -- epidemiology KW - Methadone -- therapeutic use KW - Opioid-Related Disorders -- psychology KW - Child of Impaired Parents -- psychology KW - Opioid-Related Disorders -- rehabilitation KW - Child of Impaired Parents -- statistics & numerical data KW - Personality Development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76633019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+drug+and+alcohol+abuse&rft.atitle=Children+of+substance+abusers%3A+the+life+experiences+of+children+of+opiate+addicts+in+methadone+maintenance.&rft.au=Kolar%2C+A+F%3BBrown%2C+B+S%3BHaertzen%2C+C+A%3BMichaelson%2C+B+S&rft.aulast=Kolar&rft.aufirst=A&rft.date=1994-01-01&rft.volume=20&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+drug+and+alcohol+abuse&rft.issn=00952990&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-08-24 N1 - Date created - 1994-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular characterization of the SPT23 gene: a dosage-dependent suppressor of Ty-induced promoter mutations from Saccharomyces cerevisiae. AN - 76532911; 8203154 AB - SPT genes are suppressors of mutations induced by the retrotransposon Ty in Saccharomyces cerevisiae. All SPT genes isolated to date suppress Ty-induced mutations by altering transcription. SPT23 was identified as a multicopy suppressor of the Ty-induced promoter mutations his4-912 delta and lys2-61. Multicopy expression of SPT23 suppresses a variety of Ty-induced promoter mutations, including the MAT-regulated alleles his4-917(480) and lys2-173R2. Here, we report the initial characterization of the SPT23 gene, including its nucleotide sequence and location in the yeast genome. The SPT23 gene contains a 1854 base pair open reading frame. Searches of the current data bases show no homology between SPT23 and previously described genes or proteins. The SPT23 gene is located between RAM2 and MAK11 on the left arm of chromosome XI. Tn10-LUK insertional mutagenesis of the SPT23 gene indicates that SPT23 is not essential for vegetative growth and spt23 mutations do not confer an Spt- phenotype. JF - Yeast (Chichester, England) AU - Burkett, T J AU - Garfinkel, D J AD - Laboratory of Eukaryotic Gene Expression, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 81 EP - 92 VL - 10 IS - 1 SN - 0749-503X, 0749-503X KW - SPT KW - SPT23 KW - spt23 KW - DNA Transposable Elements KW - 0 KW - Fungal Proteins KW - Membrane Proteins KW - SPT23 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - Index Medicus KW - Base Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis, Insertional KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - Genes, Fungal KW - Promoter Regions, Genetic -- genetics KW - Fungal Proteins -- genetics KW - Genes, Suppressor UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76532911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=Molecular+characterization+of+the+SPT23+gene%3A+a+dosage-dependent+suppressor+of+Ty-induced+promoter+mutations+from+Saccharomyces+cerevisiae.&rft.au=Burkett%2C+T+J%3BGarfinkel%2C+D+J&rft.aulast=Burkett&rft.aufirst=T&rft.date=1994-01-01&rft.volume=10&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Yeast+%28Chichester%2C+England%29&rft.issn=0749503X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-06 N1 - Date created - 1994-07-06 N1 - Date revised - 2017-01-13 N1 - Gene symbol - SPT; SPT23; spt23 N1 - Genetic sequence - L24760; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of phthalmustine, a new anticancer compound. I. Effect on Dalton's ascitic lymphoma in mice. AN - 76522582; 8202193 AB - The anticancer property of phthalmustine, a hitherto unknown compound containing N-mustard attached to the phthalimide ethyl chain was evaluated using a murine tumor model. The results indicate that the compound was effective in significantly restraining tumor growth. This was accompanied by marked improvement in host survival. No toxic reactions were apparent as reflected in skin and hair texture, body weight and behavioral pattern (food and water intake and activity). Blood picture showed a shift towards the normal following treatment. DNA synthesis in tumor cells was found to be affected as revealed by radioactive thymidine incorporation. JF - Neoplasma AU - Bhattacharya, S AU - Ganguly, C AU - Sanyal, U AU - Das, S AD - Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1994 PY - 1994 DA - 1994 SP - 35 EP - 38 VL - 41 IS - 1 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents KW - 0 KW - DNA, Neoplasm KW - Nitrogen Mustard Compounds KW - Phthalimides KW - phthalmustine KW - 156250-83-8 KW - Mechlorethamine KW - 50D9XSG0VR KW - Index Medicus KW - Animals KW - Body Weight -- drug effects KW - Mice KW - Drug Evaluation, Preclinical KW - DNA, Neoplasm -- biosynthesis KW - Male KW - Blood Cell Count -- drug effects KW - Nitrogen Mustard Compounds -- therapeutic use KW - Mechlorethamine -- toxicity KW - Mechlorethamine -- therapeutic use KW - Mechlorethamine -- analogs & derivatives KW - Phthalimides -- therapeutic use KW - Nitrogen Mustard Compounds -- toxicity KW - Lymphoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Phthalimides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76522582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+phthalmustine%2C+a+new+anticancer+compound.+I.+Effect+on+Dalton%27s+ascitic+lymphoma+in+mice.&rft.au=Bhattacharya%2C+S%3BGanguly%2C+C%3BSanyal%2C+U%3BDas%2C+S&rft.aulast=Bhattacharya&rft.aufirst=S&rft.date=1994-01-01&rft.volume=41&rft.issue=1&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-07-05 N1 - Date created - 1994-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinol and beta-carotene concentrations in skin, papillomas and carcinomas, liver, and serum of mice fed retinoic acid or beta-carotene to suppress skin tumor formation. AN - 76480262; 7910392 AB - Using 7,12-dimethylbenz[a]anthracene as the initiator and 12-O-tetradecanoyl-13-acetate as the tumor promoter on the dorsal skin of Sencar mice, we previously showed that pharmacological dietary all-trans-retinoic acid and beta-carotene inhibit the conversion of papillomas to carcinomas in a two-stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and beta-carotene on retinoid and beta-carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or beta-carotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 +/- 0.5 microgram/g wet wt. Equally refractory to dietary retinoic acid or beta-carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver retinol and retinyl palmitate, and beta-carotene caused an increase in beta-carotene and retinyl palmitate in liver but did not affect serum and liver retinol. We further investigated metabolic and functional aspects of retinoic acid in cultured mouse epidermal keratinocytes (LC-8 cells) and found that these cells actively metabolized [10,11-14C]retinoic acid to polar compounds. Isomers of retinoic acid were a minor product in the presence of cells and the major product when incubated in serum-containing medium in the absence of cells. From the functional point of view, exposure of LC-8 cells to 3 x 10(-6) M all-trans-retinoic acid (RA) caused a 75-fold induction in tissue transglutaminase and an approximately 9-fold induction in 10(-6) M RA at three days of culture. We conclude that retinoic acid spares endogenous retinol and that beta-carotene greatly enhances liver retinyl palmitate levels. Moreover we show that although mouse epidermal cells metabolize retinoic acid at a very high rate, they respond functionally by induction of tissue transglutaminase activity. Because this enzyme has been suggested to be involved in programmed cell death, we are presently investigating the possibility that it may be involved in the inhibition of carcinogenesis in mice fed pharmacological doses of RA. JF - Nutrition and cancer AU - Jones, C S AU - Sly, L AU - Chen, L C AU - Ben, T AU - Brugh-Collins, M AU - Lichti, U AU - De Luca, L M AD - Differentiation Control Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994 PY - 1994 DA - 1994 SP - 83 EP - 93 VL - 21 IS - 1 SN - 0163-5581, 0163-5581 KW - beta Carotene KW - 01YAE03M7J KW - Vitamin A KW - 11103-57-4 KW - Carotenoids KW - 36-88-4 KW - Tretinoin KW - 5688UTC01R KW - Transglutaminases KW - EC 2.3.2.13 KW - Index Medicus KW - Animals KW - Carcinoma -- chemistry KW - Keratinocytes -- drug effects KW - Cell Division -- drug effects KW - Mice KW - Mice, Inbred BALB C KW - Liver -- chemistry KW - Chromatography, High Pressure Liquid KW - Mice, Inbred Strains KW - Tumor Cells, Cultured KW - Transglutaminases -- analysis KW - Diet KW - Papilloma -- chemistry KW - Female KW - Skin -- chemistry KW - Vitamin A -- blood KW - Carotenoids -- blood KW - Skin Neoplasms -- chemically induced KW - Carotenoids -- analysis KW - Tretinoin -- administration & dosage KW - Vitamin A -- analysis KW - Carotenoids -- administration & dosage KW - Skin Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76480262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Retinol+and+beta-carotene+concentrations+in+skin%2C+papillomas+and+carcinomas%2C+liver%2C+and+serum+of+mice+fed+retinoic+acid+or+beta-carotene+to+suppress+skin+tumor+formation.&rft.au=Jones%2C+C+S%3BSly%2C+L%3BChen%2C+L+C%3BBen%2C+T%3BBrugh-Collins%2C+M%3BLichti%2C+U%3BDe+Luca%2C+L+M&rft.aulast=Jones&rft.aufirst=C&rft.date=1994-01-01&rft.volume=21&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-06-14 N1 - Date created - 1994-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel (taxol). AN - 76443600; 7909150 AB - Paclitaxel is a novel antineoplastic that effects cytotoxicity by promoting intracellular tubulin polymerization and stabilizes abnormal microtubule structures against depolymerization. Although its clinical development had been hampered by misconceptions about its pharmacology, its scarcity, difficulties extracting it from its natural source, formulation problems, and frequent severe hypersensitivity reactions, paclitaxel recently was approved for treatment-refractory ovarian cancer. Two major adverse effects are dosage- and schedule-related myelosuppression and mucositis. Neurotoxicity is directly related to both the individual and cumulative doses. Other relevant toxicities are hypersensitivity reactions, effects on cardiac rate and rhythm, arthralgias and myalgias, generalized hair loss, and mild nausea and emesis. Continuing clinical studies will evaluate paclitaxel as initial therapy for ovarian cancer and its utility in other malignancies. In addition, major efforts are under way to develop alternative sources to increase the availability of taxene analogs and reduce our dependence on yew species. JF - Pharmacotherapy AU - Kohler, D R AU - Goldspiel, B R AD - Department of Pharmacy, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892. PY - 1994 SP - 3 EP - 34 VL - 14 IS - 1 SN - 0277-0008, 0277-0008 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Injections, Intraperitoneal KW - Humans KW - Clinical Trials as Topic KW - Female KW - Neoplasms -- drug therapy KW - Paclitaxel -- adverse effects KW - Paclitaxel -- pharmacokinetics KW - Paclitaxel -- therapeutic use KW - Paclitaxel -- pharmacology KW - Ovarian Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Paclitaxel+%28taxol%29.&rft.au=Kohler%2C+D+R%3BGoldspiel%2C+B+R&rft.aulast=Kohler&rft.aufirst=D&rft.date=1994-01-01&rft.volume=14&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-16 N1 - Date created - 1994-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic nimodipine treatment in aged rats: analysis of motor and cognitive effects and muscarinic-induced striatal dopamine release. AN - 76443162; 8159263 AB - Nimodipine is a calcium channel blocker reported to have beneficial effects on treatment of ischemic damage as well as the potential for retarding aspects of brain and behavioral aging when provided chronically to rats. We treated aged male F-344 rats (24 months) with nimodipine in SC pellets in the following doses: 0 (controls), 20 mg (low-dose), or 40 mg (high-dose) replenished after 6 weeks. After 3 months of treatment, surviving rats and a group of young controls (6 months) were tested in a behavioral battery involving exploratory activity in an open field and in a runwheel cage as well as motor abilities required for remaining on an inclined screen, suspended from a wire, and balanced on a rotorod. Rats were also pretrained for one-way active avoidance in a straight runway before being trained in a 14-unit T maze. During 20 trials rats were required to negotiate each of 5 maze segments within 10 s to avoid foot shock (0.8 mA). Nimodipine treatment produced no significant effects on body weight, food intake, or survival of aged rats. Analysis of behavioral results indicated significant age-related decline in performance of all tasks except in open-field behavior. Nimodipine treatment had no significant effects on behavioral performance of aged rats except in maze learning. Rats on the high-dose regimen performed significantly better than aged controls in the maze. The results indicate that chronic nimodipine treatment of aged rats had no toxic effects and might be beneficial for preventing age-related decline in learning performance. JF - Neurobiology of aging AU - Ingram, D K AU - Joseph, J A AU - Spangler, E L AU - Roberts, D AU - Hengemihle, J AU - Fanelli, R J AD - Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224. PY - 1994 SP - 55 EP - 61 VL - 15 IS - 1 SN - 0197-4580, 0197-4580 KW - Parasympathomimetics KW - 0 KW - Nimodipine KW - 57WA9QZ5WH KW - Oxotremorine KW - 5RY0UWH1JL KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Animals KW - Aging -- metabolism KW - Rats, Inbred F344 KW - Oxotremorine -- pharmacology KW - Psychomotor Performance -- drug effects KW - Exploratory Behavior -- drug effects KW - Body Weight -- drug effects KW - Avoidance Learning -- drug effects KW - Male KW - Postural Balance -- drug effects KW - Neostriatum -- metabolism KW - Parasympathomimetics -- pharmacology KW - Cognition -- drug effects KW - Nimodipine -- pharmacology KW - Neostriatum -- drug effects KW - Dopamine -- metabolism KW - Motor Activity -- drug effects KW - Nimodipine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76443162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurobiology+of+aging&rft.atitle=Chronic+nimodipine+treatment+in+aged+rats%3A+analysis+of+motor+and+cognitive+effects+and+muscarinic-induced+striatal+dopamine+release.&rft.au=Ingram%2C+D+K%3BJoseph%2C+J+A%3BSpangler%2C+E+L%3BRoberts%2C+D%3BHengemihle%2C+J%3BFanelli%2C+R+J&rft.aulast=Ingram&rft.aufirst=D&rft.date=1994-01-01&rft.volume=15&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+aging&rft.issn=01974580&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-13 N1 - Date created - 1994-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. AN - 76428884; 7512194 AB - The insulin and insulin-like growth factor-I (IGF-I) receptors are related heterotetramers consisting of two extracellular ligand-binding alpha-subunits and two transmembrane beta-subunits whose cytoplasmic domains exhibit tyrosine kinase activity. Previous studies have shown that ATP binding by the cytoplasmic tyrosine kinase domains of these receptors is necessary to initiate the signal transduction pathway triggered by ligands or by ligand-mimetic antibodies, suggesting that receptor autophosphorylation is a necessary proximal step in this pathway. In the case of the insulin receptor, it has additionally been demonstrated that a cluster of three tyrosines in the kinase domain itself are the first to be phosphorylated, and that autophosphorylation of these particular residues is necessary for receptor activity. Using stably transfected NIH-3T3 cell lines, we now show that mutation of the analogous residues in the IGF-I receptor abolishes all short, intermediate, and long-term responses to IGF-I. These data suggest that the initial mechanisms of activation of the insulin and IGF-I receptors are very similar. Additionally, we have identified two parameters, induction of c-fos gene expression and ornithine decarboxylase enzyme activity, which are extremely sensitive to IGF-I stimulation and which will be particularly useful in evaluating the biological activity of other mutated versions of the IGF-I receptor. JF - Molecular endocrinology (Baltimore, Md.) AU - Kato, H AU - Faria, T N AU - Stannard, B AU - Roberts, C T AU - LeRoith, D AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 40 EP - 50 VL - 8 IS - 1 SN - 0888-8809, 0888-8809 KW - c-fos KW - c-jun KW - GTPase-Activating Proteins KW - 0 KW - Proteins KW - RNA, Messenger KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Phosphotransferases (Alcohol Group Acceptor) KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Ornithine Decarboxylase KW - EC 4.1.1.17 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Glucose -- metabolism KW - Humans KW - Mice KW - Proteins -- metabolism KW - RNA, Messenger -- biosynthesis KW - Structure-Activity Relationship KW - Mutagenesis KW - Ornithine Decarboxylase -- metabolism KW - Polymerase Chain Reaction KW - Base Sequence KW - Phosphorylation KW - Molecular Sequence Data KW - Phosphotransferases (Alcohol Group Acceptor) -- metabolism KW - Signal Transduction KW - Receptor, IGF Type 1 -- metabolism KW - Receptor, IGF Type 1 -- chemistry KW - Receptor, IGF Type 1 -- genetics KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Insulin-Like Growth Factor I -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76428884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Essential+role+of+tyrosine+residues+1131%2C+1135%2C+and+1136+of+the+insulin-like+growth+factor-I+%28IGF-I%29+receptor+in+IGF-I+action.