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 p