&rft.au=Kato%2C+H%3BFaria%2C+T+N%3BStannard%2C+B%3BRoberts%2C+C+T%3BLeRoith%2C+D&rft.aulast=Kato&rft.aufirst=H&rft.date=1994-01-01&rft.volume=8&rft.issue=1&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-05-09 N1 - Date created - 1994-05-09 N1 - Date revised - 2017-01-13 N1 - Gene symbol - c-fos; c-jun N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical development of anticancer agents from natural products. AN - 76418173; 7908243 AB - Recent years have seen the introduction into clinical trials of new classes of chemotherapeutic agents which are derived from natural sources and have novel mechanisms of action. Examples of some of these newer classes of agents are presented here to illustrate both the opportunities they represent with respect to cancer treatment applications and the challenges which they represent from the clinical development perspective. Cumulatively the problems encountered with the development of the agents described are representative of the spectrum of issues encountered in the development of natural products, ranging from initial characterization and purification through the difficulties encountered in obtaining sufficient quantities of material for preclinical studies and then ultimately for clinical trials. Since these agents have unique mechanisms of action and are often exquisitely dose- and schedule-dependent in pre-clinical studies, they represent significant complexities with respect to determining the optimal regimen of administration clinically. The particular agents chosen for description here represent the spectrum of natural source-derived materials as well as mechanisms of action. The taxanes are derived from tree sources and interfere with the mitotic spindle apparatus; the camptothecins, while also derived from trees, appear to exert their activity through interactions with topoisomerase I. Bryostatin, derived from a marine animal, has powerful effects on protein kinase C (PKC), and therefore affects signal transduction pathways within cells. Fumagillin analogs appear to exhibit their important antitumor activity not through a direct effect on cancer cells but rather through effects on the tumor neovasculature. Taken as a whole, the spectrum of agents and activities described here confirms the continued importance of natural products in current anticancer agent development and reflects the complexities involved in this area of clinical research. JF - Stem cells (Dayton, Ohio) AU - Parkinson, D R AU - Arbuck, S G AU - Moore, T AU - Pluda, J M AU - Christian, M C AD - Investigational Drug Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 30 EP - 43 VL - 12 IS - 1 SN - 1066-5099, 1066-5099 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Bryostatins KW - Cyclohexanes KW - Fatty Acids, Unsaturated KW - Lactones KW - Macrolides KW - Sesquiterpenes KW - Topoisomerase I Inhibitors KW - bryostatin 1 KW - 37O2X55Y9E KW - fumagillin KW - 7OW73204U1 KW - Paclitaxel KW - P88XT4IS4D KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Camptothecin -- pharmacology KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Paclitaxel -- pharmacology KW - Antineoplastic Agents, Phytogenic -- metabolism KW - Plants, Medicinal -- chemistry KW - Lactones -- pharmacology KW - Paclitaxel -- chemistry KW - Fatty Acids, Unsaturated -- chemistry KW - Paclitaxel -- adverse effects KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- chemistry KW - Lactones -- chemistry KW - Camptothecin -- analogs & derivatives KW - Fatty Acids, Unsaturated -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76418173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=Clinical+development+of+anticancer+agents+from+natural+products.&rft.au=Parkinson%2C+D+R%3BArbuck%2C+S+G%3BMoore%2C+T%3BPluda%2C+J+M%3BChristian%2C+M+C&rft.aulast=Parkinson&rft.aufirst=D&rft.date=1994-01-01&rft.volume=12&rft.issue=1&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-29 N1 - Date created - 1994-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of animal models in cancer drug discovery and development. AN - 76417931; 8142918 AB - The process of searching for new cancer drugs has evolved from rational empiricism using high volume murine screens towards more targeted systems designed to discover agents which are specifically active against the common solid tumors of adulthood. Irrespective of the method of discovery, animal models are necessary in cancer drug development to answer fundamental questions of drug pharmacology and end organ toxicity. This knowledge is fundamental to the design of Phase I clinical trials. Increasingly, animal models are being utilized in the earliest stages of cancer drug discovery, as well as finding new uses guiding dose escalation in man. In addition, transgenic and SCID model systems have special applicability to the preclinical and clinical development of biological agents. This article reviews the emerging roles of animal models in cancer drug discovery and development. JF - Stem cells (Dayton, Ohio) AU - Curt, G A AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 23 EP - 29 VL - 12 IS - 1 SN - 1066-5099, 1066-5099 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Drug Screening Assays, Antitumor -- methods KW - Antineoplastic Agents -- chemistry KW - Drug Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76417931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=The+use+of+animal+models+in+cancer+drug+discovery+and+development.&rft.au=Curt%2C+G+A&rft.aulast=Curt&rft.aufirst=G&rft.date=1994-01-01&rft.volume=12&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-29 N1 - Date created - 1994-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The design and synthesis of a new anticancer drug based on a natural product lead compound: from neplanocin A to cyclopentenyl cytosine (CPE-C). AN - 76412366; 8142923 AB - In 1979, an unusual, carbocyclic nucleoside was discovered in a Japanese fermentation broth and designated neplanocin A. This compound is an analog of adenosine possessing a cyclopentene-containing "sugar" glycon. Although neplanocin A was biologically active, it was quite toxic. It therefore became a lead compound for analog synthesis in an attempt to maximize antitumor and antiviral activity while minimizing toxicity. First, a total synthesis of naturally occurring (-)-neplanocin A was accomplished using a new, versatile cyclopentenone carbocyclic "sugar" intermediate. This intermediate was then used to synthesize some 20 purine and pyrimidine analogs of neplanocin A which were evaluated for their antitumor and antiviral properties. Among the purine analogs, 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase, was found to have excellent antiviral activity both in vitro and in vivo. Cyclopentenyl cytosine (CPE-C) was found to be the most biologically active compound among the carbocyclic pyrimidine nucleosides. In addition to activity against over 20 viruses, this compound had excellent preclinical antitumor activity against both murine leukemias and human tumor xenografts. CPE-C is currently under clinical evaluation as an anticancer drug. JF - Stem cells (Dayton, Ohio) AU - Driscoll, J S AU - Marquez, V E AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 7 EP - 12 VL - 12 IS - 1 SN - 1066-5099, 1066-5099 KW - Antiviral Agents KW - 0 KW - Cytidine KW - 5CSZ8459RP KW - cyclopentenyl cytosine KW - 69MO0NDN8K KW - neplanocin A KW - 72877-50-0 KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Humans KW - In Vitro Techniques KW - Antiviral Agents -- chemical synthesis KW - Adenosine -- chemistry KW - Adenosine -- analogs & derivatives KW - Cytidine -- chemical synthesis KW - Drug Design KW - Cytidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76412366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cells+%28Dayton%2C+Ohio%29&rft.atitle=The+design+and+synthesis+of+a+new+anticancer+drug+based+on+a+natural+product+lead+compound%3A+from+neplanocin+A+to+cyclopentenyl+cytosine+%28CPE-C%29.&rft.au=Driscoll%2C+J+S%3BMarquez%2C+V+E&rft.aulast=Driscoll&rft.aufirst=J&rft.date=1994-01-01&rft.volume=12&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Stem+cells+%28Dayton%2C+Ohio%29&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-29 N1 - Date created - 1994-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linkage disequilibrium in admixed populations: applications in gene mapping. AN - 76377735; 8120361 AB - A method to detect linkage of genetic traits to polymorphic DNA markers in outbred populations when pedigree analysis is not feasible is presented. The procedure takes advantage of increased linkage disequilibrium that occurs when isolated races or subspecies mate and interbreed. By selecting restriction fragment length polymorphism (RFLP) or microsatellite marker loci that have different allele frequencies in admixed populations, genetic associations produced de novo by hybridization will persist as a function of theta (map distance) for 10-20 generations after initial interbreeding. By careful selection of loci and study populations, the procedure detects linkage of traits otherwise refractory to linkage analysis. JF - The Journal of heredity AU - Briscoe, D AU - Stephens, J C AU - O'Brien, S J AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201. PY - 1994 SP - 59 EP - 63 VL - 85 IS - 1 SN - 0022-1503, 0022-1503 KW - Genetic Markers KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Pedigree KW - Animals KW - Alleles KW - Gene Frequency KW - Polymorphism, Genetic KW - Models, Genetic KW - Humans KW - Chromosome Mapping -- methods KW - Linkage Disequilibrium UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76377735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+heredity&rft.atitle=Linkage+disequilibrium+in+admixed+populations%3A+applications+in+gene+mapping.&rft.au=Briscoe%2C+D%3BStephens%2C+J+C%3BO%27Brien%2C+S+J&rft.aulast=Briscoe&rft.aufirst=D&rft.date=1994-01-01&rft.volume=85&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+heredity&rft.issn=00221503&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-04-05 N1 - Date created - 1994-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Losartan improves the natriuretic response to ANF in rats with high-output heart failure. AN - 76349696; 8301562 AB - During severe congestive heart failure (CHF), a number of sodium-retaining and vasoconstricting mechanisms are activated, including the renin-angiotensin-aldosterone system. In CHF, the renal effects of atrial natriuretic factor (ANF) are attenuated. The interaction of these endocrine factors is a major determinant of the clinical course of CHF. This study was designed to evaluate the role of the renin-angiotensin-aldosterone system in the development of avid sodium retention in CHF, induced in rats by creation of an aorto-caval fistula. Rats with aorto-caval fistula either compensate and maintain a normal sodium balance (UNaV > 1400 microEq/day) or decompensate and develop severe sodium retention (UNaV 1000 microEQ/day) in decompensated rats, but not in compensated rats or controls. ANF infusion (50 micrograms/kg/hr) increased fractional sodium excretion 46-fold in compensated rats, but only 18-fold in decompensated rats. A similar pattern of responsiveness to ANF was observed in urinary cyclic GMP excretion. Chronic losartan treatment restored the natriuretic and urinary cyclic GMP excretion responses of decompensated rats to ANF. The improvement in the natriuretic response after losartan treatment was associated with a suppression of the previously elevated plasma aldosterone. These results demonstrate the pivotal role of angiotensin II in the development of sodium retention and of the blunted renal response to ANF in CHF, and indicate why losartan is useful therapy for cardiac edema. JF - The Journal of pharmacology and experimental therapeutics AU - Abassi, Z A AU - Kelly, G AU - Golomb, E AU - Klein, H AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lund and Blood Institute, National Institutes of Health, Bethesda, Maryland. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 224 EP - 230 VL - 268 IS - 1 SN - 0022-3565, 0022-3565 KW - Angiotensin Receptor Antagonists KW - 0 KW - Biphenyl Compounds KW - Imidazoles KW - Tetrazoles KW - Atrial Natriuretic Factor KW - 85637-73-6 KW - Sodium KW - 9NEZ333N27 KW - Cyclic GMP KW - H2D2X058MU KW - Losartan KW - JMS50MPO89 KW - Index Medicus KW - Rats KW - Animals KW - Drug Interactions KW - Cyclic GMP -- secretion KW - Rats, Wistar KW - Kidney -- drug effects KW - Renin-Angiotensin System -- physiology KW - Renin-Angiotensin System -- drug effects KW - Male KW - Sodium -- metabolism KW - Tetrazoles -- pharmacology KW - Natriuresis -- drug effects KW - Imidazoles -- pharmacology KW - Atrial Natriuretic Factor -- pharmacology KW - Biphenyl Compounds -- pharmacology KW - Heart Failure -- metabolism KW - Atrial Natriuretic Factor -- physiology KW - Heart Failure -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76349696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Losartan+improves+the+natriuretic+response+to+ANF+in+rats+with+high-output+heart+failure.&rft.au=Abassi%2C+Z+A%3BKelly%2C+G%3BGolomb%2C+E%3BKlein%2C+H%3BKeiser%2C+H+R&rft.aulast=Abassi&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=268&rft.issue=1&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-10 N1 - Date created - 1994-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vasopressin-independent regulation of collecting duct water permeability. AN - 76349169; 7905713 AB - Studies were conducted in microdissected rat terminal inner medullary collecting duct (IMCD) segments to determine whether agents that activate the phosphoinositide signaling pathway regulate osmotic water permeability independent of the action of vasopressin. Water was withheld from the rats for 24 h before the experiments, a procedure that yields a stably high osmotic water permeability in isolated perfused terminal IMCDs in the absence of vasopressin. In the present studies, the vasopressin-independent osmotic water permeability was sustained at approximately 300 microns/s for at least 90 min. We used the cholinergic agent carbachol (10-100 microM) to activate the phosphoinositide pathway. This agent has previously been reported to increase the hydrolysis of inositol phospholipids in IMCD cells without altering adenosine 3',5'-cyclic monophosphate production. In preliminary studies, we demonstrated (using fura 2) that carbachol transiently increases intracellular calcium and that this response was blocked by atropine, confirming that muscarinic receptors are coupled to activation of the phosphoinositide signaling pathway in these cells. In the absence of vasopressin, both carbachol (10 microM) and phorbol myristate acetate (1 nM) inhibited osmotic water permeability by 40-50% within 10 min. These effects were partially blocked by calphostin C, an inhibitor of protein kinase C. These results demonstrate that activation of phosphatidylinositol hydrolysis and/or activation of protein kinase C markedly inhibits osmotic water permeability in isolated perfused IMCD segments, even in the absence of prior stimulation by vasopressin. JF - The American journal of physiology AU - Han, J S AU - Maeda, Y AU - Ecelbarger, C AU - Knepper, M A AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - F139 EP - F146 VL - 266 IS - 1 Pt 2 SN - 0002-9513, 0002-9513 KW - Autacoids KW - 0 KW - Hormones KW - Water KW - 059QF0KO0R KW - Vasopressins KW - 11000-17-2 KW - Atropine KW - 7C0697DR9I KW - Carbachol KW - 8Y164V895Y KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Calcium -- metabolism KW - Rats KW - Permeability KW - Rats, Sprague-Dawley KW - Autacoids -- pharmacology KW - Hormones -- pharmacology KW - In Vitro Techniques KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Intracellular Membranes -- metabolism KW - Atropine -- pharmacology KW - Carbachol -- pharmacology KW - Male KW - Kidney Tubules, Collecting -- metabolism KW - Water -- metabolism KW - Vasopressins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76349169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Vasopressin-independent+regulation+of+collecting+duct+water+permeability.&rft.au=Han%2C+J+S%3BMaeda%2C+Y%3BEcelbarger%2C+C%3BKnepper%2C+M+A&rft.aulast=Han&rft.aufirst=J&rft.date=1994-01-01&rft.volume=266&rft.issue=1+Pt+2&rft.spage=F139&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-09 N1 - Date created - 1994-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-flow microinfusion: tissue penetration and pharmacodynamics. AN - 76348889; 8304553 AB - High-flow microinfusion provides a means for delivering macromolecules to large volumes of brain in easily obtainable time intervals. Slowly degraded approximately 180-kDa macromolecules, delivered at a constant volumetric flow rate of 3 microliters/min into homogeneous brain tissue (e.g., gray matter), would penetrate to a 1.5-cm radius in 12 h. The predicted concentration profile is relatively flat until it declines precipitously at the flow front. Hence, tissues are dosed rather uniformly, providing control over the undesired toxicity that may occur with alternative methods that depend on large concentration gradients for tissue transport. The penetration advantage of high-flow (convective) over low-flow (diffusive) microinfusion has been assessed at fixed pharmacodynamic effect. A 12-h high-flow microinfusion of a macromolecule degraded with a characteristic time of 33.5 h would provide 5- to 10-fold increases in volume over low-flow infusion and total treatment volumes > 10 cm3. Slower degradation rates would result in larger treatment volumes; more rapid degradation rates would reduce the volume but still favor convective over diffusive administration. This technique may be applicable to a variety of diagnostic and therapeutic agents such as radioimmunoconjugates, immunotoxins, enzymes, growth factors, and oligonucleotides. JF - The American journal of physiology AU - Morrison, P F AU - Laske, D W AU - Bobo, H AU - Oldfield, E H AU - Dedrick, R L AD - Biomedical Engineering and Instrumentation Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - R292 EP - R305 VL - 266 IS - 1 Pt 2 SN - 0002-9513, 0002-9513 KW - Macromolecular Substances KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Models, Neurological KW - Drug Delivery Systems KW - Brain -- metabolism KW - Pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76348889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=High-flow+microinfusion%3A+tissue+penetration+and+pharmacodynamics.&rft.au=Morrison%2C+P+F%3BLaske%2C+D+W%3BBobo%2C+H%3BOldfield%2C+E+H%3BDedrick%2C+R+L&rft.aulast=Morrison&rft.aufirst=P&rft.date=1994-01-01&rft.volume=266&rft.issue=1+Pt+2&rft.spage=R292&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-03-09 N1 - Date created - 1994-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intramolecular interactions in muscarinic acetylcholine receptors studied with chimeric m2/m5 receptors. AN - 76347258; 8302281 AB - Current models of the three-dimensional structures of muscarinic acetylcholine receptors and other G protein-coupled receptors are based primarily on high-resolution electron diffraction data obtained with bacteriorhodopsin, the molecular structure of which is characterized by the presence of seven alpha-helical transmembrane domains (TM I-VII). However, bacteriorhodopsin does not couple to G proteins and its primary sequence lacks a series of amino acids that are conserved among virtually all G protein-coupled receptors. Therefore, it remains to be shown experimentally whether the molecular structures of these functionally different proteins are in fact identical. To address this question, we have analyzed the pharmacological properties of a series of hybrid human m2/m5 muscarinic receptors. Initially, we identified several chimeric constructs that, upon transient expression in COS-7 cells, were unable to bind significant amounts of the muscarinic antagonists N-[3H]methylscopolamine and [3H]quinuclidinyl benzilate. A common structural feature of these constructs was the presence of m2 receptor sequence in TM VII and of m5 receptor sequence in TM I. The ligand-binding activity of these "pharmacologically inactive" hybrid receptors could be restored by replacing TM I (consisting of m5 receptor sequence) with the corresponding m2 receptor domain. These data provide the first direct experimental evidence that the molecular architecture of muscarinic receptors (and, most likely, that of other G protein-coupled receptors) resembles that of bacteriorhodopsin, in that the seven TM helices are arranged in a ring-like fashion such that TM I lies directly adjacent to TM VII. JF - Molecular pharmacology AU - Pittel, Z AU - Wess, J AD - National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 61 EP - 64 VL - 45 IS - 1 SN - 0026-895X, 0026-895X KW - Receptors, Muscarinic KW - 0 KW - Recombinant Fusion Proteins KW - Scopolamine Derivatives KW - Quinuclidinyl Benzilate KW - 6581-06-2 KW - N-Methylscopolamine KW - VDR09VTQ8U KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Quinuclidinyl Benzilate -- metabolism KW - Scopolamine Derivatives -- metabolism KW - Humans KW - Molecular Sequence Data KW - Cell Membrane -- chemistry KW - Amino Acid Sequence KW - Radioligand Assay KW - Cell Membrane -- metabolism KW - Cell Line KW - Mutagenesis KW - Receptors, Muscarinic -- genetics KW - Receptors, Muscarinic -- drug effects KW - Receptors, Muscarinic -- chemistry KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76347258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intramolecular+interactions+in+muscarinic+acetylcholine+receptors+studied+with+chimeric+m2%2Fm5+receptors.&rft.au=Pittel%2C+Z%3BWess%2C+J&rft.aulast=Pittel&rft.aufirst=Z&rft.date=1994-01-01&rft.volume=45&rft.issue=1&rft.spage=61&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 - 1994-03-10 N1 - Date created - 1994-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Early responses of the liver of B6C3F1 mice to the hepatocarcinogen oxazepam. AN - 76340315; 8291059 AB - Oxazepam has recently been shown to induce hepatocarcinogenicity in B6C3F1 mice. Due to the widespread human exposure to this anxiolytic compound and other structurally similar benzodiazepines, we conducted toxicity and cell proliferation studies on oxazepam to determine possible mechanisms whereby this nonmutagenic chemical may have exerted a carcinogenic effect. Male B6C3F1 mice (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500, and 5000 ppm. Mice were treated for 15, 30, 45, or 90 days, at which time they were evaluated for feed consumption, liver/body weight ratios, clinical pathology, serum oxazepam levels, and histopathology of the liver. During the final 7 days before sacrifice, the mice were exposed to BrDU via osmotic minipump to quantify hepatocellular replicative DNA synthesis. Few effects were observed resulting from chronic exposure to oxazepam other than statistically significant, dose-related increases in liver/body weight ratios. Replicative DNA synthesis was significantly increased in a dose-related manner at the 15-day time point in the 125, 2500, and 5000 ppm dose groups, and attained levels of four- to five-fold above control levels which returned to control levels by 30 days. The lack of significant toxicity, sustained increased liver/body weight ratios, and the rapid and transient induction of replicative DNA synthesis are similar to the effects reported for exposure to another widely used therapeutic agent shown to be a nongenotoxic carcinogen, phenobarbital. JF - Toxicology and applied pharmacology AU - Cunningham, M L AU - Maronpot, R R AU - Thompson, M AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 31 EP - 38 VL - 124 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Oxazepam KW - 6GOW6DWN2A KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Mice KW - Male KW - DNA Replication -- drug effects KW - Cell Division -- genetics KW - Liver -- pathology KW - Oxazepam -- toxicity KW - Carcinogens -- administration & dosage KW - Liver -- drug effects KW - Carcinogens -- toxicity KW - Oxazepam -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76340315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Early+responses+of+the+liver+of+B6C3F1+mice+to+the+hepatocarcinogen+oxazepam.&rft.au=Cunningham%2C+M+L%3BMaronpot%2C+R+R%3BThompson%2C+M%3BBucher%2C+J+R&rft.aulast=Cunningham&rft.aufirst=M&rft.date=1994-01-01&rft.volume=124&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-18 N1 - Date created - 1994-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term botulinum toxin treatment of focal hand dystonia. AN - 76339363; 8290095 AB - We treated focal hand dystonia in 53 patients with botulinum toxin injections for up to 6 years. Eighty-one percent of the patients improved with at least one injection session. Sixty-five percent of the injections produced transient weakness. We followed 37 of the patients for at least 2 years from the start of treatment, 24 of whom discontinued treatment because of inadequate response, loss of response, inaccessibility of a treatment provider, or the expense of the toxin. Women, who had a greater extent and longer duration of benefit than men, were more likely to continue treatment. The mean interval between injection sessions was 6 months. In most patients, we injected the toxin into the same combination of muscles at each session. The dose of toxin generally fluctuated within a range of 20 units. Side effects were mild and transient and unrelated to the long-term use of botulinum toxin. Botulinum toxin injection is safe and effective for the long-term management of focal hand dystonia. JF - Neurology AU - Karp, B I AU - Cole, R A AU - Cohen, L G AU - Grill, S AU - Lou, J S AU - Hallett, M AD - Human Motor Control Section, NINDS, NIH, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 70 EP - 76 VL - 44 IS - 1 SN - 0028-3878, 0028-3878 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Abridged Index Medicus KW - Index Medicus KW - Muscle Cramp -- physiopathology KW - Humans KW - Adult KW - Treatment Outcome KW - Hand KW - Aged KW - Middle Aged KW - Muscle Cramp -- etiology KW - Muscle Cramp -- drug therapy KW - Time Factors KW - Male KW - Female KW - Botulinum Toxins -- administration & dosage KW - Botulinum Toxins -- therapeutic use KW - Dystonia -- etiology KW - Dystonia -- drug therapy KW - Dystonia -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76339363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Long-term+botulinum+toxin+treatment+of+focal+hand+dystonia.&rft.au=Karp%2C+B+I%3BCole%2C+R+A%3BCohen%2C+L+G%3BGrill%2C+S%3BLou%2C+J+S%3BHallett%2C+M&rft.aulast=Karp&rft.aufirst=B&rft.date=1994-01-01&rft.volume=44&rft.issue=1&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-22 N1 - Date created - 1994-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized pilot study of alternating or simultaneous zidovudine and didanosine therapy in patients with symptomatic human immunodeficiency virus infection. AN - 76332540; 7903976 AB - A randomized pilot study comparing alternating and simultaneous regimens of zidovudine and didanosine (ddl) was conducted in 41 patients with AIDS or symptomatic human immunodeficiency virus (HIV) infection. Patients on each regimen received the same overall amounts of zidovudine and didanosine over time. CD4 cell counts in patients on the simultaneous regimen reached a maximum (mean +/- SE) of 108 +/- 16/mm3 above baseline (two-tailed P < or = .0001) and were significantly higher than in patients on the alternating regimen at all time points during weeks 6-45. At 54 weeks, the CD4 cell counts in the patients on the simultaneous regimen were still 40 +/- 19/mm3 above baseline. Patients on the simultaneous regimen also had significantly greater weight gain. While toxicities were generally mild and comparable between the regimens, 1 patient on the simultaneous regimen died of pancreatitis and lactic acidosis. Thus, simultaneous therapy provided more sustained elevations in CD4 cells than alternating therapy over 1 year and may be worth exploring in larger controlled trials. JF - The Journal of infectious diseases AU - Yarchoan, R AU - Lietzau, J A AU - Nguyen, B Y AU - Brawley, O W AU - Pluda, J M AU - Saville, M W AU - Wyvill, K M AU - Steinberg, S M AU - Agbaria, R AU - Mitsuya, H AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 9 EP - 17 VL - 169 IS - 1 SN - 0022-1899, 0022-1899 KW - HIV Core Protein p24 KW - 0 KW - beta 2-Microglobulin KW - Zidovudine KW - 4B9XT59T7S KW - Didanosine KW - K3GDH6OH08 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Administration, Oral KW - Drug Administration Schedule KW - HIV Core Protein p24 -- blood KW - Humans KW - Pilot Projects KW - CD4-Positive T-Lymphocytes KW - Drug Therapy, Combination KW - Leukocyte Count -- drug effects KW - beta 2-Microglobulin -- analysis KW - AIDS-Related Opportunistic Infections KW - Adult KW - Body Weight -- drug effects KW - Middle Aged KW - Follow-Up Studies KW - Adolescent KW - Pancreatitis -- chemically induced KW - Male KW - Female KW - Zidovudine -- therapeutic use KW - Didanosine -- therapeutic use KW - Zidovudine -- adverse effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Didanosine -- administration & dosage KW - Zidovudine -- administration & dosage KW - Didanosine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76332540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+randomized+pilot+study+of+alternating+or+simultaneous+zidovudine+and+didanosine+therapy+in+patients+with+symptomatic+human+immunodeficiency+virus+infection.&rft.au=Yarchoan%2C+R%3BLietzau%2C+J+A%3BNguyen%2C+B+Y%3BBrawley%2C+O+W%3BPluda%2C+J+M%3BSaville%2C+M+W%3BWyvill%2C+K+M%3BSteinberg%2C+S+M%3BAgbaria%2C+R%3BMitsuya%2C+H&rft.aulast=Yarchoan&rft.aufirst=R&rft.date=1994-01-01&rft.volume=169&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Infect Dis 1994 Jul;170(1):260 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The presence of K54 capsular polysaccharide increases the pathogenicity of Escherichia coli in vivo. AN - 76332335; 8277173 AB - Proven isogenic capsule-negative derivatives (CP9.29, CP9.108, CP9.137, CP9.171, CP9.443, and CP9.C56), generated from an O4/K54/H5 blood isolate (CP9) of Escherichia coli by IS50L::phoA (TnphoA)-mediated transposon mutagenesis, were used to assess the function of a non-K1 capsule in three animal models. Intraperitoneal injection of CP9 (K54+) into mice resulted in an LD50 at 24 h of 5.5 x 10(6) cfu compared with LD50s of 2.6 x 10(7) cfu and 3.8 x 10(7) cfu for CP9.108 (K54-) and CP9.C56 (K54-) (P < .001). CP9 was cleared less rapidly from the bloodstream, after intravascular injection, than was CP9.108 (P < .01). In the rat granuloma pouch model, CP9 could proliferate from starting inocula as low as 1.0 x 10(3) cfu/mL. In contrast, capsule-deficient derivatives underwent transient log kills with starting inocula as high as 1.0 x 10(6) cfu/mL. Because proven isogenic strains were evaluated, a clear contribution of the K54 capsular polysaccharide to virulence in vivo is demonstrated. JF - The Journal of infectious diseases AU - Russo, T A AU - Liang, Y AU - Cross, A S AD - Bacterial Pathogenesis Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 112 EP - 118 VL - 169 IS - 1 SN - 0022-1899, 0022-1899 KW - Antigens, Bacterial KW - 0 KW - Antigens, Surface KW - DNA Transposable Elements KW - K antigens KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Immunoelectrophoresis KW - Humans KW - Spleen -- microbiology KW - Disease Models, Animal KW - Metabolic Clearance Rate KW - Mice KW - Rats KW - DNA Transposable Elements -- immunology KW - Virulence -- genetics KW - Rats, Wistar KW - Lethal Dose 50 KW - Time Factors KW - Mutagenesis, Insertional KW - Female KW - Liver -- microbiology KW - Male KW - Escherichia coli Infections -- microbiology KW - Antigens, Bacterial -- metabolism KW - Escherichia coli -- pathogenicity KW - Antigens, Bacterial -- physiology KW - Escherichia coli -- genetics KW - Antigens, Surface -- metabolism KW - Escherichia coli -- growth & development KW - Antigens, Surface -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76332335?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=The+presence+of+K54+capsular+polysaccharide+increases+the+pathogenicity+of+Escherichia+coli+in+vivo.&rft.au=Russo%2C+T+A%3BLiang%2C+Y%3BCross%2C+A+S&rft.aulast=Russo&rft.aufirst=T&rft.date=1994-01-01&rft.volume=169&rft.issue=1&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial expression of Chinese hamster regulatory type-I and catalytic subunits of cyclic AMP-dependent protein kinase and mutational analysis of the type-I regulatory subunit. AN - 76331536; 8280113 AB - The type-I regulatory subunit (RI) of the cyclic AMP-dependent protein kinase (PKA) from Chinese hamster ovary (CHO) cells has been cloned and expressed in a strain of BL21(DE3) Escherichia coli lacking adenylate cyclase [BL21(DE3)/delta cya]. RI expressed in this bacterial system free of cyclic AMP is soluble and can reconstitute functional PKA. Recombinant CHO C alpha is predominantly insoluble with some active soluble protein. C beta is entirely insoluble and inactive. Soluble recombinant RI and soluble recombinant C alpha can associate in vitro and be activated by cyclic AMP. Six site-directed mutations of RI were generated to study the interaction of cyclic AMP with RI and RI-C alpha subunit interactions. Four cyclic AMP-binding-site point mutants were generated [W261R (tryptophan to arginine at position 261), a novel mutation in site A; V376G, a novel mutation in site B; G200E (site A), and Y370F (site B), previously described in bovine RI were introduced into the CHO RI for comparison purposes]. Mutants W261R, Y370F, and G200E demonstrated decreased 8-N3-[3H]cyclic AMP binding as well as 5-fold reduced affinity for [3H]cyclic AMP, with threefold increased EC50 values for cyclic AMP activation of kinase activity from reconstituted mutant holoenzymes. The mutation at V376G did not alter cyclic AMP binding or activation by cyclic AMP of mutant holoenzyme. A truncation mutant, G200Stop, which lacks both cyclic AMP-binding sites, did not bind cyclic AMP but can inhibit C alpha subunit activity. A novel mutation outside the cyclic AMP-binding regions of RI (V89A) weakened the interaction with C alpha indicated by a 7-fold lower EC50 for mutant holoenzyme activation by cyclic AMP. JF - The Biochemical journal AU - Gosse, M E AU - Fleischmann, R AU - Marshall, M AU - Wang, N AU - Garges, S AU - Gottesman, M M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1994/01/01/ PY - 1994 DA - 1994 Jan 01 SP - 79 EP - 85 VL - 297 ( Pt 1) SN - 0264-6021, 0264-6021 KW - Macromolecular Substances KW - 0 KW - Recombinant Proteins KW - Tritium KW - 10028-17-8 KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Amino Acid Sequence KW - Binding Sites KW - Cloning, Molecular KW - Recombinant Proteins -- metabolism KW - Cyclic AMP -- pharmacology KW - Cyclic AMP -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cricetinae KW - Mutagenesis, Site-Directed KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - CHO Cells -- enzymology KW - Gene Expression KW - Escherichia coli -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76331536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Bacterial+expression+of+Chinese+hamster+regulatory+type-I+and+catalytic+subunits+of+cyclic+AMP-dependent+protein+kinase+and+mutational+analysis+of+the+type-I+regulatory+subunit.&rft.au=Gosse%2C+M+E%3BFleischmann%2C+R%3BMarshall%2C+M%3BWang%2C+N%3BGarges%2C+S%3BGottesman%2C+M+M&rft.aulast=Gosse&rft.aufirst=M&rft.date=1994-01-01&rft.volume=297+%28+Pt+1%29&rft.issue=&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-10 N1 - Date created - 1994-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1980 Jul 15;630(4):476-84 [6104988] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] J Cell Physiol. 1982 Dec;113(3):433-9 [6294128] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3608-12 [6190178] Methods Enzymol. 1983;99:3-6 [6316096] Biochemistry. 1984 Aug 28;23(18):4193-9 [6487597] Biochemistry. 1984 Aug 28;23(18):4200-6 [6386045] Cell. 1985 Jul;41(3):745-51 [2988785] J Biol Chem. 1985 Nov 15;260(26):13927-33 [2997187] J Mol Biol. 1986 May 5;189(1):113-30 [3537305] Ann N Y Acad Sci. 1986;478:162-74 [3026221] Annu Rev Biochem. 1979;48:923-59 [38740] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Somatic Cell Genet. 1980 Jan;6(1):45-61 [6245473] Annu Rev Biochem. 1987;56:567-613 [2956925] J Biol Chem. 1987 Sep 25;262(27):13111-9 [2820963] Science. 1987 Oct 16;238(4825):336-41 [2443975] Biochem Biophys Res Commun. 1987 Dec 31;149(3):939-45 [3426618] Methods Enzymol. 1987;154:367-82 [3323813] J Biol Chem. 1989 Aug 5;264(22):13321-8 [2546952] J Biol Chem. 1989 Dec 15;264(35):20940-6 [2687267] Proc Natl Acad Sci U S A. 1990 Feb;87(3):1066-70 [2105495] Annu Rev Biochem. 1990;59:971-1005 [2165385] J Biol Chem. 1991 Feb 25;266(6):3491-7 [1847375] J Biol Chem. 1991 Jun 5;266(16):10189-95 [1645343] Biotechniques. 1991 Feb;10(2):202-4, 206, 208-9 [1676289] Somat Cell Mol Genet. 1992 Mar;18(2):103-11 [1349445] Science. 1988 Jan 29;239(4839):487-91 [2448875] Biochemistry. 1988 Mar 8;27(5):1570-6 [2835094] Proc Natl Acad Sci U S A. 1988 Jun;85(11):3703-7 [3375237] J Biol Chem. 1988 Jul 5;263(19):9149-54 [3288630] J Biol Chem. 1988 Nov 25;263(33):17397-404 [2846564] Proc Natl Acad Sci U S A. 1971 Feb;68(2):358-61 [4322607] Anal Biochem. 1967 Sep;20(3):525-32 [6048188] J Biol Chem. 1989 May 25;264(15):8443-6 [2656679] J Bacteriol. 1973 Nov;116(2):582-7 [4583241] Methods Enzymol. 1974;38:308-15 [4375764] Anal Biochem. 1976 May 7;72:248-54 [942051] J Biol Chem. 1980 Sep 10;255(17):8103-8 [6251043] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress. AN - 76326843; 8282800 AB - Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury. JF - The Journal of clinical investigation AU - Yoo, J H AU - Erzurum, S C AU - Hay, J G AU - Lemarchand, P AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 297 EP - 302 VL - 93 IS - 1 SN - 0021-9738, 0021-9738 KW - DNA Primers KW - 0 KW - RNA, Messenger KW - DNA KW - 9007-49-2 KW - Catalase KW - EC 1.11.1.6 KW - Luciferases KW - EC 1.13.12.- KW - Oxygen KW - S88TT14065 KW - Abridged Index Medicus KW - Index Medicus KW - Space life sciences KW - Exons KW - Humans KW - Luciferases -- metabolism KW - Epithelium -- enzymology KW - Transcription, Genetic KW - RNA, Messenger -- biosynthesis KW - Luciferases -- biosynthesis KW - DNA -- isolation & purification KW - Base Sequence KW - Bronchi KW - Transfection KW - Gene Expression Regulation, Enzymologic -- drug effects KW - DNA -- genetics KW - Molecular Sequence Data KW - Introns KW - Cell Line, Transformed KW - Catalase -- biosynthesis KW - Oxygen -- toxicity KW - Catalase -- genetics KW - Gene Expression UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76326843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Vulnerability+of+the+human+airway+epithelium+to+hyperoxia.+Constitutive+expression+of+the+catalase+gene+in+human+bronchial+epithelial+cells+despite+oxidant+stress.&rft.au=Yoo%2C+J+H%3BErzurum%2C+S+C%3BHay%2C+J+G%3BLemarchand%2C+P%3BCrystal%2C+R+G&rft.aulast=Yoo&rft.aufirst=J&rft.date=1994-01-01&rft.volume=93&rft.issue=1&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1994-02-17 N1 - Date created - 1994-02-17 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - L13609; GENBANK N1 - SuppNotes - Cited By: Cancer Res. 1988 Apr 1;48(7):1904-9 [2450641] FEBS Lett. 1987 Nov 16;224(1):14-8 [3678487] EMBO J. 1989 Dec 20;8(13):4273-9 [2686984] Cell. 1990 Apr 6;61(1):113-24 [2180582] J Biol Chem. 1990 Aug 25;265(24):14648-53 [2387873] Biochem Pharmacol. 1990 Dec 15;40(12):2571-7 [2175606] Science. 1991 Apr 19;252(5004):431-4 [2017680] Virology. 1991 May;182(1):361-4 [2024472] J Biol Chem. 1991 Jun 25;266(18):11632-9 [1646813] Am J Physiol. 1991 Jun;260(6 Pt 1):L412-8 [2058686] Am J Physiol. 1991 Jun;260(6 Pt 1):L428-33 [1711785] Pharmacol Ther. 1989;44(2):297-307 [2519346] J Biol Chem. 1991 Dec 25;266(36):24398-403 [1761541] Cell. 1992 Jan 10;68(1):143-55 [1370653] Mol Cell Biol. 1992 Jun;12(6):2525-33 [1588955] Nucleic Acids Res. 1992 May 11;20 Suppl:2091-3 [1598237] Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6482-6 [1631146] J Clin Invest. 1993 Jan;91(1):225-34 [8423221] Nucleic Acids Res. 1993 Apr 11;21(7):1607-12 [8479912] J Appl Physiol (1985). 1993 Sep;75(3):1256-62 [8226538] Physiol Rev. 1970 Jul;50(3):319-75 [4912904] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] J Immunol Methods. 1983 Dec 16;65(1-2):55-63 [6606682] Science. 1983 Nov 11;222(4624):625-8 [6635660] Nature. 1983 Aug 25-31;304(5928):749-52 [6310405] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 [6546423] Methods Enzymol. 1984;105:121-6 [6727660] Mol Cell Biol. 1985 Feb;5(2):330-41 [2858050] Environ Health Perspect. 1985 Dec;64:111-26 [3007083] Annu Rev Physiol. 1986;48:693-702 [3010831] Mol Cell Biol. 1987 Feb;7(2):725-37 [3821727] Cell. 1987 May 8;49(3):357-67 [3032451] Methods Enzymol. 1987;152:611-32 [2821358] Am Rev Respir Dis. 1989 Aug;140(2):531-54 [2669581] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of soybean, Vicia faba, and vitamin C on the carcinogenicity of DMBA. AN - 76326490; 14502848 AB - A single dose of 10 mg of 7,12-dimethylbenz[a]anthracene (DMBA), administered to rats through intragastric intubation, was sufficient to induce many biochemical and histopathological changes in their mammary tissue. Significant increases were observed in the activity levels of the enzymes acid ribonuclease, 5-nucleotidase, alkaline phosphatase, and beta-glucuronidase in mammary tissue homogenates of DMBA-treated rats after an experimental period of five months. Histopathological studies of the mammary tissue also revealed malignant epithelial tumors (cribriform carcinoma) induced among 85% of the treated rats, with an incidence of 4 tumors in 12 mammary glands. Nevertheless, administration of 30% soybean in the diet of rats or 5,000 ppm ascorbic acid in their drinking water in addition to DMBA revealed a significant chemoprotective effect against the carcinogenesis induced by DMBA alone. This chemoprotective effect was demonstrated by the normalization of the activity levels of the enzymes studied in mammary tissue homogenates, because most of the enzymes were maintained at near the levels in the control animals. The incidence and number of tumors were also decreased. Cribriform carcinoma was observed in 50% of the rats, and the incidence of the affected glands was 2 in 12 mammary glands among both groups. On the other hand, a less chemoprotective effect was observed due to Vicia faba administration. JF - Nutrition and cancer AU - el-Aaser, A A AU - Zakhary, N I AU - el-Guindy, S M AU - Hafiez, A R AU - Halawa, F AU - Mokhtar, N AD - Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. Y1 - 1994 PY - 1994 DA - 1994 SP - 195 EP - 200 VL - 22 IS - 2 SN - 0163-5581, 0163-5581 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Mammary Glands, Animal -- pathology KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Carcinoma -- prevention & control KW - Soybeans -- chemistry KW - Mammary Neoplasms, Experimental -- enzymology KW - Mammary Neoplasms, Experimental -- prevention & control KW - Ascorbic Acid -- pharmacology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76326490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nutrition+and+cancer&rft.atitle=Effect+of+soybean%2C+Vicia+faba%2C+and+vitamin+C+on+the+carcinogenicity+of+DMBA.&rft.au=el-Aaser%2C+A+A%3BZakhary%2C+N+I%3Bel-Guindy%2C+S+M%3BHafiez%2C+A+R%3BHalawa%2C+F%3BMokhtar%2C+N&rft.aulast=el-Aaser&rft.aufirst=A&rft.date=1994-01-01&rft.volume=22&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-28 N1 - Date created - 2003-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of sequence context at stop codons on efficiency of reinitiation in GCN4 translational control. AN - 76325364; 8264629 AB - Translational control of the GCN4 gene involves two short open reading frames in the mRNA leader (uORF1 and uORF4) that differ greatly in the ability to allow reinitiation at GCN4 following their own translation. The low efficiency of reinitiation characteristic of uORF4 can be reconstituted in a hybrid element in which the last codon of uORF1 and 10 nucleotides 3' to its stop codon (the termination region) are substituted with the corresponding nucleotides from uORF4. To define the features of these 13 nucleotides that determine their effects on reinitiation, we separately randomized the sequence of the third codon and termination region of the uORF1-uORF4 hybrid and selected mutant alleles with the high-level reinitiation that is characteristic of uORF1. The results indicate that many different A+U-rich triplets present at the third codon of uORF1 can overcome the inhibitory effect of the termination region derived from uORF4 on the efficiency of reinitiation at GCN4. Efficient reinitiation is not associated with codons specifying a particular amino acid or isoacceptor tRNA. Similarly, we found that a diverse collection of A+U-rich sequences present in the termination region of uORF1 could restore efficient reinitiation at GCN4 in the presence of the third codon derived from uORF4. To explain these results, we propose that reinitiation can be impaired by stable base pairing between nucleotides flanking the uORF1 stop codon and either the tRNA which pairs with the third codon, the rRNA, or sequences located elsewhere in GCN4 mRNA. We suggest that these interactions delay the resumption of scanning following peptide chain termination at the uORF and thereby lead to ribosome dissociation from the mRNA. JF - Molecular and cellular biology AU - Grant, C M AU - Hinnebusch, A G AD - Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1994/01// PY - 1994 DA - January 1994 SP - 606 EP - 618 VL - 14 IS - 1 SN - 0270-7306, 0270-7306 KW - GCN4 KW - Codon KW - 0 KW - RNA, Fungal KW - RNA, Messenger KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Base Sequence KW - Open Reading Frames KW - Molecular Sequence Data KW - RNA, Messenger -- genetics KW - Peptide Chain Termination, Translational -- genetics KW - Mutagenesis, Insertional KW - Saccharomyces cerevisiae -- genetics KW - RNA, Fungal -- genetics KW - Protein Biosynthesis KW - Codon -- genetics KW - Genes, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/76325364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+sequence+context+at+stop+codons+on+efficiency+of+reinitiation+in+GCN4+translational+control.&rft.au=Grant%2C+C+M%3BHinnebusch%2C+A+G&rft.aulast=Grant&rft.aufirst=C&rft.date=1994-01-01&rft.volume=14&rft.issue=1&rft.spage=606&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 - 1994-01-21 N1 - Date created - 1994-01-21 N1 - Date revised - 2017-01-13 N1 - Gene symbol - GCN4 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1990 Nov 11;18(21):6339-45 [2123028] Proc Natl Acad Sci U S A. 1990 Nov;87(21):8360-4 [2172984] Nucleic Acids Res. 1991 Jun 25;19(12):3185-92 [1905801] Annu Rev Biochem. 1991;60:717-55 [1883206] J Virol. 1991 Dec;65(12):6782-9 [1658374] Cell. 1992 Feb 7;68(3):585-96 [1739968] Gene. 1992 Jan 2;110(1):119-22 [1544568] Mol Microbiol. 1992 Jun;6(11):1413-9 [1625572] J Biol Chem. 1993 Jan 5;268(1):726-31 [8416975] Nucleic Acids Res. 1993 Apr 25;21(8):1837-43 [8493101] Mol Microbiol. 1993 Jun;8(6):1011-6 [7689685] J Mol Evol. 1973;2(2-3):199-204 [4620076] J Biol Chem. 1981 Jun 10;256(11):5798-801 [7016861] J Mol Biol. 1982 Jul 15;158(4):573-97 [6750137] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Microbiol Rev. 1983 Mar;47(1):1-45 [6343825] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6442-6 [6387704] Cell. 1985 Mar;40(3):515-26 [2982496] Nucleic Acids Res. 1980 Oct 10;8(19):4365-76 [7433112] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Cell. 1986 Apr 25;45(2):201-7 [3516411] Proc Natl Acad Sci U S A. 1986 May;83(9):2850-4 [3458245] Mol Cell Biol. 1985 Sep;5(9):2349-60 [3915540] Nucleic Acids Res. 1986 Jul 11;14(13):5125-43 [3526280] Biochem J. 1986 May 1;235(3):625-37 [3530248] J Biol Chem. 1987 Jan 15;262(2):767-71 [3805006] Nucleic Acids Res. 1987 Feb 11;15(3):1281-95 [3547335] Proc Natl Acad Sci U S A. 1987 May;84(9):2863-7 [3554249] Cell. 1987 Jun 19;49(6):805-13 [3555844] Mol Cell Biol. 1987 Oct;7(10):3438-45 [3683388] Mol Cell Biol. 1988 Apr;8(4):1591-601 [2837649] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4162-5 [3288986] Annu Rev Biophys Biophys Chem. 1988;17:167-92 [2456074] FEBS Lett. 1988 Aug 1;235(1-2):1-15 [3042454] Mol Cell Biol. 1988 Jul;8(7):2964-75 [3043201] EMBO J. 1988 Nov;7(11):3559-69 [2850168] Yeast. 1985 Dec;1(2):83-138 [3916863] Mol Cell Biol. 1988 Dec;8(12):5439-47 [3072481] Genes Dev. 1989 Aug;3(8):1217-25 [2676723] J Biol Chem. 1989 Nov 25;264(33):20054-9 [2684966] J Mol Biol. 1989 Oct 5;209(3):359-78 [2511323] Nucleic Acids Res. 1990 Apr 25;18(8):2079-86 [2186375] Cell. 1990 Jul 27;62(2):339-52 [2164889] Mol Microbiol. 1990 Jun;4(6):861-5 [2215213] Mol Cell Biol. 1991 Jan;11(1):486-96 [1986242] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Rev-inducible mutant gag gene stably transferred into T lymphocytes: An approach to gene therapy against human immunodeficiency virus type 1 infection AN - 19825821; 3600065 AB - One strategy for somatic gene therapy for human immunodeficiency virus type 1 (HIV-1) infection is based on the regulated expression of dominant negative mutants of the HIV-1 gag gene. To limit expression of the mutant Gag polypeptide to HIV-1 infected cells, we have constructed a replication-defective retroviral vector that contains a Rev-responsive element. By using this construct we have obviated problems that can be associated with constitutive expression of an exogenous gene, an important step toward developing a human therapy. The results have important implications in assessing the potential of somatic gene therapy in the treatment of HIV-1 infection. JF - Proceedings of the National Academy of Sciences, USA AU - Smythe, JA AU - Sun, D AU - Thomson, M AU - Markham, P D AU - Reitz, Jr AU - Gallo, R C AU - Lisziewicz, J AD - Lab. Tumor Cell Biol., Build. 37, Rm. 6A09, NCI/NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 3657 EP - 3661 VL - 91 IS - 9 SN - 0027-8424, 0027-8424 KW - gag gene KW - lymphocytes T KW - gene transfer KW - gene therapy KW - human immunodeficiency virus 1 KW - infection KW - man KW - genes KW - oncogenes KW - Human Genome Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06860:CMI KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19825821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+Rev-inducible+mutant+gag+gene+stably+transferred+into+T+lymphocytes%3A+An+approach+to+gene+therapy+against+human+immunodeficiency+virus+type+1+infection&rft.au=Smythe%2C+JA%3BSun%2C+D%3BThomson%2C+M%3BMarkham%2C+P+D%3BReitz%2C+Jr%3BGallo%2C+R+C%3BLisziewicz%2C+J&rft.aulast=Smythe&rft.aufirst=JA&rft.date=1994-01-01&rft.volume=91&rft.issue=9&rft.spage=3657&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 - Last updated - 2010-08-20 ER - TY - JOUR T1 - Drug-selected coexpression of human glucocerebrosidase and P-glycoprotein using a bicistronic vector AN - 19807731; 3564025 AB - Bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. Using the long 5' untranslated region of encephalomyocarditis virus as translational enhancer of the second gene, a bicistronic unit composed of cDNA for human P-glycoprotein [the product of the multidrug resistance gene, MDR1 (also called PGY1)] as selectable marker and cDNA for human glucocerebrosidase (GC; EC 3.2.1.45) (a membrane-associated lysosomal hydrolase) was constructed. NIH 3T3 cells transfected with a Harvey murine sarcoma virus retroviral vector carrying this bicistronic cassette (pHaMCG) express active P-glycoprotein and GC and expression of both proteins augments coordinately with selection for increased colchicine resistance. Percoll gradient analysis of homogenates showed that GC was targeted to the lysosomal fraction. The ability to select for expression of GC with natural product drugs after introduction of the pHaMCG retroviral vector may be useful in gene therapy strategies for Gaucher disease. JF - Proceedings of the National Academy of Sciences, USA AU - Aran, J M AU - Gottesman, M M AU - Pastan, I AD - Lab. Mol. Biol., Div. Cancer Biol., Diagn. and Cent., NCI/NIH, 9000 Rockville Pike, 37/4E16, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 3176 EP - 3180 VL - 91 IS - 8 SN - 0027-8424, 0027-8424 KW - glucocerebrosidase KW - P-glycoprotein KW - gene expression KW - multidrug resistance KW - gene therapy KW - cDNA KW - transfection KW - Gaucher's disease KW - man KW - Human Genome Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - N 14672:Transfection KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19807731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Drug-selected+coexpression+of+human+glucocerebrosidase+and+P-glycoprotein+using+a+bicistronic+vector&rft.au=Aran%2C+J+M%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Aran&rft.aufirst=J&rft.date=1994-01-01&rft.volume=91&rft.issue=8&rft.spage=3176&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 - Last updated - 2010-08-21 ER - TY - JOUR T1 - Differential induction of Fos protein and a Fos-related antigen following acute and repeated cocaine administration AN - 16978984; 3632011 AB - The present study examined the effects of a single and five once daily injections of cocaine on the expression of c-fos mRNA, Fos protein and Fos-related antigens (Fra) in the striatum. A single injection, which induces locomotion, increased the expression of c-fos mRNA, Fos protein and a 35 kDa Fra. In contrast, five injections given once a day, which induces even more behavioral stimulation, diminished the increase in c-fos mRNA and Fos protein expression. However, the cocaine-induced Fra expression was sustained and not reduced after the five injections. The results demonstrate that cocaine-induced expression of the Fos/Fra gene family is dynamic and the profile of gene transcription and translation in the striatum changes when animals are behaviorally more sensitive to cocaine. JF - Molecular Brain Research AU - Rosen, J B AU - Chuang, E AU - Iadarola, MJ AD - Biol. Psychiatr. Branch, NIMH, Build. 10, Rm. 3N212, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 168 EP - 172 VL - 25 IS - 1-2 SN - 0169-328X, 0169-328X KW - cocaine KW - c-fos gene KW - rats KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts; CSA Neurosciences Abstracts KW - neostriatum KW - mRNA KW - B 26200:Fos family KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16978984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Brain+Research&rft.atitle=Differential+induction+of+Fos+protein+and+a+Fos-related+antigen+following+acute+and+repeated+cocaine+administration&rft.au=Rosen%2C+J+B%3BChuang%2C+E%3BIadarola%2C+MJ&rft.aulast=Rosen&rft.aufirst=J&rft.date=1994-01-01&rft.volume=25&rft.issue=1-2&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Molecular+Brain+Research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mRNA; neostriatum ER - TY - JOUR T1 - Identification of the ron gene product as the receptor for the human macrophage stimulating protein AN - 16964404; 3622859 AB - Macrophage-stimulating protein (MSP) is a member of the hepatocyte growth factor-scatter factor (HGF-SF) family. Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase. Cross-linking of super(125)I-labeled MSP to transfected cells (MDCK-RE7 cells) and immunoprecipitation by antibodies to Ron revealed a 220-kilodalton complex, a size consistent with that of MSP (80 kilodaltons) cross-linked to the beta chain of Ron (150 kilodaltons). The binding of super(125)I-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells. These results establish the ron gene product as a specific cell-surface receptor for MSP. JF - Science (Washington) AU - Wang, Ming-Hai AU - Ronsin, C AU - Gesnel, M-C AU - Coupey, L AU - Skeel, A AU - Leonard, E J AU - Breathnach, R AD - Immunopathol. Sect., Lab. Immunobiol., NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 117 EP - 119 VL - 266 IS - 5182 SN - 0036-8075, 0036-8075 KW - MDCK cells KW - Ron protein KW - macrophage-stimulating protein receptors KW - ron gene KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Chemoreception Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - cell surface KW - chemotactic factors KW - macrophages KW - man KW - R 18042:Others KW - B 26380:Other colony stimulating factors KW - F 06761:Activation KW - W 30965:Miscellaneous, Reviews KW - R 18007:Chemotaxis KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16964404?accountid=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=Science+%28Washington%29&rft.atitle=Identification+of+the+ron+gene+product+as+the+receptor+for+the+human+macrophage+stimulating+protein&rft.au=Wang%2C+Ming-Hai%3BRonsin%2C+C%3BGesnel%2C+M-C%3BCoupey%2C+L%3BSkeel%2C+A%3BLeonard%2C+E+J%3BBreathnach%2C+R&rft.aulast=Wang&rft.aufirst=Ming-Hai&rft.date=1994-01-01&rft.volume=266&rft.issue=5182&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - cell surface; chemotactic factors; macrophages; man ER - TY - JOUR T1 - Vaccine technologies: View to the future AN - 16954003; 3616932 AB - The development of vaccines of prevent infectious diseases has been one of the most important contributions of biomedical science. Recent advances in the basic sciences are now fueling the development of a new generation of vaccines that will be based on rational design approaches. Two factors are making this possible: an improved understanding of the microbial factors required for virulence and the nature of the immune response to infection. The status of new vaccine technologies is summarized here. JF - Science (Washington) AU - Rabinovich, N R AU - McInnes, P AU - Klein, D L AU - Hall, B F AD - Div. Microbiol. and Infect. Dis., NIAID/NIH, Bethesda, MD 20982-9902, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1401 EP - 1404 VL - 265 IS - 5177 SN - 0036-8075, 0036-8075 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - genetic engineering KW - vaccines KW - reviews KW - immune response 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/16954003?accountid=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=Science+%28Washington%29&rft.atitle=Vaccine+technologies%3A+View+to+the+future&rft.au=Rabinovich%2C+N+R%3BMcInnes%2C+P%3BKlein%2C+D+L%3BHall%2C+B+F&rft.aulast=Rabinovich&rft.aufirst=N&rft.date=1994-01-01&rft.volume=265&rft.issue=5177&rft.spage=1401&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - genetic engineering; reviews; vaccines; immune response ER - TY - JOUR T1 - Multilocus DNA fingerprinting detects population differentiation in the outbred and abundant fish species Poecilia latipinna AN - 16952382; 3614110 AB - Several workers have suggested that multilocus multilocus variable number of tandem repeat (VNTR) based "DNA fingerprints" are not useful in detecting differentiation among outbred populations. They suggest that the extremely high mutation rates and complexity associated with multilocus VNTR fragments make detection of interpopulation differences against a background of extremely high intrapopulation variation unlikely. This paper shows that DNA fingerprinting with the multilocus VNTR probes (GACA) sub(4) and (CT) sub(9) reveal significant population differences in VNTR frequencies between Florida and Georgia populations of the outbred, abundant and vagile fish species Poecilia latipinna. Differences in mutation rates among some VNTR loci may account for the ability to detect interpopulation differentiation with these probes. These results suggest that appropriate species/probe combinations would allow investigations of population structure on a microgeographical scale even in outbred species with multilocus VNTR probes where less-sensitive techniques have failed. JF - Molecular Ecology AU - Laughlin, T F AU - Turner, B J AD - Biol. Carcinog. and Dev. Program, PRI/DynCorp, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 263 EP - 266 VL - 3 IS - 3 SN - 0962-1083, 0962-1083 KW - DNA fingerprinting KW - freshwater fish KW - outbreeding KW - Ecology Abstracts; ASFA 1: Biological Sciences & Living Resources; Genetics Abstracts KW - population genetics KW - fingerprinting KW - Poecilia latipinna KW - DNA KW - Freshwater KW - Q1 08345:Genetics and evolution KW - Q1 08443:Population genetics KW - D 04668:Fish KW - G 07290:Population genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16952382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Ecology&rft.atitle=Multilocus+DNA+fingerprinting+detects+population+differentiation+in+the+outbred+and+abundant+fish+species+Poecilia+latipinna&rft.au=Laughlin%2C+T+F%3BTurner%2C+B+J&rft.aulast=Laughlin&rft.aufirst=T&rft.date=1994-01-01&rft.volume=3&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Molecular+Ecology&rft.issn=09621083&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - population genetics; fingerprinting; freshwater fish; DNA; DNA fingerprinting; outbreeding; Poecilia latipinna; Freshwater ER - TY - JOUR T1 - The effect of occupational exposure to mercury vapour on the fertility of female dental assistants AN - 16950248; 3615684 AB - Exposure to mercury vapour or inorganic mercury compounds can impair fertility in laboratory animals. To study the effects of mercury vapour on fertility in women, eligibility questionnaires were sent to 7000 registered dental assistants in California. The final eligible sample of 418 women, who had become pregnant during the previous four years, were interviewed by telephone. Detailed information was collected on mercury handling practices and the number of menstrual cycles without contraception it had taken them to become pregnant. Dental assistants not working with amalgam served as unexposed controls. Women with high occupational exposure to mercury were less fertile than unexposed controls. The fecundability (probability of conception each menstrual cycle) of women who prepared 30 or more amalgams per week and who had five or more poor mercury hygiene factors was only 63% of that for unexposed women (95% CI 42%-96%) after controlling for covariates. Women with low exposure were more fertile, however, than unexposed controls. Possible explanations for the U shaped dose response and limitations of the exposure measure are discussed. Further investigation is needed that uses biological measures of mercury exposure. JF - Occupational and Environmental Medicine AU - Rowland, A S AU - Baird, D D AU - Weinberg, C R AU - Shore, D L AU - Shy, C M AU - Wilcox, A J AD - Epidemiol. Branch A3-05, NIEHS, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 28 EP - 34 VL - 51 IS - 1 SN - 1351-0711, 1351-0711 KW - dental personnel KW - vapor KW - man KW - mercury KW - heavy metals KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - occupational exposure KW - medical personnel KW - females KW - fertility KW - vapors KW - R2 23080:Industrial and labor KW - X 24162:Chronic exposure KW - P 6000:TOXICOLOGY AND HEALTH KW - H SI0.3:HAZARD DETERMINATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16950248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=The+effect+of+occupational+exposure+to+mercury+vapour+on+the+fertility+of+female+dental+assistants&rft.au=Rowland%2C+A+S%3BBaird%2C+D+D%3BWeinberg%2C+C+R%3BShore%2C+D+L%3BShy%2C+C+M%3BWilcox%2C+A+J&rft.aulast=Rowland&rft.aufirst=A&rft.date=1994-01-01&rft.volume=51&rft.issue=1&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mercury; vapors; occupational exposure; fertility; females; heavy metals; medical personnel; dental personnel; man ER - TY - JOUR T1 - Comparison of the in vitro cytotoxic effects of cadmium in Sertoli cell and Leydig cell lines derived from the mouse testes AN - 16928249; 3608008 AB - The rodent testes are particularly sensitive to cadmium-induced lesions, although the precise mechanisms involved are not well defined. To further study the interaction of cadmium with testicular cells, mouse cell lines derived from Leydig (TM3) and Sertoli (TM4) cells were studied in vitro. The results show that the Leydig (TM3) cell line is less sensitive to cadmium-induced cytotoxicity than the Sertoli (TM4) cell line. This may be due to higher metal-binding protein levels in the Leydig cell line. JF - TOXIC SUBST. J. AU - Shiraishi, N AU - Barter, R A AU - Waalkes, M P AD - Inorg. Carcinog. Sect., Lab. Comp. Carcinog., NCI-FCRDC, Build. 538, Rm. 205E, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 113 EP - 127 VL - 13 IS - 2 SN - 0199-3178, 0199-3178 KW - cadmium KW - heavy metals KW - mice KW - Toxicology Abstracts KW - toxicity testing KW - Sertoli cells KW - Leydig cells KW - cytotoxicity KW - comparison KW - X 24164:Pathology KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16928249?accountid=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=TOXIC+SUBST.+J.&rft.atitle=Comparison+of+the+in+vitro+cytotoxic+effects+of+cadmium+in+Sertoli+cell+and+Leydig+cell+lines+derived+from+the+mouse+testes&rft.au=Shiraishi%2C+N%3BBarter%2C+R+A%3BWaalkes%2C+M+P&rft.aulast=Shiraishi&rft.aufirst=N&rft.date=1994-01-01&rft.volume=13&rft.issue=2&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=TOXIC+SUBST.+J.&rft.issn=01993178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - cytotoxicity; comparison; Sertoli cells; Leydig cells; toxicity testing ER - TY - JOUR T1 - Cadmium-induced oxidative tissue damage in mice: Role of mouse strain and tissue metallothionein levels AN - 16925378; 3608013 AB - Cadmium toxicity varies widely with strain in mice and often depends on the tissue level of metallothionein (MT). We therefore studied cadmium-induced oxidative damage and the role of tissue MT in mouse strains that are resistant (BALB/c) or susceptible (NFS) to acute and chronic cadmium toxicity. Thiobarbituric acid-reactive substances (TBARS) were assessed in liver, kidney, and testes as an indication of lipid peroxidation (LPO), and MT was measured by the cadmium-hemoglobin assay. JF - TOXIC SUBST. J. AU - Abshire, M K AU - Waalkes, M P AD - Inorg. Carcinog. Sect., NCI-FCRDC, Build. 538, Rm. 205E, Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 141 EP - 152 VL - 13 IS - 2 SN - 0199-3178, 0199-3178 KW - oxidative KW - cadmium KW - heavy metals KW - differences KW - metallothionein KW - mice KW - Toxicology Abstracts KW - damage KW - strains KW - tissues KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16925378?accountid=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=TOXIC+SUBST.+J.&rft.atitle=Cadmium-induced+oxidative+tissue+damage+in+mice%3A+Role+of+mouse+strain+and+tissue+metallothionein+levels&rft.au=Abshire%2C+M+K%3BWaalkes%2C+M+P&rft.aulast=Abshire&rft.aufirst=M&rft.date=1994-01-01&rft.volume=13&rft.issue=2&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=TOXIC+SUBST.+J.&rft.issn=01993178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - strains; tissues; damage ER - TY - JOUR T1 - Carcinogenic and chronic toxic effects of single and multiple subcutaneous doses of cadmium chloride in male BALB/c mice AN - 16923861; 3608001 AB - The carcinogenicity of cadmium has not been thoroughly studied in mice. Thus, tumor incidence in male BALB/cAnNCr (BALB/c) mice after a single or multiple doses of cadmium was assessed. Groups of mice (n = 35) were given CdCl sub(2) (20 mu mol/kg) sc in the dorsal thoracic midline either as a single dose (1 x 20) or as weekly doses for 16 wk (16 x 20) starting at 8 wk of age. Controls received saline. The animals were observed for the next 2 yr. Cadmium increased the incidence of animals bearing at least one tumor (control 22/35, 63%; 1 x 20 23/33, 70%; 16 x 20, 87%) but not the mean number of tumors per animal (control, 1.54; 1 x 20, 1.36; 16 x 20, 1.58), largely because of the cadmium-induced suppression of pulmonary tumor multiplicity. Chronic cadmium-induced nephropathy occurred only at the highest dose and was not a common finding (5/31, 16%). These results indicate that cadmium can induce hematopoietic tumors and suppress pulmonary tumors in BALA/c mice. JF - TOXIC SUBST. J. AU - Waalkes, M P AU - Rehm, S AD - Inorg. Carcinog. Sect., Lab. Comp. Carcinog., Build. 538, Rm. 205E, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 97 EP - 111 VL - 13 IS - 2 SN - 0199-3178, 0199-3178 KW - cadmium chloride KW - heavy metals KW - mice KW - Toxicology Abstracts KW - carcinogenicity KW - hemopoietic system KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16923861?accountid=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=TOXIC+SUBST.+J.&rft.atitle=Carcinogenic+and+chronic+toxic+effects+of+single+and+multiple+subcutaneous+doses+of+cadmium+chloride+in+male+BALB%2Fc+mice&rft.au=Waalkes%2C+M+P%3BRehm%2C+S&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1994-01-01&rft.volume=13&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=TOXIC+SUBST.+J.&rft.issn=01993178&rft_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; hemopoietic system ER - TY - JOUR T1 - Rotavirus vaccine development for the prevention of severe diarrhea in infants and young children AN - 16915326; 3595370 AB - Rotaviruses were first detected 20 years ago and emerged rapidly as the single most important recognized etiological agents of severe diarrhea among infants and children under 2 years in both developed and developing countries. They are estimated to cause over 870 000 deaths annually in developing countries. This review highlights recent approaches to the development of a rotavirus vaccine. JF - Trends in Microbiology AU - Hoshino, Y AU - Kapikian, A Z AD - Lab. Infect. Dis., NIAID/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 242 EP - 249 VL - 2 IS - 7 SN - 0966-842X, 0966-842X KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - rotavirus KW - diarrhea KW - vaccines KW - development KW - children KW - infants KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16915326?accountid=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+Microbiology&rft.atitle=Rotavirus+vaccine+development+for+the+prevention+of+severe+diarrhea+in+infants+and+young+children&rft.au=Hoshino%2C+Y%3BKapikian%2C+A+Z&rft.aulast=Hoshino&rft.aufirst=Y&rft.date=1994-01-01&rft.volume=2&rft.issue=7&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - diarrhea; vaccines; development; children; infants; rotavirus ER - TY - JOUR T1 - Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection AN - 16910738; 3598009 AB - The cultured T-cell line TIL1200, established from the tumor-infiltrating lymphocytes (TILs) of a patient with advanced metastatic melanoma, recognized an antigen on most HLA-A2 super(+) melanomas and on all HLA-A2 super(+) cultured neonatal melanocytes in an HLA-A2 restricted manner but not on other types of tissues or cell lines tested. A cDNA encoding an antigen recognized by TIL1200 was isolated by screening an HLA-A2 super(+) breast cancer cell line transfected with an expression cDNA library prepared from an HLA-A2 super(+) melanoma cell line. The nucleotide and amino acid sequences of this cDNA were almost identical to the genes encoding glycoprotein gp100 or Pmel17 previously registered in the GenBank. Since the administration of TIL1200 plus interleukin 2 resulted in regression of metastatic cancer in the autologous patient, gp100 is a possible tumor rejection antigen and may be useful for the development of immunotherapies for patients with melanoma. JF - Proceedings of the National Academy of Sciences, USA AU - Kawakami, Y AU - Eliyahu, S AU - Delgado, CH AU - Robbins, P F AU - Sakaguchi, K AU - Appella, E AU - Yannelli, J R AU - Adema, G J AU - Miki, T AU - Rosenberg, SA AD - Surg. Branch, NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 6458 EP - 6462 VL - 91 IS - 14 SN - 0027-8424, 0027-8424 KW - tumor-infiltrating KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - lymphocytes KW - identification KW - immunotherapy KW - rejection KW - tumors KW - melanoma KW - antigen (tumor-associated) KW - man KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16910738?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Identification+of+a+human+melanoma+antigen+recognized+by+tumor-infiltrating+lymphocytes+associated+with+in+vivo+tumor+rejection&rft.au=Kawakami%2C+Y%3BEliyahu%2C+S%3BDelgado%2C+CH%3BRobbins%2C+P+F%3BSakaguchi%2C+K%3BAppella%2C+E%3BYannelli%2C+J+R%3BAdema%2C+G+J%3BMiki%2C+T%3BRosenberg%2C+SA&rft.aulast=Kawakami&rft.aufirst=Y&rft.date=1994-01-01&rft.volume=91&rft.issue=14&rft.spage=6458&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - lymphocytes; identification; rejection; immunotherapy; tumors; melanoma; man; antigen (tumor-associated) ER - TY - JOUR T1 - Biological plausibility of synaptic associative memory models AN - 16898984; 141756 AB - Observations in brains of neuronal networks that subserve associative learning in living organisms have been exceedingly sparse until the past decade. Recently, some fundamental biophysical and biochemical properties of biological neural networks that demonstrate associative learning have been revealed in the marine mollusc, Hermissenda crassicornis. In mammals, we have localized distributed changes, specific to associative memory, in dendritic regions within biological neural networks. Based on these findings, it has been possible to construct an artificial neural network. Dystal (dynamically stable associative learning) that utilizes non-Hebbian learning rules and displays a number of useful properties, including self-organization; monotonic convergence; large storage capacity without saturation; computational complexity of O(N); the ability to learn, store, and recall associations among arbitrary, noisy patterns after four to eight training epochs; a weak dependence on global parameters; and the ability to intermix training and testing as new training information becomes available. The performance of the Dystal network is demonstrated on problems that include face recognition and hand-printed Kanji classification. The computational linearity of Dystal is demonstrated by its performance on a MasPar parallel hardware computer. JF - Neural Networks AU - Alkon, Daniel L AU - Blackwell, Kim T AU - Barbour, Garth S AU - Werness, Susan A AU - Vogl, Thomas P AD - NINDS, Bethesda, MD, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1005 EP - 1017 VL - 7 IS - 6-7 SN - 0893-6080, 0893-6080 KW - Associative learning KW - Associative storage KW - Biological plausibility KW - Classification (of information) KW - Computational complexity KW - Face recognition KW - Pattern recognition KW - Self organization KW - Self organizing storage KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Neural networks KW - Algorithms KW - Biology KW - W4 461.9:BIOLOGY KW - W 30965:Miscellaneous, Reviews KW - W4 723.4:ARTIFICIAL INTELLIGENCE KW - W4 903.1:INFORMATION SOURCES AND ANALYSIS KW - W4 722.1:DATA STORAGE (EQUIPMENT AND TECHNIQUES) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16898984?accountid=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=Neural+Networks&rft.atitle=Biological+plausibility+of+synaptic+associative+memory+models&rft.au=Alkon%2C+Daniel+L%3BBlackwell%2C+Kim+T%3BBarbour%2C+Garth+S%3BWerness%2C+Susan+A%3BVogl%2C+Thomas+P&rft.aulast=Alkon&rft.aufirst=Daniel&rft.date=1994-01-01&rft.volume=7&rft.issue=6-7&rft.spage=1005&rft.isbn=&rft.btitle=&rft.title=Neural+Networks&rft.issn=08936080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Neural networks; Algorithms; Biology ER - TY - JOUR T1 - Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in male NES and C57 mice and male Syrian hamsters AN - 16898604; 3588654 JF - TOXIC SUBST. J. AU - Waalkes, M P AU - Rehm, S AU - Sass, B AU - Kovatch, R AU - Ward, J M AD - Inorg. Carcinog. Sect., Lab. Comp. Carcinog., Build. 538, Room 205E, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 15 EP - 28 VL - 13 IS - 1 SN - 0199-3178, 0199-3178 KW - cadmium KW - hamsters KW - mice KW - heavy metals KW - Toxicology Abstracts KW - carcinogenicity KW - toxicity KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16898604?accountid=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=TOXIC+SUBST.+J.&rft.atitle=Chronic+carcinogenic+and+toxic+effects+of+a+single+subcutaneous+dose+of+cadmium+in+male+NES+and+C57+mice+and+male+Syrian+hamsters&rft.au=Waalkes%2C+M+P%3BRehm%2C+S%3BSass%2C+B%3BKovatch%2C+R%3BWard%2C+J+M&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1994-01-01&rft.volume=13&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=TOXIC+SUBST.+J.&rft.issn=01993178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - toxicity; carcinogenicity ER - TY - JOUR T1 - Behavioral effects of alcohol ingestion: Implications for drug testing AN - 16887905; 3588651 AB - Based on considerable publicity in the media, the public is becoming increasingly aware of the hazards of alcohol consumption while engaging in operating vehicles or machinery. Ethanol, the active ingredient in alcoholic beverages, has a simple molecular structure and, as such, has a multitude of effects on the brain leading to behavioral deficits. The intoxicating properties of alcohol are roughly proportional to the blood alcohol concentration. Thus, measuring the blood alcohol concentration has validity as an indicator of impairment. The degree of impairment can depend on the complexity of the task undertaken. For example, flying an airplane is more complex than driving a car. The major effects of alcohol are inappropriate processing of environmental stimuli and degraded motor skills. Both capabilities are needed for safe operations. Legislation at both the federal and state levels is strengthening the restrictions and penalties for alcohol consumption and vehicular operation. JF - TOXIC SUBST. J. AU - Hunt, WA AU - Witt, ED AD - Div. Basic Res., NIAAA, 6000 Executive Blvd., Rockville, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 41 EP - 49 VL - 13 IS - 1 SN - 0199-3178, 0199-3178 KW - ethanol KW - Toxicology Abstracts KW - behavior KW - man KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16887905?accountid=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=TOXIC+SUBST.+J.&rft.atitle=Behavioral+effects+of+alcohol+ingestion%3A+Implications+for+drug+testing&rft.au=Hunt%2C+WA%3BWitt%2C+ED&rft.aulast=Hunt&rft.aufirst=WA&rft.date=1994-01-01&rft.volume=13&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=TOXIC+SUBST.+J.&rft.issn=01993178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - behavior; man ER - TY - JOUR T1 - Dopaminergic and peptidergic mRNA levels in juvenile rat brain after prenatal cocaine treatment AN - 16863458; 3570233 AB - The effects of prenatal cocaine treatment on gene expression in dopaminergic pathways of juvenile rats were investigated by in situ hybridization histochemistry. Pregnant rats from gestational day 8 to 20 were administered one of the following treatments: (A) 40 mg/kg cocaine hydrochloride/3 ml/day s.c.; (B) 0.9% saline/3 ml/day s.c. and pair fed to cocaine-exposed dams; (C) 0.9% saline/3 ml/day s.c. and placement on cellulose-diluted diet to match the caloric intake of the cocaine-treated group without explicit food restriction; (D) no injection and lab chow diet. Levels of mRNA for the dopamine transporter, tyrosine hydroxylase, cholecystokinin, D sub(1) and D sub(2) dopamine receptors and enkephalin were quantitated in relevant dopaminergic regions of forebrain and midbrain of offspring that were sacrificed on postnatal day 21. Quantitative analysis revealed no significant changes in mRNA levels in any of the brain regions examined. In the present animal model, cocaine exposure in utero had no significant effect on mRNA levels of the dopamine transporter, D sub(1) or D sub(2) dopamine receptors, enkephalin, tyrosine hydroxylase, or cholecystokinin in juvenile rats. JF - Molecular Brain Research AU - De Bartolomeis, A AU - Austin, M C AU - Goodwin, G A AU - Spear, L P AU - Pickar, D AU - Crawley, J N AD - Sect. Behav. Neuropharmacol., Exp. Therap. Branch, NIMH, Build. 10, Room 4N214, 9000 Rockville Pike, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 321 EP - 330 VL - 21 IS - 3-4 SN - 0169-328X, 0169-328X KW - cocaine KW - effects on KW - dopamine KW - transporter KW - enkephalins KW - tyrosine 3-monooxygenase KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - juveniles KW - intrauterine exposure KW - brain KW - mRNA KW - N3 11104:Mammals (except primates) KW - N3 11106:Neurobiology of drug abuse KW - N3 11075:Molecular neurobiology KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16863458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Brain+Research&rft.atitle=Dopaminergic+and+peptidergic+mRNA+levels+in+juvenile+rat+brain+after+prenatal+cocaine+treatment&rft.au=De+Bartolomeis%2C+A%3BAustin%2C+M+C%3BGoodwin%2C+G+A%3BSpear%2C+L+P%3BPickar%2C+D%3BCrawley%2C+J+N&rft.aulast=De+Bartolomeis&rft.aufirst=A&rft.date=1994-01-01&rft.volume=21&rft.issue=3-4&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Molecular+Brain+Research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - intrauterine exposure; mRNA; juveniles; brain ER - TY - JOUR T1 - Transmammary exposure of mouse pups to Allium sativum (garlic) and its effect on the neonatal hepatic xenobiotic metabolizing enzymes of mice AN - 16833513; 3561601 AB - The present study examines the transmammary modulation of hepatic xenobiotic metabolizing enzymes in the F sub(1) generation mouse pups postnatally exposed to garlic. Lactating Swiss albino mice received either 200 or 400 mg of garlic/kg bw by oral gavage for 14 or 21 days postpartum. The acid soluble sulfhydryl content significantly increased in liver of dams on the higher dose of garlic. It however decreased in liver of 14 day old pups translactationally exposed to the lower garlic dose. Cytochrome b sub(5) content was not affected with garlic treatment in dams and most of the pups but increased in the 14 day old female pup translactationally exposed to the higher dose of garlic. Hepatic cytochrome P-450 content and glutathione S-transferase activity remained unchanged in dams and pups exposed to garlic. Glutathione reductase decreased significantly in liver of dams which received the lower garlic dose for 14 or 21 days and in the 21 day old pups. JF - Nutrition Research AU - Chhabra, S K AU - Rao, A R AD - Perinatal Carcinog. Sect., LCC, NCI-FCRDC, Build. 538, Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 195 EP - 210 VL - 14 IS - 2 SN - 0271-5317, 0271-5317 KW - mice KW - transmammary exposure KW - Toxicology Abstracts KW - Allium sativum KW - metabolism KW - liver KW - xenobiotics KW - enzymes KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16833513?accountid=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=Nutrition+Research&rft.atitle=Transmammary+exposure+of+mouse+pups+to+Allium+sativum+%28garlic%29+and+its+effect+on+the+neonatal+hepatic+xenobiotic+metabolizing+enzymes+of+mice&rft.au=Chhabra%2C+S+K%3BRao%2C+A+R&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1994-01-01&rft.volume=14&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Nutrition+Research&rft.issn=02715317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Allium sativum; liver; enzymes; xenobiotics; metabolism ER - TY - JOUR T1 - Use of Drosophila mutants to distinguish among volatile general anesthetics AN - 16830335; 3560768 AB - The way general anesthetics cause their clinically useful effects on the nervous system is not known. Since the principal determinant of the potency of these agents is their solubility in oil, the role of chemical structure in affecting anesthetic targets has been obscured. In this work, we use an intense beam of light to assess the effect of general anesthetics on the capacity of fruit flies to sense a noxious stimulus and respond to it. By examining the effect of halothane-resistant (har) mutations on the potency of various volatile anesthetics in this assay, we establish similarities and differences between these agents that highlights the way chemical structure influences anesthetic action. In general, the potencies of anesthetics with different chemical structure are affected to different extents by one or more har mutations. However, three anesthetics of related structure (enflurane, isoflurane, and desflurane) show quantitatively indistinguishable alterations in potency in each of four genetic tests. These results not only identify important structural features of anesthetics but also place limits on the classical view that all anesthetics act at a common target. JF - Proceedings of the National Academy of Sciences, USA AU - Campbell, D B AU - Nash, HA AD - Lab. Mol. Biol., NIMH, Bethesda, MD 20892-0036, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2135 EP - 2139 VL - 91 IS - 6 SN - 0027-8424, 0027-8424 KW - har KW - mutations KW - halothane KW - effects on KW - CSA Neurosciences Abstracts; Entomology Abstracts; Toxicology Abstracts; Genetics Abstracts KW - assays KW - anesthetics KW - geotaxis KW - resistance KW - Drosophila KW - N3 11014:Pain & analgesia (including headache) KW - N3 11061:Invertebrate nervous systems KW - X 24117:Biochemistry KW - G 07366:Insects/arachnids KW - N3 11115:Neurogenetics KW - Z 05183:Toxicology & resistance KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16830335?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Use+of+Drosophila+mutants+to+distinguish+among+volatile+general+anesthetics&rft.au=Campbell%2C+D+B%3BNash%2C+HA&rft.aulast=Campbell&rft.aufirst=D&rft.date=1994-01-01&rft.volume=91&rft.issue=6&rft.spage=2135&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 - Drosophila; resistance; anesthetics; geotaxis; assays ER - TY - JOUR T1 - New dawn of cannabinoid pharmacology AN - 16797899; 3752820 AB - The initial demonstration of the existence of a cannabinoid receptor in 1988 suggested the presence of endogenous cannabimimetic ligands. The cloning of a cannabinoid receptor in 1990 gave hope that the identification of receptor subtypes would follow, thus enabling medicinal chemists to develop drugs with selective actions. The recent discovery of anandamide, an endogenous cannabimimetic eicosanoid, and the cloning of a peripheral cannabinoid receptor have opened the door to a new era in cannabinoid pharmacology. JF - Trends in Pharmacological Sciences AU - Devane, WA AD - Lab. Cell Biol., NIMH, Build. 36/Rm 3A-17, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 40 EP - 41 VL - 15 IS - 2 SN - 0165-6147, 0165-6147 KW - cannabinoid receptors KW - anandamide KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - reviews KW - pharmacology KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16797899?accountid=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=Trends+in+Pharmacological+Sciences&rft.atitle=New+dawn+of+cannabinoid+pharmacology&rft.au=Devane%2C+WA&rft.aulast=Devane&rft.aufirst=WA&rft.date=1994-01-01&rft.volume=15&rft.issue=2&rft.spage=40&rft.isbn=&rft.btitle=&rft.title=Trends+in+Pharmacological+Sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - pharmacology; reviews ER - TY - JOUR T1 - An arcane role of DNA in transcription activation AN - 16780864; 3741580 AB - The mechanism by which the cAMP receptor protein (CRP) activates transcription has been investigated using the lac promoter of Escherichia coli. For transcription activation, an interaction between DNA-bound CRP and RNA polymerase is not sufficient. CRP must bind to a site in the same DNA and close to the promoter. CRP action requires an intact spacer DNA to provide a rigid support in building a CRP-RNA polymerase protein bridge or to allow a conformational change in the DNA to be transmitted to the lac promoter using the protein bridge as a structural support. JF - Proceedings of the National Academy of Sciences, USA AU - Ryu, S AU - Garges, SAdhya S AD - Lab. Mol. Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 8582 EP - 8586 VL - 91 IS - 18 SN - 0027-8424, 0027-8424 KW - CRP protein KW - lac gene KW - DNA-directed RNA polymerase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA KW - Escherichia coli KW - N 14930:Transcription factors KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16780864?accountid=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=An+arcane+role+of+DNA+in+transcription+activation&rft.au=Ryu%2C+S%3BGarges%2C+SAdhya+S&rft.aulast=Ryu&rft.aufirst=S&rft.date=1994-01-01&rft.volume=91&rft.issue=18&rft.spage=8582&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; DNA ER - TY - JOUR T1 - The homologous operons for P1 and P7 plasmid partition are autoregulated from dissimilar operator sites AN - 16773135; 3536253 AB - The plasmid-partition regions of the P1 and P7 plasmid prophages in Escherichia coli are homologues which each encode two partition proteins, ParA and ParB. The equivalent P1 and P7 proteins are closely related. In each case, the proteins are encoded by an operon that is autoregulated by the ParA and ParB proteins in concert. This regulation is species-specific, as the P1 proteins are unable to repress the P7 par operon and vice versa. The homologous ParA proteins are primarily responsible for repression and bind to regions that overlap the operon promoter in both cases. The DNA-binding domain of the P7 autorepressor lies in the amino-terminal end of the P7 ParA protein. This region includes a helix-turn-helix motif that has a clear counterpart in the P1 ParA sequence. However, despite the common regulatory mechanism and the similarity of the proteins involved in repression, the promoter-operator sequences of these two operons are very different in sequence and organization. The operator is located downstream of the promoter in P1 and upstream of it in P7, and the two regions show little, if any, homology. How these differences may have arisen from a common ancestral form is discussed. JF - Molecular Microbiology AU - Hayes, F AU - Radnedge, L AU - Davis, MA AU - Austin, S J AD - Lab. Chromosome Biol., ABL-Basic Res. Program, NCI-Frederick Cancer Res. and Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 249 EP - 260 VL - 11 IS - 2 SN - 0950-382X, 0950-382X KW - plasmid P1 KW - plasmid P7 KW - ParA protein KW - ParB protein KW - P1 protein KW - P7 protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - domains KW - promoters KW - operons KW - DNA KW - repression KW - binding KW - plasmids KW - J 02760:Plasmids KW - G 07200:P PLASMIDS UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16773135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=The+homologous+operons+for+P1+and+P7+plasmid+partition+are+autoregulated+from+dissimilar+operator+sites&rft.au=Hayes%2C+F%3BRadnedge%2C+L%3BDavis%2C+MA%3BAustin%2C+S+J&rft.aulast=Hayes&rft.aufirst=F&rft.date=1994-01-01&rft.volume=11&rft.issue=2&rft.spage=249&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 - plasmids; operons; promoters; repression; DNA; binding; domains ER - TY - JOUR T1 - Differential activity of Rickettsia rickettsii ompA and ompB promoter regions in a heterologous reporter gene system AN - 16757524; 3725652 AB - The outer membrane of the Gram-negative obligate intracellular parasite Rickettsia rickettsii contains two large surface protein antigens with approximate molecular masses of 200 and 135 kDa termed rOmpA and rOmpB, respectively. rOmpB is the most abundant protein in the outer membrane, while rOmpA is a relatively minor constituent. Densitometry of intrinsically radiolabelled protein profiles from R. rickettsii-infected Vero cells indicated a molar ratio of approximately 1:9 between rOmpA and rOmpB. The putative promoter-5' untranslated regions (5' UTR) from their recently characterized genes (rompA and rompB) were placed in the promoter assay vector pKK232-8 to test whether these elements conserve aspects of differential expression in a heterologous host-reporter system. Primer extension analysis of RNA from Escherichia coli clones containing the constructs indicated that E. coli RNA polymerase faithfully utilizes rompA and rompB transcription start sites identified previously in R. rickettsii. The rompB insert directs 28-fold higher levels of chloramphenicol acetyl transferase activity than the rompA insert. JF - Microbiology AU - Policastro, P F AU - Hackstadt, T AD - Lab. Intracell. Parasites, Rocky Mount. Lab., NIAID/NIH, Hamilton, MO 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 2941 EP - 2949 VL - 140 IS - 11 SN - 1350-0872, 1350-0872 KW - rompA gene KW - rompB gene KW - outer membrane proteins KW - rOmpB protein KW - rOmpA protein KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - promoters KW - Rickettsia rickettsii KW - G 07321:GENERAL KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16757524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Differential+activity+of+Rickettsia+rickettsii+ompA+and+ompB+promoter+regions+in+a+heterologous+reporter+gene+system&rft.au=Policastro%2C+P+F%3BHackstadt%2C+T&rft.aulast=Policastro&rft.aufirst=P&rft.date=1994-01-01&rft.volume=140&rft.issue=11&rft.spage=2941&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Rickettsia rickettsii; promoters ER - TY - JOUR T1 - The effects of induction conditions on production of a soluble anti-tumor sFv in Escherichia coli AN - 16735885; 3716737 AB - CC49 is a second generation monoclonal antibody (mAb) with high affinity to a pancarcinoma antigen, TAG-72. A single-chain Fv (sFv) of CC49 may have a role in managing human carcinomas. Most reported sFvs have been expressed as insoluble products that must be solubilized and renatured. Soluble sFv expression is advantageous as activity can be assayed directly from the periplasmic fraction. Also, gene-level immunoconjugates may not be amenable to refolding protocols. Using a vector that carries the tac promoter and omp A signal, we have examined the effects of four variables on the expression and accumulation of soluble CC49 sFv: (i) linker sequence joining V sub(L) and V sub(H), (ii) isopropylthio- beta -D-galactoside concentration for induction, (iii) temperature, and (iv) the addition of non-metabolizable sugars to the medium. We have been able to demonstrate, using rapidly prepared periplasmic extracts, that the yield of soluble sFv improves by the addition of 0.4 M sucrose to the medium and by inducing expression with a very low concentration of IPTG (0.02-0.03 mM). Under these induction conditions periplasmic extracts demonstrate increased expression of the sFv, as shown by the larger amount of a 27 kDa band on SDS-polyacrylamide gel, and an increased ability to inhibit binding of the mAb CC49 to immobilized tumor extracts. JF - Protein Engineering AU - Sawyer, J R AU - Schlom, J AU - Kashmiri, SVS AD - Lab. Tumor Immunol. Biol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1401 EP - 1406 VL - 7 IS - 11 SN - 0269-2139, 0269-2139 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Escherichia coli KW - monoclonal antibodies KW - antitumor agents KW - W3 33370:Antibiotics 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/16735885?accountid=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=Protein+Engineering&rft.atitle=The+effects+of+induction+conditions+on+production+of+a+soluble+anti-tumor+sFv+in+Escherichia+coli&rft.au=Sawyer%2C+J+R%3BSchlom%2C+J%3BKashmiri%2C+SVS&rft.aulast=Sawyer&rft.aufirst=J&rft.date=1994-01-01&rft.volume=7&rft.issue=11&rft.spage=1401&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - monoclonal antibodies; antitumor agents; Escherichia coli ER - TY - JOUR T1 - Tuberculosis prevention practices and perspectives of physicians in Dekalb County, GA AN - 16728467; 3719390 AB - Knowing the reasons some physicians do not adhere to the disease prevention and treatment recommendations of expert committees can assist in the development of future recommendations more likely to be adopted by physicians. The authors describe the attitudes and practices of physicians relative to tuberculosis prevention in DeKalb County, GA. Tuberculosis is an important problem in the county, which includes part of the City of Atlanta, as well as suburban areas. Questionnaires for anonymous reply were mailed to 1,621 physicians in the county in 1991, and 848 (53 percent) were completed and returned. The final sample was 793 physicians, who were grouped into 5 specialty areas. Primary care physicians were the group most commonly involved in specific tuberculosis screening and prevention activities. Medical and pediatric specialists, surgeons, obstetricians-gynecologists, and other physicians were significantly less likely to be involved in such activities. Given that primary care physicians constitute a decreasing proportion of physicians in the United States, the findings suggest the importance of ensuring that future strategies for tuberculosis prevention take into account the increasingly specialized nature of the medical practice environment. JF - Public Health Reports AU - Miles Braun, M AU - Wiesner, P J AD - NIH, NCI, EPN 443, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 259 EP - 265 VL - 109 IS - 2 SN - 0033-3549, 0033-3549 KW - Microbiology Abstracts B: Bacteriology KW - tuberculosis KW - prophylaxis KW - medical personnel KW - USA, Georgia KW - public health KW - J 02910:Miscellaneous topics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16728467?accountid=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=Public+Health+Reports&rft.atitle=Tuberculosis+prevention+practices+and+perspectives+of+physicians+in+Dekalb+County%2C+GA&rft.au=Miles+Braun%2C+M%3BWiesner%2C+P+J&rft.aulast=Miles+Braun&rft.aufirst=M&rft.date=1994-01-01&rft.volume=109&rft.issue=2&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Public+Health+Reports&rft.issn=00333549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Georgia; tuberculosis; medical personnel; prophylaxis; public health ER - TY - JOUR T1 - Mother-cub relationships in giant pandas in the Qinling Mountains, China, with comment on rescuing abandoned cubs AN - 16722603; 3708875 AB - Six cases of mother-cub relationships in wild giant pandas (Ailuropoda melanoleuca) were observed in the Qinling Mountains, China. It was found that panda cubs are normally left alone in the den for 4-8 h while mothers forage. The mother's absence during bouts of foraging should be considered when rescuing abandoned cubs in order to avoid adding to the decline of the wild population. JF - Zoo Biology AU - Lu, Zhi AU - Pan, Wenshi AU - Harkness, J AD - Lab. Viral Carcinog., NCI-FCDRC, Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 567 EP - 568 VL - 13 IS - 6 SN - 0733-3188, 0733-3188 KW - China KW - Animal Behavior Abstracts; Ecology Abstracts KW - foraging behavior KW - maternal behavior KW - Ailuropoda melanoleuca KW - D 04672:Mammals KW - Y 25447:Mammals (excluding primates) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16722603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Zoo+Biology&rft.atitle=Mother-cub+relationships+in+giant+pandas+in+the+Qinling+Mountains%2C+China%2C+with+comment+on+rescuing+abandoned+cubs&rft.au=Lu%2C+Zhi%3BPan%2C+Wenshi%3BHarkness%2C+J&rft.aulast=Lu&rft.aufirst=Zhi&rft.date=1994-01-01&rft.volume=13&rft.issue=6&rft.spage=567&rft.isbn=&rft.btitle=&rft.title=Zoo+Biology&rft.issn=07333188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ailuropoda melanoleuca; maternal behavior; foraging behavior ER - TY - JOUR T1 - Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates AN - 16709209; 3700843 AB - Neisseria gonorrhoeae homologues of gyrA and parC have been identified using hybridization probes generated from conserved regions of diverse gyrA genes. These genes have been tentatively identified as gyrA and parC, based on predicted amino acid sequence homologies to known GyrA homologues from numerous bacterial species and to ParC from Escherichia coli and Salmonella typhimurium. The gyrA gene maps to a physical location distant from the gyrB locus on the gonococcal chromosome, which is similar to the situation found in E. coli. The parC gene is not closely linked (i.e. greater than 9 kb) to an identifiable parE gene in N. gonorrhoeae. The gonococcal GyrA is slightly larger than its E. coli homologue and contains several small insertions near the C-terminus of the predicted open reading frame. A series of ciprofloxacin-resistant mutants were selected by passage of N. gonorrhoeae on increasing concentrations of the antibiotic. Sequential passage resulted in the selection of isolates with minimum inhibitory concentrations approximately 10 000-fold higher than the parental strain. Mutations within gyrA resulted in low to moderate levels of resistance, while strains with high-level resistance acquired analogous mutations in both gyrA and parC. Resistance mutations were readily transferred between N. gonorrhoeae strains by transformation. The frequencies of transformation, resulting in different levels of ciprofloxacin resistance, further support the notion that both gyrA and parC genes are involved in the establishment of extreme levels of ciprofloxacin resistance. JF - Molecular Microbiology AU - Belland, R J AU - Morrison, S G AU - Ison, C AU - Huang, WM AD - Lab. Microbial Struct. Funct., Rocky Mountain Lab., NIAID/NIH, Hamilton, MT 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 371 EP - 380 VL - 14 IS - 2 SN - 0950-382X, 0950-382X KW - gyrA gene KW - parC gene KW - ciprofloxacin KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - mutation KW - Salmonella typhimurium KW - Neisseria gonorrhoeae KW - nucleotide sequence KW - Escherichia coli KW - resistance KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16709209?accountid=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=Neisseria+gonorrhoeae+acquires+mutations+in+analogous+regions+of+gyrA+and+parC+in+fluoroquinolone-resistant+isolates&rft.au=Belland%2C+R+J%3BMorrison%2C+S+G%3BIson%2C+C%3BHuang%2C+WM&rft.aulast=Belland&rft.aufirst=R&rft.date=1994-01-01&rft.volume=14&rft.issue=2&rft.spage=371&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; Escherichia coli; Salmonella typhimurium; mutation; resistance; nucleotide sequence ER - TY - JOUR T1 - Identification and characterization of an intervening sequence within the 23S ribosomal RNA genes of Campylobacter jejuni AN - 16678168; 3688452 AB - Campylobacter jejuni is a significant cause of bacterial enteritis in humans. Three of seven C. jejuni isolates examined were found to contain fragmented 23S rRNA. The occurrence of fragmented 23S rRNA correlated with the presence of an intervening sequence (IVS) within the 23S rRNA genes. The IVS is 157 nucleotides in length and replaces an eight nucleotide sequence in the 23S rRNA genes of C. jejuni isolates that contain intact 23S rRNA. The two ends of the IVS share 31 bases of complementarity that could form a stem-loop structure. Fragmentation of the 23S ribosomal RNA results from the excision of the IVS from the transcribed RNA; the 3' cleavage site maps within the putative stem-loop formed by the IVS. Southern hybridization analysis revealed that the IVS is not present in the genomes of isolates that contain intact 23S rRNA, suggesting that the IVS is not derived from Campylobacter chromosomal sequences. The C. jejuni IVS is located at a position analogous to that of the IVSs found in both Salmonella and Yersinia spp. JF - Molecular Microbiology AU - Konkel, ME AU - Marconi, R T AU - Mead, D J AU - Cieplak, W Jr AD - Lab. Vectors Path., Rocky Mountain Lab., NIAID/NIH, Hamilton, MN 59840, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 235 EP - 241 VL - 14 IS - 2 SN - 0950-382X, 0950-382X KW - rRNA 23S KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - characterization KW - nucleotide sequence KW - identification KW - Campylobacter jejuni KW - N 14414:Structure and sequence KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16678168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Identification+and+characterization+of+an+intervening+sequence+within+the+23S+ribosomal+RNA+genes+of+Campylobacter+jejuni&rft.au=Konkel%2C+ME%3BMarconi%2C+R+T%3BMead%2C+D+J%3BCieplak%2C+W+Jr&rft.aulast=Konkel&rft.aufirst=ME&rft.date=1994-01-01&rft.volume=14&rft.issue=2&rft.spage=235&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 - Campylobacter jejuni; identification; characterization; nucleotide sequence ER - TY - JOUR T1 - Differential repair of UV damage in a developmentally regulated gene of Dictyostelium discoideum AN - 16676744; 3690383 AB - The repair of cyclobutane pyrimidine dimers was measured under non-replicating conditions in a 2054-bp fragment of a cAMP-inducible cysteine proteinase (CP2) gene in D. discoideum. Overall genomic repair was unaffected by cAMP. The removal of dimers from CP2 in the wild-type NP2 cells as quantified using T4 endonuclease V was independent of transcription and was the same as in the overall genome. In a UV-sensitive radC mutant in which the rate of overall dimer removal was previously shown to be reduced, the initial rate of dimer removal in the uninduced CP2 gene (-cAMP) was 3-fold lower compared to the induced gene (+cAMP), which repair was identical to that for the induced and uninduced states of NP2. D. discoideum may have two pathways for repairing dimers. One, effective in the wild-type strain but of reduced efficiency in radC repairs dimers equally well independent of transcription and at about the same rate as in the overall genome. A second pathway, retained in radC, repairs dimers more slowly in the overall genome and in the uninduced CP2 gene while undergoing the wild-type rate of repair in the transcriptionally active gene. Hence radC has reduced ability to repair transcriptionally inactive DNA, a defect similar to that of xeroderma pigmentosum group C. JF - Mutation Research AU - Mauldin, S K AU - Freeland, T M AU - Deering, R A AD - NIEHS, P.O. Box 12233, MD C2-10, Research Triangle Park, NC 27709, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 187 EP - 198 VL - 314 IS - 2 SN - 0921-8777, 0921-8777 KW - cysteine proteinase KW - CP2 gene KW - Genetics Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Toxicology Abstracts KW - Dictyostelium discoideum KW - U.V. radiation KW - DNA repair KW - X 24210:Radiation & radioactive materials KW - K 03081:Protozoa KW - G 07233:Radiation (U.V.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16676744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Differential+repair+of+UV+damage+in+a+developmentally+regulated+gene+of+Dictyostelium+discoideum&rft.au=Mauldin%2C+S+K%3BFreeland%2C+T+M%3BDeering%2C+R+A&rft.aulast=Mauldin&rft.aufirst=S&rft.date=1994-01-01&rft.volume=314&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=09218777&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dictyostelium discoideum; U.V. radiation; DNA repair ER - TY - JOUR T1 - Cocaine-induced conditioned taste aversions: Comparisons between effects in LEW/N and F344/N rat strains AN - 16667160; 3684110 AB - Recent studies have found the LEW/N rat self-administers drugs of abuse at higher rates than the F344/N rat, suggesting a genetic predisposition toward the abuse potential of drugs. The current study compared the acquisition of a conditioned taste aversion (CTA) to cocaine in these strains. During an initial 20-min daily session a 0.1% saccharin solution was available and a dose of cocaine was given immediately after that session. Water was available during sessions on the following 3 days. Fluid consumption was assessed over three saccharin/water cycles, and a final saccharin session. Vehicle injections that followed exposure to saccharin had no effect on subsequent saccharin consumption. In contrast, when cocaine followed exposure to saccharin, rates of saccharin consumption decreased over successive saccharin sessions in a dose-related manner in both strains. The lowest dose decreased consumption in LEW/N rats but not in F344/N rats. An intermediate dose decreased consumption maximally in LEW/N rats and only marginally in F344/N rats. The highest dose decreased consumption completely in LEW/N rats and almost completely in F344/N rats. These findings demonstrate that significant differences in sensitivity to stimuli paired with cocaine occur between these strains. These differences are consistent with previous reports that the LEW/N rat is uniquely sensitive to both behavioral and biochemical effects of drugs of abuse. The current report extends this sensitivity to the noxious effects of these drugs. To the extent that noxious and reinforcing effects of cocaine are unrelated, these results suggest that the LEW/N rat does not exhibit a genetic predisposition to factors related only to the abuse potential of drugs. JF - Psychopharmacology AU - Glowa, J R AU - Shaw, A E AU - Riley, AL AD - Behav. Pharmacol. Unit, LMC/NIDDK, Build. 14D, Rm 311, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 229 EP - 232 VL - 114 IS - 2 SN - 0033-3158, 0033-3158 KW - cocaine KW - rats KW - Toxicology Abstracts; Chemoreception Abstracts; Animal Behavior Abstracts; CSA Neurosciences Abstracts KW - conditioning KW - behavioral genetics KW - taste aversion learning KW - Y 25517:Mammals (excluding primates) KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse KW - R 18058:Learning & conditioning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16667160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Cocaine-induced+conditioned+taste+aversions%3A+Comparisons+between+effects+in+LEW%2FN+and+F344%2FN+rat+strains&rft.au=Glowa%2C+J+R%3BShaw%2C+A+E%3BRiley%2C+AL&rft.aulast=Glowa&rft.aufirst=J&rft.date=1994-01-01&rft.volume=114&rft.issue=2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - taste aversion learning; behavioral genetics; conditioning ER - TY - CONF T1 - Policies of tariffs. National report: P.R. China AN - 16638107; 3631358 AB - Tariffs of water supply are very important for the management, operation and maintenance of water-works systems and to guarantee development of the water industry. Water supply has been considered as a sort of welfare during the past 30 years after the foundation of the PR China. On the one hand we expanded water supply systems in urban areas and, on the other hand we improved the people's living standard by decreasing the water rate. Lower water rates played a positive role in improving people's living standards for a limited period, but with the increase of the population and inflation and the developing of the economy, more and more water works companies lost money. This led to a heavy load on government finance and the development of water supply was constrained. It also led to the unreasonable water consumption and waste of water resources, etc. The central government wish to solve the problem through the 8th and 9th Five-Year Plans. Our aim is that the domestic rate can be cost recovery and a little interest, and the industrial and commercial users pay by a Reasonable Tariff. JF - Water Supply AU - Yong, Xiao Shao Y1 - 1994 PY - 1994 DA - 1994 SP - IR3 EP - 19-IR3-20 VL - 12 IS - 1-2 KW - Water Resources Abstracts KW - pricing KW - water supply KW - utilities KW - tariff KW - government finance KW - China, People's Rep. KW - water costs KW - economic aspects KW - SW 4030:Cost allocation, cost sharing, pricing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16638107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Awaterresources&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Water+Supply&rft.atitle=Policies+of+tariffs.+National+report%3A+P.R.+China&rft.au=Yong%2C+Xiao+Shao&rft.aulast=Yong&rft.aufirst=Xiao&rft.date=1994-01-01&rft.volume=12&rft.issue=1-2&rft.spage=IR3&rft.isbn=&rft.btitle=&rft.title=Water+Supply&rft.issn=07351917&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Analysis of the rnc locus of Coxiella burnetii AN - 16630676; 3671060 AB - A 3.2 kb EcoRI genomic DNA fragment of Coxiella burnetii was isolated by virtue of its ability to suppress mucoidy in Escherichia coli. Nucleotide sequence analysis revealed the presence of the genes homologous to rnc, era and recO of E. coli. Suppression of capsule synthesis, measured by beta -galactosidase expression in lon super(-) cps-lac fusion strains of E. coli, is caused by gene-dosage effects of the plasmid-borne rnc genes of either C. burnetii or E. coli. The rnc gene of C. burnetii complemented rnc super(-) E. coli hosts for lambda plaque morphology and stimulation of lambda N gene expression. We also demonstrated heterologous complementation of an E. coli strain defective for the expression of Era, an essential protein in E. coli, using the plasmid-borne C. burnetii era. Under the control of the bacteriophage lambda P sub(L) promoter, this 3.2 kb EcoRI DNA fragment directed the synthesis in E. coli of three proteins with approximate molecular masses of 35, 27 and 25 kDa. Antibodies against purified E. coli Era protein cross-reacted with the 35 kDa protein of C. burnetii on Western blots. JF - Molecular Microbiology AU - Zuber, M AU - Hoover, T A AU - Powell, B S AU - Court, D L AD - Mol. Control Genet. Sect., Lab. Chromosome Biol., ABL-Basic Res. Prog., NCI-Frederick Cancer Res. Dev. Cent., Frederick, MD 21702, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 291 EP - 300 VL - 14 IS - 2 SN - 0950-382X, 0950-382X KW - rnc gene KW - beta -galactosidase KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - nucleotide sequence KW - Coxiella burnetii KW - Escherichia coli KW - G 07321:GENERAL KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16630676?accountid=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=Analysis+of+the+rnc+locus+of+Coxiella+burnetii&rft.au=Zuber%2C+M%3BHoover%2C+T+A%3BPowell%2C+B+S%3BCourt%2C+D+L&rft.aulast=Zuber&rft.aufirst=M&rft.date=1994-01-01&rft.volume=14&rft.issue=2&rft.spage=291&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 - Coxiella burnetii; Escherichia coli; nucleotide sequence ER - TY - JOUR T1 - Dietary factors and second primary cancers: A follow-up of oral and pharyngeal cancer patients AN - 16629911; 3667143 AB - To investigate the possible relationship between dietary factors and the development of multiple primary cancer, a nested case-control study was carried out within a cohort of 1,090 oral and pharyngeal cancer patients. This patient group, enrolled in 1984-1985 in a population-based case-control study conducted in four areas of the United States, was followed up through June 1989 for the occurrence of second primary cancer. Information on a number of risk factors, including diet, ascertained from interviews conducted at baseline (1984-1985) and at follow-up were compared between 80 patients with histologically confirmed second primary cancers (39% in the upper aerodigestive tract, 32% in the lung, 29% elsewhere) and 189 sex- and survival-matched control patients free of second cancers. Although few significant trends emerged, the results were suggestive of a protective effect provided by higher intake of vegetables. Risk of second primary cancers was 40-60% lower among those with the highest levels of intake for total vegetables and most vegetable subgroups, including dark yellow, cruciferous, and green leafy vegetables and legumes. Risks were also nonsignificantly lower among those with high consumption of vitamin C and carotenoids, with the adverse effects of alcohol being most evident among heavy drinkers with low vitamin C or carotenoid intake. There was also some evidence of an interaction between smoking and vitamin C consumption, but numbers of nonsmokers were small. Among other dietary factors considered, positive associations were found with increasing consumption of meats, liver, and retinol. The findings suggest that dietary factors contribute along with alcohol and smoking to the excess risks of second primary cancers among patients with oral and pharyngeal cancers. JF - Nutrition and Cancer AU - Day, G L AU - Shore, R E AU - Blot, W J AU - McLaughlin, J K AU - Austin, D F AU - Greenberg, R S AU - Liff, J M AU - Preston-Martin, S AU - Sarkar, S AU - Schoenberg, J B AD - Epidemiol. and Biostat. Prog., Div. Cancer Etiol., NCI/NIH, Bethesda, MD 20892, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 223 EP - 232 VL - 21 IS - 3 SN - 0163-5581, 0163-5581 KW - foods KW - vitamins KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - diets KW - nutrition KW - USA KW - food KW - cancer KW - X 24120:Food, additives & contaminants KW - R2 23060:Medical and environmental health KW - H SM10.21:CANCER UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16629911?accountid=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=Nutrition+and+Cancer&rft.atitle=Dietary+factors+and+second+primary+cancers%3A+A+follow-up+of+oral+and+pharyngeal+cancer+patients&rft.au=Day%2C+G+L%3BShore%2C+R+E%3BBlot%2C+W+J%3BMcLaughlin%2C+J+K%3BAustin%2C+D+F%3BGreenberg%2C+R+S%3BLiff%2C+J+M%3BPreston-Martin%2C+S%3BSarkar%2C+S%3BSchoenberg%2C+J+B&rft.aulast=Day&rft.aufirst=G&rft.date=1994-01-01&rft.volume=21&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; cancer; nutrition; diets; food; vitamins ER - TY - JOUR T1 - Folate and cancer: A review of the literature AN - 16619382; 3654292 AB - Folate, a water-soluble vitamin, part of the vitamin B complex, plays an important role in methylation reactions and DNA/RNA synthesis. This review examines the experimental and epidemiological evidence for the association between folate status and risk of cancer. Data have accumulated indicating that low folate status may promote carcinogenesis. Low folate levels are associated with cytogenetic abnormalities in vivo and in vitro. Findings from animal studies are conflicting and suggest that the effect of folate on neoplasia depends on factors such as the animal and tumor model, the type, timing, dose, and length of application of carcinogen, the stage of carcinogenesis, and the level and form of folate administered. Epidemiological studies examined the association between folate and cancer of the cervix, colorectum, lung, esophagus, and brain and suggest that low folate status may play an important role early in the neoplastic process. The potential for inhibition of precursor lesions in the cervix and colorectum, namely, cervical intraepithelial neoplasia and adenomatous polyps, respectively, is of particular interest. Additional research designed to clarify the role of folate in carcinogenesis is warranted. JF - Nutrition and Cancer AU - Glynn, SA AU - Albanes, D AD - NCI, Cancer Prev. Stud. Branch, NIH, Rockville, MD 20852, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 101 EP - 119 VL - 22 IS - 2 SN - 0163-5581, 0163-5581 KW - vitamins KW - folate KW - Risk Abstracts KW - nutrition KW - cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16619382?accountid=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=Nutrition+and+Cancer&rft.atitle=Folate+and+cancer%3A+A+review+of+the+literature&rft.au=Glynn%2C+SA%3BAlbanes%2C+D&rft.aulast=Glynn&rft.aufirst=SA&rft.date=1994-01-01&rft.volume=22&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Nutrition+and+Cancer&rft.issn=01635581&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - nutrition; cancer ER - TY - JOUR T1 - Crystal structure of the catalytic domain of HIV-1 integrase: Similarity to other polynucleotidyl transferases AN - 16601011; 3661646 AB - HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 angstrom resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with an extensive solvent-inaccessible interface of 1300 angstrom super(2) per monomer. JF - Science (Washington) AU - Dyda, F AU - Hickman, AB AU - Jenkins, T M AU - Engelman, A AU - Craigie, R AU - Davies AD - Lab. Mol. Biol., NIDDK, NIH, Bethesda, MD 20892-0560, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 1981 EP - 1986 VL - 266 IS - 5193 SN - 0036-8075, 0036-8075 KW - integrase KW - polynucleotidyl transferase KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - human immunodeficiency virus 1 KW - crystal structure KW - V 22002:AIDS: Molecular and in vitro aspects KW - N 14740:Miscellaneous KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16601011?accountid=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=Science+%28Washington%29&rft.atitle=Crystal+structure+of+the+catalytic+domain+of+HIV-1+integrase%3A+Similarity+to+other+polynucleotidyl+transferases&rft.au=Dyda%2C+F%3BHickman%2C+AB%3BJenkins%2C+T+M%3BEngelman%2C+A%3BCraigie%2C+R%3BDavies&rft.aulast=Dyda&rft.aufirst=F&rft.date=1994-01-01&rft.volume=266&rft.issue=5193&rft.spage=1981&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - crystal structure; human immunodeficiency virus 1 ER - TY - JOUR T1 - A molecular chaperone, ClpA, functions like DnaK and DnaJ AN - 16591396; 3685709 AB - The two major molecular chaperone families that mediate ATP-dependent protein folding and refolding are the heat shock proteins Hsp60s (GroEL) and Hsp70s (DnaK). Clp proteins, like chaperones, are highly conserved, present in all organisms, and contain ATP and polypeptide binding sites. We discovered that ClpA, the ATPase component of the ATP-dependent ClpAP protease, is a molecular chaperone. ClpA performs the ATP-dependent chaperone function of DnaK and DnaJ in the in vitro activation of the plasmid P1 RepA replication initiator protein. RepA is activated by the conversion of dimers to monomers. We show that ClpA targets RepA for degradation by ClpP, demonstrating a direct link between the protein unfolding function of chaperones and proteolysis. In another chaperone assay, ClpA protects luciferase from irreversible heat inactivation but is unable to reactivate luciferase. JF - Proceedings of the National Academy of Sciences, USA AU - Wickner, S AU - Gottesman, S AU - Skowyra, D AU - Hoskins, J AU - McKenney, K AU - Maurizi, M R AD - NCI/NIH, Build. 37, Room 2D19, Bethesda, MD 20892-4255, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 12218 EP - 12222 VL - 91 IS - 25 SN - 0027-8424, 0027-8424 KW - ClpA protein KW - Microbiology Abstracts B: Bacteriology KW - heat shock proteins KW - protein folding KW - Escherichia coli KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16591396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+molecular+chaperone%2C+ClpA%2C+functions+like+DnaK+and+DnaJ&rft.au=Wickner%2C+S%3BGottesman%2C+S%3BSkowyra%2C+D%3BHoskins%2C+J%3BMcKenney%2C+K%3BMaurizi%2C+M+R&rft.aulast=Wickner&rft.aufirst=S&rft.date=1994-01-01&rft.volume=91&rft.issue=25&rft.spage=12218&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; protein folding; heat shock proteins ER - TY - JOUR T1 - Is the A-ring lactone of brevetoxin PbTX-3 required for sodium channel orphan receptor binding and activity? AN - 16591329; 3654370 AB - Brevetoxin PbTx-3 and non-toxic derivative 4 were investigated for their abilities to bind to the specific brevetoxin receptor site on rat brain synaptosomes and to modulate the normal function of voltage-gated sodium channels as determined by patch clamping of cultured neurons. Compounds 4 and 5 are produced from PbTx-3 by opening of the A-ring lactone to the saturated and unsaturated diols using sodium borohydride in ethanol. Natural PbTx-3 exhibited tighter binding to rat brain synaptosomes by at least 3 orders of magnitude as determined by competitive radioligand binding experiments, and was also more effective at activating voltage-gated channels. Patch clamping revealed the 3 orders of magnitude greater potency of PbTx-3 toxin over 5, although each produced delayed sodium channel opening and a pronounced delay in inactivation. Conformational modeling of the Brevetoxin B backbone indicates that the two molecules are identical except for the region of the A-Ring lactone. Thus, we conclude that the brevetoxin PbTx-3 backbone requires electrophilic functionality in the region of the lactone in PbTx-3, and that opening of the ring in 5 is sufficient to substantially reduce both binding and activity. JF - Natural Toxins AU - Baden, D G AU - Rein, K S AU - Gawley, R E AU - Jeglitsch, G AU - Adams, D J AD - NIEHS, MFBS Cent., 4600 Rickenbacker Causeway, Miami, FL 33149, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 212 EP - 221 VL - 2 IS - 4 SN - 1056-9014, 1056-9014 KW - analytical techniques KW - biological poisons KW - brevetoxin PbTX-3 KW - brevetoxin PbTX-3 receptors KW - rats KW - sodium channels KW - sodium channels (voltage-gated) KW - toxins KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; CSA Neurosciences Abstracts; ASFA Marine Biotechnology Abstracts; Toxicology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - biochemical analysis KW - Marine KW - neurotoxins KW - target cells KW - receptors KW - algae KW - Ptychodiscus brevis KW - brain KW - marine organisms KW - Q4 27390:Toxins KW - N3 11104:Mammals (except primates) KW - X 24172:Plants KW - Q1 08226:Physiology, biochemistry, biophysics KW - Q5 08524:Public health, medicines, dangerous organisms KW - K 03092:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16591329?accountid=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=Natural+Toxins&rft.atitle=Is+the+A-ring+lactone+of+brevetoxin+PbTX-3+required+for+sodium+channel+orphan+receptor+binding+and+activity%3F&rft.au=Baden%2C+D+G%3BRein%2C+K+S%3BGawley%2C+R+E%3BJeglitsch%2C+G%3BAdams%2C+D+J&rft.aulast=Baden&rft.aufirst=D&rft.date=1994-01-01&rft.volume=2&rft.issue=4&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Natural+Toxins&rft.issn=10569014&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Phycotoxin research. N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - biochemical analysis; neurotoxins; biological poisons; target cells; analytical techniques; receptors; algae; brain; marine organisms; toxins; Ptychodiscus brevis; Marine ER - TY - JOUR T1 - A system for tissue-specific gene targeting: Transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors AN - 16581040; 3660657 AB - Avian leukosis viruses (ALVs) have been used extensively as genetic vectors in avian systems, but their utility in mammals or mammalian cell lines is compromised by inefficient viral entry. We have overcome this limitation by generating transgenic mice that express the receptor for the subgroup A ALV under the control of the chicken alpha sub(sk)-actin promoter. The skeletal muscles of these transgenic animals are susceptible to efficient infection by subgroup A ALV. Because infection is restricted to cell lineages that express the transgene, the method has utility for studies of development and oncogenesis and will provide models for tissue-specific gene therapy. JF - Proceedings of the National Academy of Sciences, USA AU - Federspiel, MJ AU - Bates, P AU - Young, JAT AU - Varmus, HE AU - Hughes, SH AD - NCI-FCRDC, P.O. Box B, Build. 539, Frederick, MD 21702-1201, USA Y1 - 1994 PY - 1994 DA - 1994 SP - 11241 EP - 11245 VL - 91 IS - 23 SN - 0027-8424, 0027-8424 KW - actin KW - avian leukosis virus KW - gene targeting KW - gene therapy KW - retrovirus KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Human Genome Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16581040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+system+for+tissue-specific+gene+targeting%3A+Transgenic+mice+susceptible+to+subgroup+A+avian+leukosis+virus-based+retroviral+vectors&rft.au=Federspiel%2C+MJ%3BBates%2C+P%3BYoung%2C+JAT%3BVarmus%2C+HE%3BHughes%2C+SH&rft.aulast=Federspiel&rft.aufirst=MJ&rft.date=1994-01-01&rft.volume=91&rft.issue=23&rft.spage=11241&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 - 2011-12-14 N1 - SubjectsTermNotLitGenreText - gene therapy; retrovirus; gene targeting; transgenic mice; avian leukosis virus ER - TY - JOUR T1 - Probabilistically-based optimal groundwater remediation planning and decision-making AN - 1429837564; 2013-067697 JF - Proceedings of the International Conference on Computer Methods and Advances in Geomechanics AU - Jacobs, Timothy L AU - Medina, Miguel A AU - Lin, Kuo-Ching AU - Piver, Warren T Y1 - 1994 PY - 1994 DA - 1994 SP - 1091 EP - 1096 PB - [varies], [varies] VL - 8, Vol. 2 KW - United States KW - solute transport KW - hazardous waste KW - contaminant plumes KW - pollutants KW - Monte Carlo analysis KW - statistical analysis KW - waste disposal sites KW - pollution KW - optimization KW - decision-making KW - simulation KW - cost KW - remediation KW - ground water KW - transport KW - planning KW - Hill Air Force Base KW - probability KW - Utah KW - mass transfer KW - uncertainty KW - 22:Environmental geology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1429837564?accountid=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=Proceedings+of+the+International+Conference+on+Computer+Methods+and+Advances+in+Geomechanics&rft.atitle=Probabilistically-based+optimal+groundwater+remediation+planning+and+decision-making&rft.au=Jacobs%2C+Timothy+L%3BMedina%2C+Miguel+A%3BLin%2C+Kuo-Ching%3BPiver%2C+Warren+T&rft.aulast=Jacobs&rft.aufirst=Timothy&rft.date=1994-01-01&rft.volume=8%2C+Vol.+2&rft.issue=&rft.spage=1091&rft.isbn=9054103825&rft.btitle=&rft.title=Proceedings+of+the+International+Conference+on+Computer+Methods+and+Advances+in+Geomechanics&rft.issn=&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - Eighth international conference on Computer methods and advances in geomechanics N1 - Copyright - GeoRef, Copyright 2013, American Geosciences Institute. N1 - Date revised - 2013-01-01 N1 - Number of references - 7 N1 - Document feature - illus. N1 - Last updated - 2013-09-05 N1 - CODEN - #03529 N1 - SubjectsTermNotLitGenreText - contaminant plumes; cost; decision-making; ground water; hazardous waste; Hill Air Force Base; mass transfer; Monte Carlo analysis; optimization; planning; pollutants; pollution; probability; remediation; simulation; solute transport; statistical analysis; transport; uncertainty; United States; Utah; waste disposal sites ER -